AU2002334523A1 - New formulations and use thereof - Google Patents
New formulations and use thereofInfo
- Publication number
- AU2002334523A1 AU2002334523A1 AU2002334523A AU2002334523A AU2002334523A1 AU 2002334523 A1 AU2002334523 A1 AU 2002334523A1 AU 2002334523 A AU2002334523 A AU 2002334523A AU 2002334523 A AU2002334523 A AU 2002334523A AU 2002334523 A1 AU2002334523 A1 AU 2002334523A1
- Authority
- AU
- Australia
- Prior art keywords
- nicotine
- disease
- tobacco
- composition according
- treatment
- 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.)
- Granted
Links
- 239000000203 mixture Substances 0.000 title claims description 43
- 238000009472 formulation Methods 0.000 title claims description 15
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 claims description 84
- 229960002715 nicotine Drugs 0.000 claims description 84
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 claims description 84
- 244000299461 Theobroma cacao Species 0.000 claims description 37
- 235000019219 chocolate Nutrition 0.000 claims description 31
- 241000208125 Nicotiana Species 0.000 claims description 18
- 235000002637 Nicotiana tabacum Nutrition 0.000 claims description 18
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 14
- 238000002670 nicotine replacement therapy Methods 0.000 claims description 14
- 238000000034 method Methods 0.000 claims description 13
- 238000002560 therapeutic procedure Methods 0.000 claims description 12
- 239000008194 pharmaceutical composition Substances 0.000 claims description 10
- 208000024827 Alzheimer disease Diseases 0.000 claims description 9
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 9
- 208000018737 Parkinson disease Diseases 0.000 claims description 9
- 208000000323 Tourette Syndrome Diseases 0.000 claims description 9
- 208000016620 Tourette disease Diseases 0.000 claims description 9
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 9
- 238000004260 weight control Methods 0.000 claims description 9
- 239000006172 buffering agent Substances 0.000 claims description 7
- 239000000796 flavoring agent Substances 0.000 claims description 7
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 4
- 229910019142 PO4 Inorganic materials 0.000 claims description 3
- 235000009499 Vanilla fragrans Nutrition 0.000 claims description 3
- 235000012036 Vanilla tahitensis Nutrition 0.000 claims description 3
- 210000005178 buccal mucosa Anatomy 0.000 claims description 3
- 229940112822 chewing gum Drugs 0.000 claims description 3
- 235000015218 chewing gum Nutrition 0.000 claims description 3
- -1 glycinates Chemical class 0.000 claims description 3
- 235000021317 phosphate Nutrition 0.000 claims description 3
- 150000003013 phosphoric acid derivatives Chemical class 0.000 claims description 3
- 239000007921 spray Substances 0.000 claims description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 claims description 2
- OCUCCJIRFHNWBP-IYEMJOQQSA-L Copper gluconate Chemical class [Cu+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O OCUCCJIRFHNWBP-IYEMJOQQSA-L 0.000 claims description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 2
- 235000006679 Mentha X verticillata Nutrition 0.000 claims description 2
- 235000002899 Mentha suaveolens Nutrition 0.000 claims description 2
- 235000001636 Mentha x rotundifolia Nutrition 0.000 claims description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 2
- 150000001242 acetic acid derivatives Chemical class 0.000 claims description 2
- 150000004649 carbonic acid derivatives Chemical class 0.000 claims description 2
- 239000002552 dosage form Substances 0.000 claims description 2
- 235000013355 food flavoring agent Nutrition 0.000 claims description 2
- 150000002315 glycerophosphates Chemical class 0.000 claims description 2
- 239000006186 oral dosage form Substances 0.000 claims description 2
- 239000011591 potassium Substances 0.000 claims description 2
- 229910052700 potassium Inorganic materials 0.000 claims description 2
- 230000002685 pulmonary effect Effects 0.000 claims description 2
- 239000011734 sodium Substances 0.000 claims description 2
- 229910052708 sodium Inorganic materials 0.000 claims description 2
- 244000263375 Vanilla tahitensis Species 0.000 claims 1
- 239000002585 base Substances 0.000 description 12
- 239000007937 lozenge Substances 0.000 description 11
- 239000003826 tablet Substances 0.000 description 9
- 239000000047 product Substances 0.000 description 8
- 210000000214 mouth Anatomy 0.000 description 7
- 230000000391 smoking effect Effects 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- 230000005586 smoking cessation Effects 0.000 description 6
- FEWJPZIEWOKRBE-JCYAYHJZSA-M L-tartrate(1-) Chemical compound OC(=O)[C@H](O)[C@@H](O)C([O-])=O FEWJPZIEWOKRBE-JCYAYHJZSA-M 0.000 description 5
