NL2005194C2 - Pharmaceutical composition for use in the prevention and treatment of gingivitis and parodontitis. - Google Patents
Pharmaceutical composition for use in the prevention and treatment of gingivitis and parodontitis. Download PDFInfo
- Publication number
- NL2005194C2 NL2005194C2 NL2005194A NL2005194A NL2005194C2 NL 2005194 C2 NL2005194 C2 NL 2005194C2 NL 2005194 A NL2005194 A NL 2005194A NL 2005194 A NL2005194 A NL 2005194A NL 2005194 C2 NL2005194 C2 NL 2005194C2
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- NL
- Netherlands
- Prior art keywords
- pharmaceutical composition
- composition according
- weight
- gingivitis
- parodontitis
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- 239000008194 pharmaceutical composition Substances 0.000 title claims description 33
- 201000001245 periodontitis Diseases 0.000 title claims description 19
- 208000007565 gingivitis Diseases 0.000 title claims description 13
- 230000002265 prevention Effects 0.000 title claims description 11
- 239000000203 mixture Substances 0.000 claims description 41
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 28
- 241000282412 Homo Species 0.000 claims description 12
- 241001465754 Metazoa Species 0.000 claims description 12
- 235000010323 ascorbic acid Nutrition 0.000 claims description 11
- 229960005070 ascorbic acid Drugs 0.000 claims description 11
- 239000011668 ascorbic acid Substances 0.000 claims description 11
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 10
- 150000008442 polyphenolic compounds Chemical class 0.000 claims description 10
- 235000013824 polyphenols Nutrition 0.000 claims description 10
- 229930003799 tocopherol Natural products 0.000 claims description 10
- 239000011732 tocopherol Substances 0.000 claims description 10
- 235000019149 tocopherols Nutrition 0.000 claims description 10
- QUEDXNHFTDJVIY-UHFFFAOYSA-N γ-tocopherol Chemical class OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1 QUEDXNHFTDJVIY-UHFFFAOYSA-N 0.000 claims description 10
- 229930003802 tocotrienol Natural products 0.000 claims description 8
- 239000011731 tocotrienol Substances 0.000 claims description 8
- 235000019148 tocotrienols Nutrition 0.000 claims description 8
- 229940068778 tocotrienols Drugs 0.000 claims description 8
- GJJVAFUKOBZPCB-ZGRPYONQSA-N (r)-3,4-dihydro-2-methyl-2-(4,8,12-trimethyl-3,7,11-tridecatrienyl)-2h-1-benzopyran-6-ol Chemical class OC1=CC=C2OC(CC/C=C(C)/CC/C=C(C)/CCC=C(C)C)(C)CCC2=C1 GJJVAFUKOBZPCB-ZGRPYONQSA-N 0.000 claims description 7
- MEFKEPWMEQBLKI-AIRLBKTGSA-N S-adenosyl-L-methioninate Chemical compound O[C@@H]1[C@H](O)[C@@H](C[S+](CC[C@H](N)C([O-])=O)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 MEFKEPWMEQBLKI-AIRLBKTGSA-N 0.000 claims description 6
- 229960001570 ademetionine Drugs 0.000 claims description 6
- 239000002775 capsule Substances 0.000 claims description 6
- 239000003085 diluting agent Substances 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 6
- BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical compound [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 claims description 4
- 230000037396 body weight Effects 0.000 claims description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 4
- 229910052711 selenium Inorganic materials 0.000 claims description 4
- 239000011669 selenium Substances 0.000 claims description 4
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 claims description 4
- WGVKWNUPNGFDFJ-DQCZWYHMSA-N β-tocopherol Chemical compound OC1=CC(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C WGVKWNUPNGFDFJ-DQCZWYHMSA-N 0.000 claims description 4
- GZIFEOYASATJEH-VHFRWLAGSA-N δ-tocopherol Chemical compound OC1=CC(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1 GZIFEOYASATJEH-VHFRWLAGSA-N 0.000 claims description 4
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 3
- 229940094952 green tea extract Drugs 0.000 claims description 3
- 235000020688 green tea extract Nutrition 0.000 claims description 3
- 239000008513 turmeric extract Substances 0.000 claims description 3
- 239000011701 zinc Substances 0.000 claims description 3
- 229910052725 zinc Inorganic materials 0.000 claims description 3
- GZIFEOYASATJEH-UHFFFAOYSA-N D-delta tocopherol Natural products OC1=CC(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1 GZIFEOYASATJEH-UHFFFAOYSA-N 0.000 claims description 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 2
- 235000021355 Stearic acid Nutrition 0.000 claims description 2
- 235000010389 delta-tocopherol Nutrition 0.000 claims description 2
- 235000010382 gamma-tocopherol Nutrition 0.000 claims description 2
