AU2001263035A1 - Methods for treatment of inflammatory diseases - Google Patents
Methods for treatment of inflammatory diseasesInfo
- Publication number
- AU2001263035A1 AU2001263035A1 AU2001263035A AU6303501A AU2001263035A1 AU 2001263035 A1 AU2001263035 A1 AU 2001263035A1 AU 2001263035 A AU2001263035 A AU 2001263035A AU 6303501 A AU6303501 A AU 6303501A AU 2001263035 A1 AU2001263035 A1 AU 2001263035A1
- Authority
- AU
- Australia
- Prior art keywords
- composition
- allantoin
- group
- oil
- propylparaben
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 238000000034 method Methods 0.000 title claims description 198
- 238000011282 treatment Methods 0.000 title description 9
- 208000027866 inflammatory disease Diseases 0.000 title description 3
- 239000000203 mixture Substances 0.000 claims description 640
- POJWUDADGALRAB-UHFFFAOYSA-N allantoin Chemical compound NC(=O)NC1NC(=O)NC1=O POJWUDADGALRAB-UHFFFAOYSA-N 0.000 claims description 329
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 261
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 claims description 180
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 claims description 176
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 claims description 174
- POJWUDADGALRAB-PVQJCKRUSA-N Allantoin Natural products NC(=O)N[C@@H]1NC(=O)NC1=O POJWUDADGALRAB-PVQJCKRUSA-N 0.000 claims description 161
- 229960000458 allantoin Drugs 0.000 claims description 160
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 156
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 claims description 130
- 239000003026 cod liver oil Substances 0.000 claims description 91
- 235000012716 cod liver oil Nutrition 0.000 claims description 91
- 229960000541 cetyl alcohol Drugs 0.000 claims description 90
- 239000003205 fragrance Substances 0.000 claims description 89
- 239000003921 oil Substances 0.000 claims description 89
- 235000019198 oils Nutrition 0.000 claims description 89
- 239000004166 Lanolin Substances 0.000 claims description 88
- 235000019388 lanolin Nutrition 0.000 claims description 88
- 229940039717 lanolin Drugs 0.000 claims description 88
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 claims description 88
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 claims description 88
- 229960003415 propylparaben Drugs 0.000 claims description 88
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 claims description 87
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 claims description 87
- 229960002216 methylparaben Drugs 0.000 claims description 87
- 239000004322 Butylated hydroxytoluene Substances 0.000 claims description 84
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 claims description 84
- 235000010354 butylated hydroxytoluene Nutrition 0.000 claims description 84
- 229940095259 butylated hydroxytoluene Drugs 0.000 claims description 84
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 72
- 239000003755 preservative agent Substances 0.000 claims description 66
- 239000002904 solvent Substances 0.000 claims description 63
- 230000002335 preservative effect Effects 0.000 claims description 62
- GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 claims description 60
- 239000003995 emulsifying agent Substances 0.000 claims description 54
- 239000003974 emollient agent Substances 0.000 claims description 52
- 239000002253 acid Substances 0.000 claims description 48
- UEUXEKPTXMALOB-UHFFFAOYSA-J tetrasodium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O UEUXEKPTXMALOB-UHFFFAOYSA-J 0.000 claims description 48
- 201000010099 disease Diseases 0.000 claims description 47
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 47
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 44
- 239000004615 ingredient Substances 0.000 claims description 44
- 239000007764 o/w emulsion Substances 0.000 claims description 39
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 claims description 36
- SOROIESOUPGGFO-UHFFFAOYSA-N diazolidinylurea Chemical compound OCNC(=O)N(CO)C1N(CO)C(=O)N(CO)C1=O SOROIESOUPGGFO-UHFFFAOYSA-N 0.000 claims description 36
- 229960001083 diazolidinylurea Drugs 0.000 claims description 36
- 229960004418 trolamine Drugs 0.000 claims description 36
- SATHPVQTSSUFFW-UHFFFAOYSA-N 4-[6-[(3,5-dihydroxy-4-methoxyoxan-2-yl)oxymethyl]-3,5-dihydroxy-4-methoxyoxan-2-yl]oxy-2-(hydroxymethyl)-6-methyloxane-3,5-diol Chemical compound OC1C(OC)C(O)COC1OCC1C(O)C(OC)C(O)C(OC2C(C(CO)OC(C)C2O)O)O1 SATHPVQTSSUFFW-UHFFFAOYSA-N 0.000 claims description 35
- 206010014989 Epidermolysis bullosa Diseases 0.000 claims description 35
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims description 35
- 229940082009 galactoarabinan Drugs 0.000 claims description 35
- 235000019333 sodium laurylsulphate Nutrition 0.000 claims description 35
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical group OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims description 34
- 235000021355 Stearic acid Nutrition 0.000 claims description 32
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 claims description 32
- 239000008117 stearic acid Substances 0.000 claims description 32
- 239000002202 Polyethylene glycol Substances 0.000 claims description 31
- 229940096529 carboxypolymethylene Drugs 0.000 claims description 31
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 31
- 229920001223 polyethylene glycol Polymers 0.000 claims description 31
- 208000004210 Pressure Ulcer Diseases 0.000 claims description 30
- 150000002148 esters Chemical class 0.000 claims description 30
- 239000003814 drug Substances 0.000 claims description 27
- 229920000642 polymer Polymers 0.000 claims description 26
- 229940124597 therapeutic agent Drugs 0.000 claims description 26
- 229920001282 polysaccharide Polymers 0.000 claims description 25
- 239000012874 anionic emulsifier Substances 0.000 claims description 24
- 235000013871 bee wax Nutrition 0.000 claims description 24
- 239000012166 beeswax Substances 0.000 claims description 24
- 230000002378 acidificating effect Effects 0.000 claims description 22
- 229920006318 anionic polymer Polymers 0.000 claims description 22
- 235000011187 glycerol Nutrition 0.000 claims description 22
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 claims description 21
- 150000007524 organic acids Chemical class 0.000 claims description 21
- 208000002352 blister Diseases 0.000 claims description 20
- 150000002170 ethers Chemical group 0.000 claims description 19
- 125000004432 carbon atom Chemical group C* 0.000 claims description 18
- 229940100460 peg-100 stearate Drugs 0.000 claims description 18
- 241000208680 Hamamelis mollis Species 0.000 claims description 17
- 229940089116 arnica extract Drugs 0.000 claims description 17
- 229940119217 chamomile extract Drugs 0.000 claims description 17
- 235000020221 chamomile extract Nutrition 0.000 claims description 17
- 239000012875 nonionic emulsifier Substances 0.000 claims description 17
- 229940118846 witch hazel Drugs 0.000 claims description 17
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 claims description 16
- 206010027626 Milia Diseases 0.000 claims description 16
- 235000020759 St. John’s wort extract Nutrition 0.000 claims description 16
- 239000000284 extract Substances 0.000 claims description 16
- 229940075529 glyceryl stearate Drugs 0.000 claims description 16
- 229940099416 st. john's wort extract Drugs 0.000 claims description 16
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 15
- 206010056340 Diabetic ulcer Diseases 0.000 claims description 15
- 206010061218 Inflammation Diseases 0.000 claims description 15
- 230000004054 inflammatory process Effects 0.000 claims description 15
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 14
- 208000025865 Ulcer Diseases 0.000 claims description 14
- 230000036269 ulceration Effects 0.000 claims description 14
- 239000012676 herbal extract Substances 0.000 claims description 13
- 239000003199 leukotriene receptor blocking agent Substances 0.000 claims description 13
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 claims description 13
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 claims description 13
- 150000007530 organic bases Chemical class 0.000 claims description 13
- 150000003431 steroids Chemical class 0.000 claims description 13
- -1 oleyl succinate Chemical compound 0.000 claims description 12
- 229940046000 sodium isostearoyl lactylate Drugs 0.000 claims description 12
- ODFAPIRLUPAQCQ-UHFFFAOYSA-M sodium stearoyl lactylate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC(=O)OC(C)C(=O)OC(C)C([O-])=O ODFAPIRLUPAQCQ-UHFFFAOYSA-M 0.000 claims description 12
- 229940080352 sodium stearoyl lactylate Drugs 0.000 claims description 12
- FOSNFLMXYRQNAF-UHFFFAOYSA-M sodium;2-[2-(16-methylheptadecanoyloxy)propanoyloxy]propanoate Chemical compound [Na+].CC(C)CCCCCCCCCCCCCCC(=O)OC(C)C(=O)OC(C)C([O-])=O FOSNFLMXYRQNAF-UHFFFAOYSA-M 0.000 claims description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 10
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 10
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 10
- 229940073639 ceteareth-6 Drugs 0.000 claims description 10
- 229940081733 cetearyl alcohol Drugs 0.000 claims description 10
- 239000000839 emulsion Substances 0.000 claims description 9
- 150000007522 mineralic acids Chemical class 0.000 claims description 9
- 229920000499 poly(galactose) polymer Polymers 0.000 claims description 9
- 239000011734 sodium Substances 0.000 claims description 9
- 229910052708 sodium Inorganic materials 0.000 claims description 9
- GVGUFUZHNYFZLC-UHFFFAOYSA-N dodecyl benzenesulfonate;sodium Chemical compound [Na].CCCCCCCCCCCCOS(=O)(=O)C1=CC=CC=C1 GVGUFUZHNYFZLC-UHFFFAOYSA-N 0.000 claims description 8
- 229940083542 sodium Drugs 0.000 claims description 8
- 229940080264 sodium dodecylbenzenesulfonate Drugs 0.000 claims description 8
- 229940057950 sodium laureth sulfate Drugs 0.000 claims description 8
- SXHLENDCVBIJFO-UHFFFAOYSA-M sodium;2-[2-(2-dodecoxyethoxy)ethoxy]ethyl sulfate Chemical compound [Na+].CCCCCCCCCCCCOCCOCCOCCOS([O-])(=O)=O SXHLENDCVBIJFO-UHFFFAOYSA-M 0.000 claims description 8
- ADWNFGORSPBALY-UHFFFAOYSA-M sodium;2-[dodecyl(methyl)amino]acetate Chemical compound [Na+].CCCCCCCCCCCCN(C)CC([O-])=O ADWNFGORSPBALY-UHFFFAOYSA-M 0.000 claims description 8
- 229940079862 sodium lauryl sarcosinate Drugs 0.000 claims description 7
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 5
- 150000007529 inorganic bases Chemical class 0.000 claims description 5
- 229940086735 succinate Drugs 0.000 claims description 5
- ZHALDANPYXAMJF-UHFFFAOYSA-N octadecanoate;tris(2-hydroxyethyl)azanium Chemical compound OCC[NH+](CCO)CCO.CCCCCCCCCCCCCCCCCC([O-])=O ZHALDANPYXAMJF-UHFFFAOYSA-N 0.000 claims description 4
- 229940029614 triethanolamine stearate Drugs 0.000 claims description 4
- BTBJBAZGXNKLQC-UHFFFAOYSA-N ammonium lauryl sulfate Chemical group [NH4+].CCCCCCCCCCCCOS([O-])(=O)=O BTBJBAZGXNKLQC-UHFFFAOYSA-N 0.000 claims description 3
- 229940063953 ammonium lauryl sulfate Drugs 0.000 claims description 3
- ZWXYEWJNBYQXLK-UHFFFAOYSA-N azanium;4-dodecoxy-4-oxo-3-sulfobutanoate Chemical compound [NH4+].CCCCCCCCCCCCOC(=O)C(S(O)(=O)=O)CC([O-])=O ZWXYEWJNBYQXLK-UHFFFAOYSA-N 0.000 claims description 3
- BOUCRWJEKAGKKG-UHFFFAOYSA-N n-[3-(diethylaminomethyl)-4-hydroxyphenyl]acetamide Chemical compound CCN(CC)CC1=CC(NC(C)=O)=CC=C1O BOUCRWJEKAGKKG-UHFFFAOYSA-N 0.000 claims description 3
- 125000003827 glycol group Chemical group 0.000 claims 1
- 239000002884 skin cream Substances 0.000 description 57
- 239000006071 cream Substances 0.000 description 51
- 230000006872 improvement Effects 0.000 description 23
- 238000002156 mixing Methods 0.000 description 19
- 238000002360 preparation method Methods 0.000 description 19
- 239000003963 antioxidant agent Substances 0.000 description 18
- 230000003078 antioxidant effect Effects 0.000 description 18
- 235000006708 antioxidants Nutrition 0.000 description 18
- 239000002738 chelating agent Substances 0.000 description 18
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 230000003902 lesion Effects 0.000 description 12
- 239000000820 nonprescription drug Substances 0.000 description 7
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical group OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 6
- 229920002125 Sokalan® Polymers 0.000 description 6
- 230000003247 decreasing effect Effects 0.000 description 6
- 229940093915 gynecological organic acid Drugs 0.000 description 6
- 235000005985 organic acids Nutrition 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 230000000475 sunscreen effect Effects 0.000 description 6
- 239000000516 sunscreening agent Substances 0.000 description 6
- 201000004624 Dermatitis Diseases 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- 210000002414 leg Anatomy 0.000 description 5
- 208000017520 skin disease Diseases 0.000 description 5
- KFDNQUWMBLVQNB-UHFFFAOYSA-N 2-[2-[bis(carboxymethyl)amino]ethyl-(carboxymethyl)amino]acetic acid;sodium Chemical group [Na].[Na].[Na].[Na].OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KFDNQUWMBLVQNB-UHFFFAOYSA-N 0.000 description 4
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
- 210000001217 buttock Anatomy 0.000 description 4
- 230000015556 catabolic process Effects 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 239000003086 colorant Substances 0.000 description 4
- 239000002537 cosmetic Substances 0.000 description 4
- 238000006731 degradation reaction Methods 0.000 description 4
- 238000005562 fading Methods 0.000 description 4
- 230000035876 healing Effects 0.000 description 4
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 4
- SNPLKNRPJHDVJA-ZETCQYMHSA-N D-panthenol Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCCO SNPLKNRPJHDVJA-ZETCQYMHSA-N 0.000 description 3
- 206010020751 Hypersensitivity Diseases 0.000 description 3
- YBGZDTIWKVFICR-JLHYYAGUSA-N Octyl 4-methoxycinnamic acid Chemical compound CCCCC(CC)COC(=O)\C=C\C1=CC=C(OC)C=C1 YBGZDTIWKVFICR-JLHYYAGUSA-N 0.000 description 3
- 229920002385 Sodium hyaluronate Polymers 0.000 description 3
- 229960001631 carbomer Drugs 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 230000001684 chronic effect Effects 0.000 description 3
- 235000014113 dietary fatty acids Nutrition 0.000 description 3
- 229930195729 fatty acid Natural products 0.000 description 3
- 239000000194 fatty acid Substances 0.000 description 3
- 150000004665 fatty acids Chemical class 0.000 description 3
- 239000003906 humectant Substances 0.000 description 3
- 150000001261 hydroxy acids Chemical class 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 150000002632 lipids Chemical class 0.000 description 3
- 229910021645 metal ion Inorganic materials 0.000 description 3
- 229960001679 octinoxate Drugs 0.000 description 3
- DXGLGDHPHMLXJC-UHFFFAOYSA-N oxybenzone Chemical compound OC1=CC(OC)=CC=C1C(=O)C1=CC=CC=C1 DXGLGDHPHMLXJC-UHFFFAOYSA-N 0.000 description 3
- 229960001173 oxybenzone Drugs 0.000 description 3
- 229940101267 panthenol Drugs 0.000 description 3
- 239000011619 pantothenol Substances 0.000 description 3
- 235000020957 pantothenol Nutrition 0.000 description 3
- 239000000419 plant extract Substances 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 229940010747 sodium hyaluronate Drugs 0.000 description 3
- YWIVKILSMZOHHF-QJZPQSOGSA-N sodium;(2s,3s,4s,5r,6r)-6-[(2s,3r,4r,5s,6r)-3-acetamido-2-[(2s,3s,4r,5r,6r)-6-[(2r,3r,4r,5s,6r)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2- Chemical compound [Na+].CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 YWIVKILSMZOHHF-QJZPQSOGSA-N 0.000 description 3
- 239000002562 thickening agent Substances 0.000 description 3
- 239000011782 vitamin Substances 0.000 description 3
- 235000013343 vitamin Nutrition 0.000 description 3
- 229940088594 vitamin Drugs 0.000 description 3
- 229930003231 vitamin Natural products 0.000 description 3
- 239000000341 volatile oil Substances 0.000 description 3
- OZZQHCBFUVFZGT-UHFFFAOYSA-N 2-(2-hydroxypropanoyloxy)propanoic acid Chemical compound CC(O)C(=O)OC(C)C(O)=O OZZQHCBFUVFZGT-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- RFVNOJDQRGSOEL-UHFFFAOYSA-N 2-hydroxyethyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCCO RFVNOJDQRGSOEL-UHFFFAOYSA-N 0.000 description 2
- 239000005711 Benzoic acid Substances 0.000 description 2
- QFOHBWFCKVYLES-UHFFFAOYSA-N Butylparaben Chemical compound CCCCOC(=O)C1=CC=C(O)C=C1 QFOHBWFCKVYLES-UHFFFAOYSA-N 0.000 description 2
- 239000003109 Disodium ethylene diamine tetraacetate Substances 0.000 description 2
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 description 2
- 241000218652 Larix Species 0.000 description 2
- 229920002701 Polyoxyl 40 Stearate Polymers 0.000 description 2
- 206010040851 Skin fragility Diseases 0.000 description 2
- 206010052428 Wound Diseases 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 230000032683 aging Effects 0.000 description 2
- 125000001931 aliphatic group Chemical group 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- 229940003587 aquaphor Drugs 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 235000010323 ascorbic acid Nutrition 0.000 description 2
- 239000011668 ascorbic acid Substances 0.000 description 2
- 229960005070 ascorbic acid Drugs 0.000 description 2
- 235000010233 benzoic acid Nutrition 0.000 description 2
- 230000003115 biocidal effect Effects 0.000 description 2
- 150000001991 dicarboxylic acids Chemical class 0.000 description 2
- 150000007520 diprotic acids Chemical class 0.000 description 2
- 235000019301 disodium ethylene diamine tetraacetate Nutrition 0.000 description 2
- 230000001815 facial effect Effects 0.000 description 2
- 150000002334 glycols Chemical class 0.000 description 2
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 150000002763 monocarboxylic acids Chemical class 0.000 description 2
- 150000007518 monoprotic acids Chemical class 0.000 description 2
- 229940124583 pain medication Drugs 0.000 description 2
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 2
- 239000004584 polyacrylic acid Substances 0.000 description 2
- 201000000744 recessive dystrophic epidermolysis bullosa Diseases 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 229960004889 salicylic acid Drugs 0.000 description 2
- 150000003839 salts Chemical group 0.000 description 2
- 231100000241 scar Toxicity 0.000 description 2
- 230000037390 scarring Effects 0.000 description 2
- 159000000000 sodium salts Chemical class 0.000 description 2
- 150000003628 tricarboxylic acids Chemical class 0.000 description 2
- 150000007521 triprotic acids Chemical class 0.000 description 2
- MTZBBNMLMNBNJL-UHFFFAOYSA-N xipamide Chemical compound CC1=CC=CC(C)=C1NC(=O)C1=CC(S(N)(=O)=O)=C(Cl)C=C1O MTZBBNMLMNBNJL-UHFFFAOYSA-N 0.000 description 2
- RFIMISVNSAUMBU-UHFFFAOYSA-N 2-(hydroxymethyl)-2-(prop-2-enoxymethyl)propane-1,3-diol Chemical compound OCC(CO)(CO)COCC=C RFIMISVNSAUMBU-UHFFFAOYSA-N 0.000 description 1
- QCDWFXQBSFUVSP-UHFFFAOYSA-N 2-phenoxyethanol Chemical compound OCCOC1=CC=CC=C1 QCDWFXQBSFUVSP-UHFFFAOYSA-N 0.000 description 1
- 241000208140 Acer Species 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 208000032544 Cicatrix Diseases 0.000 description 1
- 244000000626 Daucus carota Species 0.000 description 1
- 235000002767 Daucus carota Nutrition 0.000 description 1
- 206010015150 Erythema Diseases 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- 206010053240 Glycogen storage disease type VI Diseases 0.000 description 1
- 241000282414 Homo sapiens Species 0.000 description 1
- 235000017309 Hypericum perforatum Nutrition 0.000 description 1
- 244000141009 Hypericum perforatum Species 0.000 description 1
- 235000005590 Larix decidua Nutrition 0.000 description 1
- 235000007688 Lycopersicon esculentum Nutrition 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 240000003768 Solanum lycopersicum Species 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 235000021307 Triticum Nutrition 0.000 description 1
- 241000209140 Triticum Species 0.000 description 1
- 241001147416 Ursus maritimus Species 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 230000001133 acceleration Effects 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- 208000030961 allergic reaction Diseases 0.000 description 1
- 229940086737 allyl sucrose Drugs 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 229960004365 benzoic acid Drugs 0.000 description 1
- 229940067596 butylparaben Drugs 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 229960004106 citric acid Drugs 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 208000031513 cyst Diseases 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 231100000321 erythema Toxicity 0.000 description 1
- 229960001617 ethyl hydroxybenzoate Drugs 0.000 description 1
- 235000010228 ethyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004403 ethyl p-hydroxybenzoate Substances 0.000 description 1
- NUVBSKCKDOMJSU-UHFFFAOYSA-N ethylparaben Chemical compound CCOC(=O)C1=CC=C(O)C=C1 NUVBSKCKDOMJSU-UHFFFAOYSA-N 0.000 description 1
- 235000013312 flour Nutrition 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 229960004275 glycolic acid Drugs 0.000 description 1
- 238000000265 homogenisation Methods 0.000 description 1
- 230000004968 inflammatory condition Effects 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- XDOFQFKRPWOURC-UHFFFAOYSA-N iso-octadecanoic acid Natural products CC(C)CCCCCCCCCCCCCCC(O)=O XDOFQFKRPWOURC-UHFFFAOYSA-N 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 210000003141 lower extremity Anatomy 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 229940127249 oral antibiotic Drugs 0.000 description 1
- 229960005323 phenoxyethanol Drugs 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 108700004121 sarkosyl Proteins 0.000 description 1
- 230000037387 scars Effects 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000007480 spreading Effects 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000004797 therapeutic response Effects 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000011277 treatment modality Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
- A61K8/04—Dispersions; Emulsions
- A61K8/06—Emulsions
- A61K8/062—Oil-in-water emulsions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/20—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
- A61K8/04—Dispersions; Emulsions
- A61K8/06—Emulsions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/37—Esters of carboxylic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/46—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing sulfur
- A61K8/463—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing sulfur containing sulfuric acid derivatives, e.g. sodium lauryl sulfate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/494—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with more than one nitrogen as the only hetero atom
- A61K8/4946—Imidazoles or their condensed derivatives, e.g. benzimidazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
- A61K8/73—Polysaccharides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
- A61K8/81—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions involving only carbon-to-carbon unsaturated bonds
- A61K8/8141—Compositions of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by only one carboxyl radical, or of salts, anhydrides, esters, amides, imides or nitriles thereof; Compositions of derivatives of such polymers
- A61K8/8147—Homopolymers or copolymers of acids; Metal or ammonium salts thereof, e.g. crotonic acid, (meth)acrylic acid; Compositions of derivatives of such polymers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
- A61K8/84—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions otherwise than those involving only carbon-carbon unsaturated bonds
- A61K8/86—Polyethers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/92—Oils, fats or waxes; Derivatives thereof, e.g. hydrogenation products thereof
- A61K8/927—Oils, fats or waxes; Derivatives thereof, e.g. hydrogenation products thereof of insects, e.g. shellac
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0014—Skin, i.e. galenical aspects of topical compositions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Chemical & Material Sciences (AREA)
- Birds (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Dermatology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Dispersion Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Emergency Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Insects & Arthropods (AREA)
- Zoology (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Cosmetics (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Description
METHODS FOR TREATMENT OF INFLAMMATORY DISEASES by Elliott Farber
CROSS-REFERENCES
This application is a continuation-in-part application of Application Serial No. 09/570,120, entitled "Methods for Treatment of Inflammatory Diseases," filed May 12, 2000 by Elliott Farber, which in turn is a continuation-in-part application of Application Serial No. 09/360,095, entitled "Oil-in- Water Emulsion With Improved Stability," filed July 23, 1999 by Elliott Farber. Both of these prior applications are hereby incorporated in their entirety by this reference.