- 235000009470 Theobroma cacao Nutrition 0.000 description 5
- 238000010521 absorption reaction Methods 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 235000019634 flavors Nutrition 0.000 description 5
- 150000003839 salts Chemical class 0.000 description 5
- 230000036765 blood level Effects 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 230000002411 adverse Effects 0.000 description 3
- 230000000202 analgesic effect Effects 0.000 description 3
- 239000008370 chocolate flavor Substances 0.000 description 3
- 235000019868 cocoa butter Nutrition 0.000 description 3
- 229940110456 cocoa butter Drugs 0.000 description 3
- 239000008141 laxative Substances 0.000 description 3
- 229920000858 Cyclodextrin Polymers 0.000 description 2
- 206010057852 Nicotine dependence Diseases 0.000 description 2
- 244000290333 Vanilla fragrans Species 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 235000019877 cocoa butter equivalent Nutrition 0.000 description 2
- 235000019876 cocoa butter improver Nutrition 0.000 description 2
- 235000019878 cocoa butter replacer Nutrition 0.000 description 2
- 235000019879 cocoa butter substitute Nutrition 0.000 description 2
- 235000009508 confectionery Nutrition 0.000 description 2
- 235000019788 craving Nutrition 0.000 description 2
- 230000003628 erosive effect Effects 0.000 description 2
- RRAFCDWBNXTKKO-UHFFFAOYSA-N eugenol Chemical compound COC1=CC(CC=C)=CC=C1O RRAFCDWBNXTKKO-UHFFFAOYSA-N 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 230000007794 irritation Effects 0.000 description 2
- 230000002475 laxative effect Effects 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 239000000155 melt Substances 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 238000003801 milling Methods 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 229940127557 pharmaceutical product Drugs 0.000 description 2
- KJFMBFZCATUALV-UHFFFAOYSA-N phenolphthalein Chemical compound C1=CC(O)=CC=C1C1(C=2C=CC(O)=CC=2)C2=CC=CC=C2C(=O)O1 KJFMBFZCATUALV-UHFFFAOYSA-N 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 235000019505 tobacco product Nutrition 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- IPQVTOJGNYVQEO-UHFFFAOYSA-N 9-[2-carboxy-4-hydroxy-10-oxo-5-[3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-9h-anthracen-9-yl]-4-hydroxy-10-oxo-5-[3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-9h-anthracene-2-carboxylic acid Chemical class OC1C(O)C(O)C(CO)OC1OC1=CC=CC2=C1C(=O)C1=C(O)C=C(C(O)=O)C=C1C2C1C2=CC(C(O)=O)=CC(O)=C2C(=O)C2=C(OC3C(C(O)C(O)C(CO)O3)O)C=CC=C21 IPQVTOJGNYVQEO-UHFFFAOYSA-N 0.000 description 1
- NPBVQXIMTZKSBA-UHFFFAOYSA-N Chavibetol Natural products COC1=CC=C(CC=C)C=C1O NPBVQXIMTZKSBA-UHFFFAOYSA-N 0.000 description 1
- 239000005770 Eugenol Substances 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 241000233805 Phoenix Species 0.000 description 1
- UVMRYBDEERADNV-UHFFFAOYSA-N Pseudoeugenol Natural products COC1=CC(C(C)=C)=CC=C1O UVMRYBDEERADNV-UHFFFAOYSA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 235000005764 Theobroma cacao ssp. cacao Nutrition 0.000 description 1
- 235000005767 Theobroma cacao ssp. sphaerocarpum Nutrition 0.000 description 1
- 206010059612 Tobacco withdrawal symptoms Diseases 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 235000001046 cacaotero Nutrition 0.000 description 1
- 239000007963 capsule composition Substances 0.000 description 1
- 239000003729 cation exchange resin Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 235000019504 cigarettes Nutrition 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 235000019875 cocoa butter alternative Nutrition 0.000 description 1
- 230000007748 combinatorial effect Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 235000019221 dark chocolate Nutrition 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 210000002249 digestive system Anatomy 0.000 description 1
- 238000007907 direct compression Methods 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 229960002217 eugenol Drugs 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 238000001125 extrusion Methods 0.000 description 1
- 235000013861 fat-free Nutrition 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 230000014509 gene expression Effects 0.000 description 1
- 108091005708 gustatory receptors Proteins 0.000 description 1
- 230000031891 intestinal absorption Effects 0.000 description 1
- 229940125722 laxative agent Drugs 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000008263 liquid aerosol Substances 0.000 description 1
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 1
- 239000000347 magnesium hydroxide Substances 0.000 description 1