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 claims description 2
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 2
- 239000007788 liquid Substances 0.000 claims description 2
- 235000019359 magnesium stearate Nutrition 0.000 claims description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 claims description 2
- 239000002674 ointment Substances 0.000 claims description 2
- 235000010603 pastilles Nutrition 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims description 2
- 239000008117 stearic acid Substances 0.000 claims description 2
- 239000000725 suspension Substances 0.000 claims description 2
- 235000004835 α-tocopherol Nutrition 0.000 claims description 2
- 239000002076 α-tocopherol Substances 0.000 claims description 2
- 235000007680 β-tocopherol Nutrition 0.000 claims description 2
- 239000011590 β-tocopherol Substances 0.000 claims description 2
- 239000002478 γ-tocopherol Substances 0.000 claims description 2
- QUEDXNHFTDJVIY-DQCZWYHMSA-N γ-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1 QUEDXNHFTDJVIY-DQCZWYHMSA-N 0.000 claims description 2
- 239000002446 δ-tocopherol Substances 0.000 claims description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims 1
- MECHNRXZTMCUDQ-UHFFFAOYSA-N Vitamin D2 Natural products C1CCC2(C)C(C(C)C=CC(C)C(C)C)CCC2C1=CC=C1CC(O)CCC1=C MECHNRXZTMCUDQ-UHFFFAOYSA-N 0.000 claims 1
- 235000019219 chocolate Nutrition 0.000 claims 1
- 229960002061 ergocalciferol Drugs 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims 1
- 239000008108 microcrystalline cellulose Substances 0.000 claims 1
- 229940016286 microcrystalline cellulose Drugs 0.000 claims 1
- MECHNRXZTMCUDQ-RKHKHRCZSA-N vitamin D2 Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)/C=C/[C@H](C)C(C)C)=C\C=C1\C[C@@H](O)CCC1=C MECHNRXZTMCUDQ-RKHKHRCZSA-N 0.000 claims 1
- 235000001892 vitamin D2 Nutrition 0.000 claims 1
- 239000011653 vitamin D2 Substances 0.000 claims 1
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 description 12
- 235000005282 vitamin D3 Nutrition 0.000 description 11
- 239000011647 vitamin D3 Substances 0.000 description 11
- QYSXJUFSXHHAJI-YRZJJWOYSA-N vitamin D3 Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C\C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-YRZJJWOYSA-N 0.000 description 11
- 229940021056 vitamin d3 Drugs 0.000 description 11
- 230000003078 antioxidant effect Effects 0.000 description 6
- 239000011785 micronutrient Substances 0.000 description 5
- 235000013369 micronutrients Nutrition 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- 208000032843 Hemorrhage Diseases 0.000 description 4
- 206010061218 Inflammation Diseases 0.000 description 4
- 208000034158 bleeding Diseases 0.000 description 4
- 231100000319 bleeding Toxicity 0.000 description 4
- 230000000740 bleeding effect Effects 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 239000000470 constituent Substances 0.000 description 4
- 230000004054 inflammatory process Effects 0.000 description 4
- 239000000902 placebo Substances 0.000 description 4
- 229940068196 placebo Drugs 0.000 description 4
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 229930003268 Vitamin C Natural products 0.000 description 3
- 230000015556 catabolic process Effects 0.000 description 3
- 229940088598 enzyme Drugs 0.000 description 3
- 210000004195 gingiva Anatomy 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- 239000001301 oxygen Substances 0.000 description 3
- 208000028169 periodontal disease Diseases 0.000 description 3
- 235000019154 vitamin C Nutrition 0.000 description 3
- 239000011718 vitamin C Substances 0.000 description 3
- 102000008186 Collagen Human genes 0.000 description 2
- 108010035532 Collagen Proteins 0.000 description 2
- 244000163122 Curcuma domestica Species 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- 208000005888 Periodontal Pocket Diseases 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 229920001436 collagen Polymers 0.000 description 2
- 235000003373 curcuma longa Nutrition 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
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- 239000000047 product Substances 0.000 description 2
- 230000009979 protective mechanism Effects 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- WIGIZIANZCJQQY-UHFFFAOYSA-N 4-ethyl-3-methyl-N-[2-[4-[[[(4-methylcyclohexyl)amino]-oxomethyl]sulfamoyl]phenyl]ethyl]-5-oxo-2H-pyrrole-1-carboxamide Chemical compound O=C1C(CC)=C(C)CN1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCC(C)CC2)C=C1 WIGIZIANZCJQQY-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 102000029816 Collagenase Human genes 0.000 description 1