BACKGROUND OF THE INVENTION
The present invention is directed to improved methods of treating inflammatory skin disease.
Inflammatory skin disease, particularly chronic inflammatory skin disease, is still a major source of morbidity. Such inflammatory skin diseases are disfiguring and cause severe physical and psychological harm to patients, disrupting their quality of life substantially. Such diseases include decubitus ulcers, pressure ulcers, diabetic ulcers, epidermolysis bullosa, and milia. Such skin diseases tend to be chronic and difficult to treat, particularly in patients with poor circulation or other underlying disease states.
Among the most difficult of these diseases to treat is epidermolysis bullosa. Epidermolysis bullosa occurs in newborns and infants and causes severe inflammation, blistering, and scarring.
Accordingly, there is a need for an improved method of treating these inflammatory skin diseases. Such a method should be effective in a wide variety of skin diseases, and should be suitable for use together with other treatment modalities. It should be well tolerated by the patients without side effects. This is particularly important because
many of these diseases have an underlying allergic component that makes their treatment difficult and may prevent the use of a number of previously known agents.
SUMMARY
An improved method of treating such skin diseases comprises applying to the skin of a patient suffering such a skin disease an allantoin-containing composition in a therapeutically effective quantity.
The allantoin-containing composition comprises an oil-in-water emulsion including at least one emulsifier and can contain other ingredients, such as a chelating agent to bind metal ions that might accelerate degradation of the composition. A particularly preferred chelating agent is EDTA. The EDTA can be added in various acid or salt forms depending on the pH of the composition, such as EDTA itself, disodium EDTA, or tetrasodium EDTA.
In one embodiment of the invention, the allantoin-containing composition comprises an oil-in-water emulsion comprising: (1) allantoin;
(2) an emulsifier system including:
(a) beeswax; and
(b) an anionic emulsifier that is substantially hydrophilic and is soluble in water, the pH of the composition being from about 3.0 to about 6.0 after the addition of acid to bring the pH to a value within the range of from about 3.0 to about 6.0. Preferably, the pH of the composition is from about 4.5 to about 5.8.
The emulsifier can be selected from the group consisting of ammonium lauryl sulfate, sodium lauryl sulfate, sodium laureth sulfate, sodium oleyl succinate, ammonium lauryl sulfosuccinate, sodium dodecylbenzenesulfonate, ammonium laureth sulfate, and sodium lauryl sarcosinate. Preferably, the emulsifier is sodium lauryl sulfate.
In another embodiment, the allantoin-containing composition comprises an oil-in-water emulsion comprising:
(1) allantoin;
(2) an emollient component comprising:
(a) lanolin oil;
(b) cetyl alcohol; (c) stearyl alcohol; and
(d) cod liver oil;
(3) butylated hydroxytoluene;
(4) an emulsifier system comprising at least one nonionic emulsifier that is an ethoxylated ether or an ethoxylated ester whose carbon chain length ranges from 8 to 22 carbon atoms; and
(5) at least one acid selected from the group consisting of:
(a) an organic acid of from 2 to 22 carbon atoms; and
(b) an inorganic acid selected from the group consisting of hydrochloric acid, sulfuric acid, and phosphoric acid to adjust the pH from about 3.0 to about 6.0. Preferably, the pH of the composition is from about 4.5 to about 5.8.
In yet another embodiment, the allantoin-containing composition comprises an oil-in-water emulsion comprising: (1) allantoin; (2) an emulsifier system including at least one nonionic emulsifier that is an ethoxylated ether or an ethoxylated ester whose carbon chain length ranges from 8 to 22 carbon atoms, the pH of the emulsion being from about 3.0 to about 6.0 after the addition of acid to bring the pH to a value within the range of from about 3.0 to about 6.0. Preferably, the pH of the composition is from about 4.5 to about 5.8.
In still another embodiment, the allantoin-containing composition comprises an oil-in-water emulsion comprising:
(1) allantoin; and
(2) an emulsifier system comprising: (a) an acidic anionic polymer; and
(b) a polyethylene glycol ester of stearic acid.
The pH of the composition is adjusted to a value within a range of from about 3.0 to about 6.0. Preferably, the pH of the composition is from about 5.0 to about 6.0.
The composition can further comprise a carbohydrate polymer selected from the group consisting of galactoarabinan, polygalactose, and polyarabinose; preferably, the carbohydrate polymer is galactoarabinan.
In yet another alternative embodiment, the allantoin-containing composition comprises an oil-in-water emulsion comprising:
(1) allantoin; and
(2) an emulsifier system comprising: (a) an acidic anionic polymer; and
(b) an anionic emulsifier that is substantially hydrophilic and is soluble in water.
The pH of the composition is adjusted to a value in a range from about 3.0 to about 6.0. Preferably, the pH of the composition is from about 5.0 to about 6.0.
The anionic emulsifier can be selected from the group consisting of sodium lauryl sulfate, sodium laureth sulfate, sodium oleyl succinate, sodium dodecylbenzenesulfonate and sodium lauryl sarcosinate. Preferably, the anionic emulsifier is sodium lauryl sulfate.
Typically, the acidic anionic polymer is carboxypolymethylene.
Preferably, in this embodiment, the composition further comprises a carbohydrate polymer selected from the group consisting of galactoarabinan, polygalactose, and polyarabinose. More preferably, the carbohydrate polymer is galactoarabinan.
In yet another alternative, the allantoin-containing composition comprises an oil-in-water emulsion comprising: (1) allantoin; and
(2) an emulsifier system comprising:
(a) an acidic anionic polymer; and
(b) a nonionic emulsifier that is an ethoxylated ether or an ethoxylated ester whose carbon chain length ranges from 8 to 22 carbon atoms, wherein the pH of the
composition is from about 3.0 to about 6.0. Preferably, the pH of the composition is from about 5.0 to about 6.0.
The acidic anionic polymer is preferably carboxypolymethylene as described above.
Preferably, in this embodiment as well, the composition further comprises a carbohydrate polymer selected from the group consisting of galactoarabinan, polygalactose and polyarabinose. More preferably, the carbohydrate polymer is galactoarabinan.
In this embodiment, the emulsifier system can further comprise glyceryl stearate.
In yet another embodiment of a method according to the present invention, the ethyoxylated ether or ethoxylated ester is omitted in the composition. In this embodiment, the composition comprises an oil-in-water emulsion comprising:
(1) allantoin;
(2) an emulsifier system comprising an acidic anionic polymer;
(3) an organic or inorganic base to adjust the pH to a value in a range of from about 3.0 to about 6.0. Preferably, the pH of the composition is from about 5.0 to about 5.5.
Preferably, the base is triethanolamine, and the acidic anionic polymer is a carboxypolymethylene polymer as described above.
Yet another embodiment of a method according to the present invention uses an allantoin-containing composition comprising an oil-in-water emulsion comprising:
(1) allantoin;
(2) an emulsifier system comprising:
(a) cetyl alcohol; and (b) stearic acid; and
(3) a weak organic base to adjust the pH to a value within a range of from about 3.0 to about 6.0. Preferably, the pH of the composition is from about 5.0 to about 5.8.
Typically, the weak organic base is triethanolamine.
Still another embodiment of a method according to the present invention uses an allantoin-containing composition comprising an oil-in-water emulsion comprising: (1) allantoin; and (2) an emulsifier system comprising:
(a) sodium stearoyl lactylate;
(b) sodium isostearoyl lactylate;
(c) optionally, triethanolamine stearate; and
(d) optionally, at least one nonionic emulsifier selected from the group consisting of a nonionic emulsifier that is an ethoxylated ether or an ethoxylated ester whose carbon chain length ranges from 8 to 22 carbon atoms; and
(3) an acid to adjust the pH to a value within a range of from about 3.0 to about 6.0. Preferably, the pH of the composition is from about 5.0 to about 5.8.
Typically, the acid is citric acid.
Still another embodiment of a method according to the present invention uses an allantoin-containing composition comprising an oil-in-water emulsion comprising:
(1) allantoin; and (2) an emulsifier system comprising at least one polyethyleneglycol ether of cetearyl alcohol; and
(3) an acid to adjust the pH of the composition to a value within a range of from about 3.0 to about 6.0. Preferably, the pH of the composition is from about 5.0 to about 5.8.
Typically, the acid is citric acid.
In polyethylene glycol ethers of cetearyl alcohol suitable for use in compositions in this embodiment of a method according to the present invention, the number of ethylene glycol moieties can range from 6 to 40, e.g., R(OCH2CH )25OH where R = CH3(CH2)16.18. In one preferred composition suitable for use in this embodiment of a method according to the present invention, the emulsifier system comprises both ceteareth-25 and ceteareth-6, i.e., polyethylene glycol ethers of cetearyl alcohol with 25 and 6 ethylene glycol units respectively.
Yet another embodiment of a method according to the present invention uses an allantoin-containing composition comprising an oil-in-water emulsion comprising: (1) allantoin; and (2) an emulsifier system comprising:
(a) a polyethylene glycol ester of stearic acid; and
(b) glyceryl stearate; and
(3) an acid to adjust the pH of the composition to a value within a range of from about 3.0 to about 6.0. Preferably, the pH of the composition is from about 5.0 to about 5.8.
Typically, the number of ethylene glycol moieties in the polyethylene glycol ester of stearic acid is from 25 to 100. Two preferred polyethylene glycol esters of stearic acid for use in compositions for an embodiment of a method according to the present invention are PEG-40 stearate and PEG- 100 stearate, with 40 and 100 ethylene glycol moieties respectively. A particularly preferred polyethylene glycol ester of stearic acid is PEG-100 stearate.
Typically, the acid is citric acid.
In yet another alternative embodiment, the allantoin-containing composition comprises an oil-in-water emulsion comprising:
(1) allantoin;
(2) a carbohydrate polymer; and (3) an emulsifier system comprising:
(a) beeswax; and
(b) an anionic emulsifier that is substantially hydrophilic and is soluble in water.
The pH of the composition is between about 3.0 and about 6.0. Preferably, the pH of the composition is from about 5.0 to about 6.0.
In all of these alternative embodiments, the composition can further comprise additional ingredients if they are not already included.
For example, the composition can further comprise an emollient component. The emollient component can comprise at least one emollient selected from the group consisting of lanolin oil, cetyl alcohol, stearyl alcohol, and cod liver oil.
The composition can further comprise an antioxidant such as butylated hydroxytoluene.
The composition can further comprise a preservative component. The preservative component can comprise at least one preservative selected from the group consisting of methylparaben and propylparaben.
The composition can further comprise a chelating agent. A preferred chelating agent is tetrasodium EDTA.
The composition can further comprise a solvent component. The solvent component can comprise at least one solvent selected from the group consisting of propylene glycol, butylene glycol, and glycerin. Preferably, the solvent component is propylene glycol.
The composition can further comprise a preservative component. The preservative component can comprise at least one preservative selected from the group consisting of methylparaben, propylparaben, and diazolidinyl urea.
The skin condition or disease to be treated can be one of epidermolysis bullosa, decubitus ulcers, pressure ulcers, diabetic ulcers, and milia. An important skin condition or disease that is treated by methods according to the present invention is epidermolysis bullosa.
Methods according to the present invention can further comprise administering an additional therapeutic agent in a therapeutically effective quantity. The additional therapeutic agent can be selected from the group consisting of steroids, nonsteroidal anti-inflammatory agents, leukotriene antagonists, and monoclonal antibodies.
BRIEF DESCRIPTION OF THE DRAWINGS
These and other features, aspects, and advantages of the present invention will become better understood with reference to the following description, appended claims, and accompanying drawings where:
Figures 1(a) and 1(b) are pictures of the right foot of a first patient (A.B.) before the use of the cream of Example 2 from two different views, showing the severity of the disease;
Figure 2 is a picture of the right foot of the patient A.B. after two months of use of the cream of Example 2, showing considerable improvement;
Figures 3(a) and 3(b) are pictures of the right foot of the patient A.B. after 12 months of use of the cream of Example 2, showing substantial improvement and clearing of the lesions;
Figures 4(a), 4(b), and 4(c) are additional pictures of the right foot of the patient A.B. after 12 months of use of the cream of Example 2, again showing substantial improvement and clearing of the lesions;
Figures 5(a) and 5(b) are pictures of the buttocks area of the patient A.B. before the use of the cream (Fig. 5(a)) and after 2 weeks of use of the cream of Example 2 (Fig. 5(b)), showing substantial improvement and clearing of the lesions; Figures 6(a) and 6(b) are pictures of the facial area of the patient A.B. before the use of the cream (Fig. 6(a)) and after 3 months of use of the cream of Example 2 (Fig. 6(b)), showing substantial improvement, fading, and clearing of the lesions;
Figure 7 is a photograph of a second patient (CD.) before commencement of the use of the allantoin-containing skin cream of Example 2; Figure 8 is a photograph of patient CD. after 8 weeks of use of the allantoin- containing skin cream of Example 2, showing substantial improvement of the lesions;
Figure 9(a) is a photograph of the back area of patient CD. before commencement of the use of the allantoin-containing skin cream of Example 2;
Figure 9(b) is another photograph of the back area of patient CD. before commencement of the use of the allantoin-containing skin cream of Example 2;
Figure 10(a) is a photograph of the upper back area of patient CD. after 2 weeks of use of the allantoin-containing skin cream of Example 2, showing considerable improvement;
Figure 10(b) is a photograph of the upper back area of patient CD. after 8 weeks of use of the allantoin-containing skin cream of Example 2, showing continued improvement evidenced by fading of the lesions;
Figure 11(a) is a photograph of the upper leg area of patient CD. before commencement of the use of the allantoin-containing skin cream of Example 2;
Figure 11(b) is a photograph of the lower leg area of patient CD. before commencement of the use of the allantoin-containing skin cream of Example 2;
Figure 11(c) is a photograph of the legs of patient CD. after 2 weeks of use of the allantoin-containing skin cream of Example 2, showing substantial improvement; and Figure 11(d) is a photograph of the legs of patient CD. after 8 weeks of use of the allantoin-containing skin cream of Example 2, showing continuing improvement.
DESCRIPTION
I have unexpectedly found that a stabilized oil-in-water emulsion containing allantoin plus other ingredients provides a high degree of relief for inflammatory skin conditions characterized by ulceration, inflammation, or blistering of the skin.
In general, a method of treating such a skin condition or disease comprises applying to the skin an allantoin-containing composition in a therapeutically effective amount. The allantoin-containing composition comprises an oil-in-water emulsion as described below.
The allantoin-containing composition comprises an oil-in-water emulsion including at least one emulsifier and can contain other ingredients, such as a chelating agent to bind metal ions that might accelerate degradation of the composition. A particularly preferred chelating agent is EDTA. The EDTA can be added in various acid or salt forms depending on the pH of the composition, such as EDTA itself, disodium EDTA, or tetrasodium EDTA.
The skin condition or disease to be treated can be decubitus ulcers, pressure ulcers, diabetic ulcers, or milia. As described below in Examples 10-11, methods of the present invention are particularly suited for the treatment of epidermolysis bullosa.
In one embodiment of the present invention, the allantoin-containing composition comprises an oil-in-water emulsion comprising: (1) allantoin; and (2) an emulsifier system including:
(i) beeswax; and
(ii) an anionic emulsifier that is substantially hydrophilic and is soluble in water.
The pH of the emulsion is from about 3.0 to about 6.0 after the addition of acid to bring the pH into this range. Preferably, the pH of the emulsion is from about 4.5 to about 5.8.
The anionic emulsifier is typically one of ammonium lauryl sulfate, sodium laureth sulfate, sodium oleyl succinate, ammonium lauryl sulfosuccinate, sodium dodecylbenzenesulfonate, ammonium laureth sulfate, sodium N-lauryl sarcosinate, or sodium lauryl sulfate. A particularly preferred anionic emulsifier is sodium lauryl sulfate.
The composition further includes an acid to reduce the pH to a value within a range from about 3.0 to about 6.0, preferably a range from about 4.5 to about 5.8. The acid can be an organic acid, an inorganic acid, or a mixture of both.
Preferred organic acids include organic acids whose carbon chain length ranges from 2 to 22 carbon atoms and can be monocarboxylic, dicarboxylic, or tricarboxylic acids. The acids can be aliphatic or aromatic. Particularly preferred organic acids include citric acid, ascorbic acid, glycolic acid, benzoic acid, and salicylic acid. A most particularly preferred organic acid is citric acid.
Typically, the inorganic acid is a strong acid. It can be a monoprotic, diprotic, or triprotic acid. Particularly preferred inorganic acids include hydrochloric acid, sulfuric acid, or phosphoric acid.
For the embodiments described above, the composition can further include other ingredients. For example, the composition can include an emollient component for
smoothness. The emollient component can include at least one of lanolin oil, cetyl alcohol, stearyl alcohol, and cod liver oil. Preferably, the emollient component comprises all of lanolin oil, cetyl alcohol, stearyl alcohol, and cod liver oil.
The composition can also include an antioxidant to prevent rancidity of ingredients such as cod liver oil. A preferred antioxidant is butylated hydroxytoluene (BHT).
The composition can further include a solvent component. Typically, the solvent component is one or more of propylene glycol, butylene glycol, and glycerin. Preferably, the solvent component is propylene glycol.
The composition can further include a chelating agent to bind metal ions that might acceleration degradation of the composition. A particularly preferred chelating agent is tetrasodium EDTA.
The composition can further include herbal extracts. The herbal extracts can include one or more of St. John's wort extract, witch hazel extract, chamomile extract, and arnica extract. The composition can include all of St. John's wort extract, witch hazel extract, chamomile extract, and arnica extract. However, typically, in compositions used in methods according to the present invention, herbal extracts are omitted.
The composition can further include a preservative such as at least one of methylparaben, ethylparaben, propylparaben, butylparaben, or phenoxyethanol. Preferably, the composition comprises methlylparaben and propylparaben as preservatives.