- 229910001862 magnesium hydroxide Inorganic materials 0.000 description 1
- 230000000873 masking effect Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 239000007922 nasal spray Substances 0.000 description 1
- 229940097496 nasal spray Drugs 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 239000000820 nonprescription drug Substances 0.000 description 1
- 239000007968 orange flavor Substances 0.000 description 1
- 239000007967 peppermint flavor Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000007670 refining Methods 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 229930186851 sennoside Natural products 0.000 description 1
- 230000035807 sensation Effects 0.000 description 1
- 235000019615 sensations Nutrition 0.000 description 1
- 229940124535 smoking cessation aid Drugs 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 230000007928 solubilization Effects 0.000 description 1
- 238000005063 solubilization Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 230000009747 swallowing Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000037317 transdermal delivery Effects 0.000 description 1
- 235000019155 vitamin A Nutrition 0.000 description 1
- 239000011719 vitamin A Substances 0.000 description 1
- 235000019154 vitamin C Nutrition 0.000 description 1
- 239000011718 vitamin C Substances 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 235000019222 white chocolate Nutrition 0.000 description 1
- 235000019220 whole milk chocolate Nutrition 0.000 description 1
Description
NEWFORMULATIONSAND USETHEREOF
Field of the Invention
This invention relates to novel pharmaceutical compositions of nicotine and use thereof. More particularly, the present invention relates to compositions comprising nicotine and chocolate, methods to prepare said compositions, and to methods for using said compositions in nicotine replacement therapy (NRT), including tobacco substitution and smoking cessation
Background and Prior Art
Nicotine replacement therapy as a smoking cessation strategy has been successful in the past. Previous nicotine-containing compositions aiming towards the purpose of reducing nicotine craving for subjects wishing to stop their use of tobacco products include e g US 3,845,217 disclosing chewable compositions, US 4,579,858 disclosing high-viscous nicotine nose-drop compositions, US 5,525,351 disclosing nicotine-containing saliva-soluble gels, US 5,656,255 disclosing low-viscous nicotine-containing compositions suitable for nasal spray administration, US 4,920,989 and US 4,953,572 disclosing the use of inhalation aerosol, BP 1,528,391 and BP 2,030,862 disclosing liquid aerosol formulations adapted as mouth-sprays, and devices for transdermal delivery of nicotine.
A well-known side effect of nicotine is related to its concentration dependent local irritation. This adverse effect is particularly noticeable when nicotine formulations are applied topically, including the transmucosal, comprising buccal and nasal, and transdermal administration routes. UK Patent application GB 2230 439 A describes nicotine lozenges with a shell or coating containing an oral-acting local analgesic, preferably eugenol. Though not stated explicitly to be the cause of the so included local analgesic, the aforesaid disclosure is said to substantially ameliorate the sensation of burning in the mouth experienced with conventional nicotine lozenges. Similarly, nicotine-compositions formulated in lozenges containing local analgesic have been disclosed in AU 662877 in which the latter agent is said to temporarily interfere with taste receptors which is said to reduce the desire to eat.
The concentration of nicotine in several of the above-mentioned inventions, and product designs thereof, is hence limited by adverse effects caused by or related to its local irritation.
Prior art describes other capsules, tablets, and lozenges for oral delivery of nico- tine. For example, WO 88/03803 discloses a chewable capsule filled with a liquid containing 0.1 - 10.0 mg of nicotine, together with additives for improving flavour and dispersion. The capsules are provided in a variety of pH values to allow the patient a choice of nicotine absorption rates, and are especially intended as an aid to quit smoking. Another nicotine capsule formulation is disclosed by Jarvik et al. (Clinical
Pharmacology and Therapeutics 1970; 11:574) for ingestion as a smoking cessation aid. The subjects, according to the theory that intestinal absorption of nicotine could produce significant blood levels, however, apparently swallowed these capsules whole. The study showed a small but significant decrease in the number of cigarettes smoked by subjects, but no quantitative measurements of nicotine blood levels were obtained.
