CN101495089B - 用于口用组合物的组合物及其制备和应用 - Google Patents
用于口用组合物的组合物及其制备和应用 Download PDFInfo
- Publication number
- CN101495089B CN101495089B CN200780027437.2A CN200780027437A CN101495089B CN 101495089 B CN101495089 B CN 101495089B CN 200780027437 A CN200780027437 A CN 200780027437A CN 101495089 B CN101495089 B CN 101495089B
- Authority
- CN
- China
- Prior art keywords
- composition
- composition according
- water
- bioflavonoid
- range
- 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.)
- Active
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 172
- 238000002360 preparation method Methods 0.000 title claims description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 58
- IKGXIBQEEMLURG-NVPNHPEKSA-N rutin Chemical compound O[C@@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@H](OC=2C(C3=C(O)C=C(O)C=C3OC=2C=2C=C(O)C(O)=CC=2)=O)O1 IKGXIBQEEMLURG-NVPNHPEKSA-N 0.000 claims abstract description 55
- 229920002385 Sodium hyaluronate Polymers 0.000 claims abstract description 23
- 229940010747 sodium hyaluronate Drugs 0.000 claims abstract description 23
- YWIVKILSMZOHHF-QJZPQSOGSA-N sodium;(2s,3s,4s,5r,6r)-6-[(2s,3r,4r,5s,6r)-3-acetamido-2-[(2s,3s,4r,5r,6r)-6-[(2r,3r,4r,5s,6r)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2- Chemical compound [Na+].CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 YWIVKILSMZOHHF-QJZPQSOGSA-N 0.000 claims abstract description 23
- 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 50
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 45
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 37
- 239000007788 liquid Substances 0.000 claims description 31
- 235000019441 ethanol Nutrition 0.000 claims description 23
- 241000894006 Bacteria Species 0.000 claims description 22
- 235000010323 ascorbic acid Nutrition 0.000 claims description 21
- 239000011668 ascorbic acid Substances 0.000 claims description 21
- 229960005070 ascorbic acid Drugs 0.000 claims description 21
- 244000005700 microbiome Species 0.000 claims description 21
- 239000003814 drug Substances 0.000 claims description 19
- 239000002028 Biomass Substances 0.000 claims description 18
- 239000003795 chemical substances by application Substances 0.000 claims description 17
- 239000000796 flavoring agent Substances 0.000 claims description 17
- 235000013355 food flavoring agent Nutrition 0.000 claims description 17
- 210000000214 mouth Anatomy 0.000 claims description 17
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 claims description 16
- 239000000606 toothpaste Substances 0.000 claims description 16
- 229940034610 toothpaste Drugs 0.000 claims description 16
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 claims description 15
- 235000015165 citric acid Nutrition 0.000 claims description 15
- 239000001630 malic acid Substances 0.000 claims description 15
- 235000011090 malic acid Nutrition 0.000 claims description 15
- DFPMSGMNTNDNHN-ZPHOTFPESA-N naringin Chemical compound O[C@@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@H]1O[C@H]1[C@H](OC=2C=C3O[C@@H](CC(=O)C3=C(O)C=2)C=2C=CC(O)=CC=2)O[C@H](CO)[C@@H](O)[C@@H]1O DFPMSGMNTNDNHN-ZPHOTFPESA-N 0.000 claims description 14
- ARGKVCXINMKCAZ-UHFFFAOYSA-N neohesperidine Natural products C1=C(O)C(OC)=CC=C1C1OC2=CC(OC3C(C(O)C(O)C(CO)O3)OC3C(C(O)C(O)C(C)O3)O)=CC(O)=C2C(=O)C1 ARGKVCXINMKCAZ-UHFFFAOYSA-N 0.000 claims description 13
- 229960001231 choline Drugs 0.000 claims description 12
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 claims description 11
- -1 neodiomin Natural products 0.000 claims description 11
- ARGKVCXINMKCAZ-UZRWAPQLSA-N neohesperidin Chemical compound C1=C(O)C(OC)=CC=C1[C@H]1OC2=CC(O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O3)O[C@H]3[C@@H]([C@H](O)[C@@H](O)[C@H](C)O3)O)=CC(O)=C2C(=O)C1 ARGKVCXINMKCAZ-UZRWAPQLSA-N 0.000 claims description 10
- QUQPHWDTPGMPEX-UTWYECKDSA-N aurantiamarin Natural products COc1ccc(cc1O)[C@H]1CC(=O)c2c(O)cc(O[C@@H]3O[C@H](CO[C@@H]4O[C@@H](C)[C@H](O)[C@@H](O)[C@H]4O)[C@@H](O)[C@H](O)[C@H]3O)cc2O1 QUQPHWDTPGMPEX-UTWYECKDSA-N 0.000 claims description 9
- 208000015181 infectious disease Diseases 0.000 claims description 8
- NLAWPKPYBMEWIR-SKYQDXIQSA-N (2S)-poncirin Chemical compound C1=CC(OC)=CC=C1[C@H]1OC2=CC(O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O3)O[C@H]3[C@@H]([C@H](O)[C@@H](O)[C@H](C)O3)O)=CC(O)=C2C(=O)C1 NLAWPKPYBMEWIR-SKYQDXIQSA-N 0.000 claims description 7