The composition can further include fragrance. The use of fragrance is well known in the art of over-the-counter drug formulation, and many suitable fragrances are known in the art. The stability and function of the composition is not altered by the presence or absence of fragrance. In many alternatives, it may be desirable to avoid the use of fragrance which may trigger allergic reactions in patients predisposed to such reactions.
The composition can further include other ingredients, such as proteins, humectants, other preservatives, essential oils, other vitamins, colorants, hydroxyacids, other plant extracts, sunscreens, sodium hyaluronate, lipids, fatty acids, thickeners, panthenol, and .
the like. The use of such components is conventional in the over-the-counter drug art. Typical sunscreens are octyl methoxycinnamate and benzophenone-3.
The following discussion describes ranges, preferred concentrations, and optimum concentrations for preferred compositions when the pH of the composition is from about 4.5 to about 5.8 useful in this embodiment of methods according to the present invention.
Water can comprise from about 50.0% to about 90.0 % of the composition. Preferably, water comprises from about 55.0% to about 75.0% of the composition. An optimum concentration of water is about 68.68%.
Sodium lauryl sulfate, as a 30% solution, can comprise from about 0.5% to about 2.5% of the composition. Preferably, sodium lauryl sulfate comprises from about 1.0% to about 2.5% of the composition. An optimum concentration of sodium lauryl sulfate in the composition is about 1.90%.
Propylene glycol can comprise from about 2.0% to about 9.0% of the composition. Preferably, propylene glycol comprises from about 3.0% to about 6.0% of the composition. An optimum concentration of propylene glycol is about 5.30% of the composition.
Tetrasodium EDTA can comprise from about 0.05% to about 0.50% of the composition. Preferably, tetrasodium EDTA comprises from about 0.1% to about 0.30% of the composition. An optimum concentration of tetrasodium EDTA is about 0.15% of the composition.
Citric acid can comprise from about 0.05% to about 0.50% of the composition. A preferred concentration of citric acid is from about 0.08%> to about 0.35% of the composition. An optimum concentration of citric acid is about 0.12% of the composition.
Lanolin oil can comprise from about 5.0% to about 15.0% of the composition. Preferably, lanolin oil comprises from about 8.0% to about 12.0% of the composition. An optimum concentration of lanolin oil is about 10.60% of the composition.
Cetyl alcohol can comprise from about 3.0% to about 10.0% of the composition. A preferred concentration of cetyl alcohol is from about 3.5% to about 7.5% of the composition. An optimum concentration of cetyl alcohol is about 4.20% of the composition.
Stearyl alcohol can comprise from about 1.0% to about 5.0% of the composition. A preferred concentration of stearyl alcohol is from about 1.0% to about 3.0% of the composition. An optimum concentration of stearyl alcohol is about 2.00% of the composition.
Beeswax can comprise from about 0.5% to about 2.5% of the composition. A preferred concentration of beeswax is from about 1.0% to about 2.5% of the composition. An optimum concentration of beeswax is about 1.90% of the composition.
Cod liver oil can comprise from about 1.0% to about 7.0% of the composition. Preferably, cod liver oil comprises from about 1.0% to about 4.0% of the composition. An optimum concentration of cod liver oil is about 2.00% of the composition.
Butylated hydroxytoluene can comprise from about 0.1% to about 1.0% of the composition. Preferably, butylated hydroxytoluene comprises from about 0.2% to about 0.8% of the composition. An optimum concentration of butylated hydroxytoluene is about 0.50% of the composition.
St. John's wort extract can comprise from about 0.05% to about 0.5% of the composition. Preferably, St. John's wort extract comprises from about 0.05% to about 0.15% of the composition. An optimum concentration of St. John's wort extract is about 0.10% of the composition.
Witch hazel extract can comprise from about 0.05% to about 0.5% of the composition. Preferably, witch hazel extract comprises from about 0.05%) to about 0.15% of the composition. An optimum concentration of witch hazel extract is about 0.10% of the composition.
Chamomile extract can comprise from about 0.05% to about 0.50% of the composition. A preferred concentration of chamomile extract is from about 0.05% to about 0.15% of the composition. An optimum concentration of chamomile extract is about 0.10% of the composition.
Arnica extract can comprise from about 0.05% to about 0.50% of the composition. Preferably, arnica extract comprises from about 0.05% to about 0.15% of the composition. An optimum concentration of arnica extract is about 0.10% of the composition.
Methylparaben can comprise from about 0.10% to about 0.50% of the composition. A preferred concentration of methylparaben is from about 0.15% to about 0.40% of the composition. An optimum concentration of methylparaben is about 0.30% of the composition.
Propylparaben can comprise from about 0.10% to about 0.50% of the composition. A preferred concentration of propylparaben is from about 0.10% to about 0.30% of the composition. An optimum concentration of propylparaben is about 0.25% of the composition.
Allantoin can comprise from about 0.50% to about 2.0% of the composition.
A preferred concentration of allantoin is from about 0.50% to about 2.0% of the composition. An optimum concentration of allantoin is about 1.50% of the composition.
If present, fragrance can comprise from about 0.05% to about 0.50% of the composition. Preferably, fragrance comprises from about 0.10% to about 0.30% of the composition. If present, an optimum concentration of fragrance is about 0.20% of the composition. As indicated above, in many embodiments it is desirable to omit fragrance to avoid the possibility of allergic reactions.
In another embodiment, the composition comprises an oil-in-water emulsion comprising:
(1) allantoin; and
(2) an emulsifier system including at least one nonionic emulsifier that is an ethoxylated ether or an ethoxylated ester whose carbon chain length ranges from 8 to 22
carbon atoms. As described above, the pH of the composition is from about 3.0 to about 6.0 after addition of acid. Preferably, the pH of the composition is from about 4.5 to about 5.8.
The composition used in this embodiment of the method can further include other ingredients as described above. For example, the composition can further include:
(1) an emollient component comprising at least one emollient selected from the group consisting of lanolin oil, cetyl alcohol, stearyl alcohol, and cod liver oil;
(2) butylated hydroxytoluene;
(3) at least one herbal extract selected from the group consisting of St. John's wort extract, witch hazel extract, chamomile extract, and arnica extract;
(4) a preservative component comprising at least one preservative selected from the group consisting of methylparaben, propylparaben, and diazolidinyl urea;
(5) tetrasodium EDTA; and
(6) a solvent component comprising at least one solvent selected from the group consisting of propylene glycol, butylene glycol, and glycerin.
In yet another embodiment of a method according to the present invention, the composition comprises an oil-in-water emulsion comprising: (1) allantoin; (2) an emollient component comprising:
(a) lanolin oil;
(b) cetyl alcohol;
(c) stearyl alcohol; and
(d) cod liver oil; (3) butylated hydroxytoluene;
(4) an emulsifier system comprising at least one nonionic emulsifier that is an ethoxylated ether or an ethoxylated ester whose carbon chain length ranges from 8 to 22 carbon atoms; and
(5) at least one acid selected from the group consisting of: (a) an organic acid of from 2 to 22 carbon atoms; and
(b) an inorganic acid selected from the group consisting of hydrochloric acid, sulfuric acid, and phosphoric acid to adjust the pH from about 3.0 to about 6.0. Preferably ,the pH of the composition is from about 4.5 to about 5.8
The composition can further include other ingredients as described above. For example, the composition can further include:
(1) at least one herbal extract selected from the group consisting of St. John's wort extract, witch hazel extract, chamomile extract, and arnica extract;
(2) a preservative component comprising at least one preservative selected from the group consisting of methylparaben, propylparaben, and diazolidinyl urea;
(3) tetrasodium EDTA; and
(4) a solvent component comprising at least one solvent selected from the group consisting of propylene glycol, butylene glycol, and glycerin.
In still another embodiment of the method, the allantoin-containing composition comprises an oil-in-water emulsion comprising:
(1) allantoin; and
(2) an emulsifier system comprising: (a) an acidic anionic polymer; and
(b) a polyethylene glycol ester of stearic acid.
The pH of the composition is adjusted to a value in the range of from about 3.0 to about 6.0. Preferably, the pH of the composition is from about 5.0 to about 6.0. The pH is adjusted with sodium hydroxide or other base as required.
The acidic anionic polymer is preferably a carboxypolymethylene polymer. Such polymers are marketed under the brand names "Carbomer" and "Carbopol." A suitable carboxypolymethylene polymer is marketed by B.F. Goodrich under the brand name "Carbomer." This is a slightly cross-linked polyacrylic acid that is from 1% to 2% cross- linked by allylsucrose or allylpentaerythritol with the polyacrylic acid. The resulting molecular weight range of this polymer is from about 2 x 106 daltons to about 1 x 109 daltons. The average molecular weight of this polymer is about 4 x 106 daltons.
Preferably, the concentration of the carboxypolymethylene polymer is from about 0.5% to about 2% of the composition.
The composition can further comprise a carbohydrate polymer. Typically, the carbohydrate polymer is selected from the group consisting of galactoarabinan,
polygalactose, and polyarabinose. Preferably, the carbohydrate polymer is galactoarabinan. Galactoarabinan is derived from trees of the genus Larix (larch) and is a hemicellulosic product easily extractable by water in a pure form. The molecular weight of the galactoarabinan is about 20,000. Galactoarabinan has been consumed by humans in common foods such as carrots, tomatoes, maple syrup, soybeans, and wheat flour, among others. A suitable source of galactoarabinan is Larex, Inc (White Bear Lake, MN). Typically, the composition contains from about 1% to about 25% of galactoarabinan. Preferably, the composition contains from about 2% to about 10% of the carbohydrate polymer.
The composition used in this embodiment of a method according to the present invention can further include other ingredients. For example, the composition can include an emollient component for smoothness. The emollient component can include at least one emollient selected from the group consisting of lanolin oil, cetyl alcohol, stearyl alcohol, and cod liver oil.
The composition can also include an antioxidant to prevent rancidity of ingredients such as cod liver oil. A preferred antioxidant is butylated hydroxytoluene (BHT).
The composition can further include a solvent component. Typically, the solvent component can include at least one solvent selected from the group consisting of propylene glycol, glycerin, and butylene glycol. Preferably, the solvent component is propylene glycol.
The composition can further include a preservative component. The preservative component can include at least one preservative selected from the group consisting of methylparaben, propylparaben, and diazolidinyl urea. Preferably, the preservative component comprises methylparaben, propylparaben, and diazolidinyl urea.
The composition can further include fragrance. The use of fragrance is well known in the cosmetic art and in the art of over-the-counter drug formulation, and many suitable fragrances are known in the art. The stability and function of the cream is not altered by the presence or absence of fragrance.
Optionally, the composition can further include herbal extracts. The herbal extracts can include one or more of St. John's wort extract, witch hazel extract, chamomile extract, and arnica extract. However, these herbal extracts are typically omitted in the composition used in this embodiment of a method according to the present invention.
The composition can optionally further include other components, such as proteins, humectants, other preservatives, essential oils, other vitamins, colorants, hydroxyacids, other plant extracts, chelators, sunscreens, sodium hyaluronate, lipids, fatty acids, thickeners, panthenol, and the like. The use of such components is conventional in the cosmetic art and in the over-the-counter drug art. Typical sunscreens are octyl methoxycinnamate and benzophenone-3.
The following discussion describes ranges, preferred concentrations and optimum concentrations for preferred compositions useful in this embodiment of the present invention when the pH of the composition is from about 5.0 to about 6.0.
Water can comprise from about 50.0% to about 90.0% of the composition. Preferably, water comprises from about 60.0% to about 85.0% of the composition. An optimum concentration of water in the composition is about 69.95%.
The carboxypolymethylene polymer can comprise from about 0.30% to about 3.0% of the composition. Preferably, the carboxypolymethylene polymer comprises from about 0.50% to about 2.0% of the composition. An optimum concentration of the carboxypolymethylene polymer is about 0.85% of the composition.
Propylene glycol can comprise from about 2.0% to about 9.0% of the composition. Preferably, propylene glycol comprises from about 4.0% to about 7.0% of the composition. An optimum concentration of propylene glycol is about 5.70% of the composition.
PEG-100 stearate can comprise from about 0.25% to about 2.5% of the composition. Preferably, PEG-100 stearate comprises from about 0.50% to about 2.0% of the composition. An optimum concentration of PEG-100 stearate is about 1.50% of the composition.
Lanolin oil can comprise from about 5.0% to about 15.0% of the composition. Preferably, lanolin oil comprises from about 8.0% to about 12.0% of the composition. An optimum concentration of lanolin oil is about 10.60% of the composition.
Cetyl alcohol can comprise from about 1.0% to about 8.0% of the composition. A preferred concentration of cetyl alcohol is from about 2.0% to about 7.0% of the composition. An optimum concentration of cetyl alcohol is about 4.20% of the composition.
Stearyl alcohol can comprise from about 0.5% to about 6.0% of the composition. A preferred concentration of stearyl alcohol is from about 0.75% to about 5.0% of the composition. An optimum concentration of stearyl alcohol is about 1.50% of the composition.
Cod liver oil can comprise from about 1.0% to about 7.0% of the composition. Preferably, cod liver oil comprises from about 1.0% to about 4.0% of the composition. An optimum concentration of cod liver oil is about 2.00% of the composition.
Butylated hydroxytoluene can comprise from about 0.10% to about 1.0% of the composition. Preferably, butylated hydroxytoluene comprises from about 0.20% to about 0.80% of the composition. An optimum concentration of butylated hydroxytoluene is about 0.50% of the composition.
Methylparaben can comprise from about 0.10% to about 0.50% of the composition. A preferred concentration of methylparaben is from about 0.15% to about 0.40% of the composition. An optimum concentration of methylparaben is about 0.30% of the composition.
Propylparaben can comprise from about 0.10% to about 0.50% of the composition. Preferably, propylparaben comprises from about 0.15% to about 0.40% of the composition. An optimum concentration of propylparaben is about 0.25% of the composition.
Diazolidinyl urea can comprise from about 0.05% to about 0.25% of the composition. Preferably, diazolidinyl urea comprises from about 0.10% to about 0.20% of the composition. An optimum concentration of diazolidinyl urea is about 0.15% of the composition.
Allantoin can comprise from about 0.50% to about 2.0% of the composition. A preferred concentration of allantoin is from about 1.0% to about 2.0% of the composition. An optimum concentration of allantoin is about 1.50% of the composition.
Fragrance can comprise from about 0.05% to about 0.50% of the composition.
Preferably, fragrance comprises from about 0.10% to about 0.40% of the composition. An optimum concentration of fragrance is about 0.20% of the composition. As indicated above, fragrance can be omitted, and it may be desirable to omit fragrance in circumstances in which the composition is intended for use on sensitive individuals or individuals who may undergo an allergic reaction to fragrance.
Triethanolamine can comprise from about 0.05% to about 3.0% of the composition to adjust the pH. A preferred concentration of triethanolamine is from about 0.20% to about 2.0% of the composition. An optimum concentration of triethanolamine is about 0.80% of the composition.
In another alternative embodiment of a method according to the present invention, the emulsifier of the composition can be an anionic emulsifier that is substantially hydrophilic and is soluble in water. In this embodiment, the anionic emulsifier replaces the polyethylene glycol ester of stearic acid. The composition further includes the acidic anionic polymer such as carboxypolymethylene. Optionally, but preferably, the composition includes the carbohydrate polymer such as galactoarabinan.
The anionic emulsifier that is substantially hydrophilic and soluble in water can be selected from the group consisting of sodium lauryl sulfate, sodium laureth sulfate, sodium oleyl succinate, sodium dodecylbenzenesulfonate, and sodium lauryl sarcosinate. A particularly preferred anionic emulsifier is sodium lauryl sulfate.
Commercially available preparations of sodium lauryl sulfate contain sufficient excess sodium hydroxide so that they have a pH of about 10.0. This sodium hydroxide can be used to adjust the pH when the anionic emulsifier is sodium lauryl sulfate; in this alternative, no additional alkali may be needed. When another anionic emulsifier is used, additional alkali may be required to adjust the pH.
In yet another alternative embodiment of a method according to the present invention, the emulsifier system of the composition used in the method comprises the acidic anionic polymer as described above and a nonionic emulsifier that is an ethoxylated ether or an ethoxylated ester whose carbon chain length ranges from 8 to 22 carbon atoms.
Preferably, the acidic anionic polymer is carboxypolymethylene as described above.
This alternative of the composition used in the method can further include glyceryl stearate in the emulsifier system.
The composition has a pH from about 3.0 to 6.0, adjusted as necessary, typically with an acid. The acid can be an organic acid, an inorganic acid, or a mixture of both. Preferably, the composition has a pH from about 5.0 to about 6.0.
This embodiment of the composition can further comprise a carbohydrate polymer such as galactoarabinan as described above.
In the composition, preferred organic acids include organic acids whose carbon chain length ranges from 2 to 22 carbon atoms and can be monocarboxylic, dicarboxylic, or tricarboxylic acids. The acids can be aliphatic or aromatic. Particularly preferred organic acids include citric acid, ascorbic acid, glycolic acid, lactic acid, benzoic acid, and salicylic acid. A most particularly preferred organic acid is citric acid.
Typically, in the composition, the inorganic acid is a strong acid. It can be a monoprotic, diprotic, or triprotic acid. Particularly preferred inorganic acids include hydrochloric acid, sulfuric acid, and phosphoric acid.
The composition can further include other ingredients as described above, including an emollient component, an antioxidant, a solvent component, a chelating agent, herbal extracts, a preservative, and fragrance.
In particular, the composition can further include at least one of:
(1) an emollient component comprising at least one emollient selected from the group consisting of lanolin oil, cetyl alcohol, stearyl alcohol, cod liver oil;
(2) butylated hydroxytoluene;
(3) at least one herbal extract selected from the group consisting of St. John's wort extract, witch hazel extract, chamomile extract, and arnica extract;
(4) a preservative component comprising at least one preservative selected from the group consisting of methylparaben, propylparaben and diazolidinyl urea;
(5) tetrasodium EDTA; and
(6) a solvent component comprising at least one solvent selected from the group consisting of propylene glycol, butylene glycol, and glycerin.
The composition can further include other components, such as proteins, humectants, other preservatives, essential oils, other vitamins, colorants, hydroxyacids, other plant extracts, sunscreens, sodium hyaluronate, lipids, fatty acids, thickeners, panthenol, and the like. The use of such components is conventional in the cosmetic art and in the over-the- counter drug art. Typical sunscreens are octyl methoxycinnamate and benzophenone-3.
In yet another embodiment of a method according to the present invention, the emulsifier system of the composition used in the method comprises the acidic anionic polymer described above; one example of this acidic anionic polymer is marketed as Carbomer. In this embodiment, the pH is adjusted with an organic or inorganic base to a value within a range of from about 3.0 to about 6.0. Preferably, the pH of the composition is from about 5.0 to about 5.5. A preferred organic base is triethanolamine. A preferred inorganic base is sodium hydroxide. In general, it is preferred to use an organic base such as triethanolamine.
The composition used in this embodiment of the method can further comprise other ingredients. For example, the composition can further comprise a solvent component. Typically, the solvent component includes at least one solvent selected from the group
consisting of propylene glycol, glycerin, or butylene glycol. Preferably, the solvent component is propylene glycol.
The composition can further comprise an emollient component. The emollient component can comprise at least one solvent selected from the group consisting of lanolin oil, cetyl alcohol, and cod liver oil. Preferably, the emollient component comprises all of lanolin oil, cetyl alcohol, and cod liver oil.
The composition can also include an antioxidant to prevent rancidity of ingredients such as cod liver oil. A preferred antioxidant is butylated hydroxytoluene (BHT).
The composition can further comprise a preservative component. The preservative component can comprise at least one preservative selected from the group consisting of methylparaben and propylparaben. Preferably, the preservative component comprises both methylparaben and propylparaben.
The composition can further include fragrance as described above. The stability and function of the cream is not altered by the presence or absence of fragrance. As indicated above, it may be desirable to omit fragrance in some cases.
The following discussion describes ranges, preferred concentrations and optimum concentrations for preferred compositions with a pH of from about 5.0 to about 5.5 according to this embodiment of the method of the present invention.
Water can comprise from about 50.0% to about 90.0% of the composition.
Preferably, water comprises from about 60.0% to about 80.0% of the composition. An optimum concentration of water is about 73.55% of the composition.
The carboxypolymethylene polymer can comprise from about 0.40% to about 3.0% of the composition. Preferably, the carboxypolymethylene polymer comprises from about 0.5% to about 2.0% of the composition. An optimum concentration of the carboxypolymethylene polymer is about 1.00% of the composition.
Propylene glycol can comprise from about 2.0% to about 9.0% of the composition. Preferably, the propylene glycol comprises from about 4.0% to about 7.0% of the composition. An optimum concentration of the propylene glycol is about 5.70% of the composition.
Lanolin oil can comprise from about 5.0% to about 15.0% of this embodiment of the composition. Preferably, lanolin oil comprises from about 8.0% to about 12.0% of this embodiment of the composition. An optimum concentration of lanolin oil is about 10.00% of this embodiment of the composition.
Cetyl alcohol can comprise from about 1.0% to about 8.0% of the composition. Preferably, cetyl alcohol comprises from about 2.0% to about 7.0% of the composition. An optimum concentration of cetyl alcohol is about 3.00% of the composition.
Cod liver oil can comprise from about 1.0% to about 7.0% of the composition.
