AU700252B2 - Composition for dental use comprising krill enzyme - Google Patents
Composition for dental use comprising krill enzyme Download PDFInfo
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- AU700252B2 AU700252B2 AU72779/94A AU7277994A AU700252B2 AU 700252 B2 AU700252 B2 AU 700252B2 AU 72779/94 A AU72779/94 A AU 72779/94A AU 7277994 A AU7277994 A AU 7277994A AU 700252 B2 AU700252 B2 AU 700252B2
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- plaque
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- krill
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- 102000004190 Enzymes Human genes 0.000 title claims description 36
- 108090000790 Enzymes Proteins 0.000 title claims description 36
- 241000239366 Euphausiacea Species 0.000 title claims description 28
- 239000000203 mixture Substances 0.000 title claims description 16
- 208000002064 Dental Plaque Diseases 0.000 claims description 13
- 241000282414 Homo sapiens Species 0.000 claims description 10
- 241000894006 Bacteria Species 0.000 claims description 8
- 230000007505 plaque formation Effects 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 6
- 241000239370 Euphausia superba Species 0.000 claims description 5
- 210000000214 mouth Anatomy 0.000 claims description 5
- 239000000853 adhesive Substances 0.000 claims description 4
- 230000001070 adhesive effect Effects 0.000 claims description 4
- 230000003247 decreasing effect Effects 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 230000000069 prophylactic effect Effects 0.000 claims description 3
- 238000011321 prophylaxis Methods 0.000 claims description 2
- 229940088598 enzyme Drugs 0.000 description 31
- 239000003795 chemical substances by application Substances 0.000 description 7
- 210000005253 yeast cell Anatomy 0.000 description 7
- 230000002882 anti-plaque Effects 0.000 description 6
- 241000222122 Candida albicans Species 0.000 description 5
- 230000000844 anti-bacterial effect Effects 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 241000282472 Canis lupus familiaris Species 0.000 description 4
- NIXOWILDQLNWCW-UHFFFAOYSA-N acrylic acid group Chemical group C(C=C)(=O)O NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 4
- 229940095731 candida albicans Drugs 0.000 description 4
- 208000002925 dental caries Diseases 0.000 description 4
- 244000005706 microflora Species 0.000 description 4
- 210000004872 soft tissue Anatomy 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 206010061218 Inflammation Diseases 0.000 description 3
- INVGWHRKADIJHF-UHFFFAOYSA-N Sanguinarin Chemical compound C1=C2OCOC2=CC2=C3[N+](C)=CC4=C(OCO5)C5=CC=C4C3=CC=C21 INVGWHRKADIJHF-UHFFFAOYSA-N 0.000 description 3
- 108010056079 Subtilisins Proteins 0.000 description 3
- 102000005158 Subtilisins Human genes 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000000551 dentifrice Substances 0.000 description 3
- 238000013461 design Methods 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 230000004054 inflammatory process Effects 0.000 description 3
- 230000007774 longterm Effects 0.000 description 3
- 208000028169 periodontal disease Diseases 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 230000002265 prevention Effects 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 239000004094 surface-active agent Substances 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- GHXZTYHSJHQHIJ-UHFFFAOYSA-N Chlorhexidine Chemical compound C=1C=C(Cl)C=CC=1NC(N)=NC(N)=NCCCCCCN=C(N)N=C(N)NC1=CC=C(Cl)C=C1 GHXZTYHSJHQHIJ-UHFFFAOYSA-N 0.000 description 2
- 108010001682 Dextranase Proteins 0.000 description 2
- FCEXWTOTHXCQCQ-UHFFFAOYSA-N Ethoxydihydrosanguinarine Natural products C12=CC=C3OCOC3=C2C(OCC)N(C)C(C2=C3)=C1C=CC2=CC1=C3OCO1 FCEXWTOTHXCQCQ-UHFFFAOYSA-N 0.000 description 2
- 208000034619 Gingival inflammation Diseases 0.000 description 2
- 102000035195 Peptidases Human genes 0.000 description 2
- 108091005804 Peptidases Proteins 0.000 description 2
- 241000324401 Superba Species 0.000 description 2
- 239000004784 Superba Substances 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 230000000845 anti-microbial effect Effects 0.000 description 2