- FTVWIRXFELQLPI-ZDUSSCGKSA-N (S)-naringenin Chemical compound C1=CC(O)=CC=C1[C@H]1OC2=CC(O)=CC(O)=C2C(=O)C1 FTVWIRXFELQLPI-ZDUSSCGKSA-N 0.000 claims description 7
- 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 7
- NLAWPKPYBMEWIR-VGQRFNKBSA-N Poncirin Natural products O([C@H]1[C@@H](O)[C@H](O)[C@H](CO)O[C@H]1Oc1cc(O)c2C(=O)C[C@@H](c3ccc(OC)cc3)Oc2c1)[C@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@H](C)O1 NLAWPKPYBMEWIR-VGQRFNKBSA-N 0.000 claims description 7
- 241000194017 Streptococcus Species 0.000 claims description 7
- WGEYAGZBLYNDFV-UHFFFAOYSA-N naringenin Natural products C1(=O)C2=C(O)C=C(O)C=C2OC(C1)C1=CC=C(CC1)O WGEYAGZBLYNDFV-UHFFFAOYSA-N 0.000 claims description 7
- 235000007625 naringenin Nutrition 0.000 claims description 7
- 229940117954 naringenin Drugs 0.000 claims description 7
- 229910052708 sodium Inorganic materials 0.000 claims description 7
- 239000011734 sodium Substances 0.000 claims description 7
- 241000186044 Actinomyces viscosus Species 0.000 claims description 6
- 241000605862 Porphyromonas gingivalis Species 0.000 claims description 6
- 239000004909 Moisturizer Substances 0.000 claims description 5
- 241000194023 Streptococcus sanguinis Species 0.000 claims description 5
- RPMNUQRUHXIGHK-PYXJVEIZSA-N apigenin 7-O-neohesperidoside Chemical compound O[C@@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=C2C(=O)C=C(C=3C=CC(O)=CC=3)OC2=C1 RPMNUQRUHXIGHK-PYXJVEIZSA-N 0.000 claims description 5
- 229930034861 apigenin-7-O-neohesperidoside Natural products 0.000 claims description 5
- 229940093797 bioflavonoids Drugs 0.000 claims description 5
- 230000001333 moisturizer Effects 0.000 claims description 5
- RPMNUQRUHXIGHK-SBDOOABHSA-N rhoifolin Natural products O([C@@H]1[C@@H](O)[C@H](O)[C@H](CO)O[C@H]1Oc1cc(O)c2C(=O)C=C(c3ccc(O)cc3)Oc2c1)[C@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@H](C)O1 RPMNUQRUHXIGHK-SBDOOABHSA-N 0.000 claims description 5
- 241000186041 Actinomyces israelii Species 0.000 claims description 4
- 241000186045 Actinomyces naeslundii Species 0.000 claims description 4
- 241000222120 Candida <Saccharomycetales> Species 0.000 claims description 4
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 claims description 4
- 240000001046 Lactobacillus acidophilus Species 0.000 claims description 4
- 235000013956 Lactobacillus acidophilus Nutrition 0.000 claims description 4
- 239000008280 blood Substances 0.000 claims description 4
- 210000004369 blood Anatomy 0.000 claims description 4
- 235000003599 food sweetener Nutrition 0.000 claims description 4
- 229940039695 lactobacillus acidophilus Drugs 0.000 claims description 4
- NOOLISFMXDJSKH-UHFFFAOYSA-N p-menthan-3-ol Chemical compound CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 claims description 4
- 239000003765 sweetening agent Substances 0.000 claims description 4
- 239000002562 thickening agent Substances 0.000 claims description 4
- 241000222122 Candida albicans Species 0.000 claims description 3
- 241000203719 Rothia dentocariosa Species 0.000 claims description 3
- 239000011230 binding agent Substances 0.000 claims description 3
- 229940095731 candida albicans Drugs 0.000 claims description 3
- 238000000605 extraction Methods 0.000 claims description 3
- 208000007565 gingivitis Diseases 0.000 claims description 3
- 229930182470 glycoside Natural products 0.000 claims description 3
- 238000000227 grinding Methods 0.000 claims description 3
- 239000000049 pigment Substances 0.000 claims description 3
- 239000004094 surface-active agent Substances 0.000 claims description 3
- 241000186066 Actinomyces odontolyticus Species 0.000 claims description 2
- 206010001889 Alveolitis Diseases 0.000 claims description 2
- 241000193830 Bacillus <bacterium> Species 0.000 claims description 2
- 244000276331 Citrus maxima Species 0.000 claims description 2
- 235000001759 Citrus maxima Nutrition 0.000 claims description 2
- 208000007027 Oral Candidiasis Diseases 0.000 claims description 2
- 241001135217 Prevotella buccae Species 0.000 claims description 2
- 241000509620 Prevotella dentalis Species 0.000 claims description 2
- 241001135221 Prevotella intermedia Species 0.000 claims description 2
- 241000194026 Streptococcus gordonii Species 0.000 claims description 2