Preferably, cod liver oil comprises from about 1.0% to about 4.0% of the composition. An optimum concentration of cod liver oil is about 2.00% of the composition.
Butylated hydroxytoluene can comprise from about 0.10% to about 1.0% of the composition. Preferably, butylated hydroxytoluene comprises from about 0.30% to about 0.80% of the composition. An optimum concentration of butylated hydroxytoluene is about 0.50% of the composition.
Methylparaben can comprise from about 0.10% to about 0.50% of the composition. Preferably, methylparaben comprises from about 0.15% to about 0.40% of the composition. An optimum concentration of methylparaben is about 0.30% of the composition.
Propylparaben can comprise from about 0.10% to about 0.50% of the composition. Preferably, propylparaben comprises from about 0.15% to about 0.40% of the composition. An optimum concentration of propylparaben is about 0.25% of the composition.
Allantoin can comprise from about 0.50% to about 2.0% of the composition. Preferably, allantoin comprises from about 1.0% to about 2.0% of the composition. An optimum concentration of allantoin is about 1.50% of the composition.
Fragrance, if present, can comprise from about 0.05% to about 0.50% of the composition. Preferably, if present, fragrance comprises from about 0.10% to about 0.40% of the composition. An optimum concentration of fragrance, if present, is about 0.20% of the composition.
Triethanolamine, as a 95% solution, can comprise from about 0.05% to about
3.0% of the composition to adjust the pH to a value in the range of from about 5.0 to about 5.5. Preferably, triethanolamine comprises from about 0.20% to about 2.0% of the composition to adjust the pH as indicated. An optimum concentration of triethanolamine is about 0.80%) of the composition to adjust the pH as indicated.
Yet another embodiment of a method according to the present invention employs a composition comprising an oil-in-water emulsion comprising:
(1) allantoin; and
(2) an emulsifier system comprising: (a) cetyl alcohol; and
(b) stearic acid.
In this embodiment, the pH of the composition is adjusted to a value within a range of from about 3.0 to about 6.0 by addition of a quantity of a weak organic base. Preferably, the pH of the composition is from about 5.0 to about 5.8. The weak organic base can be an amine-containing base such as ethanolamine, diethanolamine, or triethanolamine.
A preferred organic base is triethanolamine.
The composition used in this embodiment of a method according to the present invention can further comprise other ingredients. For example, the composition can further comprise a solvent component. Typically, the solvent component includes at least one solvent selected from the group consisting of propylene glycol, glycerin, and butylene glycol. Preferably, the solvent component is propylene glycol.
The composition can further comprise an emollient component. The emollient component can comprise at least one solvent selected from the group consisting of lanolin oil, cetyl alcohol, and cod liver oil. Preferably, the emollient component comprises all of lanolin oil, cetyl alcohol, and cod liver oil.
The composition can also include an antioxidant. A preferred antioxidant is butylated hydroxytoluene.
The composition can further comprise a preservative component. The preservative component can comprise at least one preservative selected from the group consisting of methylparaben and propylparaben. Preferably, the preservative component comprises both methylparaben and propylparaben.
The composition can further include fragrance as described above. The stability and function of the cream is not altered by the presence or absence of fragrance. As indicated above, it may be desirable to omit fragrance in some cases.
The following discussion describes ranges, preferred concentrations and optimum concentrations for preferred compositions with a pH of from about 5.0 to about 5.8 according to this embodiment of a method of the present invention.
Water can comprise from about 50.0% to about 90.0% of the composition. Preferably, water comprises from about 60.0% to about 85.0% of the composition. An optimum concentration of water is about 71.70% of the composition.
Propylene glycol can comprise from about 2.0% to about 9.0% of the composition. Preferably, propylene glycol comprises from about 4.0% to about 7.0% of the composition. An optimum concentration of propylene glycol is about 5.70% of the composition.
Triethanolamine can comprise from about 0.2% to about 4.0% of the composition. Preferably, triethanolamine comprises from about 0.5% to about 3.0% of the composition. An optimum concentration of triethanolamine is about 1.25% of the composition.
Lanolin oil can comprise from about 5.0% to about 15.0% of the composition. Preferably, lanolin oil comprises from about 8.0%> to about 12.0% of the composition. An optimum concentration of lanolin oil is about 10.60% of the composition.
Cetyl alcohol can comprise from about 1.0% to about 7.0% of the composition. Preferably, cetyl alcohol comprises from about 2.0% to about 6.0% of the composition. An optimum concentration of cetyl alcohol is about 3.50% of the composition.
Stearic acid can comprise from about 0.50% to about 5.0% of the composition.
Preferably, stearic acid comprises from about 1.0% to about 4.0% of the composition. An optimum concentration of stearic acid is about 2.50% of the composition.
Cod liver oil can comprise from about 1.0% to about 7.0% of the composition. Preferably, cod liver oil comprises from about 1.50% to about 5.0% of the composition. An optimum concentration of cod liver oil is about 2.00% of the composition.
Butylated hydroxytoluene can comprise from about 0.1% to about 1.0% of the composition. Preferably, butylated hydroxytoluene comprises from about 0.2% to about 0.8% of the composition. An optimum concentration of butylated hydroxytoluene is about 0.5% of the composition.
Methylparaben can comprise from about 0.10% to about 0.50% of the composition. Preferably, methylparaben comprises from about 0.15% to about 0.40% of the composition. An optimum concentration of methylparaben is about 0.30% of the composition.
Propylparaben can comprise from about 0.10% to about 0.50% of the composition. Preferably, propylparaben comprises from about 0.15% to about 0.40% of the composition. An optimum concentration of propylparaben is about 0.25% of the composition.
Allantoin can comprise from about 0.50% to about 2.0% of the composition. Preferably, allantoin comprises from about 1.0% to about 2.0% of the composition. An optimum concentration of allantoin is about 1.50% of the composition.
If present, fragrance can comprise from about 0.05% to about 0.50% of the composition. Preferably, fragrance comprises from about 0.10% to about 0.40% of the composition. An optimum concentration of fragrance is about 0.20% of the composition.
Still another embodiment of a method according to the present invention employs a composition comprising an oil-in-water emulsion comprising:
(1) allantoin; and
(2) an emulsifier system comprising:
(a) sodium stearoyl lactylate;
(b) sodium isostearoyl lactylate; (c) optionally, triethanolamine stearate;
(d) optionally, at least one nonionic emulsifier selected from the group consisting of a nonionic emulsifier that is an ethoxylated ether or an ethoxylated ester whose carbon chain length ranges from 8 to 22 carbon atoms.
Sodium stearoyl lactylate is the sodium salt of the stearic acid ester of lactyl lactate. Sodium isostearoyl lactylate is the sodium salt of the isostearic acid ester of lactyl lactate.
In the composition used in this embodiment of a method according to the present invention, the composition further comprises an acid to adjust the pH to a value in a range of from about 3.0 to about 6.0. Preferably, the composition has a pH of from about 5.0 to about 5.8. The acid can be an inorganic or an organic acid as described above. Preferably, the acid is a weak organic acid. Most preferably, the acid is citric acid.
The composition can further comprise other ingredients. For example, the composition can further comprise a solvent component. Typically, the solvent component includes at least one solvent selected from the group consisting of propylene glycol, glycerin, and butylene glycol. Preferably, the solvent component is propylene glycol.
The composition can further comprise an emollient component. The emollient component can comprise at least one emollient selected from the group consisting of lanolin oil, cetyl alcohol, and cod liver oil. Preferably, the emollient component comprises all of lanolin oil, cetyl alcohol, and cod liver oil.
The composition can also include an antioxidant. A preferred antioxidant is butylated hydroxytoluene.
The composition can further comprise a chelator component. Preferably, the chelator component is tetrasodium ethylenediaminetetraacetic acid.
The composition can further comprise a preservative component. The preservative component can comprise at least one preservative selected from the group consisting of methylparaben and propylparaben. Preferably, the preservative component comprises both methylparaben and propylparaben.
The composition can further include fragrance as described above. The stability and function of the cream is not altered by the presence or absence of fragrance. As indicated above, it may be desirable to omit fragrance in some cases.
The following discussion describes ranges, preferred concentrations and optimum concentrations for preferred compositions with a pH of from about 5.0 to about 5.8 according to this embodiment of a method according to the present invention.
Water can comprise from about 50.0% to about 90.0% of the composition.
Preferably, water comprises from about 60.0% to about 80.0% of the composition. An optimum concentration of water is about 73.72% of the composition.
Propylene glycol can comprise from about 2.0% to about 9.0% of the composition. Preferably, propylene glycol comprises from about 4.0% to about 7.0% of the composition. An optimum concentration of propylene glycol is about 5.70% of the composition.
Citric acid can comprise from about 0.05% to about 0.50% of the composition. Preferably, citric acid comprises from about 0.10% to about 0.40% of the composition. An optimum concentration of citric acid is about 0.18% of the composition.
Sodium stearoyl lactylate can comprise from about 0.30% to about 3.0% of the composition. Preferably, sodium stearoyl lactylate comprises from about 0.50% to about 2.50% of the composition. An optimum concentration of sodium stearoyl lactylate is about 1.00% of the composition.
Sodium isostearoyl lactylate can comprise from about 0.05% to about 1.0% of the composition. Preferably, sodium isostearoyl lactylate comprises from about 0.10% to about 0.70% of the composition. An optimum concentration of sodium isostearoyl lactylate is about 0.25% of the composition.
Tetrasodium EDTA can comprise from about 0.05% to about 0.25% of the composition. Preferably, tetrasodium EDTA comprises from about 0.10% to about 0.20% of the composition. An optimum concentration of tetrasodium EDTA is about 0.15% of the composition.
Lanolin oil can comprise from about 5.0% to about 15.0% of the composition.
Preferably, lanolin oil comprises from about 8.0% to about 12.0% of the composition. An optimum concentration of lanolin oil is about 10.60% of the composition.
Cetyl alcohol can comprise from about 1.0% to about 8.0% of the composition. Preferably, cetyl alcohol comprises from about 2.0% to about 7.0% of the composition. An optimum concentration of cetyl alcohol is about 3.80% of the composition.
Cod liver oil can comprise from about 1.0% to about 7.0% of the composition. Preferably, cod liver oil comprises from about 1.0% to about 4.0% of the composition. An optimum concentration of cod liver oil is about 2.00% of the composition.
Butylated hydroxytoluene can comprise from about 0.10% to about 1.0% of the composition. Preferably, butylated hydroxytoluene comprises from about 0.20% to about
0.80% of the composition. An optimum concentration of butylated hydroxytoluene is about 0.50% of the composition.
Methylparaben can comprise from about 0.10% to about 0.50% of the composition. Preferably, methylparaben comprises from about 0.15% to about 0.40% of the composition. An optimum concentration of methylparaben is about 0.30% of the composition.
Propylparaben can comprise from about 0.10% to about 0.50% of the composition. Preferably, propylparaben comprises from about 0.15% to about 0.40% of the composition. An optimum concentration of propylparaben is about 0.25% of the composition.
Allantoin can comprise from about 0.50% to about 2.0% of the composition. Preferably, allantoin comprises from about 1.0% to about 2.0% of this embodiment of the composition. An optimum concentration of allantoin is about 1.50% of this embodiment of the composition.
If present, fragrance can comprise from about 0.05% to about 0.50% of the composition. Preferably, fragrance comprises from about 0.10% to about 0.40% of the composition. An optimum concentration of fragrance is about 0.20% of the composition.
Still another embodiment of a method according to the present invention uses a composition comprising an oil-in-water emulsion comprising: (1) allantoin; and
(2) an emulsifier system comprising at least one polyethyleneglycol ether of cetearyl alcohol.
In polyethylene glycol ethers of cetearyl alcohol suitable for use in compositions according to this embodiment of methods of the present invention, the number of ethylene glycol moieties can range from 6 to 40, e.g., R(OCH2CH2)25OH where R = CH3(CH2)16.18. In one preferred embodiment of compounds of the present invention, the emulsifier system comprises both ceteareth-25 and ceteareth-6, i.e., polyethylene glycol ethers of cetearyl alcohol with 25 and 6 ethylene glycol units respectively.
In this embodiment of a method according to the present invention, the composition further comprises an acid to adjust the pH to a value within a range of from about 3.0 to about 6.0. Preferably, the pH of the composition is from about 5.0 to about 5.8. The acid can be an inorganic or an organic acid as described above. Preferably, the acid is a weak organic acid. Most preferably, the acid is citric acid.
The composition can further comprise other ingredients. For example, the composition can further comprise a solvent component. Typically, the solvent component is selected from the group consisting of propylene glycol, glycerin, or butylene glycol. Preferably, the solvent component is propylene glycol.
The composition can further comprise a chelator component. Preferably, the chelator component is tetrasodium ethylenediaminetetraacetic acid.
The composition can further comprise an emollient component. The emollient component can comprise at least one emollient selected from the group consisting of lanolin oil, cetyl alcohol, stearyl alcohol, and cod liver oil. Preferably, the emollient component comprises all of lanolin oil, cetyl alcohol, stearyl alcohol, and cod liver oil.
The composition can also further comprise an antioxidant. A preferred antioxidant is butylated hydroxytoluene.
The composition can further comprise a preservative component. The preservative component can comprise at least one preservative selected from the group consisting of methylparaben, propylparaben, and diazolidinyl urea. Preferably, the preservative component comprises all of methylparaben, propylparaben, and diazolidinyl urea.
The composition can further include fragrance as described above. The stability and function of the cream is not altered by the presence or absence of fragrance. As indicated above, it may be desirable to omit fragrance in some cases.
The following discussion describes ranges, preferred concentrations and optimum concentrations for preferred compositions with a pH of from about 5.0 to about 5.8 according to this embodiment of a method according to the present invention.
Water can comprise from about 50.0% to about 90.0% of the composition.
Preferably, water comprises from about 55.0% to about 75.0% of the composition. An optimum concentration of water is about 66.33% of the composition.
Propylene glycol can comprise from about 2.0% to about 9.0% of the composition. Preferably, propylene glycol comprises from about 4.2% to about 7.0% of the composition. An optimum concentration of propylene glycol is about 5.70% of the composition.
Tetrasodium EDTA can comprise from about 0.05% to about 0.50% of the composition. Preferably, tetrasodium EDTA comprises from about 0.10% to about 0.30% of the composition. An optimum concentration of tetrasodium EDTA is about 0.15% of the composition.
Ceteareth-25 can comprise from about 0.50% to about 4.0% of the composition. Preferably, ceteareth-25 comprises from about 2.0% to about 3.5% of the composition. An optimum concentration of ceteareth-25 is about 2.60% of the composition.
Citric acid can comprise from about 0.04% to about 0.40% of the composition. Preferably, citric acid comprises from about 0.10% to about 0.30% of the composition. An optimum concentration of citric acid is about 0.12% of the composition.
Lanolin oil can comprise from about 5.0%> to about 15.0% of the composition. Preferably, lanolin oil comprises from about 8.0% to about 12.0%) of the composition. An optimum concentration of lanolin oil is about 10.60% of the composition.
Cetyl alcohol can comprise from about 3.0%> to about 10.0% of the composition. Preferably, cetyl alcohol comprises from about 3.5% to about 7.5% of the composition. An optimum concentration of cetyl alcohol is about 4.30% of the composition.
Stearyl alcohol can comprise from about 1.0% to about 5.0% of the composition. Preferably, stearyl alcohol comprises from about 2.0% to about 4.0% of the composition. An optimum concentration of stearyl alcohol is about 3.50% of the composition.
Ceteareth-6 can comprise from about 0.5% to about 4.0% of the composition. Preferably, ceteareth-6 comprises from about 1.0% to about 3.0% of the composition. An optimum concentration of ceteareth-6 is about 1.80% of the composition.
Cod liver oil can comprise from about 1.0% to about 7.0% of the composition.
Preferably, cod liver oil comprises from about 1.0% to about 4.0% of the composition. An optimum concentration of cod liver oil is about 2.00% of the composition.
Butylated hydroxytoluene can comprise from about 0.10% to about 1.0% of the composition. Preferably, butylated hydroxytoluene comprises from about 0.20% to about 0.80% of the composition. An optimum concentration of butylated hydroxytoluene is about 0.50% of the composition.
Methylparaben can comprise from about 0.10% to about 0.50% of the composition. Preferably, methylparaben comprises from about 0.15% to 0.40% of the composition. An optimum concentration of methylparaben is about 0.30% of the composition.
Propylparaben can comprise from about 0.10% to about 0.50% of the composition. Preferably, propylparaben comprises from about 0.15% to about 0.40% of the composition. An optimum concentration of propylparaben is about 0.25% of the composition.
Diazolidinyl urea can comprise from about 0.05% to about 0.50%> of the composition. Preferably, diazolidinyl urea comprises from about 0.10% to about 0.30% of the composition. An optimum concentration of diazolidinyl urea is about 0.15% of the composition.
Allantoin can comprise from about 0.50% to about 2.0% of the composition. Preferably, allantoin comprises from about 1.0% to about 2.0% of the composition. A preferred concentration of allantoin is about 1.50% of the composition.
If present, fragrance can comprise from about 0.05% to about 0.50% of the composition. Preferably, fragrance comprises from about 0.10% to about 0.40% of the composition. An optimum concentration of fragrance is about 0.20% of the composition.
Yet another embodiment of a method according to the present invention uses a composition comprising an oil-in-water emulsion comprising:
(1) allantoin; and
(2) an emulsifier system comprising:
(a) a polyethylene glycol ester of stearic acid; and
(b) glyceryl stearate.
Typically, the number of ethylene glycol moieties in the polyethylene glycol ester of stearic acid is from 25 to 100. Two preferred polyethylene glycol esters of stearic acid for use in compositions suitable for use in this embodiment of a method according to the present invention are PEG-40 stearate and PEG-100 stearate, with 40 and 100 ethylene glycol moieties respectively. A particularly preferred polyethylene glycol ester of stearic acid is PEG-100 stearate.
In this embodiment of a method according to the present invention, the composition further comprises an acid to adjust the pH to a value in a range of from about 3.0 to about 6.0. Preferably, the pH of the composition is from about 5.0 to about 5.8. The acid can be an inorganic or an organic acid as described above. Preferably, the acid is a weak organic acid. Most preferably, the acid is citric acid.
The composition can further comprise other ingredients. For example, the composition can further comprise a solvent component. Typically, the solvent component includes at least one solvent selected from the group consisting of propylene glycol, glycerin, and butylene glycol. Preferably, the solvent component is propylene glycol.
The composition can further comprise a chelator component. Preferably, the chelator component is tetrasodium ethylenediaminetetraacetic acid.
The composition can further comprise an emollient component. The emollient component can comprise at least one emollient selected from the group consisting of lanolin oil, cetyl alcohol, stearyl alcohol, and cod liver oil. Preferably, the emollient component comprises all of lanolin oil, cetyl alcohol, stearyl alcohol, and cod liver oil.
The composition can also further comprise an antioxidant. A preferred antioxidant is butylated hydroxytoluene.
The composition can further comprise a preservative component. The preservative component can comprise at least one preservative selected from the group consisting of methylparaben, propylparaben, and diazolidinyl urea. Preferably, the preservative component comprises all of methylparaben, propylparaben, and diazolidinyl urea.
The composition can further include fragrance as described above. The stability and function of the cream is not altered by the presence or absence of fragrance. As indicated above, it may be desirable to omit fragrance in some cases.
The following discussion describes ranges, preferred concentrations and optimum concentrations for preferred compositions with a pH of from about 5.0 to about 5.8 useful in methods of this embodiment of the present invention.
Water can comprise from about 50.0% to about 90.0% of the composition. Preferably, water comprises from about 55.0% to about 80.0% of the composition. An optimum concentration of water is about 67.86% of the composition.
Propylene glycol can comprise from about 2.00% to about 9.00% of the composition. Preferably, propylene glycol comprises from about 4.30% to about 7.00% of the composition. An optimum concentration of propylene glycol is about 5.70% of the composition.
Tetrasodium EDTA can comprise from about 0.05% to about 0.50% of the composition. Preferably, PEG-100 stearate comprises from about 1.50% to about 3.00% of the composition. An optimum concentration of PEG-100 stearate is about 2.60% of the composition.
Lanolin oil can comprise from about 5.0% to about 15.0% of the composition. Preferably, lanolin oil comprises from about 8.0% to about 12.0% of the composition. An optimum concentration of lanolin oil is about 10.60% of the composition.
Cetyl alcohol can comprise from about 2.0% to about 10.0% of the composition. Preferably, cetyl alcohol comprises from about 2.50% to about 7.50% of the composition. An optimum concentration of cetyl alcohol is about 3.00% of the composition.
Stearyl alcohol can comprise from about 1.0% to about 4.0% of the composition. Preferably, stearyl alcohol comprises from about 1.0% to about 3.5% of the composition. An optimum concentration of stearyl alcohol is about 2.50% of the composition.
Glyceryl stearate can comprise from about 1.0% to about 5.0% of the composition. Preferably, glyceryl stearate comprises from about 2.0% to about 4.0% of the composition. An optimum concentration of glyceryl stearate is about 2.50% of the composition.
Cod liver oil can comprise from about 1.0% to about 7.0% of the composition. Preferably, cod liver oil comprises from about 1.0% to about 4.0% of the composition. An optimum concentration of cod liver oil is about 2.00% of the composition.