- 108060005980 Collagenase Proteins 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 206010018276 Gingival bleeding Diseases 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 102000000380 Matrix Metalloproteinase 1 Human genes 0.000 description 1
- 108010016113 Matrix Metalloproteinase 1 Proteins 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 102000016387 Pancreatic elastase Human genes 0.000 description 1
- 108010067372 Pancreatic elastase Proteins 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 208000001647 Renal Insufficiency Diseases 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- 244000269722 Thea sinensis Species 0.000 description 1
- 208000008312 Tooth Loss Diseases 0.000 description 1
- 229930003316 Vitamin D Natural products 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000006053 animal diet Substances 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 239000003181 biological factor Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 150000001765 catechin Chemical class 0.000 description 1
- ADRVNXBAWSRFAJ-UHFFFAOYSA-N catechin Natural products OC1Cc2cc(O)cc(O)c2OC1c3ccc(O)c(O)c3 ADRVNXBAWSRFAJ-UHFFFAOYSA-N 0.000 description 1
- 235000005487 catechin Nutrition 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229960002424 collagenase Drugs 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- GVJHHUAWPYXKBD-UHFFFAOYSA-N d-alpha-tocopherol Natural products OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 210000004513 dentition Anatomy 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000000378 dietary effect Effects 0.000 description 1
- 235000015872 dietary supplement Nutrition 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 230000002500 effect on skin Effects 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 210000001723 extracellular space Anatomy 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 235000006486 human diet Nutrition 0.000 description 1
- 230000033444 hydroxylation Effects 0.000 description 1
- 238000005805 hydroxylation reaction Methods 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 230000003239 periodontal effect Effects 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 239000002516 radical scavenger Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 238000012353 t test Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 235000013616 tea Nutrition 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 229940042585 tocopherol acetate Drugs 0.000 description 1
- 230000036346 tooth eruption Effects 0.000 description 1
- 229940034610 toothpaste Drugs 0.000 description 1
- 239000000606 toothpaste Substances 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 235000019166 vitamin D Nutrition 0.000 description 1
- 239000011710 vitamin D Substances 0.000 description 1
- 150000003710 vitamin D derivatives Chemical class 0.000 description 1
- 229940046008 vitamin d Drugs 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/906—Zingiberaceae (Ginger family)
- A61K36/9066—Curcuma, e.g. common turmeric, East Indian arrowroot or mango ginger
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
- A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
- A61K31/355—Tocopherols, e.g. vitamin E
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
- A61K31/375—Ascorbic acid, i.e. vitamin C; Salts thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/82—Theaceae (Tea family), e.g. camellia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
Landscapes
- Health & Medical Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Medical Informatics (AREA)
- Alternative & Traditional Medicine (AREA)
- Biotechnology (AREA)
- Botany (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
PHARMACEUTICAL COMPOSITION FOR USE IN THE PREVENTION AND TREATMENT OF GINGIVITIS AND PARODONTITIS
FIELD OF THE INVENTION 5
The present invention relates to a pharmaceutical composition comprising tocopherols and/or tocotrienols, ascorbic acid, polyphenols and pharmaceutically acceptable excipients and/or diluents. The invention further relates to a method for preparing such a pharmaceutical composition, to the use of such a pharmaceutical 10 composition in the treatment or prevention of gingivitis or parodontitis in humans or animals, and to a kit comprising such a pharmaceutical composition.
BACKGROUND OF THE INVENTION
15 Every inflammation reaction of tissue in an organism can be regarded as a response to tissue damage caused by chemical, physical or biological factors. The aim of such a reaction is to eliminate the causes of these reactions and to create favourable conditions for recovery of the damaged tissue.