- 241000194019 Streptococcus mutans Species 0.000 claims description 2
- 241000194025 Streptococcus oralis Species 0.000 claims description 2
- 241000193987 Streptococcus sobrinus Species 0.000 claims description 2
- 241001494431 [Eubacterium] nodatum Species 0.000 claims description 2
- 208000002399 aphthous stomatitis Diseases 0.000 claims description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 2
- 201000001155 extrinsic allergic alveolitis Diseases 0.000 claims description 2
- 150000002338 glycosides Chemical class 0.000 claims description 2
- 208000022098 hypersensitivity pneumonitis Diseases 0.000 claims description 2
- 201000011486 lichen planus Diseases 0.000 claims description 2
- 201000009240 nasopharyngitis Diseases 0.000 claims description 2
- 201000001245 periodontitis Diseases 0.000 claims description 2
- 239000003124 biologic agent Substances 0.000 claims 1
- 230000002906 microbiologic effect Effects 0.000 claims 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 abstract description 10
- 239000011975 tartaric acid Substances 0.000 abstract description 10
- 235000002906 tartaric acid Nutrition 0.000 abstract description 10
- 150000003839 salts Chemical class 0.000 abstract description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 64
- 239000004615 ingredient Substances 0.000 description 32
- 229930003935 flavonoid Natural products 0.000 description 23
- 150000002215 flavonoids Chemical class 0.000 description 23
- 235000017173 flavonoids Nutrition 0.000 description 23
- 235000011187 glycerol Nutrition 0.000 description 22
- 239000000243 solution Substances 0.000 description 21
- 238000000034 method Methods 0.000 description 16
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 14
- 229920002674 hyaluronan Polymers 0.000 description 14
- 229960003160 hyaluronic acid Drugs 0.000 description 14
- 238000003756 stirring Methods 0.000 description 11
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 10
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 10
- 239000006184 cosolvent Substances 0.000 description 10
- 230000012010 growth Effects 0.000 description 10
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 10
- PUZPDOWCWNUUKD-UHFFFAOYSA-M sodium fluoride Chemical compound [F-].[Na+] PUZPDOWCWNUUKD-UHFFFAOYSA-M 0.000 description 10
- 239000002904 solvent Substances 0.000 description 10
- 235000010447 xylitol Nutrition 0.000 description 10
- 239000000811 xylitol Substances 0.000 description 10
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 10
- 229960002675 xylitol Drugs 0.000 description 10
- FSJVVVCZSRCTBM-RXSVEWSESA-N (2S)-2-[(2R)-3,4-dihydroxy-5-oxo-2H-furan-2-yl]-2-hydroxyethanolate 2-hydroxyethyl(trimethyl)azanium Chemical compound C[N+](C)(C)CCO.O[C@@H](C[O-])[C@H]1OC(=O)C(O)=C1O FSJVVVCZSRCTBM-RXSVEWSESA-N 0.000 description 9
- FTLYMKDSHNWQKD-UHFFFAOYSA-N (2,4,5-trichlorophenyl)boronic acid Chemical compound OB(O)C1=CC(Cl)=C(Cl)C=C1Cl FTLYMKDSHNWQKD-UHFFFAOYSA-N 0.000 description 8
- 229910019142 PO4 Inorganic materials 0.000 description 8
- 229920001213 Polysorbate 20 Polymers 0.000 description 8
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical group [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 8
- 239000000546 pharmaceutical excipient Substances 0.000 description 8
- 239000010452 phosphate Substances 0.000 description 8
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 8
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 8
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 8
- 229940068977 polysorbate 20 Drugs 0.000 description 8
- 229940085605 saccharin sodium Drugs 0.000 description 8
- 239000007858 starting material Substances 0.000 description 8
- 230000000844 anti-bacterial effect Effects 0.000 description 7
- 229960001927 cetylpyridinium chloride Drugs 0.000 description 7
- YMKDRGPMQRFJGP-UHFFFAOYSA-M cetylpyridinium chloride Chemical compound [Cl-].CCCCCCCCCCCCCCCC[N+]1=CC=CC=C1 YMKDRGPMQRFJGP-UHFFFAOYSA-M 0.000 description 7
- 235000020971 citrus fruits Nutrition 0.000 description 7
- 238000002156 mixing Methods 0.000 description 7
- 241000207199 Citrus Species 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 159000000000 sodium salts Chemical class 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 5