Butylated hydroxytoluene can comprise from about 0.10% to about 1.0% of the composition. Preferably, butylated hydroxytoluene comprises from about 0.20% to about 0.80% of the composition. An optimum concentration of butylated hydroxytoluene is about 0.50% of the composition.
Methylparaben can comprise from about 0.10% to about 0.50% of the composition. Preferably, methylparaben comprises from about 0.15% to 0.40% of the
composition. An optimum concentration of methylparaben is about 0.30% of the composition.
Propylparaben can comprise from about 0.10% to about 0.50% of the composition. Preferably, propylparaben comprises from about 0.15% to about 0.40% of the composition. An optimum concentration of propylparaben is about 0.25% of the composition.
Diazolidinyl urea can comprise from about 0.05% to about 0.50% of the composition. Preferably, diazolidinyl urea comprises from about 0.10% to about 0.30% of the composition. An optimum concentration of diazolidinyl urea is about 0.20% of the composition.
Allantoin can comprise from about 0.50% to about 2.0% of the composition. Preferably, allantoin comprises from about 1.0% to about 2.0% of the composition. A preferred concentration of allantoin is about 1.50% of the composition.
If present, fragrance can comprise from about 0.05% to about 0.50% of the composition. Preferably, fragrance comprises from about 0.10% to about 0.40% of the composition. An optimum concentration of fragrance is about 0.20% of the composition.
Yet another embodiment of a method according to the present invention employs a composition comprising an oil-in-water emulsion comprising: (1) allantoin; (2) a carbohydrate polymer; and
(3) an emulsifier system comprising:
(a) beeswax; and
(b) an anionic emulsifier that is substantially hydrophilic and is soluble in water.
The carbohydrate polymer is typically selected from the group consisting of galactoarabinan, polygalactose, and polyarabinose. Preferably, the carbohydrate polymer is galactoarabinan.
The anionic emulsifier that is substantially hydrophilic and soluble in water can be selected from the group consisting of sodium lauryl sulfate, sodium laureth sulfate, sodium oleyl succinate, sodium dodecylbenzenesulfonate, and sodium lauryl sarcosinate. A particularly preferred anionic emulsifier is sodium lauryl sulfate.
The pH of the composition is adjusted to a value in a range of between about 3.0 and about 6.0, typically with an acid. Preferably, the pH of the composition is from about 5.0 to about 6.0. The acid can be an inorganic or an organic acid as described above. Preferably, the acid is a weak organic acid. Most preferably, the acid is citric acid.
The composition used in this embodiment of a method according to the present invention can further comprise other ingredients. For example, the composition can further comprise a solvent component. Typically, the solvent component comprises at least one solvent selected from the group consisting of propylene glycol, glycerin, and butylene glycol. Preferably, the solvent component is propylene glycol.
The composition can further comprise a chelator component. Preferably, the chelator component is tetrasodium ethylenediaminetetraacetic acid.
The composition can further comprise an emollient component. The emollient component can comprise at least one emollient selected from the group consisting of lanolin oil, cetyl alcohol, stearyl alcohol, and cod liver oil. Preferably, the emollient component comprises all of lanolin oil, cetyl alcohol, stearyl alcohol, and cod liver oil
The composition can also further comprise an antioxidant. A preferred antioxidant is butylated hydroxytoluene.
The composition can further comprise a preservative component. The preservative component can comprise at least one preservative selected from the group consisting of methylparaben or propylparaben. Preferably, the preservative component comprises methylparaben and propylparaben.
The composition can further include fragrance as described above. The stability and function of the cream is not altered by the presence or absence of fragrance. As indicated above, it may be desirable to omit fragrance in some cases.
The following discussion describes ranges, preferred concentrations and optimum concentrations for preferred compositions with a pH of from about 5.0 to about 6.0 according to this embodiment of a method according to the present invention.
Water can comprise from about 50.0% to about 90.0% of the composition. Preferably, water comprises from about 60.0% to about 80.0% of the composition. An optimum concentration of water is about 61.65% of the composition.
Propylene glycol can comprise from about 2.0% to about 9.0% of the composition. Preferably, propylene glycol comprises from about 4.0% to about 7.0% of the composition. An optimum concentration of propylene glycol is about 5.70% of the composition.
Sodium lauryl sulfate, as a 30% solution, can comprise from about 0.50% to about 5.0% of the composition. Preferably, sodium lauryl sulfate, as a 30% solution, comprises from about 1.0% to about 3.0% of the composition. An optimum concentration of sodium lauryl sulfate, as a 30% solution, is about 1.90% of the composition.
Tetrasodium EDTA can comprise from about 0.05% to about 0.30% of the composition. Preferably, tetrasodium EDTA comprises from about 0.10% to about 0.20% of the composition. An optimum concentration of tetrasodium EDTA is about 0.15% of the composition.
Galactoarabinan can comprise from about 1.0% to about 25.0% of the composition. Preferably, galactoarabinan comprises from about 3.0% to about 15.0% of the composition. An optimum concentration of galactoarabinan is about 5.00% of the composition.
Citric acid can comprise from about 0.05% to about 0.25% of the composition. Preferably, citric acid comprises from about 0.10% to about 0.20% of the composition. An optimum concentration of citric acid is about 0.15% of the composition.
Lanolin oil can comprise from about 5.0% to about 15.0% of the composition.
Preferably, lanolin oil comprises from about 8.0% to about 12.0% of the composition. An optimum concentration of lanolin oil is about 10.60% of the composition.
Cetyl alcohol can comprise from about 1.0% to about 8.0% of the composition. Preferably, cetyl alcohol comprises from about 2.0% to about 7.0% of the composition. An optimum concentration of cetyl alcohol is about 4.20% of the composition.
Stearyl alcohol can comprise from about 0.50% to about 6.0% of the composition. Preferably, stearyl alcohol comprises from about 1.0% to about 4.0% of the composition. An optimum concentration of stearyl alcohol is about 2.00% of the composition.
Beeswax can comprise from about 0.50% to about 5.0% of the composition. Preferably, beeswax comprises from about 1.0% to about 3.0% of the composition. An optimum concentration of beeswax is about 1.90% of the composition.
Cod liver oil can comprise from about 0.50% to about 15.0% of the composition. Preferably, cod liver oil comprises from about 1.0% to about 10.0% of the composition. An optimum concentration of cod liver oil is about 2.00% of the composition.
Butylated hydroxytoluene can comprise from about 0.1% to about 3.0% of the composition. Preferably, butylated hydroxytoluene comprises from about 0.25% to about 2.50% of the composition. An optimum concentration of butylated hydroxytoluene is about 0.50% of the composition.
Methylparaben can comprise from about 0.10% to about 0.50%o of the composition. Preferably, methylparaben comprises from about 0.15% to about 0.40% of the composition. An optimum concentration of methylparaben is about 0.30% of the composition.
Propylparaben can comprise from about 0.10% to about 0.50% of the composition. Preferably, propylparaben comprises from about 0.15% to about 0.40% of the composition. An optimum concentration of propylparaben is about 0.25% of the composition.
Allantoin can comprise from about 0.50% to about 2.0% of the composition. Preferably, allantoin comprises from about 1.0% to about 2.0% of the composition. An optimum concentration of allantoin is about 1.50% of the composition.
If present, fragrance can comprise from about 0.05% to about 0.50% of the composition. Preferably, if present, fragrance can comprise from about 0.10% to about 0.40% of the composition. An optimum concentration of fragrance is about 0.20% of the composition.
The compositions are prepared by standard mixing techniques, such as are conventional in the cosmetic art and in the art of over-the-counter drug formulation for blending lipid-soluble components and water-soluble components. These mixing techniques include both manual and mechanical mixing, and include homogenization mixing and sweep mixing. The mixing techniques to be used can be chosen by one of ordinary skill in the art based on variables such as the viscosity of the components to be mixed and the volume of those components, as well as the relative proportion of lipid-soluble and water-soluble ingredients. The compositions can be mixed in two or more batches, such as one batch containing lipid-soluble ingredients and another batch containing water-soluble ingredients, and the batches can then be mixed at the final stage of preparation. In some cases, if triethanolamine is used, it is added last, as otherwise it may tend to thicken the emulsion. Other preparation methods are known in the art.
The dosages of the allantoin-containing composition to be administered and the frequency of those dosages can be determined by one of ordinary skill in the art depending on the particular disease affecting the patient, the clinical severity of the disease, the age and weight of the patient, the exposure of the patient to conditions that may precipitate outbreaks of dermatological or systemic inflammatory conditions, the degree of exposure to environmental insults, other drugs being administered, the response of the
patient, and other pharmacokinetic factors generally understood in the art, such as liver and kidney metabolism. The interrelationship of dosages for animals of various sizes and species and humans based on mg/m3 of surface area is described in E.J. Freireich et al., "Quantitative Comparison of Toxicity of Anticancer Agents in Mouse, Rat, Hamster, Dog, Monkey and Man," Cancer Chemother. Rep. 50:219-244 (1966).
Adjustments in the dosage regimen can be made to optimize the therapeutic response. Doses can be divided and administered on a daily basis or the dose can be reduced proportionately depending upon the therapeutic situation.
The allantoin-containing composition can be administered from once per day up to at least five times per day depending on the severity of the disease, the total dosage to be administered, and the judgment of the treating physician. In some cases, the allantoin- containing composition need not be administered on a daily basis, but can be administered every other day, every third day, or on other such schedules. However, it is generally preferred to administer the allantoin-containing composition daily.
In methods according to the present invention, the allantoin-containing composition can be administered alone or with other conventional therapeutic agents in a therapeutically effective quantity. These other therapeutic agents can either be applied topically to the skin or can be administered systemically, such as orally, intravenously, or by other conventional routes as generally known in the art. These agents can include steroids, nonsteroidal anti-inflammatory agents, leukotriene antagonists, monoclonal antibodies, and other agents. Additional agents can be administered to promote healing in the form of conventional creams or emulsions.
The invention is illustrated by the following Examples. These Examples are for illustrative purposes only and are not intended to limit the invention.
EXAMPLES
Example 1
Preparation of Skin Protectant Over-the-Counter Cream with pH of 7.4
(Prior Art Example)
A skin protectant over-the-counter (OTC) cream was prepared in accordance with the formulation of Table 1.
TABLE 1 COMPOSITION OF ALLANTOIN-CONTAINING SKIN CREAM WITH DH OF 7.4
The Part A ingredients were combined and heated to 175°F with mixing. The Part B ingredients were combined and heated to 175°F with mixing. The Part B mixture was then added to the Part A mixture with mixing. The resulting mixture was then cooled to 120°F with continued mixing. The Part C ingredients were then added with mixing. The final emulsion was allowed to cool with continued mixing. The resulting cream had a pH of
7.4. Samples of the cream prepared from Example 1 were used for accelerated aging stability studies and analyzed for their allantoin concentration after a period of time at 40°C The results are shown in Table 2.
As can be seen from Table 2, the allantoin in the cream from Example 1 undergoes degradation and would not meet the specifications required for an OTC drug.
TABLE 2
STABILITY OF ALLANTOIN IN SKIN CREAM COMPOSITION OF EXAMPLE 1 WITH STORAGE AT 40°C
Example 2
Preparation of a Cream Containing Allantoin with Lower pH
An OTC skin cream containing allantoin was prepared using the ingredients in Table 3 to provide a cream with a lower pH.
TABLE 3
COMPOSITION OF ALLANTOIN-CONTAINING SKIN CREAM WITH pH OF 5.3
The Part A ingredients were combined and heated to 175°F with mixing. The Part B ingredients were combined and heated to 175°F with mixing. The Part B mixture was added to the Part A mixture with mixing. The resulting mixture was then cooled to 120°F with mixing at which time the Part C ingredients were added with mixing. The final emulsion was allowed to cool with continue mixing. The resulting cream had a pH of 5.3.
It was found that a similar cream was produced if Part B was added to Part A or Part A was added to Part B. However, the cream has a better appearance if the oil phase
and water phase are homogenized under high shear after the two phases are added to one another.
Samples of the cream of this example were used for accelerated aging stability studies and analyzed for their allantoin concentration. The results are shown in Table 4. As can be seen from Table 4, the allantoin is stable over time in a cream with a pH of 5.3.
TABLE 4
STABILITY OF ALLANTOIN IN SKIN CREAM COMPOSITION OF EXAMPLE 2 WITH STORAGE AT 40°C
Example 3
Preparation of Allantoin-Containing Skin Cream with Ionic Emulsifiers
An allantoin-containing skin cream with ionic emulsifiers is prepared according to Table 5. The preparation follows the method used in Example 2, with the ingredients in each of Part A, Part B, and Part C being combined separately and then Part B being added to Part A, with Part C then being added to the combination of Part A and Part B. The pH is adjusted to a value in a range of from about 5.0 to about 5.8 by neutralizing the stearic acid with enough triethanolamine to reach this pH. Other bases can be used instead of triethanolamine.
TABLE 5
ALLANTOΓN-CONTAΓNΓNG SKIN CREAM WITH IONIC EMULSIFIERS
INGREDIENT RANGE PREFERRED OPTIMUM
Part A
Water 50.0 - 90.0 60.0 - 85.0 71.70
Propylene Glycol 2.0 - 9.0 4.0 - 7.0 5.70
Triethanolamine (99%) 0.20 - 4.0 0.50 - 3.0 1.25
PartB
Lanolin Oil 5.0-15.0 8.0 - 12.0 10.60
Cetyl Alcohol 1.0-7.0 2.0 - 6.0 3.50
Stearic Acid 0.50-5.0 1.0-4.0 2.50
Cod Liver Oil 1.0-7.0 1.5-5.0 2.00
Butylated Hydroxytoluene 0.10-1.0 0.20 - 0.80 0.50
PartC
Methylparaben 0.10-0.50 0.15-0.40 0.30
Propylparaben 0.10-0.50 0.15-0.40 0.25
Allantoin 0.50-2.0 1.0-2.0 1.50
Fragrance 0.05 - 0.50 0.10 - 0.40 0.20
Example 4
Preparation of Allantoin-Containing Skin Cream with Lactylate Emulsifiers
An allantoin-containing skin cream with the emulsifiers sodium stearoyl lactylate and sodium isostearoyl lactylate is prepared according to Table 6. The preparation follows the method used in Example 3. The pH is adjusted by the addition of the appropriate quantity of citric acid.
TABLE 6
ALLANTOΓN-CONTAΓNΓNG SKIN CREAM WITH LACTYLATE EMULSIFIERS
INGREDIENT RANGE PREFERRED OPTIMUM
Part A
Water 50.0 - 90.0 60.0 - 80.0 73.42
Propylene Glycol 2.0-9.0 4.0 - 7.0 5.70
Citric Acid 0.05 - 0.50 0.10-0.40 0.18
Sodium Stearoyl Lactylate 0.30-3.0 0.50-2.50 1.00
Sodium Isostearoyl Lactylate 0.05-1.0 0.10 - 0.70 0.25
Tetrasodium EDTA 0.05 - 0.25 0.10-0.20 0.15
PartB
Lanolin Oil 5.0-15.0 8.0 - 12.0 10.60
Cetyl Alcohol 1.0-8.0 2.0 - 7.0 3.80
Cod Liver Oil 1.0-7.0 1.0-4.0 2.00
Butylated Hydroxytoluene 0.10-1.0 0.20 - 0.80 0.50
PartC
Methylparaben 0.10-0.50 0.15-0.40 0.30
Propylparaben 0.10-0.50 0.15-0.40 0.25
Allantoin 0.50 - 2.0 1.0-2.0 1.50
Fragrance 0.05 - 0.50 0.10 - 0.40 0.20
Example 5
Preparation of Allantoin-Containing Skin Cream with Carboxypolvmethylene Polvmer
An allantoin-containing skin cream with carboxypolymethylene polymer is prepared according to Table 7. The preparation follows the method used in Example 3, except that the triethanolamine (Part D) is added last, after the combining of Parts A, B, and C, to avoid thickening of the emulsion. The triethanolamine is added to adjust the pH.
TABLE 7
ALLANTOIN-CONTAINLNG SKIN CREAM WITH
CARBOXYPOLYMETHYLENE POLYMER
INGREDIENT RANGE PREFERRED OPTIMUM
Part A
Water 50.0-90.0 60.0 - 80.0 73.55
Carboxypolymethylene 0.40 - 3.0 0.50-2.0 1.00
Polymer
Propylene Glycol 2.0 - 9.0 4.0 - 7.0 5.70
PartB
Lanolin Oil 5.0-15.0 8.0-12.0 10.00
Cetyl Alcohol 1.0-8.0 2.0 - 7.0 3.00
Cod Liver Oil 1.0-7.0 1.0-4.0 2.00
Butylated Hydroxytoluene 0.10-1.0 0.20 - 0.80 0.50
PartC
Methylparaben 0.10-0.50 0.15-0.40 0.30
Propylparaben 0.10-0.50 0.15-0.40 0.25
Allantoin 0.50 - 2.0 1.0-2.0 1.50
Fragrance 0.05 - 0.50 0.10-0.40 0.20
PartD
Triethanolamine (99%) 0.05 - 3.0 0.20 - 2.0 0.80
Example 6
Preparation of Allantoin-Containing Skin Cream with Polvethylene Glycol Ethers of Cetearyl
Alcohol
An allantoin-containing skin cream with polyethylene glycol ethers of cetearyl alcohol is prepared according to Table 8. The preparation follows the method used in Example 3. The citric acid is added to adjust the pH.
TABLE 8
ALLANTOΓN-CONTAΓNΓNG SKIN CREAM WITH
POLYETHYLENE GLYCOL ETHERS OF CETEARYL ALCOHOL
INGREDIENT RANGE PREFERRED OPTIMUM
Part A
Water 50.0 - 90.0 55.0-75.0 66.33
Propylene Glycol 2.0 - 9.0 4.0 - 7.0 5.70
Tetrasodium EDTA 0.05 - 0.50 0.10-0.30 0.15
Ceteareth-25 0.50 - 4.0 2.00 - 3.50 2.60
Citric Acid 0.04 - 0.40 0.10-0.30 0.12
PartB
Lanolin Oil 5.0-15.0 8.0 - 12.0 10.60
Cetyl Alcohol 3.0-10.0 3.5-7.5 4.30
Stearyl Alcohol 1.0-5.0 2.0-4.0 3.50
Ceteareth-6 0.50 - 4.0 1.0-3.0 1.80
Cod Liver Oil 1.0-7.0 1.0-4.0 2.00
Butylated Hydroxytoluene 0.10-1.0 0.20 - 0.80 0.50
PartC
Methylparaben 0.10-0.50 0.15-0.40 0.30
Propylparaben 0.10-0.50 0.15-0.40 0.25
Diazolidinyl Urea 0.05 - 0.50 0.10-0.30 0.15
Allantoin 0.50 - 2.0 1.0-2.0 1.50
Fragrance 0.05 - 0.50 0.10-0.30 0.20
Example 7
Preparation of Allantoin-Containing Skin Cream with Polyethylene Glycol Ester of Stearic
Acid and Glyceryl Stearate
An allantoin-containing skin cream with a polyethylene glycol ester of stearic acid and glyceryl stearate is prepared according to Table 9. The preparation follows the method used in Example 3. The citric acid is added to adjust the pH.
TABLE 9
ALLANTOΓN-CONTAΓNTNG SKIN CREAM WITH
POLYETHYLENE GLYCOL ESTER OF STEARIC ACID
AND GLYCERYL STEARATE
INGREDIENT RANGE PREFERRED OPTIMUM
Part A
Water 50.0 - 90.0 55.0 - 80.0 67.86
Propylene Glycol 2.0 - 9.0 4.3 - 7.0 5.70
Tetrasodium EDTA 0.05 - 0.50 0.10-0.30 0.15
Citric Acid 0.04 - 0.40 0.10-0.30 0.14
PEG-100 Stearate 1.0-5.0 1.5-3.0 2.60
PartB
Lanolin Oil 5.0-15.0 2.0-12.0 10.60
Cetyl Alcohol 3.0-10.0 2.5 - 7.5 3.0
Stearyl Alcohol 1.0-4.0 1.0-3.5 2.50
Glyceryl Stearate 1.0-5.0 2.0-4.0 2.50
Cod Liver Oil 1.0-7.0 1.0-4.0 2.00
Butylated Hydroxytoluene 0.10-1.0 0.20 - 0.80 0.50
PartC
Methylparaben 0.10-0.50 0.15-0.40 0.30
Propylparaben 0.10-0.50 0.15 - 0.40 0.25
Diazolidinyl Urea 0.05 - 0.50 0.10-0.30 0.20
Allantoin 0.50 - 2.00 1.0-2.0 1.50
Fragrance 0.05 - 0.50 0.10-0.40 0.20
Example 8
Preparation of Allantoin-Containing Skin Cream with Carboxypolymethylene Polvmer and
Polvethylene Glycol Ester of Stearic Acid
An allantoin-containing skin cream with a carboxypolymethylene polymer and a polyethylene glycol ester of stearic acid is prepared according to Table 10. The preparation follows the method used in Example 5, with the triethanolamine (Part D) being added last. The triethanolamine is added to adjust the pH.