- 239000007853 buffer solution Substances 0.000 description 2
- 229940112822 chewing gum Drugs 0.000 description 2
- 235000015218 chewing gum Nutrition 0.000 description 2
- 229960003260 chlorhexidine Drugs 0.000 description 2
- 238000004140 cleaning Methods 0.000 description 2
- RBLGLDWTCZMLRW-UHFFFAOYSA-K dicalcium;phosphate;dihydrate Chemical compound O.O.[Ca+2].[Ca+2].[O-]P([O-])([O-])=O RBLGLDWTCZMLRW-UHFFFAOYSA-K 0.000 description 2
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 2
- 108010000165 exo-1,3-alpha-glucanase Proteins 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- 210000004195 gingiva Anatomy 0.000 description 2
- 208000007565 gingivitis Diseases 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 239000002324 mouth wash Substances 0.000 description 2
- 230000007406 plaque accumulation Effects 0.000 description 2
- 230000002797 proteolythic effect Effects 0.000 description 2
- 229940084560 sanguinarine Drugs 0.000 description 2
- YZRQUTZNTDAYPJ-UHFFFAOYSA-N sanguinarine pseudobase Natural products C1=C2OCOC2=CC2=C3N(C)C(O)C4=C(OCO5)C5=CC=C4C3=CC=C21 YZRQUTZNTDAYPJ-UHFFFAOYSA-N 0.000 description 2
- PUZPDOWCWNUUKD-UHFFFAOYSA-M sodium fluoride Chemical compound [F-].[Na+] PUZPDOWCWNUUKD-UHFFFAOYSA-M 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- MGSRCZKZVOBKFT-UHFFFAOYSA-N thymol Chemical compound CC(C)C1=CC=C(C)C=C1O MGSRCZKZVOBKFT-UHFFFAOYSA-N 0.000 description 2
- 238000011282 treatment Methods 0.000 description 2
- 229960003500 triclosan Drugs 0.000 description 2
- WEEGYLXZBRQIMU-UHFFFAOYSA-N 1,8-cineole Natural products C1CC2CCC1(C)OC2(C)C WEEGYLXZBRQIMU-UHFFFAOYSA-N 0.000 description 1
- JFZBMJJFVBMZNC-UHFFFAOYSA-N 2-[3-(4-propylheptyl)morpholin-4-yl]ethanol;hydrochloride Chemical compound Cl.CCCC(CCC)CCCC1COCCN1CCO JFZBMJJFVBMZNC-UHFFFAOYSA-N 0.000 description 1
- XGRSAFKZAGGXJV-UHFFFAOYSA-N 3-azaniumyl-3-cyclohexylpropanoate Chemical compound OC(=O)CC(N)C1CCCCC1 XGRSAFKZAGGXJV-UHFFFAOYSA-N 0.000 description 1
- 206010007134 Candida infections Diseases 0.000 description 1
- 241000282465 Canis Species 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 239000000253 Denture Cleanser Substances 0.000 description 1
- 208000006819 Denture Stomatitis Diseases 0.000 description 1
- 239000004150 EU approved colour Substances 0.000 description 1
- WEEGYLXZBRQIMU-WAAGHKOSSA-N Eucalyptol Chemical compound C1C[C@H]2CC[C@]1(C)OC2(C)C WEEGYLXZBRQIMU-WAAGHKOSSA-N 0.000 description 1
- 241000239368 Euphausia Species 0.000 description 1
- 108010073178 Glucan 1,4-alpha-Glucosidase Proteins 0.000 description 1
- 108010015776 Glucose oxidase Proteins 0.000 description 1
- 239000004366 Glucose oxidase Substances 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 208000001388 Opportunistic Infections Diseases 0.000 description 1
- 208000025157 Oral disease Diseases 0.000 description 1
- 108010067035 Pancrelipase Proteins 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 239000004141 Sodium laurylsulphate Substances 0.000 description 1
- 206010041290 Soft tissue inflammation Diseases 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 239000004098 Tetracycline Substances 0.000 description 1
- 239000005844 Thymol Substances 0.000 description 1
- XEFQLINVKFYRCS-UHFFFAOYSA-N Triclosan Chemical compound OC1=CC(Cl)=CC=C1OC1=CC=C(Cl)C=C1Cl XEFQLINVKFYRCS-UHFFFAOYSA-N 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 229950010221 alexidine Drugs 0.000 description 1
- LFVVNPBBFUSSHL-UHFFFAOYSA-N alexidine Chemical compound CCCCC(CC)CNC(=N)NC(=N)NCCCCCCNC(=N)NC(=N)NCC(CC)CCCC LFVVNPBBFUSSHL-UHFFFAOYSA-N 0.000 description 1
- 150000001414 amino alcohols Chemical class 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000001680 brushing effect Effects 0.000 description 1
- 201000003984 candidiasis Diseases 0.000 description 1
- 235000021024 carbohydrate-rich diet Nutrition 0.000 description 1
- BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical group NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000000973 chemotherapeutic effect Effects 0.000 description 1