- 235000013024 sodium fluoride Nutrition 0.000 description 5
- 239000011775 sodium fluoride Substances 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 239000001100 (2S)-5,7-dihydroxy-2-(3-hydroxy-4-methoxyphenyl)chroman-4-one Substances 0.000 description 4
- KIZQNNOULOCVDM-UHFFFAOYSA-M 2-hydroxyethyl(trimethyl)azanium;hydroxide Chemical compound [OH-].C[N+](C)(C)CCO KIZQNNOULOCVDM-UHFFFAOYSA-M 0.000 description 4
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 4
- 229930003268 Vitamin C Natural products 0.000 description 4
- RTIXKCRFFJGDFG-UHFFFAOYSA-N chrysin Chemical compound C=1C(O)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=CC=C1 RTIXKCRFFJGDFG-UHFFFAOYSA-N 0.000 description 4
- 239000003086 colorant Substances 0.000 description 4
- 235000013399 edible fruits Nutrition 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 229930003944 flavone Natural products 0.000 description 4
- 235000011949 flavones Nutrition 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- 230000000813 microbial effect Effects 0.000 description 4
- 239000003755 preservative agent Substances 0.000 description 4
- 230000002335 preservative effect Effects 0.000 description 4
- 235000019154 vitamin C Nutrition 0.000 description 4
- 239000011718 vitamin C Substances 0.000 description 4
- QUQPHWDTPGMPEX-UHFFFAOYSA-N Hesperidine Natural products C1=C(O)C(OC)=CC=C1C1OC2=CC(OC3C(C(O)C(O)C(COC4C(C(O)C(O)C(C)O4)O)O3)O)=CC(O)=C2C(=O)C1 QUQPHWDTPGMPEX-UHFFFAOYSA-N 0.000 description 3
- 244000246386 Mentha pulegium Species 0.000 description 3
- 235000016257 Mentha pulegium Nutrition 0.000 description 3
- 235000004357 Mentha x piperita Nutrition 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 241000222126 [Candida] glabrata Species 0.000 description 3
- 238000005054 agglomeration Methods 0.000 description 3
- 230000002776 aggregation Effects 0.000 description 3
- 239000003513 alkali Substances 0.000 description 3
- 229910052783 alkali metal Inorganic materials 0.000 description 3
- 208000032343 candida glabrata infection Diseases 0.000 description 3
- APSNPMVGBGZYAJ-GLOOOPAXSA-N clematine Natural products COc1cc(ccc1O)[C@@H]2CC(=O)c3c(O)cc(O[C@@H]4O[C@H](CO[C@H]5O[C@@H](C)[C@H](O)[C@@H](O)[C@H]5O)[C@@H](O)[C@H](O)[C@H]4O)cc3O2 APSNPMVGBGZYAJ-GLOOOPAXSA-N 0.000 description 3
- 210000002808 connective tissue Anatomy 0.000 description 3
- 238000010790 dilution Methods 0.000 description 3
- 239000012895 dilution Substances 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 150000002213 flavones Chemical class 0.000 description 3
- 229940091249 fluoride supplement Drugs 0.000 description 3
- 229930182478 glucoside Natural products 0.000 description 3
- 150000008131 glucosides Chemical class 0.000 description 3
- 239000001963 growth medium Substances 0.000 description 3
- QUQPHWDTPGMPEX-QJBIFVCTSA-N hesperidin Chemical compound C1=C(O)C(OC)=CC=C1[C@H]1OC2=CC(O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@@H](CO[C@H]4[C@@H]([C@H](O)[C@@H](O)[C@H](C)O4)O)O3)O)=CC(O)=C2C(=O)C1 QUQPHWDTPGMPEX-QJBIFVCTSA-N 0.000 description 3
- 229940025878 hesperidin Drugs 0.000 description 3
- VUYDGVRIQRPHFX-UHFFFAOYSA-N hesperidin Natural products COc1cc(ccc1O)C2CC(=O)c3c(O)cc(OC4OC(COC5OC(O)C(O)C(O)C5O)C(O)C(O)C4O)cc3O2 VUYDGVRIQRPHFX-UHFFFAOYSA-N 0.000 description 3
- 235000001050 hortel pimenta Nutrition 0.000 description 3
- 239000006101 laboratory sample Substances 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000008194 pharmaceutical composition Substances 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 241000894007 species Species 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 239000004408 titanium dioxide Substances 0.000 description 3
- 241001148471 unidentified anaerobic bacterium Species 0.000 description 3
- NOOLISFMXDJSKH-UTLUCORTSA-N (+)-Neomenthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@@H]1O NOOLISFMXDJSKH-UTLUCORTSA-N 0.000 description 2
- HMBHAQMOBKLWRX-UHFFFAOYSA-N 2,3-dihydro-1,4-benzodioxine-3-carboxylic acid Chemical compound C1=CC=C2OC(C(=O)O)COC2=C1 HMBHAQMOBKLWRX-UHFFFAOYSA-N 0.000 description 2
- NYCXYKOXLNBYID-UHFFFAOYSA-N 5,7-Dihydroxychromone Natural products O1C=CC(=O)C=2C1=CC(O)=CC=2O NYCXYKOXLNBYID-UHFFFAOYSA-N 0.000 description 2