BE 899037 discloses a tablet containing 0.1 to 5 mg nicotine as a base or water- soluble acid salt as an aid for quitting smoking.
Shaw (for example in GB 2 142 822 and US 4,806,356) describes a nicotine lozenge prepared from a mixture of inert filler material, a binder, and either pure nicotine or a nicotine-containing substance by cold compression.
US 5,512,306 discloses a nicotine product for oral delivery in the form of an inclusion complex of nicotine and a cyclodextrin compound. It also discusses the use of various excipients and direct compression for manufacture of the product.
US 5,662,920 discloses a nicotine lozenge that may contain candy taste flavo- rants, such as chocolate, orange, vanilla, as well as other flavorants. Their use also for taste-masking is though not suggested. Further, no amounts of these flavorants being sufficient for achieving a taste-masking effect is disclosed.
WO 97/42941 discloses a slowly erodible nicotine lozenge that allows delivery to the buccal mucosa over an extended period of time. GB 2 147 501 A discloses an oral dosage form comprising a microencapsulated active principle embedded in a soft sweet palatable matrix. This matrix may be chocolate. Nicotine is not suggested as an active principle.
The literature describes different designs of tablets for delivering nicotine to the mouth and to the digestive system.
Wesnes and Warburton (Psychopharmacology 1984; 82:147; ibid. 1986;89:55) discuss the use of nicotine containing dextrose and magnesium hydroxide tablets. The subjects were instructed to keep the tablets in the mouth for some minutes before swallowing, in order to maximize contact with the buccal mucosa.
Several products based on the above mentioned patents are now marketed on an international scale. In addition, several nicotine lozenges are available as over-the- counter products in the UK Resolution lozenges, manufactured by Phoenix Pharmaceu- ticals and distributed by Ernest Jackson, contain 0.5 mg nicotine, together with the anti- oxidant vitamins A, C, and E. Stoppers lozenges, distributed by Charwell Pharmaceuticals Ltd., contain 0.5 mg nicotine and are available in chocolate, orange and peppermint flavours.
There are, however, subjects who may have cravings for higher doses of nicotine than those acceptable in applications of prior art and subjects that may not experience a decrease in other withdrawal symptoms because of unsatisfactory nicotine absorption. Furthermore, it has to date been difficult to deliver nicotine in a profile mimicking the nicotine blood levels achieved by consistent smoking, to satisfy cravings for nicotine in people who are attempting to quit smoking, and thus, to provide greater protection against relapse than nicotine replacement therapies is possible with hitherto known.
Thus, absorption of nicotine in the use of currently marketed products and as disclosed in prior art of nicotine replacement therapies is not satisfactorily resembling the use of tobacco products, in particular smoking. With chewing gum nicotine replacement therapy for smoking cessation blood peak levels of nicotine is reached after 30 minutes with venous blood nicotine levels about 1/3 to 2/3 of the levels attained when smoking
(British Medical Journal 1976;1:1043). A smoker will usually reach peak blood levels of nicotine 5 - 10 minutes after starting smoking. It is therefore desirable to provide improved compositions and methods which avoid the disadvantages of these conventional nicotine delivery devices and methods while providing an effective means for delivering nicotine for smoking cessation treatment, for reducing nicotine craving, and for treating other conditions responsive to nicotine therapy.
An attempt to solve the captioned problems is made with a nicotine-containing composition, preferably for buccal uptake, according to WO 00/30641. Herein is dis-
closed a composition comprising nicotine, at least one apolar component, at least one polar component and at least one surface-active component. Many apolar components are suggested, including lipids such as cocoa butter and cocoa butter alternatives, including cocoa butter equivalents (CBE), cocoa butter substitutes (CBS), cocoa butter replacers (CBR) and cocoa butter improvers (CBI). Anyhow, the composition according to WO 00/30641 has the disadvantage of insufficient taste-masking of nicotine and buffering agents, and the drawback of causing nausea with some users. WO 00/30641 does not disclose chocolate as an ingredient.
It has now surprisingly been found that a rapid buccal absorption of nicotine concomitantly with sufficient taste-masking of badly tasting ingredients, such as buffering agents and nicotine, is achieved through the use of nicotine-containing formulations comprising chocolate as vehicle. No similar formulations have been disclosed hitherto.