- 229960005233 cineole Drugs 0.000 description 1
- 230000007012 clinical effect Effects 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 229960003854 delmopinol Drugs 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 108091007734 digestive enzymes Proteins 0.000 description 1
- 102000038379 digestive enzymes Human genes 0.000 description 1
- 230000000471 effect on teeth Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 150000002222 fluorine compounds Chemical class 0.000 description 1
- FDPVYRPMVZNBLZ-UHFFFAOYSA-N fluorophosphonic acid hydrofluoride Chemical compound F.OP(O)(F)=O FDPVYRPMVZNBLZ-UHFFFAOYSA-N 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 235000012631 food intake Nutrition 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 229940116332 glucose oxidase Drugs 0.000 description 1
- 235000019420 glucose oxidase Nutrition 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 238000009533 lab test Methods 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 230000002366 lipolytic effect Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 238000000386 microscopy Methods 0.000 description 1
- 208000030194 mouth disease Diseases 0.000 description 1
- 229940051866 mouthwash Drugs 0.000 description 1
- 229940006093 opthalmologic coloring agent diagnostic Drugs 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 201000001245 periodontitis Diseases 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- 239000000419 plant extract Substances 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 235000019833 protease Nutrition 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 238000001629 sign test Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 239000011775 sodium fluoride Substances 0.000 description 1
- 235000013024 sodium fluoride Nutrition 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 229960004711 sodium monofluorophosphate Drugs 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 229910021653 sulphate ion Inorganic materials 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 229960002180 tetracycline Drugs 0.000 description 1
- 229930101283 tetracycline Natural products 0.000 description 1
- 235000019364 tetracycline Nutrition 0.000 description 1
- 150000003522 tetracyclines Chemical class 0.000 description 1
- 229960000790 thymol Drugs 0.000 description 1
- LMJSLTNSBFUCMU-UHFFFAOYSA-N trichlormethiazide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NC(C(Cl)Cl)NS2(=O)=O LMJSLTNSBFUCMU-UHFFFAOYSA-N 0.000 description 1
- 239000000341 volatile oil Substances 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/10—Antimycotics
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Oncology (AREA)
- Engineering & Computer Science (AREA)
- Communicable Diseases (AREA)
- Gastroenterology & Hepatology (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Epidemiology (AREA)
- Cosmetics (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Enzymes And Modification Thereof (AREA)
Description
WO 95/33470 PCT/SE94/00549 COMPOSITION FOR DENTAL USE COMPRISING KRILL ENZYME Technical Field Regular oral hygiene such as tooth brushing is normally insufficient to provide adequate control of dental microbial plaque. Consequently, the incorporation of antimicrobial and plaque dissolving agents in dental products such as dentifrices has been proposed by dental researchers for a long time review by P.D. Marsh, J. Clin. Periodont., 18, 462-67 (1991).
Apart from certain fluorides most compounds of potential use as antiplaque agents have turned out to be incompatible with either vehicle substances employed or the oral environment.
Furthermore, recent research demonstrates that antiplaque agents should be designed to control rather than eliminate the dental plaque microflora Marsh, Brit. Dent. J. 9, 174-77 (1991). Like other parts of the digestive tract the oral cavity possesses a natural microflora which is beneficial to the host. Changes in the natural microflora may result in caries and periodontal disease.