TABLE 10
ALLANTOiN-CONTAINING SKIN CREAM WITH
A CARBOXYPOLYMETHYLENE POLYMER AND A
POLYETHYLENE GLYCOL ESTER OF STEARIC ACID
INGREDIENT RANGE PREFERRED OPTIMUM
Part A
Water 50.0 - 90.0 60.0 - 85.0 69.95
Carboxypolymethylene Polymer 0.30-3.0 0.50-2.0 0.85
Propylene Glycol 2.0 - 9.0 4.0 - 7.0 5.70
PEG-100 Stearate 0.25 - 2.5 0.50 - 2.0 1.50
PartB
Lanolin Oil 5.0-15.0 8.0 - 12.0 10.60
Cetyl Alcohol 1.0-8.0 2.0 - 7.0 4.20
Stearyl Alcohol 0.50 - 6.0 0.75 - 5.0 1.50
Cod Liver Oil 1.0-7.0 1.0-4.0 2.00
Butylated Hydroxytoluene 0.10-1.0 0.20 - 0.80 0.50
PartC
Methylparaben 0.10-0.50 0.15 - 0.40 0.30
Propylparaben 0.10-0.50 0.15-0.40 0.25
Diazolidinyl Urea 0.05 - 0.25 0.10-0.20 0.15
Allantoin 0.50-2.0 1.0-2.0 1.50
Fragrance 0.05 - 0.50 0.10 - 0.40 0.20
PartD
Triethanolamine (99%) 0.05-3.0 0.20 - 2.0 0.80
Example 9
Preparation of Allantoin-Containing Skin Cream with Galactoarabinan, Sodium Lauryl
Sulfate. and Beeswax
An allantoin-containing skin cream with galactoarabinan, sodium lauryl sulfate, and beeswax is prepared according to Table 11. The preparation follows the method used in Example 3. The citric acid is used to adjust the pH.
TABLE 11
ALLANTOIN-CONTAiNING SKIN CREAM WITH
GALACTOARABINAN. SODIUM LAURYL SULFATE.
AND BEESWAX
<
INGREDIENT RANGE PREFERRED OPTIMUM
Part A
Water 50.0 - 90.0 60.0 - 80.0 61.65
Propylene Glycol 2.0 - 9.0 4.0 - 7.0 5.70
Sodium Lauryl Sulfate (30%) 0.50-5.0 1.0-3.0 1.90
Tetrasodium EDTA 0.05 - 0.30 0.10-0.20 0.15
Galactoarabinan 1.0-25.0 3.0-15.0 5.00
Citric Acid 0.05 - 0.25 0.10-0.20 0.15
PartB
Lanolin Oil 5.0-15.0 8.0-12.0 10.60
Cetyl Alcohol 1.0-8.0 2.0 - 7.0 4.20
Stearyl Alcohol 0.50 - 6.0 1.0-4.0 2.00
Beeswax 0.50-5.0 1.0-3.0 1.90
Cod Liver Oil 0.50-15.0 1.0-10.0 2.00
Butylated Hydroxytoluene 0.10-3.0 0.25 - 2.5 0.50
PartC
Methylparaben 0.10-0.50 0.15-0.40 0.30
Propylparaben 0.10-0.50 0.15-0.40 0.25
Allantoin 0.50-2.0 1.0-2.0 1.50
Fragrance 0.05 - 0.50 0.10-0.40 0.20
Example 10 Treatment of Epidermolysis Bullosa with Allantoin-Containing Skin Cream
A female epidermolysis bullosa patient (A.B.) was treated with the allantoin- containing skin cream of Example 2 prepared in accordance with the optimum formulation recited in Table 3. The allantoin-containing skin cream used for treatment comprised 68.68% water, 1.90% 30% sodium lauryl sulfate solution, 0.15% tetrasodium EDTA, 0.12% citric acid, 10.60% lanolin oil, 4.20% cetyl alcohol, 2.00% stearyl alcohol, 1.90% beeswax, 2.00% cod liver oil, 0.50% butylated hydroxytoluene, 0.10% St. John's wort, 0.10% chamomile extract, 0.10% witch hazel exfract, 0.10% arnica extract, 0.30%> methylparaben, 0.20% propylparaben, 1.50% allantoin, and 0.20% fragrance. The patient A.B. was born with
recessive dystrophic epidermolysis bullosa. She was born with no skin on her right foot from the shin down and spent the first 32 days of her life in intensive care. Her skin, which was constantly covered with Aquaphor, had the strength of tissue paper and blistered from the slightest touch. Although her feet, legs, arms, and hands were bandaged constantly, they continued to blister beneath the bandages. Her daily dressing changes took over an hour, and she required pain medication prior to each dressing change. Regardless of the meticulous care that the patient received, she battled infection constantly and chronic areas refused to heal. She began to develop infections that her doctors were unable to treat with antibiotics. Since her birth, the patient had required several different topical and oral antibiotics, as well as intramuscular injections. Because of the poor condition of her feet, the occupational and physical therapists treating the patient seriously doubted that she would ever walk.
The skin cream of Example 2 began to be applied to the patient A.B. when she was approximately 9 lA months old. The registered nurses that cared for the patient A.B. at her home immediately observed that the cream cut the healing time for an open wound in half and actually kept blisters from spreading over larger areas. As absolutely no irritation was observed and tremendous improvement was seen for the areas receiving the cream, the cream then was applied to all unbandaged areas of the body of the patient 5 to 6 times daily. A remarkable reduction in the number of blisters was noticed, and the purplish colors of the scars began to fade. After continued success with the skin cream of Example 2, it began to be used on the patient under the bandaged areas in place of the Aquaphor.
For approximately four months, the cream was applied to both the bandaged and the unbandaged areas of the patient A.B. For the first time since her birth, her right foot completely healed and was without any open sore or blister. The registered nurses that cared for the patient in her home continued to note a remarkable reduction in the amount of blistering, both under the bandages and on the open skin. The healing time for newly blistered areas was much faster. The areas healed without the milia cysts that, prior to using the cream, accompanied each scar.
No type of antibiotic has been applied to the patient since the cream started to be used on the patient. Despite the lack of use of antibiotic, her foot remained infection free. The period during which the cream of Example 2 was used was the longest period for which her foot had gone without reblistering and/or becoming infected.
At the last visit of the doctors to the patient, the doctors were amazed to see skin on areas of the foot that they never thought would heal. The patient is able to walk better and for longer areas of time, and she was able to actually run across the floor.
The patient had experienced an overall decrease in skin fragility. Her right lower extremity, the area of greatest blistering, has continued to have decreased erythema, decreased pain, and decreased skin fragility. The patient did not require any bacterial cultures or antibiotics over the period during which the skin cream of Example 2 was used.
Dressing changes were accomplished in half the time and without any pain medication. The mother of the patient was able to actually change her dressings alone. Before the cream of Example 2 was applied to the patient, this task was impossible for the mother of the patient because of the poor condition of her feet and the additional steps and time necessary to change the dressings prior to the use of the cream of Example 2 on the patient.
One area of the patient did not receive the cream: the buttocks area. At one point, the patient developed two very small blisters in that area about the size of a dime. One of the blisters continued to spread and spread until the blister covered the entire buttocks area. The area was raw and the blister continued to refill. No area on her body had had blisters spread since the cream of Example 2 had been used on the patient. This is the only area in which the cream was not used because no blisters had developed in that area prior to this. This strongly suggests that the cream was responsible for making a remarkable difference in the healing and protection of the skin of the patient.
Although the patient, as with all patients with recessive dystrophic epidermolysis bullosa, continued to have areas of scarring on hands with concern of eventual fusion and decreased function, her disease had stabilized after the use of the cream of Example 2.
Figures 1(a) and 1(b) are pictures of the right foot of the patient A.B. before the use of the cream of Example 2 from two different views, showing the severity of the disease.
Figure 2 is a picture of the right foot of the patient A.B. after two months of use of the cream of Example 2, showing considerable improvement.
Figures 3(a) and 3(b) are pictures of the right foot of the patient A.B. after 12 months of use of the cream of Example 2, showing substantial improvement and clearing of the lesions.
Figures 4(a), 4(b), and 4(c) are additional pictures of the right foot of the patient A.B. after 12 months of use of the cream of Example 2, again showing substantial improvement and clearing of the lesions.
Figures 5(a) and 5(b) are pictures of the buttocks area of the patient A.B. before the use of the cream (Fig. 5(a)) and after 2 weeks of use of the cream (Fig. 5(b)), showing substantial improvement and clearing of the lesions.
Figures 6(a) and 6(b) are pictures of the facial area of the patient A.B. before the use of the cream (Fig. 6(a)) and after 3 months of use of the cream (Fig. 6(b)), showing substantial improvement, fading, and clearing of the lesions.
Example 11
Treatment of Epidermolysis Bullosa
A female epidermolysis bullosa patient (CD.) was treated with the allantoin- containing skin cream of Example 2. The patient CD. had epidermolysis bullosa of the Dowling-Meara type.
The patient CD. received two to three applications per day of the allantoin- containing skin cream of Example 2. The cream produced considerable improvement in the skin of the patient CD. This was the first time that her skin had remained moderately clear for a long period of time. The areas that experienced severe blistering had remained clean with the exception of some minor blistering. This blistering was not nearly as severe as what
had been experienced prior to the use of the skin cream of Example 2. Also, a blister that did start on the back of the patient CD. did not develop into a full-blown, spread- wide blister as had happened previously. This tendency of these blisters to spread is characteristic of the Dowling-Meara form of epidermolysis bullosa. Even problem areas that have taken a longer time to heal have not spread out of control.
The time required for the care of the patient CD., such as the time required for lancing and wrapping her wounds, has decreased by at least 75% subsequent to the administration of the allantoin-containing skin cream of Example 2. The requirements for medical supplies used for the care of the patient CD., such as sterile needles, sterile bandages, and sterile dressing sponges, also decreased tremendously subsequent to the administration of the allantoin-containing skin cream of Example 2.
Figure 7 is a photograph of patient CD. before commencement of the use of the allantoin-containing skin cream of Example 2.
Figure 8 is a photograph of patient CD. after 8 weeks of use of the allantoin- containing skin cream of Example 2, showing substantial improvement of the lesions.
Figure 9(a) is a photograph of the back area of patient CD. before commencement of the use of the allantoin-containing skin cream of Example 2.
Figure 9(b) is another photograph of the back area of patient CD. before commencement of the use of the allantoin-containing skin cream of Example 2.
Figure 10(a) is a photograph of the upper back area of patient CD. after 2 weeks of use of the allantoin-containing skin cream of Example 2, showing considerable improvement.
Figure 10(b) is a photograph of the upper back area of patient CD. after 8 weeks of use of the allantoin-containing skin cream of Example 2, showing continued improvement evidenced by fading of the lesions.
Figure 11(a) is a photograph of the upper leg area of patient CD. before commencement of the use of the allantoin-containing skin cream of Example 2.
Figure 11(b) is a photograph of the lower leg area of patient CD. before commencement of the use of the allantoin-containing skin cream of Example 2.
Figure 11(c) is a photograph of the legs of patient CD. after 2 weeks of use of the allantoin-containing skin cream of Example 2, showing substantial improvement.
Figure 11(d) is a photograph of the legs of patient CD. after 8 weeks of use of the allantoin-containing skin cream of Example 2, showing continuing improvement.
ADVANTAGES OF THE PRESENT INVENTION
The present invention provides an improved method of treating skin diseases and conditions characterized by ulceration, inflammation, and blistering. This includes such difficult-to-treat conditions as epidermolysis bullosa, decubitus ulcers, diabetic ulcers, pressure ulcers, and milia. Methods according to the present invention provide rapid improvement, are well tolerated by patients, are easy to apply, and can be used alone or with other methods for treatment of skin conditions.
Although the present invention has been described in considerable detail, with reference to certain preferred versions thereof, other versions and embodiments are possible. Therefore, the scope of the invention is determined by the following claims.
Claims (133)
1. A method of treating a skin condition or disease characterized by ulceration, inflammation, or blistering of the skin comprising applying to the skin an allantoin-containing composition in a therapeutically effective amount, the allantoin- containing composition comprising an oil-in-water emulsion comprising:
(a) allantoin;
(b) an emulsifier system including: (i) beeswax; and
(ii) an anionic emulsifier that is substantially hydrophilic and is soluble in water, the pH of the composition being from about 3.0 to about 6.0 after the addition of acid to bring the pH into the range of from about 3.0 to about 6.0.
2. The method of claim 1 wherein the pH of the composition is from about 4.5 to about 5.8.
3. The method of claim 1 wherein the emulsifier is selected from the group consisting of ammonium lauryl sulfate, sodium lauryl sulfate, sodium laureth sulfate, sodium oleyl succinate, ammonium lauryl sulfosuccinate, sodium dodecylbenzenesulfonate, ammonium laureth sulfate, and sodium lauryl sarcosinate.
4. The method of claim 3 wherein the emulsifier is sodium lauryl sulfate.
5. The method of claim 1 wherein the skin condition or disease is selected from the group consisting of epidermolysis bullosa, decubitus ulcers, pressure ulcers, diabetic ulcers, and milia.
6. The method of claim 5 where the skin condition or disease is epidermolysis bullosa.
7. The method of claim 1 further comprising administering an additional therapeutic agent in a therapeutically effective quantity.
8. The method of claim 7 wherein the additional therapeutic agent is selected from the group consisting of steroids, nonsteroidal anti-inflammatory agents, leukotriene antagonists, and monoclonal antibodies.
9. The method of claim 1 wherein the composition further comprises at least one of:
(a) an emollient component comprising at least one ingredient selected from the group consisting of lanolin oil, cetyl alcohol, stearyl alcohol, and cod liver oil;
(b) butylated hydroxytoluene; (c) at least one herbal extract selected from the group consisting of St. John's wort extract, witch hazel extract, chamomile extract, and arnica extract;
(d) a preservative component comprising at least one preservative selected from the group consisting of methylparaben and propylparaben;
(e) tetrasodium EDTA; and (f) a solvent component comprising at least one solvent selected from the group consisting of propylene glycol, butylene glycol, and glycerin.
10. The method of claim 2 wherein the composition comprises: an oil-in-water emulsion comprising: (a) water;
(b) sodium lauryl sulfate;
(c) propylene glycol;
(d) tetrasodium EDTA;
(e) citric acid; (f) lanolin oil;
(g) cetyl alcohol; (h) stearyl alcohol; (i) beeswax; (j) cod liver oil; (k) butylated hydroxytoluene;
(1) St. John's wort extract; (m) witch hazel extract; (n) chamomile extract; (o) arnica extract; (p) methylparaben; (q) propylparaben; (r) allantoin; and (s) fragrance.
11. The method of claim 10 wherein the composition comprises :
(a) from about 50% to about 90% of water;
(b) from about 0.5% to about 2.5% of 30% sodium lauryl sulfate;
(c) from about 2.0% to about 9.0% of propylene glycol; (d) from about 0.05% to about 0.5% of tetrasodium EDTA;
(e) from about 0.05% to about 0.5%> of citric acid;
(f) from about 5% to about 15% of lanolin oil;
(g) from about 3% to about 10% of cetyl alcohol; (h) from about 1% to about 5% of stearyl alcohol; (i) from about 0.5% to about 2.5% of beeswax;
(j) from about 1.0% to about 7.0% of cod liver oil;
(k) from about 0.1% to about 1.0% of butylated hydroxytoluene;
(1) from about 0.05% to about 0.5% of St. John's wort extract;
(m) from about 0.05% to about 0.5% of witch hazel extract; (n) from about 0.05% to about 0.5% of chamomile extract;
(o) from about 0.05% to about 0.5% of arnica extract;
(p) from about 0.1% to about 0.5% of methylparaben;
(q) from about 0.1% to about 0.5% of propylparaben;
(r) from about 0.5% to about 2% of allantoin; and (s) from about 0.05% to about 0.5% of fragrance.
12. The method of claim 11 wherein the composition comprises:
(a) from about 55% to about 75% of water;
(b) from about 1.0% to about 2.5% of 30% sodium lauryl sulfate; (c) from about 3.0% to about 6.0% of propylene glycol;
(d) from about 0.1% to about 0.3% of tetrasodium EDTA;
(e) from about 0.08 to about 0.35% of citric acid;
(f) from about 8.0% to about 12.0%) of lanolin oil;
(g) from about 3.5% to about 7.5%> of cetyl alcohol; (h) from about 1.0% to about 3.0% of stearyl alcohol; (i) from about 1.0% to about 2.5% of beeswax; (j) from about 1.0% to about 4.0% of cod liver oil; (k) from about 0.2% to about 0.8% of butylated hydroxytoluene; (1) from about 0.05% to about 0.15% of St. John' s wort extract;
(m) from about 0.05% to about 0.15% of witch hazel extract; (n) from about 0.05% to about 0.15% of chamomile extract;
(0) from about 0.05% to about 0.15% of arnica extract; (p) from about 0.15% to about 0.40% of methylparaben; (q) from about 0.10% to about 0.30% of propylparaben;
(r) from about 0.50% to about 2.0% of allantoin; and (s) from about 0.1 %> to about 0.3% of fragrance.
13. The method of claim 12 wherein the composition comprises: (a) about 68.68% of water;
(b) about 1.9% of sodium lauryl sulfate;
(c) about 5.3% of propylene glycol;
(d) about 0.15% of tetrasodium EDTA;
(e) about 0.12% of citric acid; (f) about 10.6% of lanolin oil;
(g) about 4.2% of cetyl alcohol; (h) about 2.0% of stearyl alcohol; (i) about 1.90% of beeswax; (j) about 2.0% of cod liver oil; (k) about 0.5% of butylated hydroxytoluene;
(1) about 0.1% of St. John's wort extract; (m) about 0.1% of witch hazel extract; (n) about 0.1% of chamomile extract; (o) about 0.1% of arnica extract; (p) about 0.3% of methylparaben;
(q) about 0.25% of propylparaben; (r) about 1.50% of allantoin; and (s) about 0.20% of fragrance.
14. A method of treating a skin condition or disease characterized by ulceration, inflammation, or blistering of the skin, comprising applying to the skin an allantoin-containing composition in a therapeutically effective amount, the allantoin- containing composition comprising an oil-in-water emulsion comprising: (a) allantoin;
(b) an emollient component comprising:
(i) lanolin oil; (ii) cetyl alcohol; (iii) stearyl alcohol; and (iv) cod liver oil; and
(c) butylated hydroxytoluene;
(d) an emulsifier system comprising at least one nonionic emulsifier that is an ethoxylated ether or an ethoxylated ester whose carbon chain length ranges from 8 to 22 carbon atoms; and (e) at least one acid selected from the group consisting of:
(i) an organic acid of from 2 to 22 carbon atoms; and (ii) an inorganic acid selected from the group consisting of hydrochloric acid, sulfuric acid, and phosphoric acid to adjust the pH from about 3.0 to about 6.0.
15. The method of claim 14 wherein the pH of the composition is from about 4.5 to about 5.8.
16. The method of claim 14 wherein the skin condition or disease is selected from the group consisting of epidermolysis bullosa, decubitus ulcers, pressure ulcers, diabetic ulcers, and milia.
17. The method of claim 16 wherein the skin condition or disease is epidermolysis bullosa.
18. The method of claim 14 further comprising administering an additional therapeutic agent in a therapeutically effective quantity.
19. The method of claim 18 wherein the additional therapeutic agent is selected from the group consisting of steroids, nonsteroidal anti-inflammatory agents, leukotriene antagonists, and monoclonal antibodies.
20. A method of treating a skin condition or disease characterized by ulceration, inflammation, or blistering of the skin comprising applying to the skin an allantoin-containing composition in a therapeutically effective amount, the allantoin- containing composition comprising an oil-in-water emulsion comprising: (a) allantoin; (b) an emulsifier system including at least one nonionic emulsifier that is an ethoxylated ether or an ethoxylated ester whose carbon chain length ranges from 8 to 22 carbon atoms, the pH of the emulsion being from about 3.0 to about 6.0 after the addition of acid to bring the pH into the range of from about 3.0 to about 6.0.
21. The method of claim 20 wherein the pH of the composition is from about 4.5 to about 5.8.
22. The method of claim 20 wherein the skin condition or disease is selected from the group consisting of epidermolysis bullosa, decubitus ulcers, pressure ulcers, diabetic ulcers, and milia.
23. The method of claim 22 wherein the skin condition or disease is epidermolysis bullosa.
24. The method of claim 20 further comprising administering an additional therapeutic agent in a therapeutically effective quantity.
25. The method of claim 24 wherein the additional therapeutic agent is selected from the group consisting of steroids, nonsteroidal anti-inflammatory agents, leukotriene antagonists, and monoclonal antibodies.
26. The method of claim 20 wherein the composition further comprises at least one of: (a) an emollient component comprising at least one ingredient selected from the group consisting of lanolin oil, cetyl alcohol, stearyl alcohol, and cod liver oil;
(b) butylated hydroxytoluene;
(c) at least one herbal extract selected from the group consisting of St. John's wort extract, witch hazel extract, chamomile extract, and arnica extract;
(d) a preservative component comprising at least one preservative selected from the group consisting methylparaben, propylparaben, and diazolidinyl urea;
(e) tetrasodium EDTA; and
(f) a solvent component comprising at least one solvent selected from the group consisting of propylene glycol, butylene glycol, and glycerin.