Chocolate has hardly been used as a vehicle for human pharmaceutical products, although chocolate-like pharmaceutical products of types laxatives exist. Also exist chocolate-type veterinary products. Ex-Lax®, being chocolated laxative pieces marketed by Novartis comprising sennosides, are formulated with a chocolate-like vehicle. In the 1950s was marketed Purex, a laxative wherein phenolphtaleine was formulated with chocolate. The Stoppers lozenges mentioned above do not comprise chocolate, but only chocolate flavours. Such chocolate flavours are not useful for the objectives of the present invention. It has not been disclosed use of chocolate as a vehicle for nicotine.
Summary of the invention
Compositions for the therapeutic delivery of nicotine are provided. Said compo- sitions comprising nicotine provide rapid transmucosal absorption of nicotine. The compositions are preferably used for therapeutic administration of nicotine.
The meaning of "disintegration" as used in the description and in the claims denotes melting, solubilization, erosion or a combinatorial effect of these physical changes of the invention. In the absence of explicit statements to the contrary, as used herein expressions like "comprising", "including", "having", "with" and similar terminology shall not be understood to be exclusively restricted to the recited element(s), but shall be understood to allow for the presence of further elements as well, and shall be understood to cover
any element(s) in integral, sub-divided or aggregate forms, as well to imply the inclusion of a stated integer or step or group of integers or steps, but not the exclusion of any other integer or step or group of integers or steps.
An object of the invention is to provide new pharmaceutical compositions of nicotine for buccal uptake, especially such compositions comprising a large percentage of chocolate. By "buccal" in the present application is meant "for uptake buccaly or by other mucosa in the oral cavity"
A second object of the invention is to provide methods for preparing said compositions. A third object of the invention is methods for using said formulations in nicotine replacement therapy (NRT), including tobacco substitution and smoking cessation.
Further objects of the invention will become apparent to one skilled in the art, and still other objects will become apparent hereinafter from the specification and claims.
Detailed Description of the Invention
It is the primary object of the present invention to provide a tobacco supplement or a tobacco substitute, for use in e g smoking cessation and nicotine replacement therapies, which provide the user with a satisfactory dose of nicotine so as to reduce tobacco withdrawal symptoms without causing unacceptable adverse effects. More specifically it is the object of the invention to provide such a nicotine containing tablet, for transmucosal, preferably buccal, delivery, which disintegrates and/or melts at body temperature with or without the aid of salivary fluid or mechanical erosion, or a combination thereof after which the formulation preferably shows adhesiveness towards the tissues in the oral cavity.
The nicotine may be present in any suitable form, e g as free base, as a salt or as a complex. There is no need to use nicotine in a microencapsulated form.
The preferred formulation is a tablet melting in the mouth, weighing around 400 mg, having the following preferred compositions: 1)
Nicotine (as base or hydrogen tartrate) 1 - 6 mg measured as base,
Sodium carbonate around 15 mg,
Dark chocolate q. s.
or
2)
Nicotine (as base or hydrogen tartrate) 1 - 6 mg measured as base,
Sodium carbonate around 15 mg, White chocolate q. s.
3)
Nicotine (as base or hydrogen tartrate) 1 - 6 mg measured as base,
Sodium carbonate around 15 mg,
Milk chocolate q. s. According to Industrial Chocolate Manufacture and Use, S. T. Beckett, ed., 2nd edition, Bladder Academic & Professional, London, 1994, p.382, chocolate is defined as a product obtained from cocoa nib, cocoa mass powder and sucrose with or without added cocoa butter, having a minimum dry cocoa solids content of 35%, at least 14% of dry non-fat cocoa solids and 18% cocoa butter. Chocolate has two major distinguishing characteristics: its flavor and its texture. A primary feature of the texture is that the chocolate must be solid at a temperature of 20 - 25°C and yet melt rapidly in the mouth at 37°C thereby being transferred to a liquid, which appears smooth to the tongue. The processing of chocolate is related to obtaining these two criteria (ibid, p 2). The higher the content of dry cocoa solids in the chocolate the better the taste masking effect of the chocolate in the present invention. Chocolate may also be defined according to different national directives, such as European Council Directive 2000/36/EC of 23 June 2000, the old Council Directive 73/241/EEC of 24 July 1973 (to be repealed from 3 August 2003) and the US directive 21 CFR CH 1 (edition 4-1-00), part 163 Cacao products.