- RTMBGDBBDQKNNZ-UHFFFAOYSA-L C.I. Acid Blue 3 Chemical compound [Ca+2].C1=CC(N(CC)CC)=CC=C1C(C=1C(=CC(=C(O)C=1)S([O-])(=O)=O)S([O-])(=O)=O)=C1C=CC(=[N+](CC)CC)C=C1.C1=CC(N(CC)CC)=CC=C1C(C=1C(=CC(=C(O)C=1)S([O-])(=O)=O)S([O-])(=O)=O)=C1C=CC(=[N+](CC)CC)C=C1 RTMBGDBBDQKNNZ-UHFFFAOYSA-L 0.000 description 2
- 241000222173 Candida parapsilosis Species 0.000 description 2
- 241000222178 Candida tropicalis Species 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 244000037364 Cinnamomum aromaticum Species 0.000 description 2
- 235000014489 Cinnamomum aromaticum Nutrition 0.000 description 2
- 244000183685 Citrus aurantium Species 0.000 description 2
- 235000007716 Citrus aurantium Nutrition 0.000 description 2
- 235000005976 Citrus sinensis Nutrition 0.000 description 2
- 241000193163 Clostridioides difficile Species 0.000 description 2
- OJIYIVCMRYCWSE-UHFFFAOYSA-M Domiphen bromide Chemical compound [Br-].CCCCCCCCCCCC[N+](C)(C)CCOC1=CC=CC=C1 OJIYIVCMRYCWSE-UHFFFAOYSA-M 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- 244000004281 Eucalyptus maculata Species 0.000 description 2
- 244000024873 Mentha crispa Species 0.000 description 2
- 235000014749 Mentha crispa Nutrition 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 241000235645 Pichia kudriavzevii Species 0.000 description 2
- ZONYXWQDUYMKFB-UHFFFAOYSA-N SJ000286395 Natural products O1C2=CC=CC=C2C(=O)CC1C1=CC=CC=C1 ZONYXWQDUYMKFB-UHFFFAOYSA-N 0.000 description 2
- 229910004298 SiO 2 Inorganic materials 0.000 description 2
- 208000025865 Ulcer Diseases 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 150000001340 alkali metals Chemical class 0.000 description 2
- 230000000845 anti-microbial effect Effects 0.000 description 2
- 230000000840 anti-viral effect Effects 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 229960003237 betaine Drugs 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 229940055022 candida parapsilosis Drugs 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 229940075419 choline hydroxide Drugs 0.000 description 2
- 235000015838 chrysin Nutrition 0.000 description 2
- 229940043370 chrysin Drugs 0.000 description 2
- 239000000084 colloidal system Substances 0.000 description 2
- 230000000295 complement effect Effects 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 239000000470 constituent Substances 0.000 description 2
- 239000002537 cosmetic Substances 0.000 description 2
- 239000000551 dentifrice Substances 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 229960001859 domiphen bromide Drugs 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 229930003949 flavanone Natural products 0.000 description 2
- 150000002207 flavanone derivatives Chemical class 0.000 description 2
- 235000011981 flavanones Nutrition 0.000 description 2
- HVQAJTFOCKOKIN-UHFFFAOYSA-N flavonol Natural products O1C2=CC=CC=C2C(=O)C(O)=C1C1=CC=CC=C1 HVQAJTFOCKOKIN-UHFFFAOYSA-N 0.000 description 2
- 150000002216 flavonol derivatives Chemical class 0.000 description 2
- 235000011957 flavonols Nutrition 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- KWIUHFFTVRNATP-UHFFFAOYSA-N glycine betaine Chemical compound C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 description 2
- GPRLSGONYQIRFK-UHFFFAOYSA-N hydron Chemical compound [H+] GPRLSGONYQIRFK-UHFFFAOYSA-N 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 239000006210 lotion Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 229940041616 menthol Drugs 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 238000004806 packaging method and process Methods 0.000 description 2
- 239000001814 pectin Substances 0.000 description 2
- 235000010987 pectin Nutrition 0.000 description 2
- 229920001277 pectin Polymers 0.000 description 2
- 239000004033 plastic Substances 0.000 description 2
- 229920003023 plastic Polymers 0.000 description 2
- 230000000717 retained effect Effects 0.000 description 2
- 229940081974 saccharin Drugs 0.000 description 2
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 2
- 235000019204 saccharin Nutrition 0.000 description 2
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 2
- 208000003265 stomatitis Diseases 0.000 description 2
- 239000004575 stone Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 230000002195 synergetic effect Effects 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 231100000397 ulcer Toxicity 0.000 description 2