27. A method of treating a skin condition or disease characterized by ulceration, inflammation, or blistering of the skin, comprising applying to the skin an allantoin-containing composition in a therapeutically effective amount, the allantoin- containing composition comprising an oil-in-water emulsion comprising:
(a) allantoin; and
(b) an emulsifier system comprising:
(1) an acidic anionic polymer; and
(2) a polyethylene glycol ester of stearic acid; wherein the pH of the composition is adjusted to a value within a range of from about 3.0 to about 6.0.
28. The method of claim 27 wherein the pH of the composition is from about 5.0 to about 6.0.
29. The method of claim 27 wherein the acidic anionic polymer is a carboxypolymethylene polymer.
30. The method of claim 27 wherein the composition further comprises a carbohydrate polymer selected from the group consisting of galactoarabinan, polygalactose, and polyarabinose.
31. The method of claim 30 wherein the carbohydrate polymer is galactoarabinan.
32. The method of claim 27 wherein the skin condition or disease is selected from the group consisting of epidermolysis bullosa, decubitus ulcers, pressure ulcers, diabetic ulcers, and milia.
33. The method of claim 32 wherein the skin condition or disease is epidermolysis bullosa.
34. The method of claim 27 further comprising administering an additional therapeutic agent in a therapeutically effective quantity.
35. The method of claim 34 wherein the additional therapeutic agent is selected from the group consisting of steroids, nonsteroidal anti-inflammatory agents, leukotriene antagonists, and monoclonal antibodies.
36. The method of claim 27 wherein the composition further comprises:
(a) an emollient component comprising at least one emollient selected from the group consisting of lanolin oil, cetyl alcohol, stearyl alcohol, and cod liver oil;
(b) butylated hydroxytoluene; (c) a solvent component comprising at least one solvent selected from the group consisting of propylene glycol, glycerin, and ethylene glycol; and
(d) a preservative component comprising at least one preservative selected from the group consisting of methylparaben, propylparaben, and diazolidinyl urea.
37. The method of claim 28 wherein the composition comprises:
(a) from about 50.0% to about 90.0% of water;
(b) from about 0.30% to about 3.0%> of a carboxypolymethylene polymer;
(c) from about 2.0% to about 9.0% of propylene glycol;
(d) from about 0.25% to about 2.5% of PEG-100 stearate; (e) from about 5.0% to about 15.0% of lanolin oil;
(f) from about 1.0% to about 8.0% of cetyl alcohol;
(g) from about 0.5% to about 6.0% of stearyl alcohol; (h) from about 1.0% to about 7.0% of cod liver oil;
(i) from about 0.10% to about 1.0% of butylated hydroxytoluene; (j) from about 0.10% to about 0.50% of methylparaben;
(k) from about 0.10% to about 0.50% of propylparaben;
(1) from about 0.05% to about 0.25% of diazolidinyl urea;
(m) from about 0.50% to about 2.0% of allantoin; (n) from about 0.05% to about 0.50% of fragrance; and
(o) from about 0.05% to about 3.0% of triethanolamine.
38. The method of claim 37 wherein the composition comprises :
(a) from about 60.0% to about 85.0% of water; (b) from about 0.50% to about 2.0% of a carboxypolymethylene polymer;
(c) from about 4.0% to about 7.0% of propylene glycol;
(d) from about 0.50% to about 2.0% of PEG-100 stearate;
(e) from about 8.0% to about 12.0% of lanolin oil;
(f) from about 2.0% to about 7.0%) of cetyl alcohol; (g) from about 0.75% to about 5.0% of stearyl alcohol;
(h) from about 1.0% to about 4.0% of cod liver oil;
(i) from about 0.20% to about 0.80% of butylated hydroxytoluene;
(j) from about 0.15% to about 0.40% of methylparaben;
(k) from about 0.15% to about 0.45% of propylparaben; (1) from about 0.10% to about 0.20% of diazolidinyl urea;
(m) from about 1.0% to about 2.0% of allantoin;
(n) from about 0.10% to about 0.40% of fragrance; and
(o) from about 0.20% to about 2.0% of triethanolamine.
39. The method of claim 38 wherein the composition comprises:
(a) about 69.95% of water;
(b) about 0.85% of a carboxypolymethylene polymer;
(c) about 5.70% of propylene glycol;
(d) about 2.0% of PEG- 100 stearate; (e) about 10.60% of lanolin oil;
(f) about 4.20% of cetyl alcohol;
(g) about 1.50% of stearyl alcohol; (h) about 2.00% of cod liver oil;
(i) about 0.50% of butylated hydroxytoluene; (j) about 0.30% of methylparaben;
(k) about 0.25% of propylparaben;
(1) about 0.15% of diazolidinyl urea;
(m) about 1.50% of allantoin; (n) about 0.20% of fragrance; and
(o) about 0.80% of triethanolamine.
40. A method of treating a skin condition or disease characterized by ulceration, inflammation, or blistering of the skin, comprising applying to the skin an allantoin-containing composition in a therapeutically effective amount, the allantoin- containing composition comprising an oil-in-water emulsion comprising:
(a) allantoin; and
(b) an emulsifier system comprising:
(i) an acidic anionic polymer; and (ii) an anionic emulsifier that is substantially hydrophilic and is soluble in water, the pH of the composition being adjusted to a range from about 3.0 to about 6.0.
41. The method of claim 40 wherein the pH of the composition is from about 5.0 to about 6.0.
42. The method of claim 40 wherein the anionic emulsifier is selected from the group consisting of sodium lauryl sulfate, sodium laureth sulfate, sodium oleyl succinate, sodium dodecylbenzenesulfonate and sodium lauryl sarcosinate.
43. The method of claim 42 wherein the anionic emulsifier is sodium lauryl sulfate.
44. The method of claim 40 wherein the acidic anionic polymer is carboxypolymethylene.
45. The method of claim 44 wherein the composition further comprises a carbohydrate polymer selected from the group consisting of galactoarabinan, polygalactose and polyarabinose.
46. The method of claim 45 wherein the carbohydrate polymer is galactoarabinan.
47. A method of treating a skin condition or disease characterized by ulceration, inflammation, or blistering of the skin, comprising applying to the skin an allantoin-containing composition in a therapeutically effective amount, the allantoin- containing composition comprising an oil-in-water emulsion comprising:
(a) allantoin; and
(b) an emulsifier system comprising: (i) an acidic anionic polymer; and
(ii) a nonionic emulsifier that is an ethoxylated ether or an ethoxylated ester whose carbon chain length ranges from 8 to 22 carbon atoms, wherein the pH of the composition is from about 3.0 to about 6.0.
48. The method of claim 47 wherein the pH of the composition is from about 5.0 to about 6.0.
49. The method of claim 47 wherein the acidic anionic polymer is carboxypolymethylene.
50. The method of claim 47 wherein the composition further comprises a carbohydrate polymer selected from the group consisting of galactoarabinan, polygalactose and polyarabinose.
51. The method of claim 50 wherein the carbohydrate polymer is galactoarabinan.
52. The method of claim 47 wherein the emulsifier system further comprises glyceryl stearate.
53. The method of claim 47 wherein the skin condition or disease is selected from the group consisting of epidermolysis bullosa, decubitus ulcers, pressure ulcers, diabetic ulcers, and milia.
54. The method of claim 53 wherein the skin condition or disease is epidermolysis bullosa.
55. The method of claim 47 further comprising administering an additional therapeutic agent in a therapeutically effective quantity.
56. The method of claim 55 wherein the additional therapeutic agent is selected from the group consisting of steroids, nonsteroidal anti-inflammatory agents, leukotriene antagonists, and monoclonal antibodies.
57. The method of claim 47 wherein the composition further comprises at least one of:
(a) an emollient component comprising at least one emollient selected from the group consisting of lanolin oil, cetyl alcohol, stearyl alcohol, and cod liver oil; (b) butylated hydroxytoluene;
(c) at least one herbal extract selected from the group consisting of St. John's wort extract, witch hazel extract, chamomile extract, and arnica extract;
(d) a preservative component comprising at least one preservative selected from the group consisting of methylparaben, propylparaben and diazolidinyl urea; (e) tetrasodium EDTA; and
(f) a solvent component comprising at least one solvent selected from the group consisting of propylene glycol, butylene glycol, and glycerin.
58. A method of treating a skin condition or disease characterized by ulceration, inflammation, or blistering of the skin, comprising applying to the skin an allantoin-containing composition in a therapeutically effective amount, the allantoin- containing composition comprising an oil-in-water emulsion comprising:
(a) allantoin;
(b) an emulsifier system comprising an acidic anionic polymer; (c) an organic or inorganic base to adjust the pH to a value in a range of from about 3.0 to about 6.0
59. The method of claim 58 wherein the pH of the composition is from about 5.0 to about 5.5.
60. The method of claim 58 wherein the organic or inorganic base is triethanolamine.
61. The method of claim 58 wherein the acidic anionic polymer is carboxypolymethylene.
62. The method of claim 58 wherein the skin condition or disease is selected from the group consisting of epidermolysis bullosa, decubitus ulcers, pressure ulcers, diabetic ulcers, and milia.
63. The method of claim 62 wherein the skin condition or disease is epidermolysis bullosa.
64. The method of claim 58 further comprising administering an additional therapeutic agent in a therapeutically effective quantity.
65. The method of claim 64 wherein the additional therapeutic agent is selected from the group consisting of steroids, nonsteroidal anti-inflammatory agents, leukotriene antagonists, and monoclonal antibodies.
66. The method of claim 58 wherein the composition further comprises at least one of:
(a) an emollient component comprising at least one ingredient selected from the group consisting of lanolin oil, cetyl alcohol, stearyl alcohol, and cod liver oil;
(b) butylated hydroxytoluene;
(c) a preservative component comprising at least one preservative selected from the group consisting of methylparaben and propylparaben; and
(d) a solvent component comprising at least one solvent selected from the group consisting of propylene glycol, butylene glycol, and glycerin.
67. The method of claim 59 wherein the composition comprises:
(a) from about 50.0% to about 90.0% of water;
(b) from about 0.40% to about 3.0% of carboxypolymethylene polymer; (c) from about 2.0% to about 9.0% of propylene glycol.
(d) from about 5.0% to about 15.0% of lanolin oil;
(e) from about 1.0% to about 8.0% of cetyl alcohol;
(f) from about 1.0% to about 7.0% of cod liver oil; (g) from about 0.10% to about 1.0% of butylated hydroxytoluene;
(h) from about 0.10% to about 0.50% of methylparaben; (i) from about 0.10% tα about 0.50% of propylparaben; (j) from about 0.50% to about 2.0% of allantoin; (k) from about 0.05% to about 0.5% of fragrance; and (1) from about 0.05% to about 3.0% of 95% triethanolamine.
68. The method of claim 67 wherein the composition comprises:
(a) from about 60.0% to about 80.0% of water;
(b) from about 0.50% to about 2.0% of carboxypolymethylene polymer; (c) from about 4.0% to about 7.0% of propylene glycol.
(d) from about 8.0% to about 12.0% of lanolin oil;
(e) from about 2.0% to about 7.0% of cetyl alcohol;
(f) from about 1.0% to about 4.0% of cod liver oil;
(g) from about 0.30% to about 0.80% of butylated hydroxytoluene; (h) from about 0.15% to about 0.40% of methylparaben;
(i) from about 0.15% to about 0.40% of propylparaben; (j) from about 1.0% to about 2.0% of allantoin; (k) from about 0.10% to about 0.40% of fragrance; and (1) from about 0.20% to about 2.0% of 95% triethanolamine.
69. The method of claim 68 wherein the composition comprises:
(a) about 73.55% of water;
(b) about 1.00% of carboxypolymethylene polymer;
(c) about 5.7% of propylene glycol. (d) about 10.0% of lanolin oil;
(e) about 3.00% of cetyl alcohol;
(f) about 2.00% of cod liver oil;
(g) about 0.50% of butylated hydroxytoluene; (h) about 0.30% of methylparaben; (i) about 0.25% of propylparaben;
(j) about 1.50%) of allantoin;
(k) about 0.20% of fragrance; and
(1) about 0.80% of 95% triethanolamine.
70. A method of treating a skin condition or disease characterized by ulceration, inflammation, or blistering of the skin, comprising applying to the skin an allantoin-containing composition in a therapeutically effective amount, the allantoin- containing composition comprising an oil-in-water emulsion comprising: (a) allantoin;
(b) an emulsifier system comprising:
(i) cetyl alcohol; and (ii) stearic acid; and
(c) a weak organic base to adjust the pH to a range of from about 3.0 to about 6.0.
71. The method of claim 70 wherein the pH of the composition is from about 5.0 to about 5.8.
72. The method of claim 70 wherein the weak organic base is triethanolamine.
73. The method of claim 70 wherein the skin condition or disease is selected from the group consisting of epidermolysis bullosa, decubitus ulcers, pressure ulcers, diabetic ulcers, and milia.
74. The method of claim 73 wherein the skin condition or disease is epidermolysis bullosa.
75. The method of claim 70 further comprising administering an additional therapeutic agent in a therapeutically effective quantity.
76. The method of claim 75 wherein the additional therapeutic agent is selected from the group consisting of steroids, nonsteroidal anti-inflammatory agents, leukotriene antagonists, and monoclonal antibodies.
77. The method of claim 70 wherein the composition further comprises at least one of:
(a) an emollient component comprising at least one ingredient selected from the group consisting of lanolin oil, stearyl alcohol, and cod liver oil;
(b) butylated hydroxytoluene; (c) a preservative component comprising at least one preservative selected from the group consisting of methylparaben and propylparaben; and
(d) a solvent component comprising at least one solvent selected from the group consisting of propylene glycol, butylene glycol, and glycerin.
78. The method of claim 71 wherein the composition comprises:
(a) from about 50.0% to about 90.0% of water;
(b) from about 2.0% to about 9.0% of propylene glycol;
(c) from about 0.2% to about 4.0% of triethanolamine;
(d) from about 5.0% to about 15.0% of lanolin oil; (e) from about 1.0% to about 7.0% of cetyl alcohol;
(f) from about 0.50% to about 5.0% of stearic acid;
(g) from about 1.0% to about 7.0% of cod liver oil;
(h) from about 0.10% to about 1.0% of butylated hydroxytoluene; (i) from about 0.10% to about 0.50% of methylparaben; (j) from about 0.10% to about 0.50% of propylparaben;
(k) from about 0.50% to about 2.0% of allantoin; and (1) from about 0.05% to about 0.50% of fragrance.
79. The method of claim 78 wherein the composition comprises: (a) from about 60.0% to about 85.0%> of water;
(b) from about 4.0% to about 7.0% of propylene glycol;
(c) from about 0.5% to about 3.0% of triethanolamine;
(d) from about 8.0% to about 12.0% of lanolin oil;
(e) from about 2.0% to about 6.0% of cetyl alcohol; (f) from about 1.0% to about 4.0% of stearic acid;
(g) from about 1.5% to about 5.0% of cod liver oil;
(h) from about 0.20% to about 0.80% of butylated hydroxytoluene; (i) from about 0.15% to about 0.40% of methylparaben; (j) from about 0.15% to about 0.40% of propylparaben;
(k) from about 1.0% to about 2.0% of allantoin; and (1) from about 0.10% to about 0.40% of fragrance.
80. The method of claim 79 wherein the composition comprises: (a) about 71.70% of water;
(b) about 5.70% of propylene glycol;
(c) about 1.25% of triethanolamine;
(d) about 10.60% of lanolin oil;
(e) about 3.50% of cetyl alcohol; (f) about 2.50% of stearic acid;
(g) about 2.00% of cod liver oil; (h) about 0.50% of butylated hydroxytoluene; (i) about 0.30% of methylparaben; (j) about 0.25% of propylparaben; (k) about 1.50% of allantoin; and
(1) about 0.20% of fragrance.
81. A method of treating a skin condition or disease characterized by ulceration, inflammation, or blistering of the skin, comprising applying to the skin an allantoin-containing composition in a therapeutically effective amount, the allantoin- containing composition comprising an oil-in-water emulsion comprising:
(a) allantoin;
(b) an emulsifier system comprising:
(i) sodium stearoyl lactylate; (ii) sodium isostearoyl lactylate;
(iii) optionally, triethanolamine stearate;
(iv) optionally, at least one nonionic emulsifier selected from the group consisting of a nonionic emulsifier that is an ethoxylated ether or an ethoxylated ester whose carbon chain length ranges from 8 to 22 carbon atoms; and (c) an acid to adjust the pH to a range of from about 3.0 to about 6.0.
82. The method of claim 81 wherein the pH of the composition is from about 5.0 to about 5.8.
83. The method of claim 81 wherein the acid is citric acid.
84. The method of claim 81 wherein the composition comprises triethanolamine stearate.
85. The method of claim 81 wherein the composition comprises at least one nonionic emulsifier selected from the group consisting of a nonionic emulsifier that is an ethoxylated ether or an ethoxylated ester whose carbon chain length ranges from 8 to 22 carbon atoms.
86. The method of claim 81 wherein the skin condition or disease is selected from the group consisting of epidermolysis bullosa, decubitus ulcers, pressure ulcers, diabetic ulcers, and milia.
87. The method of claim 86 wherein the skin condition or disease is epidermolysis bullosa.
88. The method of claim 81 further comprising administering an additional therapeutic agent in a therapeutically effective quantity.
89. The method of claim 88 wherein the additional therapeutic agent is selected from the group consisting of steroids, nonsteroidal anti-inflammatory agents, leukotriene antagonists, and monoclonal antibodies.
90. The method of claim 81 wherein the composition further comprises at least one of:
(a) an emollient component comprising at least one ingredient selected from the group consisting of lanolin oil, cetyl alcohol, and cod liver oil;
(b) butylated hydroxytoluene; (c) a preservative component comprising at least one preservative selected from the group consisting of methylparaben and propylparaben;
(d) a solvent component comprising at least one solvent selected from the group consisting of propylene glycol, butylene glycol, and glycerin; and (e) tetrasodium EDTA.
91. The method of claim 82 wherein the composition comprises:
(a) from about 50.0% to about 90.0%o of water;
(b) from about 2.0% to about 9.0% of propylene glycol; (c) from about 0.05% to about 0.5% of citric acid;
(d) from about 0.30% to about 3.0% of sodium stearoyl lactylate;
(e) from about 0.05% to about 1.0% of sodium isostearoyl lactylate;
(f) from about 0.05% to about 0.25% of tetrasodium EDTA;
(g) from about 5.0% to about 15.0% of lanolin oil; (h) from about 1.0% to about 8.0% of cetyl alcohol;
(i) from about 1.0% to about 7.0% of cod liver oil;
(j) from about 0.10% to about 1.0% of butylated hydroxytoluene;
(k) from about 0.10% to about 0.50% of methylparaben;
(1) from about 0.10% to about 0.50% of propylparaben; (m) from about 0.50% to about 2.0% of allantoin; and
(n) from about 0.05% to about 0.50% of fragrance.
92. The method of claim 91 wherein the composition comprises: (a) from about 60.0% to about 80.0% of water; (b) from about 4.0% to about 7.0% of propylene glycol;
(c) from about 0.10% to about 0.40% of citric acid;
(d) from about 0.50% to about 2.5% of sodium stearoyl lactylate;
(e) from about 0.10% to about 0.70% of sodium isostearoyl lactylate;
(f) from about 0.10% to about 0.20% of tetrasodium EDTA; (g) from about 8.0% to about 12.0% of lanolin oil;
(h) from about 2.0% to about 7.0% of cetyl alcohol;
(i) from about 1.0% to about 4.0% of cod liver oil;
(j) from about 0.20% to about 0.80% of butylated hydroxytoluene;
(k) from about 0.15% to about 0.40% of methylparaben; (1) from about 0.15% to about 0.40% of propylparaben; (m) from about 1.0% to about 2.0% of allantoin; and (n) from about 0.10% to about 0.40% of fragrance.
93. The method of claim 92 wherein the composition comprises:
(a) about 73.42%) of water;
(b) about 5.70% of propylene glycol;
(c) about 0.18% of citric acid;
(d) about 1.00% of sodium stearoyl lactylate; (e) about 0.25% of sodium isostearoyl lactylate;
(f) about 0.15% of tetrasodium EDTA;
(g) about 15.0% of lanolin oil; (h) about 3.80% of cetyl alcohol; (i) about 2.00% of cod liver oil; (j) about 0.50% of butylated hydroxytoluene;
(k) about 0.30% of methylparaben;
(1) about 0.25% of propylparaben;
(m) about 1.50% of allantoin; and
(n) about 0.20% of fragrance.
94. A method of treating a skin condition or disease characterized by ulceration, inflammation, or blistering of the skin, comprising applying to the skin an allantoin-containing composition in a therapeutically effective amount, the allantoin- containing composition comprising an oil-in-water emulsion comprising: (a) allantoin; and
(b) an emulsifier system comprising at least one polyethyleneglycol ether of cetearyl alcohol, wherein the number of polyethylene glycol moieties in the polyethyleneglycol ether of cetearyl alcohol is from 6 to 40; and
(c) an acid to adjust the pH of the composition to a range of from about 3.0 to about 6.0.