Example 1: Preparation of a preferred embodiment
A tablet, weighing around 400 mg, having the following preferred composition (w/w):
Active: nicotine (as base or salt, preferably hydrogen tartrate)
1 - 6 mg measured as base, The nicotine may also be present in a complex, e g with a cation exchange resin or with cyclodextrin. Buffering agent: sodium carbonate around 15 mg Vehicle: chocolate q. s.
is prepared in the following way:
A part of the chocolate is melted. The solid components, i e nicotine, if in salt form, and sodium carbonate are added and mixed. A reduction of particle size of the solid components is performed by milling in a roll-refiner. If the solid components have already got the required particle size, e g by milling before the mixing with the chocolate, roll refining is dispensed with. After treatment in the roll-refiner the mixture is mixed with the rest of the melted chocolate or remelted (if solidified) and mixed with the rest of the melted chocolate. Chocolate can be used as a raw material. Chocolate can also be produced in connection with the production of the embodiment. A mixing of the melt is performed in a suitable mixer. The liquid component, i e nicotine, if in liquid base form, is added. When chocolate is used as raw material a certain percentage of lecithin is already included (normally around 0.3%). Tablets or other solid dosage forms are subsequently made using suitable techniques, such as molding, extrusion or congealing, including pastillation, if necessary after suitable preconditioning. Also other suitable manufacturing methods may be used.
Example 2: Further embodiments
Useful embodiments are obtained by exchanging some of the above-mentioned excipients for equivalently functioning alternative compounds. The buffer sodium carbonate may be exchanged for e g carbonates, bicarbonates, phosphates, glycinates, acetates, gluconates or glycerophosphates of sodium, potassium or ammonium, or mixtures thereof. Most phosphates are though less suitable because their taste usually is disagreeable and difficult to mask.
In Example 1 is disclosed a preferred embodiment. Anyhow, useful embodi- ments are obtainable within certain concentration ranges for the respective components of the formulation per unit dose as follows
Active: nicotine, (as base or salt, preferably hydrogen tartrate) from around 0.5 mg to around 10 mg measured as base, Buffering agent: from around 5 mg to around 40 mg, Vehicle: chocolate q. s.
Optionally flavoring agents, such as mint, coffee, orange, vanilla and milk- butterscotch, may be added.
The present nicotine-containing composition may be administered in combination with a second formulation for nicotine replacement therapy. This second formulation may be a device for transdermal administration of nicotine, a spray for nasal, buccal or pulmonary uptake, a chewing gum, or a dosage form for oral or peroral use or any device for administration of tobacco.
The present invention may also be used in cessation, reduction and temporary abstinence of tobacco, and for treatment of Alzheimer's disease, Parkinson's disease, ulcer ative colitis and/or Tourette's syndrome; and/or weight control therapy.
Claims (14)
1. A nicotine-containing pharmaceutical composition, characterized in that it comprises chocolate as a vehicle.
2. A nicotine-containing pharmaceutical composition according to claim 1, characterized in that it further comprises one or more buffering agents.
3. A nicotine-containing pharmaceutical composition according to claim 2, characterized in that the one or more buffering agents is/are chosen from carbonates, bicarbonates, phosphates, glycinates, acetates, gluconates or glycerophosphates of sodium, potassium or ammonium, or mixtures thereof.
4. A nicotine-containing pharmaceutical composition according to anyone of the preceding claims, characterized in that it further comprises one or more flavoring agents, such as mint, coffee, orange, vanilla and milk-butterscotch.
5. A nicotine-containing pharmaceutical composition according to anyone of the preceding claims, characterized in that a unit dose thereof comprises
Nicotine: from around 0.5 mg to around 10 mg, measured as base,
Buffering agent: from around 5 mg to around 40 mg, Chocolate vehicle: q. s.
6. A nicotine-containing pharmaceutical composition according to claim 5, characterized in that a unit dose thereof comprises 1-6 mg nicotine measured as base, around 95% (w/w) chocolate, and around 15 mg sodium carbonate.
7. A nicotine-containing pharmaceutical composition according to anyone of the preceding claims which is formulated as an oral dosage form and which provides for delivery of nicotine essentially through the buccal mucosa.
8. Use of a nicotine-containing pharmaceutical composition according to anyone of the preceding claims for the manufacture of a medicament for nicotine replacement (NRT), cessation, reduction and temporary abstinence of tobacco, and for treatment of Alzheimer's disease, Parkinson's disease, ulcerative colitis and/or Tourette's syndrome; and/or weight control therapy.