During inflammation of tissue, so called polymorphic nuclear leukocytes 20 produce a considerable amount of free oxygen radicals. These radicals disrupt the equilibrium between the oxidative and anti-oxidative processes. Due to this disturbance of the equilibrium fibroblasts are stimulated to make collagenase, which leads to the breakdown of collagen fibres in the area of inflammation (Brenneisen et al., Hydrogen peroxide (H202) increases the steady-state mRNA levels of collagenease/MMP-1 in 25 human dermal fibroblasts. Free Radio Biol Med 1997:22: 515-524).
Furthermore, many of the inflammation cells die and release other enzymes such as cathepsine, gelatinise or elastase. These enzymes are able to breakdown various proteins in connective tissue, creating even more damage.
The living cells (and extra-cellular spaces) have certain protective mechanisms 30 against oxidative processes. The two most important protective mechanism are enzymes that break down free oxygen radicals, e.g. katalase, and the presence of anti-oxidative micronutrients in the area of the damaged tissue.
One of the most important anti-oxidative micronutrients is ascorbic acid (vitamin C). This compound is essential for the hydroxylation of proline and lysine and 2 is thus critical for the formation of collagen fibres. It has been shown in several studies that a low serum concentration of ascorbic acid increases the chances of developing parodontitis (Nishida et al., Dietary vitamin C and the risk for periodontal disease. J. Peridontol. 2000: 71: 1215-1223; Amaliya et al., Java project on periodontal diseases: 5 the relationship between vitamin C and the severity of peridontitis. J. Clin. Peridontol. 2007: 34: 299-304). However, the use of other anti oxidative micronutrients or combinations of micronutrients for the prevention or treatment of parodontitis has not been thoroughly investigated.
The individual use of polyphenols for use in the treatment op parodontitis has 10 been described in the literature (Makimura et al., Inhibitory effect of tea catechins on collagenese activity. J. Peridontol 1993: 64:630-636). However, the results obtained were poor. Combination of polyphenols with for example anti-oxidative micronutrients such as ascorbic acid have not previously been investigated.
From clinical and experimental research it has become clear that cholecalciferol 15 (vitamine D) could play an important role in the prevention of parodontitis (Krall et al., Calcium and vitamin D supplements reduce tooth loss in the elderly. Am. J. Med. 2001: 111: 452-456). The effect of cholecalciferol is probably not only based on the prevention of breakdown of periodontal bone, but also on its anti-microbial function (Jagelaviciene et al., The relationship between general osteoporosis of the organism 20 and periodontal diseases. Medicina Kaunas 2006: 42: 613-618).
Although different approaches have been followed to find a way to prevent or treat gingivitis or parodontitis the results obtained thus far are relatively poor. There is thus still an unmet need for a product that can prevent or treat gingivitis or parodontitis.
25 DETAILED DESCRIPTION OF THE INVENTION
As indicated above, a balanced pharmaceutical composition which can be used for the prevention or treatment of gingivitis or parodontitis has not yet been described, let alone been placed on the market. It is therefore an object of the present invention to 30 provide a medicament which can be used for the prevention or treatment of gingivitis or parodontitis. The term pharmaceutical composition used in the application means a composition which is suitable for human and animal use and is able to induce a health increasing reaction in or on the human or animal body. A food supplement having the 3 above mentions properties would thus also fall within the scope of the present application.
A first aspect of the present invention relates to a pharmaceutical composition comprising: 5 - 2 to 25 wt% tocopherols and/or tocotrienols; - 15 to 40 wt% ascorbic acid; - 5 to 30 wt% polyphenols; and - 15 to 30 wt% pharmaceutically acceptable excipients and/or diluents.
As can be derived from the experimental part below, the composition according 10 the invention realizes a surprisingly great reduction in the occurrence of bleeding of the gingiva. Reducing the occurrence of bleeding is generally considered as an indication that the tissue is recovering from parodontitis. Clearly, the composition according to the invention is able to prevent or treat gingivitis or parodontitis.
Although some of the constituents of the present invention have previously been 15 used or tested for their efficacy in the prevention or treatment of gingivitis or parodontitis, they have never been used in combination. Moreover, the efficacy of the constituents separately is considerably lower than the efficacy of the composition according to the invention. In other words, there is a synergistic effect between the constituents of the claimed composition when the composition is used for the 20 prevention or treatment of gingivitis or parodontitis.
The ascorbic acid used in the composition according to the invention is believed to increase the favourable effect of tocopherols and/or tocotrienols. It helps to regenerate tocopherols and/or tocotrienols radicals and enhances thereby the antioxidant effect of tocopherols and/or tocotrienols (Niki, Action of ascorbic acid as a 25 scavenger of active and stable oxygen radicals, The American Journal of Clinical Nutrition, 1991; 54.1119S-24S).