95. The method of claim 94 wherein the pH of the composition is from about 5.0 to about 5.8.
96. The method of claim 94 wherein the acid is citric acid.
97. The method of claim 94 wherein the emulsifier system comprises ceteareth-25 and ceteareth-6.
98. The method of claim 94 wherein the skin condition or disease is selected from the group consisting of epidermolysis bullosa, decubitus ulcers, pressure ulcers, diabetic ulcers, and milia.
99. The method of claim 98 wherein the skin condition or disease is epidermolysis bullosa.
100. The method of claim 94 further comprising administering an additional therapeutic agent in a therapeutically effective quantity.
101. The method of claim 100 wherein the additional therapeutic agent is selected from the group consisting of steroids, nonsteroidal anti-inflammatory agents, leukotriene antagonists, and monoclonal antibodies.
102. The method of claim 94 wherein the composition further comprises at least one of:
(a) an emollient component comprising at least one ingredient selected from the group consisting of lanolin oil, cetyl alcohol, stearyl alcohol, and cod liver oil;
(b) butylated hydroxytoluene; (c) a preservative component comprising at least one preservative selected from the group consisting of methylparaben, propylparaben, and diazolidinyl urea;
(d) a solvent component comprising at least one solvent selected from the group consisting of propylene glycol, butylene glycol, and glycerin; and (e) tetrasodium EDTA.
103. The method of claim 95 wherein the composition comprises:
(a) from about 50.0% to about 90.0% of water;
(b) from about 2.0% to about 9.0% of propylene glycol;
(c) from about 0.05% to about 0.50% of tetrasodium EDTA; (d) from about 0.50% to about 4.0%) of ceteareth-25;
(e) from about 0.04% to about 0.40% of citric acid;
(f) from about 5.0% to about 15.0% of lanolin oil;
(g) from about 3.0% to about 10.0% of cetyl alcohol; (h) from about 1.0% to about 5.0% of stearyl alcohol;
(i) from about 0.50% to about 4.0% of ceteareth-6; (j) from about 1.0% to about 7.0% of cod liver oil; (k) from about 0.1% to about 1.0% of butylated hydroxytoluene; (1) from about 0.10% to about 0.50% of methylparaben; (m) from about 0.10% to about 0.50% of propylparaben;
(n) from about 0.05% to about 0.50% of diazolidinyl urea;
(0) from about 0.50% to about 2.0% of allantoin; and (p) from about 0.05% to about 0.50% of fragrance.
104. The method of claim 103 wherein the composition comprises:
(a) from about 55.0% to about 75.0% of water;
(b) from about 4.2% to about 7.0% of propylene glycol;
(c) from about 0.10% to about 0.30% of tetrasodium EDTA;
(d) from about 2.0% to about 3.5% of ceteareth-25; (e) from about 0.10% to about 0.30% of citric acid;
(f) from about 8.0% to about 12.0% of lanolin oil;
(g) from about 3.5% to about 7.5% of cetyl alcohol; (h) from about 2.0% to about 4.0%> of stearyl alcohol; (i) from about 1.0% to about 3.0% of ceteareth-6; (j) fr°m about 1.0%) to about 4.0% of cod liver oil;
(k) from about 0.20% to about 0.80% of butylated hydroxytoluene;
(1) from about 0.15% to about 0.40% of methylparaben; (m) from about 0.15% to about 0.40% of propylparaben; (n) from about 0.10% to about 0.30% of diazolidinyl urea; (o) from about 1.0% to about 2.0% of allantoin; and
(p) from about 0.10% to about 0.30% of fragrance.
105. The method of claim 104 wherein the composition comprises: (a) about 66.33% of water; (b) about 5.70% of propylene glycol;
(c) about 0.15% of tetrasodium EDTA;
(d) about 2.60% of ceteareth-25;
(e) about 0.12% of citric acid; (f) about 10.60% of lanolin oil;
(g) about 4.30% of cetyl alcohol;
(h) about 3.50% of stearyl alcohol;
(i) about 1.80% of ceteareth-6; , (j) about 2.00% of cod liver oil; (k) about 0.50% of butylated hydroxytoluene;
(1) about 0.30%o of methylparaben;
(m) about 0.25% of propylparaben;
(n) about 0.15% of diazolidinyl urea;
(o) about 1.50% of allantoin; and (p) about 0.20% of fragrance.
106. A method of treating a skin condition or disease characterized by ulceration, inflammation, or blistering of the skin, comprising applying to the skin an allantoin-containing composition in a therapeutically effective amount, the allantoin- containing composition comprising an oil-in-water emulsion comprising:
(a) allantoin;
(b) an emulsifier system comprising:
(i) a polyethylene glycol ester of stearic acid; and (ii) glyceryl stearate; and (c) an acid to adjust the pH of the composition to a range of from about 3.0 to about 6.0.
107. The method of claim 106 wherein the pH of the composition is from about 5.0 to about 5.8.
108. The method of claim 106 wherein the number of ethylene glycol moieties in the polyethylene glycol ester of stearic acid is from 25 to 100.
109. The method of claim 106 wherein the polyethylene glycol ester of stearic acid is PEG-100 stearate.
110. The method of claim 106 wherein the acid is citric acid.
111. The method of claim 106 wherein the skin condition or disease is selected from the group consisting of epidermolysis bullosa, decubitus ulcers, pressure ulcers, diabetic ulcers, and milia.
112. The method of claim 111 wherein the skin condition or disease is epidermolysis bullosa.
113 The method of claim 106 further comprising administering an additional therapeutic agent in a therapeutically effective quantity.
114. The method of claim 113 wherein the additional therapeutic agent is selected from the group consisting of steroids, nonsteroidal anti-inflammatory agents, leukotriene antagonists, and monoclonal antibodies.
115. The method of claim 107 wherein the composition further comprises at least one of:
(a) an emollient component comprising at least one ingredient selected from the group consisting of lanolin oil, cetyl alcohol, stearyl alcohol, and cod liver oil;
(b) butylated hydroxytoluene; (c) a preservative component comprising at least one preservative selected from the group consisting of methylparaben, propylparaben, and diazolidinyl urea;
(d) a solvent component comprising at least one solvent selected from the group consisting of propylene glycol, butylene glycol, and glycerin; and (e) tetrasodium EDTA.
116. The method of claim 108 wherein the composition comprises :
(a) from about 50.0% to about 90.0% of water;
(b) from about 2.0% to about 9.0%. of propylene glycol;
(c) from about 0.05% to about 0.50% of tetrasodium EDTA; (d) from about 0.04% to about 0.40% of citric acid;
(e) from about 1.0% to about 5.0% of PEG-100 stearate;
(f) from about 5.0% to about 15.0% of lanolin oil;
(g) from about 2.0% to about 10.0% of cetyl alcohol; (h) from about 1.0% to about 4.0% of stearyl alcohol;
(i) from about 1.0% to about 5.0% of glyceryl stearate; (j) from about 1.0% to about 7.0% of cod liver oil; (k) from about 0.10% to about 1.0% of butylated hydroxytoluene; (1) from about 0.10% to about 0.50% of methylparaben; (m) from about 0.10% to about 0.50% of propylparaben;
(n) from about 0.05% to about 0.50% of diazolidinyl urea;
(0) from about 0.50% to about 2.0% of allantoin; and (p) from about 0.05% to about 0.50% of fragrance.
117. The method of claim 116 wherein the composition comprises:
(a) from about 55.0% to about 80.0% of water;
(b) from about 4.0% to about 7.0% of propylene glycol;
(c) from about 0.10% to about 0.30% of tetrasodium EDTA;
(d) from about 0.10% to about 0.30% of citric acid; (e) from about 1.50% to about 3.0% of PEG-100 stearate;
(f) from about 8.0% to about 12.0% of lanolin oil;
(g) from about 2.5% to about 7.5% of cetyl alcohol; (h) from about 1.0% to about 3.5% of stearyl alcohol; (i) from about 2.0% to about 4.0% of glyceryl stearate; (j) from about 1.0% to about 4.0% of cod liver oil;
(k) from about 0.20% to about 0.80% of butylated hydroxytoluene;
(1) from about 0.15%o to about 0.40% of methylparaben; (m) from about 0.15% to about 0.40% of propylparaben; (n) from about 0.10% to about 0.30% of diazolidinyl urea; (o) from about 1.0% to about 2.0% of allantoin; and
(p) from about 0.10%) to about 0.40% of fragrance.
118. The method of claim 117 wherein the composition comprises: (a) about 67.86% of water; (b) about 5.70% of propylene glycol;
(c) about 0.15% of tetrasodium EDTA;
(d) about 0.14% of citric acid;
(e) about 2.60% of PEG-100 stearate; (f) about 10.60% of lanolin oil;
(g) about 3.00% of cetyl alcohol;
(h) about 2.50% of stearyl alcohol;
(i) about 2.50% of glyceryl stearate;
(j) about 2.00% of cod liver oil; (k) about 0.50% of butylated hydroxytoluene;
(1) about 0.30% of methylparaben;
(m) about 0.25% propylparaben;
(n) about 0.20% of diazolidinyl urea;
(o) about 1.50% to about 2.0% of allantoin; and (p) about 0.20% of fragrance.
119. A method of treating a skin condition or disease characterized by ulceration, inflammation, or blistering of the skin, comprising applying to the skin an allantoin-containing composition in a therapeutically effective amount, the allantoin- containing composition comprising an oil-in-water emulsion comprising:
(a) allantoin;
(b) a carbohydrate polymer; and
(c) an emulsifier system comprising:
(1) beeswax; and (2) an anionic emulsifier that is substantially hydrophilic and is soluble in water; wherein the pH of the composition is between about 3.0 and about 6.0.
120. The method of claim 119 wherein the pH of the composition is between about 5.0 and about 6.0.
121. The method of claim 119 wherein the carbohydrate polymer is selected from the group consisting of galactoarabinan, polygalactose, and polyarabinose.
122. The method of claim 119 wherein the carbohydrate polymer is galactoarabinan.
123. The method of claim 119 wherein the anionic emulsifier that is substantially hydrophilic and soluble in water is selected from the group consisting of sodium lauryl sulfate, sodium laureth sulfate, sodium oleyl succinate, sodium dodecylbenzenesulfonate, and sodium lauryl sarcosinate.
124. The method of claim 123 wherein the anionic emulsifier that is substantially hydrophilic and soluble in water is sodium lauryl sulfate.
125. The method of claim 119 wherein the composition further comprises citric acid.
126. The method of claim 119 wherein the skin condition or disease is selected from the group consisting of epidermolysis bullosa, decubitus ulcers, pressure ulcers, diabetic ulcers, and milia.
127. The method of claim 126 wherein the skin condition or disease is epidermolysis bullosa.
128. The method of claim 119 further comprising administering an additional therapeutic agent in a therapeutically effective quantity.
129. The method of claim 128 wherein the additional therapeutic agent is selected from the group consisting of steroids, nonsteroidal anti-inflammatory agents, leukotriene antagonists, and monoclonal antibodies.
130. The method of claim 119 wherein the composition further comprises at least one of:
(a) a solvent component comprising at least one solvent selected from the group consisting of propylene glycol, butylene glycol, and glycerin;
(b) an emollient component comprising at least one emollient selected from the group consisting of lanolin oil, cetyl alcohol, stearyl alcohol, and cod liver oil; (c) butylated hydroxytoluene;
(d) tetrasodium EDTA; and
(e) a preservative component comprising at least one preservative selected from the group consisting of methylparaben and propylparaben.
131. The method of claim 120 wherein the composition comprises:
(a) from about 50.0% to about 90.0% of water;
(b) from about 2.0% to about 9.0% of propylene glycol;
(c) from about 0.50% to about 5.0% of a 30% solution of sodium lauryl sulfate;
(d) from about 0.05% to about 0.30%> of tetrasodium EDTA;
(e) from about 1.0% to about 25.0% of galactoarabinan;
(f) from about 0.05% to about 0.25%o of citric acid;
(g) from about 5.0% to about 15.0% of lanolin oil; (h) from about 1.0% to about 8.0% of cetyl alcohol; (i) from about 0.50% to about 6.0% of stearyl alcohol; (j) from about 0.50% to about 5.0% of beeswax;
(k) from about 0.50% to about 15.0% of cod liver oil;
(1) from about 0.1 % to about 3.0% of butylated hydroxytoluene;
(m) from about 0.10% to about 0.50% of methylparaben;
(n) from about 0.10% to about 0.50% of propylparaben;
(o) from about 0.50% to about 2.0% of allantoin; and
(p) from about 0.05% to about 0.50% of fragrance.
132. The method of claim 131 wherein the composition comprises:
(a) from about 60.0% to about 80.0% of water;
(b) from about 4.0% to about 7.0% of propylene glycol;
(c) from about 1.0% to about 3.0% of a 30% solution of sodium lauryl sulfate;
(d) from about 0.10% to about 0.20% of tetrasodium EDTA;
(e) from about 3.0% to about 15.0% of galactoarabinan;
(f) from about 0.10% to about 0.20% of citric acid;
(g) from about 8.0% to about 12.0% of lanolin oil; (h) from about 2.0% to about 7.0% of cetyl alcohol; (i) from about 1.0% to about 4.0% of stearyl alcohol;
(j) from about 1.0% to about 3.0% of beeswax;
(k) from about 1.0% to about 10.0% of cod liver oil;
(1) from about 0.25% to about 2.50% of butylated hydroxytoluene; (m) from about 0.15% to about 0.40% of methylparaben;
(n) from about 0.15% to about 0.40% of propylparaben;
(0) from about 1.0% to about 2.0% of allantoin; and (p) from about 0.10% to about 0.40% of fragrance.
133. The method of claim 132 wherein the composition comprises:
(a) about 61.65% of water;
(b) about 5.70% of propylene glycol;
(c) about 1.90% of a 30% solution of sodium lauryl sulfate;
(d) about 0.15% of tetrasodium EDTA; (e) about 5.00% of galactoarabinan;
(f) about 0.15 % of citric acid;
(g) about 10.60% of lanolin oil; (h) about 4.20% of cetyl alcohol; (i) about 2.00% of stearyl alcohol; (j) about 1.90% of beeswax;
(k) about 2.00% of cod liver oil;
(1) about 0.50% of butylated hydroxytoluene; (m) about 0.30% of methylparaben;
(n) about 0.25% of propylparaben; (o) about 1.50% of allantoin; and
(p) about 0.20% of fragrance.
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US09/570,266 US6329413B1 (en) | 1999-07-23 | 2000-05-12 | Allantoin-containing skin cream |
| US09/570,266 | 2000-05-12 | ||
| US09/758,696 US6673826B2 (en) | 1999-07-23 | 2001-01-11 | Methods for treatment of inflammatory diseases |
| US09/758,696 | 2001-01-11 | ||
| PCT/US2001/015102 WO2001087301A1 (en) | 2000-05-12 | 2001-05-09 | Methods for treatment of inflammatory diseases |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AU2001263035A1 true AU2001263035A1 (en) | 2001-11-26 |
Family
ID=27075286
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2001263035A Abandoned AU2001263035A1 (en) | 2000-05-12 | 2001-05-09 | Methods for treatment of inflammatory diseases |
Country Status (8)
| Country | Link |
|---|---|
| EP (1) | EP1337248A1 (en) |
| JP (1) | JP2003533481A (en) |
| CN (1) | CN1441672A (en) |
| AU (1) | AU2001263035A1 (en) |
| BR (1) | BR0110775A (en) |
| CA (1) | CA2408163A1 (en) |
| MX (1) | MXPA02011159A (en) |
| WO (1) | WO2001087301A1 (en) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20020054895A1 (en) | 1999-07-23 | 2002-05-09 | Alwyn Company, Inc. | Allantoin-containing skin cream |
| CN101005856A (en) * | 2004-08-19 | 2007-07-25 | 皮肤应用遗传学股份有限公司 | Biomimetic of evodia rutaecarpa fruit extract for amelioration of inflammation |
| CN1969843B (en) * | 2006-12-13 | 2010-10-06 | 吴春高 | Application of allantoin in preparation of medicament for treating gallbladder disease and gastrointestinal convulsion |
| US9056209B2 (en) | 2009-06-17 | 2015-06-16 | Kao Corporation | Apigenin-containing composition |
| US20140135372A1 (en) | 2010-02-02 | 2014-05-15 | Elliott Farber | Compositions and methods of treatment of inflammatory skin conditions using allantoin |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3954989A (en) * | 1974-04-22 | 1976-05-04 | Schuylkill Chemical Company | Topical compositions containing an allantoin ascorbic acid complex |
| LU83173A1 (en) * | 1981-02-27 | 1981-06-05 | Oreal | NOVEL COSMETIC COMPOSITIONS FOR THE TREATMENT OF HAIR AND SKIN CONTAINING POWDER RESULTING FROM THE SPRAYING OF AT LEAST ONE PLANT AND A COHESION AGENT |
| US4670263A (en) * | 1983-12-29 | 1987-06-02 | Noorlander Daniel O | Nontoxic, germicide, and healing compositions |
| IL94806A0 (en) * | 1990-06-20 | 1991-04-15 | Ernest Bar On | Pharmaceutical preparation containing thiol derivatives together with other active compounds |
| JP2522719B2 (en) * | 1990-07-26 | 1996-08-07 | ヒノキ新薬株式会社 | Topical preparation for treatment of pressure ulcer and skin ulcer |
| US5455033A (en) * | 1993-05-21 | 1995-10-03 | Degree/Silverman M.D. Inc. | Medicinal composition for treatment of inflammation |
| US5661170A (en) * | 1994-03-21 | 1997-08-26 | Woodward Laboratories, Inc. | Antimicrobial compositions and methods for using the same |
| US5616347A (en) * | 1995-02-14 | 1997-04-01 | Alliger; Howard | Chlorine dioxide skin medicating compositions for preventing irritation |
-
2001
- 2001-05-09 WO PCT/US2001/015102 patent/WO2001087301A1/en not_active Ceased
- 2001-05-09 JP JP2001583769A patent/JP2003533481A/en not_active Withdrawn
- 2001-05-09 CA CA002408163A patent/CA2408163A1/en not_active Abandoned
- 2001-05-09 EP EP01937283A patent/EP1337248A1/en active Pending
- 2001-05-09 AU AU2001263035A patent/AU2001263035A1/en not_active Abandoned
- 2001-05-09 BR BR0110775-5A patent/BR0110775A/en not_active IP Right Cessation
- 2001-05-09 CN CN01812651A patent/CN1441672A/en active Pending
- 2001-05-09 MX MXPA02011159A patent/MXPA02011159A/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| WO2001087301A9 (en) | 2002-12-19 |
| BR0110775A (en) | 2004-07-20 |
| EP1337248A1 (en) | 2003-08-27 |
| MXPA02011159A (en) | 2004-08-19 |
| WO2001087301A1 (en) | 2001-11-22 |
| JP2003533481A (en) | 2003-11-11 |
| CN1441672A (en) | 2003-09-10 |
| CA2408163A1 (en) | 2001-11-22 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP0787005B1 (en) | Dermatological compositions containing benzoyl peroxide and a compound reducing skin irritation | |
| TW592714B (en) | Composition to enhance permeation of topical skin agents | |
| US20110152335A1 (en) | Allantoin-containing skin cream | |
| MXPA04000002A (en) | AGENT WITH A GAS CONTENT (OIL), THAT CONTAINS AN EXTRACT OF ONION HIS PREPARATION AND ITS USE FOR THE CARE, THE PREVENTION OR THE TREATMENT OF A DONATED CUTANEOUS TISSUE, IN PARTICULAR OF SCARS. | |
| JP2012184258A (en) | Composition containing at least one derivative of naphthoic acid and at least one polyurethane polymer type compound or derivative thereof, preparation method, and use of the same | |
| CN111801108A (en) | Topical skin care compositions | |
| AU2001261290A1 (en) | Allantoin-containing skin cream | |
| US20090170919A1 (en) | Methods for treatment of inflammatory diseases | |
| US6531500B2 (en) | Methods for treatment of inflammatory diseases | |
| US6673826B2 (en) | Methods for treatment of inflammatory diseases | |
| US6329413B1 (en) | Allantoin-containing skin cream | |
| EP1537857A1 (en) | Mupirocin compositions for topical use, a process of making same and uses thereof | |
| AU2001263035A1 (en) | Methods for treatment of inflammatory diseases | |
| US20020055531A1 (en) | Methods for treatment of inflammatory diseases | |
| US5128375A (en) | Keloid treating agent | |
| US20010029266A1 (en) | Composition containing a pentacyclic triterpenic acid, method | |
| US20120165379A1 (en) | Allantoin-containing skin cream | |
| BRPI0617045A2 (en) | composition, process for preparing a composition, use of a composition and cosmetic use of a composition | |
| US20080075745A1 (en) | Topical pharmaceutical compositions containing ciclopirox or a pharmaceutically acceptable salt thereof | |
| US5078993A (en) | Ointment pharmaceutical formulation | |
| JPH08165244A (en) | Skin disease treatment | |
| RU2481845C2 (en) | Stabilised topical composition possessing comedolytic and antibiotic action |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MK4 | Application lapsed section 142(2)(d) - no continuation fee paid for the application |