9. Method for nicotine replacement therapy (NRT), cessation, reduction and temporary abstinence of tobacco, and for treatment of Alzheimer's disease, Parkinson's disease, ulcerative colitis and/or Tourette's syndrome; and/or weight control therapy whereby to a person in need of such therapy is administered a composition according to anyone of claims 1 - 7.
10. Method for nicotine replacement therapy (NRT), cessation, reduction and temporary abstinence of tobacco, and for treatment of Alzheimer's disease, Parkinson's disease, ulcerative colitis and/or Tourette's syndrome; and/or weight control therapy whereby to a person in need of such therapy is administered a composition according to anyone of claims 1 - 7 in combination with a second formulation for nicotine replacement therapy (NRT), cessation, reduction and temporary abstinence of tobacco, and for treatment of Alzheimer's disease, Parkinson's disease, ulcerative colitis and/or Tourette's syndrome; and/or weight control therapy.
11. Method for nicotine replacement therapy (NRT), cessation, reduction and temporary abstinence of tobacco, and for treatment of Alzheimer's disease, Parkinson's disease, ulcerative colitis and/or Tourette's syndrome; and/or weight control therapy according to claim 10 wherein said second formulation is a device for transdermal administration of nicotine, a spray for nasal, buccal or pulmonary uptake, a chewing gum, or a dosage form for oral or peroral use or any device for administration of tobacco.
12. Method for treating dependence of tobacco, cessation, reduction and temporary abstinence of tobacco, and for treatment of Alzheimer's disease, Parkinson's disease, ulcerative colitis and/or Tourette's syndrome; and/or weight control therapy whereby to a person in need of such treatment is administered a composition according to anyone of claims 1 - 7.
13. Method for treating dependence of tobacco, cessation, reduction and temporary abstinence of tobacco, and for treatment of Alzheimer's disease, Parkinson's disease, ulcerative colitis and/or Tourette's syndrome; and/or weight control therapy whereby to a person in need of such treatment is administered a composition according to anyone of claims 1 - 7 in combination with a second formulation for nicotine replacement therapy.
14. Method for treating dependence of tobacco, cessation, reduction and tempo- rary abstinence of tobacco, and for treatment of Alzheimer's disease, Parkinson's disease, ulcerative colitis and/or Tourette's syndrome; and/or weight control therapy according to claim 13 wherein said second formulation is a device for transdermal administration of nicotine.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE0103210A SE0103210D0 (en) | 2001-09-27 | 2001-09-27 | New formulations and use thereof |
| SE0103210-1 | 2001-09-27 | ||
| PCT/SE2002/001612 WO2003026656A1 (en) | 2001-09-27 | 2002-09-10 | New formulations and use thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU2002334523A1 true AU2002334523A1 (en) | 2003-06-26 |
| AU2002334523B2 AU2002334523B2 (en) | 2007-02-15 |
Family
ID=20285456
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2002334523A Ceased AU2002334523B2 (en) | 2001-09-27 | 2002-09-10 | New formulations and use thereof |
Country Status (19)
| Country | Link |
|---|---|
| EP (1) | EP1429770B1 (en) |
| JP (1) | JP4262094B2 (en) |
| KR (1) | KR20040047868A (en) |
| CN (1) | CN1561213A (en) |
| AR (1) | AR036679A1 (en) |
| AT (1) | ATE431144T1 (en) |
| AU (1) | AU2002334523B2 (en) |
| BR (1) | BR0212834A (en) |
| CA (1) | CA2461757C (en) |
| DE (1) | DE60232344D1 (en) |
| DK (1) | DK1429770T3 (en) |
| ES (1) | ES2325684T3 (en) |
| IL (1) | IL160886A0 (en) |
| MX (1) | MXPA04002876A (en) |
| NZ (1) | NZ532528A (en) |
| RU (1) | RU2282447C2 (en) |
| SE (1) | SE0103210D0 (en) |
| WO (1) | WO2003026656A1 (en) |