Preferably the tocopherols used are alpha-, beta, gamma or delta tocopherol, or a mixture thereof. The polyphenols used are preferably derived from a green tea extract. Besides the above mentioned constituents the composition according to the 30 invention comprises in a preferred embodiment of cholecalciferol. The amount of cholecalciferol used in the composition is preferably 0,001 wt% to 0,5 wt%. The presence of cholecalciferol in the composition according to the invention is particularly relevant when the composition is used in humans. Generally, the human diet does not comprises sufficient amounts of cholecalciferol. Especially in the winter time the 4 cholecalciferol levels in humans are relatively low. Generally, the animal diet comprises more than enough cholecalciferol and extra addition thereof is most often not necessary.
In a composition which is particularly suitable for use in animals 5 to 10 wt% curcuma longa extract is used. Preferably the product Biocurcumax is used, although 5 other curcuma longa extracts may also be used. The advantage of using Biocurcumax is that its bio availability is very good. In addition to curcuma longa the composition specially suitable for animals also comprises 15 to 45 wt%, preferably 20-30 wt% SAMe ( S-adenosylmethionine) It is further preferred to also add to this composition 0,1 to 3 wt% zinc and/or traces of selenium. The amount of selenium used is preferably 10 0,0001 wt% to 0,01 wt%.
In a highly preferred embodiment of the composition for use in animals, although it may also be administered to humans, the composition comprises 2-5 wt% tocopherols and/or tocotrienols, 10-20 wt% ascorbic acid, 5 to 15 wt% polyphenols, 20-30 wt% excipients and/or diluents, 5-10 wt% curcuma longa extract and 30-45 wt%, 15 S-adenosylmethionine. Preferably the composition also comprises 0,1-3 wt% zinc or salts thereof and optionally traces of selenium. If the above mentioned composition is administered to humans, the composition comprises optionally also 0,1-1 wt% cholecalciferol.
In a preferred embodiment of the composition for use in humans the 20 composition comprises 20-25 wt% tocopherols and/or tocotrienols, 30-40wt% ascorbic acid, 20-30 wt% polyphenols, 15-25 wt% pharmaceutically acceptable excipients and/or diluents and optionally 0,1-1 wt% cholecalciferol.
In a further preferred embodiment the above mentioned composition for humans may also comprise S-adenosylmethionine. In such a composition preferably 15 to 45 25 wt%, more preferably 20-30 wt% S-adenosylmethionine is used.
The composition according to the invention also comprises excipients and/or diluents in order to have a formulation that can be administered or applied conveniently and remains stable over prolonged periods of time. Excipients used in the pharmaceutical composition according to the invention are for example microcrystalline 30 cellulose, hydroxypropylcellulose, magnesium stearate, or stearic acid. However, it is also possible to use other comparable excipients, as for example described in The Handbook of Pharmaceutical Excipients of Rowe et al., 2006.
5
The composition is preferably formulated into a tablet, sugar-coated pill, capsule, pastille, liquid, drinkable suspension or ointment. Most preferably the composition is formulated into a tablet.
Preferably the human or animal patients are administered a total daily dose 10-5 200 mg/kg body weight of the composition, preferably 25-150 mg/kg body weight, most preferably 75-125 mg/kg. This total daily dose is preferably obtained via a once or twice daily administration of the pharmaceutical composition according to the invention A particularly preferred single unit dosage of the composition according to the invention for humans comprises 400 mg to 2000 mg, preferably 500 mg to 1250 mg, 10 most preferably around 1000 mg.
Another single unit dosage of the composition according to the invention, which is particularly useful for administering to animals (e.g. dogs and cats), although it may also be administered to humans, comprises preferably 200 to 1000 mg, preferably 300 to 600 mg, most preferably around 550 mg.
15 It is preferred to administer the composition according to the invention to humans or animals having a history of suffering from gingivitis or parodontitis. A second aspect of the present invention relates to a method for preparing a pharmaceutical composition as described above.
A third aspect of the present invention relates to a kit comprising the above 20 mentioned pharmaceutical composition. Preferably the kit is a blister package or a container, such as for example a bottle.