A number of antibacterial and surface active substances have been evaluated and tested for plaque control (Table i).
Bisquanides and phenols (Chlorohexidine and Triclosan) have proved to be most effective. However, although showing a strong antibacterial action, they have undesirable short-term effects. Furthermore, possible long-term effects are causing concern.
Recently, surface active agents such as amino alcohols have been introduced with the purpose of affecting the adhesion of bacteria to oral surfaces. Again, little is known about possible adverse long-term effects. Furthermore, bacteria are known to develop resistance to chemotherapeutic agents on prolonged use.
PCT/SE94/00 5 49 WO 95/3347 0 2 Table 1: Classes and examples of antimicrobial antiplaque agents proposed for use in dentifrices.
Class of inhibitor Some examples Antibiotics Tetracycline, penicillin Antibiguanidines Chlorhexidine, alexidine 0 EnBisbiguanidines Mutanase, amyloglucosidase/ Enzyes glucose oxidase Essential oils Thymol, eucalyptol Fluoride Monofluorophosphate M etal ions Zinc, stannous copper Metal l o n s Sanguinarine Plant extracts Sanguinarine Phenols Triclosan Quaternary ammonium Quaternary ammonium Cetylpyridinum chloride compounds Sodium lauryl, sulphate Surfactants o Several enzymes have been employed as antiplaque agents.
However, in most cases it has not been possible to confirm promising laboratory tests in clinical trials. Proteases, 25 mutanases and dextranases have been used primarily to dissolve the plaque matrix which allows bacteria to adhere to tooth surface. An enzyme dentifrice which is presently being marketed (Zendium) contains an aminoglycosidase, the effect of which is based on an indirect antibacterial action. How- 30 ever, the clinical effects seems to be too limited.
The enzyme mixture from the digestive tract of the krill schrimp, Euphuasia superba, has proved to be unique in composition and amazingly potent in action when used on organic substrates as compared to previously known digestive enzymes.
Thus, a method of therapeutic an non-therapeutic cleaning is described in EP-B1-0,107,6 34 Disclosure of Invention In accordance with a first aspect of the present invention, there is provided a method for decreasing the adhesive ability of plaque bacteria in a human subject and preventing dental plaque formation in the human subject comprising administering WO 95/33470 3 PCT/SE94/00549 in the oral cavity of said subject a prophylactically effective amount of enzymes from Antarctic krill (Euphausia superba) in a carrier adapted for prophylactic treatment.
In accordance with a second aspect of the present invention, there is provided the use of enzymes from Antarctic krill (Euphausia superba) in the manufacture of a prophylactic composition for decreasing the adhesive ability of plaque bacteria in a human subject and preventing dental plaque formation in the human subject.
Thus, in general, the invention concerns the use of these krill enzymes (KE) to prevent dental plaque on natural and artificial teeth, dental appliances, implants and soft tissues of the 15 mouth. By applying krill enzymes to these surfaces, plaque formation, caries, yeast-cell infections and soft-tissue inflammation will be prevented.
Compositions of enzymes from Antarctic krill (Euphausia 20 superba) have been studied as potential oral prophylactic antiplaque/agents. A number of in vitro/in vivo studies have demonstrated that krill enzymes: retard plaque accumulation both in vitro and in vivo more effectively than Alcalase do not exhibit an antibacterial effect; and show mild antifungal 25 properties against Candida albicans, common in oral opportunistic infections. Hence, it is concluded that krill enzymes offer highly promising properties as an antiplaque agent due to the high efficiency of krill enzymes in dissolving plaques and apparent biocompatibility.
Oral diseases such as caries, gingivitis/periodontitis and candidiasis are caused when microorganisms of the natural oral microflora accumulate on retentive surfaces such as teeth and artificial restorations, thereby forming dental plaque Poor or inadequate oral hygiene causes this plaque formation.