- 239000000230 xanthan gum Substances 0.000 description 2
- 229920001285 xanthan gum Polymers 0.000 description 2
- 235000010493 xanthan gum Nutrition 0.000 description 2
- 229940082509 xanthan gum Drugs 0.000 description 2
- GDSOZVZXVXTJMI-SNAWJCMRSA-N (e)-1-methylbut-1-ene-1,2,4-tricarboxylic acid Chemical compound OC(=O)C(/C)=C(C(O)=O)\CCC(O)=O GDSOZVZXVXTJMI-SNAWJCMRSA-N 0.000 description 1
- ZZJFIXMCLZTHQV-UHFFFAOYSA-O 2-carboxyoxyethyl(trimethyl)azanium Chemical compound C[N+](C)(C)CCOC(O)=O ZZJFIXMCLZTHQV-UHFFFAOYSA-O 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
- 208000002874 Acne Vulgaris Diseases 0.000 description 1
- 241000186046 Actinomyces Species 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 208000010266 Aggressive Periodontitis Diseases 0.000 description 1
- 108700023418 Amidases Proteins 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 241000144583 Candida dubliniensis Species 0.000 description 1
- 206010007134 Candida infections Diseases 0.000 description 1
- 235000008534 Capsicum annuum var annuum Nutrition 0.000 description 1
- 240000008384 Capsicum annuum var. annuum Species 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 241000561734 Celosia cristata Species 0.000 description 1
- 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 1
- 241000206575 Chondrus crispus Species 0.000 description 1
- 244000223760 Cinnamomum zeylanicum Species 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- HMEKVHWROSNWPD-UHFFFAOYSA-N Erioglaucine A Chemical compound [NH4+].[NH4+].C=1C=C(C(=C2C=CC(C=C2)=[N+](CC)CC=2C=C(C=CC=2)S([O-])(=O)=O)C=2C(=CC=CC=2)S([O-])(=O)=O)C=CC=1N(CC)CC1=CC=CC(S([O-])(=O)=O)=C1 HMEKVHWROSNWPD-UHFFFAOYSA-N 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 1
- 240000006927 Foeniculum vulgare Species 0.000 description 1
- 235000004204 Foeniculum vulgare Nutrition 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 206010018785 Gingival infections Diseases 0.000 description 1
- 229920002683 Glycosaminoglycan Polymers 0.000 description 1
- 108010003272 Hyaluronate lyase Proteins 0.000 description 1
- 102000001974 Hyaluronidases Human genes 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 240000009023 Myrrhis odorata Species 0.000 description 1
- 235000007265 Myrrhis odorata Nutrition 0.000 description 1
- 235000012550 Pimpinella anisum Nutrition 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 241000605894 Porphyromonas Species 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 241000235342 Saccharomycetes Species 0.000 description 1
- 241000607142 Salmonella Species 0.000 description 1
- FKNQFGJONOIPTF-UHFFFAOYSA-N Sodium cation Chemical compound [Na+] FKNQFGJONOIPTF-UHFFFAOYSA-N 0.000 description 1
- GAMYVSCDDLXAQW-AOIWZFSPSA-N Thermopsosid Natural products O(C)c1c(O)ccc(C=2Oc3c(c(O)cc(O[C@H]4[C@H](O)[C@@H](O)[C@H](O)[C@H](CO)O4)c3)C(=O)C=2)c1 GAMYVSCDDLXAQW-AOIWZFSPSA-N 0.000 description 1
- 241000287411 Turdidae Species 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 239000004234 Yellow 2G Substances 0.000 description 1
- 230000001133 acceleration Effects 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 206010000496 acne Diseases 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 241001148470 aerobic bacillus Species 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 102000005922 amidase Human genes 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000675 anti-caries Effects 0.000 description 1
- 210000001742 aqueous humor Anatomy 0.000 description 1
- 239000008122 artificial sweetener Substances 0.000 description 1
- 235000021311 artificial sweeteners Nutrition 0.000 description 1
- 230000003143 atherosclerotic effect Effects 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000006161 blood agar Substances 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 230000003139 buffering effect Effects 0.000 description 1
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
- 201000003984 candidiasis Diseases 0.000 description 1
- YKPUWZUDDOIDPM-SOFGYWHQSA-N capsaicin Chemical compound COC1=CC(CNC(=O)CCCC\C=C\C(C)C)=CC=C1O YKPUWZUDDOIDPM-SOFGYWHQSA-N 0.000 description 1
- 229960002504 capsaicin Drugs 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 229960003260 chlorhexidine Drugs 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- 235000017803 cinnamon Nutrition 0.000 description 1