The invention will now be described further by the following, non-limiting examples
25 EXAMPLES
Material and method
The pharmaceutical composition according to the invention was tested on 32 30 patients suffering from parodontitis. The patients were between 18 and 65 years old and had at least eight periodontal pockets of 4 mm or more, spread over at least four dentition elements. Exclusion criteria were diabetes mellitus, kidney insufficiency, pregnancy, use of anticoagulentia and regular use of immunosuppressive medicaments.
6
All patients received the same instructions with respect to dental care and also received the same toothpaste. The patients administered their selves either the composition according to the invention or a placebo. The total daily dosage of the active ingredients of the pharmaceutical composition used was: 5 - 200 mg D, L alpha-tocopherol acetate, - 600 mg ascorbic acid - 10 microgram cholecalciferol - 400 mg green tea extract, 98%. polyphenols 10 This total daily dosage was divided over four single unit dosages, namely capsules. Two capsules were taken in the morning and two in the evening. The capsules with the pharmaceutical composition according to the invention could not be distinguished visually from the placebo capsules.
15 The occurrence of bleeding of the gingiva as well as the amount and depth of periodontal pockets was assessed before the start of the trial by dentists. This was done again after three months and after six months. An evident improvement was defined as a decrease of the amount of gingival bleedings or as a reduction of the sum of the pocket depth by at least forty percent. For statistical analysis use was made of the so called 20 one-tailed t-test.
Results
After six months the amount of gingiva bleedings in the patients treated with the 25 composition according the invention decreased with 46% compared to 27% in the placebo group. In the group that received the composition according to the invention 38% of the patients showed a markedly decrease of the summed up pocketsize. In the placebo group this decrease was onlyl2,5% These results clearly show the beneficial effects of the composition according to the invention.
Claims (18)
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| NL2005194A NL2005194C2 (en) | 2010-08-05 | 2010-08-05 | Pharmaceutical composition for use in the prevention and treatment of gingivitis and parodontitis. |
| BE2011/0484A BE1020183A3 (en) | 2010-08-05 | 2011-08-05 | PHARMACEUTICAL COMPOSITION FOR USE IN THE TREATMENT AND PREVENTION OF GINGIVITIS AND PARODONTITIS. |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| NL2005194 | 2010-08-05 | ||
| NL2005194A NL2005194C2 (en) | 2010-08-05 | 2010-08-05 | Pharmaceutical composition for use in the prevention and treatment of gingivitis and parodontitis. |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NL2005194C2 true NL2005194C2 (en) | 2012-02-07 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NL2005194A NL2005194C2 (en) | 2010-08-05 | 2010-08-05 | Pharmaceutical composition for use in the prevention and treatment of gingivitis and parodontitis. |
Country Status (2)
| Country | Link |
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| BE (1) | BE1020183A3 (en) |
| NL (1) | NL2005194C2 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014161872A1 (en) * | 2013-04-05 | 2014-10-09 | Nestec S.A. | Compositions for use in stimulating bone growth |
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| JP2002029953A (en) * | 2000-07-19 | 2002-01-29 | Sunstar Inc | Food composition and composition for oral cavity for prophylaxis or treatment of periodontal disease |
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| WO2014161872A1 (en) * | 2013-04-05 | 2014-10-09 | Nestec S.A. | Compositions for use in stimulating bone growth |
| JP2016520544A (en) * | 2013-04-05 | 2016-07-14 | ネステク ソシエテ アノニム | Composition for use in stimulating bone growth |
| AU2014247122B2 (en) * | 2013-04-05 | 2018-12-06 | Société des Produits Nestlé S.A. | Compositions for use in stimulating bone growth |
| JP2020058351A (en) * | 2013-04-05 | 2020-04-16 | ソシエテ・デ・プロデュイ・ネスレ・エス・アー | Compositions for use in stimulating bone growth |
| US10675290B2 (en) | 2013-04-05 | 2020-06-09 | Societe Des Produits Nestle S.A. | Compositions for use in stimulating bone growth |
| US11166965B2 (en) | 2013-04-05 | 2021-11-09 | Societe Des Produits Nestle S.A. | Compositions for use in stimulating bone growth |
| JP2022031660A (en) * | 2013-04-05 | 2022-02-22 | ソシエテ・デ・プロデュイ・ネスレ・エス・アー | Composition for use in stimulating bone growth |
| JP2024150494A (en) * | 2013-04-05 | 2024-10-23 | ソシエテ・デ・プロデュイ・ネスレ・エス・アー | Compositions for use in stimulating bone growth - Patents.com |
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| BE1020183A3 (en) | 2013-06-04 |
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