Mechanical toothbrushing is still the most efficient way to remove dental plaque WO 95/33470 4 PCT/SE94/00549 As dental plaque consist of oral bacteria/microbes which aggregate on dental/oral surfaces by adherence, growth and production of extracellular organic matrix enzymes for debriding this organic debris have for a long time been considered an ideal dental plaque remover Peptidase, pancrease, dextranases and Alcalase® (12) are all different enzymes tried over the years as dental plaque debriders with limited clinical success, the main reason for failure being weakness in catalyst action and in retaining adequate and sufficient enzyme concentrations on substrates in the salivarich oral environment 9 The concept of chemical plaque control has consequently been concentrated on antibacterial substances such as chlor- 15 hexidine 16) and surface active agents These substances, though, have some adverse side effects and the long term effect on the organism is uncertain. (19).
When enzymes are employed to remove plaque or to facilitate mechanical removal by toothbrushing they will merely have a i limited effect on the inflammatory reactions in the gingiva 1 soft tissue 3) since there is strong evidence that food debris has its strongest devastating effect on teeth in the earliest phase after food consumption.
The adherence of yeast-cells (Candida albicans) to dentures and oral soft tissue causes inflammatory reactions which are difficult to cure. The main reason is, again, poor denture hygiene Enzyme-containing denture-cleaners are already on the market Alcalase® being the more prominent (8, 9, 10, 12).
As shown in the examples of this application, krill enzymes Shave proved effective in prevention of dental plaque and yeast-cell adherence affecting adherence and metabolism of oral microorganisms and further improving the reduction of underlying inflammations in soft tissues.
WO 95/33470 PCT/SE94/00549 The proteolytic activity krill enzymes is often quantified in casein units. In a krill enzyme mixture, the proteolytic activity is measured as a part of the total enzymatic activity, which may comprise carbohydrate-splitting and lipolytic activity Example 1 Preparation of the enzyme composition Krill enzymes were extracted from the raw material, krill (Euphausia superba) according to standard procedures described in (EP-A 107,634, EP-A 177,605). In short, krill was frozen immediately after caught and stored at -30 0
C
before preparation. The thawed krill was mixed with water, homogenised and centrifuged in the cold. The supernatant was decanted and saved. Lipids were removed by extraction with organic solvents, the water phase concentrated and freezedried thus resulting in a "crude krill enzyme preparation" suitable for dental use.
Exampel 2 Detachement of yeast cells adhered to acrylic surfaces In accordance with a Japanese study design strains of Candida albicans were incubated in 4 acrylic beakers for 24 h at 37°C. The yeast cell then adhered to the acrylic surfaces which could be seen as a matt coating in the beakers. This model resembles yeast-cell infections on dental protheses.
Solutions of krill enzymes (1 resp were added to two beakers while two other beakers served as controls. 1 h later stereo microscopy showed that >90% of countable yeast cells had detached from acrylic surfaces of krill enzyme treated beakers compared to controls. The results were photodocumented (Table 1) WO 95/33470 PCT/SE94/00549 6 Example 3 Retardation of plaque formation in dogs Two healthy beagle dogs were used in this study. In this split-mouth design, teeth on the control side were treated with a water solution applied 2 times daily for 2 minutes at 6 h intervals. Teeth on the active side were treated in the same way with krill enzymes in a 2% buffer solution. Baseline status of the teeth was gingival health (GI=0) and no plaque (PLI=0) obtained by thorough cleaning twice daily for two weeks prior to test start. The test run lasted for 3 weeks during which time the dogs were fed a carbohydrate-rich diet.
The dogs were briefly sedated at treatment and registration.
Gingival index according to Loe and plaque index according to Silness L6e were used for registration of plaque and gingival inflammation. Plaque on teeth was made visible with eosin colorin (Diaplac). Teeth no P3 P4 and canines were used for registration. In addition to clinical registration all registrations were photodocumented.
From the photos the amount of plaque on teeth buccal and approximal surfaces was assessed. The amount of plaque was less on active side compared to control teeth. Some of these results were statistically significant at p< 0.05 using the sign test.
Example 4 Retardation of plaque formation in humans A test subject started with clinically clean and healthy teeth and gingiva (GI=0 PLI=0) restrained from all oral hygiene for one week. During this time a water and a krill enzyme 2% buffer solution was applied to control and active sides, respectively, in a split mouth design 3 times daily WO 95/33470 PCT/SE94/00549 7 for 2 minutes. At the end of test period the result was photodocumented after that plaque on teeth had been visualized with eosin color (Diaplac). There was a noticable difference in plaque accumulation and associated gingival inflammation between control and test sides.