- MRUAUOIMASANKQ-UHFFFAOYSA-N cocamidopropyl betaine Chemical compound CCCCCCCCCCCC(=O)NCCC[N+](C)(C)CC([O-])=O MRUAUOIMASANKQ-UHFFFAOYSA-N 0.000 description 1
- 229940075614 colloidal silicon dioxide Drugs 0.000 description 1
- 210000001520 comb Anatomy 0.000 description 1
- 239000013068 control sample Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 235000019700 dicalcium phosphate Nutrition 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- FTZLWXQKVFFWLY-UHFFFAOYSA-L disodium;2,5-dichloro-4-[3-methyl-5-oxo-4-[(4-sulfonatophenyl)diazenyl]-4h-pyrazol-1-yl]benzenesulfonate Chemical compound [Na+].[Na+].CC1=NN(C=2C(=CC(=C(Cl)C=2)S([O-])(=O)=O)Cl)C(=O)C1N=NC1=CC=C(S([O-])(=O)=O)C=C1 FTZLWXQKVFFWLY-UHFFFAOYSA-L 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 230000003028 elevating effect Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 239000003797 essential amino acid Substances 0.000 description 1
- 235000020776 essential amino acid Nutrition 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 239000003337 fertilizer Substances 0.000 description 1
- 239000011094 fiberboard Substances 0.000 description 1
- 150000002212 flavone derivatives Chemical class 0.000 description 1
- 238000003682 fluorination reaction Methods 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 235000021022 fresh fruits Nutrition 0.000 description 1
- UPBDXRPQPOWRKR-UHFFFAOYSA-N furan-2,5-dione;methoxyethene Chemical compound COC=C.O=C1OC(=O)C=C1 UPBDXRPQPOWRKR-UHFFFAOYSA-N 0.000 description 1
- 210000000232 gallbladder Anatomy 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 230000009036 growth inhibition Effects 0.000 description 1
- 239000008233 hard water Substances 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- AIONOLUJZLIMTK-AWEZNQCLSA-N hesperetin Chemical compound C1=C(O)C(OC)=CC=C1[C@H]1OC2=CC(O)=CC(O)=C2C(=O)C1 AIONOLUJZLIMTK-AWEZNQCLSA-N 0.000 description 1
- AIONOLUJZLIMTK-UHFFFAOYSA-N hesperetin Natural products C1=C(O)C(OC)=CC=C1C1OC2=CC(O)=CC(O)=C2C(=O)C1 AIONOLUJZLIMTK-UHFFFAOYSA-N 0.000 description 1
- 235000010209 hesperetin Nutrition 0.000 description 1
- 229960001587 hesperetin Drugs 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- FTODBIPDTXRIGS-UHFFFAOYSA-N homoeriodictyol Natural products C1=C(O)C(OC)=CC(C2OC3=CC(O)=CC(O)=C3C(=O)C2)=C1 FTODBIPDTXRIGS-UHFFFAOYSA-N 0.000 description 1
- 229960002773 hyaluronidase Drugs 0.000 description 1
- DQKGOGJIOHUEGK-UHFFFAOYSA-M hydron;2-hydroxyethyl(trimethyl)azanium;carbonate Chemical compound OC([O-])=O.C[N+](C)(C)CCO DQKGOGJIOHUEGK-UHFFFAOYSA-M 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 238000007654 immersion Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 239000002917 insecticide Substances 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 239000002075 main ingredient Substances 0.000 description 1
- 229940049920 malate Drugs 0.000 description 1
- 239000000845 maltitol Substances 0.000 description 1
- 235000010449 maltitol Nutrition 0.000 description 1
- VQHSOMBJVWLPSR-WUJBLJFYSA-N maltitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-WUJBLJFYSA-N 0.000 description 1
- 229940035436 maltitol Drugs 0.000 description 1
- 235000012054 meals Nutrition 0.000 description 1
- 235000013372 meat Nutrition 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
- 208000030194 mouth disease Diseases 0.000 description 1
- 235000021096 natural sweeteners Nutrition 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 230000000474 nursing effect Effects 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000003973 paint Substances 0.000 description 1
- 239000000123 paper Substances 0.000 description 1
- 239000004177 patent blue V Substances 0.000 description 1
- 235000012736 patent blue V Nutrition 0.000 description 1
- 208000028169 periodontal disease Diseases 0.000 description 1
- 201000006727 periodontosis Diseases 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 231100000572 poisoning Toxicity 0.000 description 1
- 230000000607 poisoning effect Effects 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 125000001453 quaternary ammonium group Chemical group 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000009738 saturating Methods 0.000 description 1