| ZA (1) | ZA200402091B (en) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7767698B2 (en) | 2002-06-03 | 2010-08-03 | Mcneil Ab | Formulation and use thereof |
| US8627828B2 (en) | 2003-11-07 | 2014-01-14 | U.S. Smokeless Tobacco Company Llc | Tobacco compositions |
| BRPI0415741B1 (en) | 2003-11-07 | 2013-07-23 | tobacco compositions and methods of manufacturing a tobacco composition | |
| RU2320674C1 (en) * | 2006-07-12 | 2008-03-27 | Каш Тенгис | Method for preparing n-vinylpyrrolidone copolymer with lauryl methacrylate for transdermal administration of nicotine, copolymer prepared by this method, gel for transdermal administration of nicotine |
| CZ200980A3 (en) * | 2009-02-11 | 2010-04-28 | Heglund A.S. | Composition intended particularly for buccal absorption of nicotine for the purpose of getting rid of smoking |
| RU2453754C1 (en) * | 2010-12-27 | 2012-06-20 | Федеральное государственное автономное образовательное учреждение высшего профессионального образования Сибирский федеральный университет (СФУ) | Device for trenchless replacement of pipelines |
| RU2448573C1 (en) * | 2010-12-27 | 2012-04-27 | Олег Иванович Квасенков | Method for production of non-smoking products of rustic tobacco |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE8404808L (en) * | 1983-10-03 | 1985-04-04 | Avner Rotman | MICROCAPCLE PLATE MEDICINE IN SOT MATRIX |
| US5549906A (en) * | 1993-07-26 | 1996-08-27 | Pharmacia Ab | Nicotine lozenge and therapeutic method for smoking cessation |
| SE9803986D0 (en) * | 1998-11-23 | 1998-11-23 | Pharmacia & Upjohn Ab | New compositions |
| SE0103211D0 (en) * | 2001-09-27 | 2001-09-27 | Pharmacia Ab | New formulations and use thereof |
-
2001
- 2001-09-27 SE SE0103210A patent/SE0103210D0/en unknown
-
2002
- 2002-09-10 CA CA002461757A patent/CA2461757C/en not_active Expired - Lifetime
- 2002-09-10 RU RU2004108853/15A patent/RU2282447C2/en not_active IP Right Cessation
- 2002-09-10 NZ NZ532528A patent/NZ532528A/en not_active IP Right Cessation
- 2002-09-10 MX MXPA04002876A patent/MXPA04002876A/en active IP Right Grant
- 2002-09-10 JP JP2003530292A patent/JP4262094B2/en not_active Expired - Fee Related
- 2002-09-10 WO PCT/SE2002/001612 patent/WO2003026656A1/en not_active Ceased
- 2002-09-10 ES ES02799531T patent/ES2325684T3/en not_active Expired - Lifetime
- 2002-09-10 EP EP02799531A patent/EP1429770B1/en not_active Expired - Lifetime
- 2002-09-10 DK DK02799531T patent/DK1429770T3/en active
- 2002-09-10 AT AT02799531T patent/ATE431144T1/en not_active IP Right Cessation
- 2002-09-10 KR KR10-2004-7004483A patent/KR20040047868A/en not_active Ceased
- 2002-09-10 AU AU2002334523A patent/AU2002334523B2/en not_active Ceased
- 2002-09-10 BR BR0212834-9A patent/BR0212834A/en not_active IP Right Cessation
- 2002-09-10 CN CNA028190386A patent/CN1561213A/en active Pending
- 2002-09-10 DE DE60232344T patent/DE60232344D1/en not_active Expired - Lifetime
- 2002-09-10 IL IL16088602A patent/IL160886A0/en unknown
- 2002-09-26 AR ARP020103631A patent/AR036679A1/en unknown
-
2004
- 2004-03-16 ZA ZA2004/02091A patent/ZA200402091B/en unknown
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2002334522B2 (en) | New formulations and use thereof | |
| AU2002252470B2 (en) | Nicotine-containing oral dosage form | |
| AU2003267268B2 (en) | Modified release oral dosage form | |
| AU2002334522A1 (en) | New formulations and use thereof | |
| WO2000030641A1 (en) | Nicotine-containing pharmaceutical compositions giving a rapid transmucosal absorption | |
| US20070122457A1 (en) | Nicotine and Chocolate Compositions | |
| AU2002334523B2 (en) | New formulations and use thereof | |
| AU2002334523A1 (en) | New formulations and use thereof | |
| HK1068556A (en) | New formulations and use thereof | |
| Allen | Formulation of specialty tablets for slow oral dissolution | |
| HK1068555B (en) | New formulations and use thereof |