Example A dental paste or gel is prepared with the following composition: Sodium monofluorophosphate, dicalcium phosphate dihydrate, glycerol, sorbitol, sodium citrate, sodium lauryl sulphate, aromatic flavour, sodium saccharinate, methylhydroxy-4-benzoate, krill enzyme extract, citric acid colouring agents.
Example 6 A chewing gum is prepared with the following composition: Chewing gum base, sodium fluoride, krill enzyme extract.
Example 7 A mouth wash and prosthesis cleaner is prepared with the following composition: Base, carrier, saline water solution, krill enzyme extract.
WO 95/33470 PCT/SE94/00549 8 References 1. L6e, H, Theilade, e Jensen, S.B. (1965) Experimental gingivitis in man. J. of Periodontology 36, 177-1887.
2. Budts-Jbrgensen, E. (1974) The significance of Candida albicans in denture stomatitis. Scand J Dent Res 82 151.
3. Socransky, S.S. (1970) Relationship of bacteria to the aethiology of periodontal disease. J of Dent Res 49, 223-228.
4. Hull, P.S. (1980) Chemical inhibition of plaque. J of Clin Periodontology 7, 431-442.
5. Budtz-Jbrgensen, Theilade, E, Theilade, J. (1983) Quantitative relationship between yeasts and bacteria in denture-induced stomatitis. Scand J Dent Res 91, 134.
6. Arendorf, T, Walker, D.M. (1979) Oral candidal populations in health and disease. Br Dent J 147 267.
7. Connor, Schoenfels, Taylor, R.L. (1977) An evaluation of an enzyme denture cleanser. J Prosthet Dent 37, 147.
8. Budtz-Jbrgensen, E. (1979) Material methods for cleansing dentures. J Prosthet Dent 42, 619.
Budts-J6rgensen, E Kelstrup, J. (1977) Enzymes as denture cleansers. Scan J Dent Res 85, 209.
11. Axelsson, P, Lindhe, J. (1974) The effect a preventive programme on dental plaque, gingivitis and caries in schoolchildren J of Clin Periodontology 1, 126-138.
WO 95/33470 PCT/SE94/00549 9 12. Budtz-J6rgensen, E, Kelstrup, J Poulsen, S. (1983) Reduction of formation of denture plaque by a protease (Alcalase). Acta Odontol Scand 41, 93-98 13. Lang, N.P. Cumming, B.R. Lbe, H. (1973) Toothbrush frequency is it is related to plaque development and gingival health. J of Periodontology 44, 396-405.
14. Kornman, (1986) The role of supragingival plaque in the prevention and treatment of periodontal diseases Reveiw. J of Periodont Res 21, Suppl., 5-22.
Axelsson, P, Lindhe, J Nystr6m, B, (1991) On the prevention of caries and periodontal disease. Results of a year longitudinal study in adults. J of Clin Periodontology 18, 182-189.
16. Marsh, P.D. (1991) Dentifrices containing new agents for the control of plaque. J Clin Periodontaol 18, 462-467.
17. Lbvdal, A et al., Combined effect of subgingival scaling and controlled oral hygiene in the incidence og gingivitis.
Acta Odontol Scand 19, 537-555 (1961).
18. Krembel, J et al, (1969) Fractionation of human dental plaques. Arch oral Bio 14, 563-565.
19. FlUtra, L Gjarmo P et al (1971) Side effects of chlorhexidrive mouthwashes Scand J of Dent Res 79 119-125.
Collaert, Bruno (1992) Chemotherapeutic supragingival plaque control with delmopinol hydrochloride. Thesis.
21. Shogo Minagi et al. (1987) Objective testing of the efficiency of denture-cleansing agents. J of Prosthetic Dentistry 58 595-598.
Claims (5)
1. Use of enzymes from Antarctic krill (Euphausia superba) in the manufacture of a prophylactic composition for decreasing the adhesive ability of plaque bacteria in a human subject and preventing dental plaque formation in the human subject.
2. Use as claimed in claim 1, wherein the composition comprises 0.01 to 100 units of said enzymes per 100 g of composition.
3. A method for decreasing the adhesive ability of plaque bacteria in a human subject and preventing dental plaque formation in the human subject comprising administering in the oral cavity of said subject a prophylactically effective amount of enzymes from Antarctic krill (Euphausia superba) in a carrier adapted for prophylactic treatment.
4. A method as claimed in claim 3, wherein the amount administered is 1 to 3 g, twice daily. *20
5. A method as claimed in claim 3 or 4 wherein a composition comprising 0.01 to 100 units of said enzymes per 100 g of composition is administered. DATED this 21st day of October 1998 KRISTIAN HELLGREN, LARS HELLGREN, VIGGO MOHR and JAN VINCENT, By their Patent Attorneys, E. F. WELLINGTON CO., By:ruce Welli (Bruce Wellington) A/BA/4566
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
PCT/SE1994/000549 WO1995033470A1 (en) | 1994-06-07 | 1994-06-07 | Composition for dental use comprising krill enzyme |
Publications (2)
Publication Number | Publication Date |
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AU7277994A AU7277994A (en) | 1996-01-04 |
AU700252B2 true AU700252B2 (en) | 1998-12-24 |
Family
ID=20392981
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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AU72779/94A Ceased AU700252B2 (en) | 1994-06-07 | 1994-06-07 | Composition for dental use comprising krill enzyme |
Country Status (4)
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EP (1) | EP0759764A1 (en) |
JP (1) | JPH10500991A (en) |
AU (1) | AU700252B2 (en) |
WO (1) | WO1995033470A1 (en) |
Families Citing this family (4)
Publication number | Priority date | Publication date | Assignee | Title |
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US6232088B1 (en) | 1995-02-08 | 2001-05-15 | Phairson Medical, Inc. | Treatment and prevention of immune rejection reactions |
US6040155A (en) * | 1996-08-28 | 2000-03-21 | Kay; John | Multifunctional protein and DNA sequence encoding same |
WO1998008863A1 (en) * | 1996-08-28 | 1998-03-05 | Phairson Medical, Inc. | Enzyme and dna sequence encoding same |
WO2009060013A2 (en) * | 2007-11-06 | 2009-05-14 | Kristian Hellgren | A method for treating ailments of the oral cavity with a krill enzyme composition |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1984001705A1 (en) * | 1982-10-29 | 1984-05-10 | London Hospital Med Coll | Cardio-respiratory monitor apparatus & method |
WO1993024142A1 (en) * | 1992-05-22 | 1993-12-09 | Phairson Medical Ab | New pharmaceutical uses of krill enzymes |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
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WO1984001715A1 (en) * | 1982-10-25 | 1984-05-10 | Hellgren Lars G I | Enzyme composition for therapeutical and/or non-therapeutical cleaning, the use thereof and preparation of the composition |
-
1994
- 1994-06-07 EP EP94923112A patent/EP0759764A1/en not_active Withdrawn
- 1994-06-07 AU AU72779/94A patent/AU700252B2/en not_active Ceased
- 1994-06-07 JP JP8500723A patent/JPH10500991A/en not_active Ceased
- 1994-06-07 WO PCT/SE1994/000549 patent/WO1995033470A1/en not_active Application Discontinuation
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1984001705A1 (en) * | 1982-10-29 | 1984-05-10 | London Hospital Med Coll | Cardio-respiratory monitor apparatus & method |
WO1993024142A1 (en) * | 1992-05-22 | 1993-12-09 | Phairson Medical Ab | New pharmaceutical uses of krill enzymes |
Also Published As
Publication number | Publication date |
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JPH10500991A (en) | 1998-01-27 |
EP0759764A1 (en) | 1997-03-05 |
AU7277994A (en) | 1996-01-04 |
WO1995033470A1 (en) | 1995-12-14 |
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Owner name: ANTARCTIC PHARMA AB Free format text: FORMER OWNER WAS: KRISTIAN HELLGREN, JAN VINCENT, VIGGO MOHR, LARS HELLGREN |