- 210000000697 sensory organ Anatomy 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- 239000002893 slag Substances 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 229910001415 sodium ion Inorganic materials 0.000 description 1
- 229960004711 sodium monofluorophosphate Drugs 0.000 description 1
- 238000002798 spectrophotometry method Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000001040 synthetic pigment Substances 0.000 description 1
- 150000003505 terpenes Chemical class 0.000 description 1
- 230000017423 tissue regeneration Effects 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 210000003954 umbilical cord Anatomy 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- VHBFFQKBGNRLFZ-UHFFFAOYSA-N vitamin p Natural products O1C2=CC=CC=C2C(=O)C=C1C1=CC=CC=C1 VHBFFQKBGNRLFZ-UHFFFAOYSA-N 0.000 description 1
- 235000019235 yellow 2G Nutrition 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
- A61K8/73—Polysaccharides
- A61K8/735—Mucopolysaccharides, e.g. hyaluronic acid; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/35—Ketones, e.g. benzophenone
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/194—Carboxylic acids, e.g. valproic acid having two or more carboxyl groups, e.g. succinic, maleic or phthalic acid
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/726—Glycosaminoglycans, i.e. mucopolysaccharides
- A61K31/728—Hyaluronic acid
-
- 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)
- A61K36/75—Rutaceae (Rue family)
- A61K36/752—Citrus, e.g. lime, orange or lemon
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/36—Carboxylic acids; Salts or anhydrides thereof
- A61K8/362—Polycarboxylic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/36—Carboxylic acids; Salts or anhydrides thereof
- A61K8/365—Hydroxycarboxylic acids; Ketocarboxylic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
- A61K8/41—Amines
- A61K8/416—Quaternary ammonium compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/4973—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom
- A61K8/498—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom having 6-membered rings or their condensed derivatives, e.g. coumarin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/60—Sugars; Derivatives thereof
- A61K8/602—Glycosides, e.g. rutin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/67—Vitamins
- A61K8/676—Ascorbic acid, i.e. vitamin C
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
- A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
- A61K8/9783—Angiosperms [Magnoliophyta]
- A61K8/9789—Magnoliopsida [dicotyledons]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0014—Skin, i.e. galenical aspects of topical compositions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
-
- 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
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Birds (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Emergency Medicine (AREA)
- Dermatology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Mycology (AREA)
- Microbiology (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Botany (AREA)
- Biotechnology (AREA)
- Molecular Biology (AREA)
- Alternative & Traditional Medicine (AREA)
- Medical Informatics (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Nutrition Science (AREA)
- Physiology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Cosmetics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
一种组合物,pH范围为3至8.5,其包含:(a)范围为0.1%至<10%w/w的原液(基于该组合物的总重量),所述原液包含生物类黄酮混合物和果酸或其盐;(b)透明质酸钠;和(c)水;以及任选的(d)制药学上可接受的所用载体;其中所述透明质酸钠的平均分子量为800,000~4,000,000。
Description
技术领域
本发明涉及用于制备如霜剂、凝胶、牙膏、洗口药水或牙科漱剂之类的组合物的含类黄酮组合物,该含类黄酮组合物包括高分子量透明质酸的钠盐。特别地,涉及一种包含与高分子量透明质酸的钠盐组合的抗菌生物类黄酮原液的组合物,优选为口用组合物,及其制备和应用。
背景技术
人们已知某些包含类黄酮的组合物,该类黄酮具有抗微生物活性,特别是抗细菌活性,尤其是抗病毒活性。然而,术语“类黄酮”涵盖了大量的各种不同化合物,这些化合物可从各种自然来源提取而制得。根据提取的来源和性质或方法的不同,所得类黄酮混合物的总的化学成分可能相差甚大。就毒性和抗微生物如抗病毒和抗细菌的效力而言,各种类黄酮的生物活性可能有很大不同(或无活性)。因此,组合起来,这样的类黄酮在其生物活性上也可能各不相同。
人们发现,通过往所述类黄酮组合物中添加其他作用剂,可以与类黄酮的某些组合的生物活性起协同作用、或者增强或促进类黄酮的某些组合的生物活性。因此,人们一直致力于寻找类黄酮的适当组合,通过添加或不添加其他的作用剂,使之具有理想的抵抗某些微生物的效力,而又不会在应用中伴随中毒或其他不良影响发生。这种组合的一个实例可在一种橙提取物组合物中发现,这种橙提取物就是大家知道的生物类黄酮和如维生素C之类的天然果酸,其在氧禽业中用于杀灭跟食物有关的微生物,如大肠杆菌及沙门氏菌。
然而,直到本发明之前,都未见有人提出过将橙源性生物类黄酮/果酸组合物用于个人卫生用,如口用制剂。特别是,这些已知的组合物对于口用来说会太酸。此外,虽然有人建议,将类黄酮用于诸如牙膏和洗口药水这样的组合物,但是,谁也没有特别指明其类黄酮成分,和/或限定具体的类黄酮。例如,专利说明书WO 02/47615公开了一种口用组合物,包含感官上适合的载体和分散在载体中的类萜和/或类黄酮;DE19949575公开了一种用于治疗牙病和预防龋齿的氟化物和类黄酮的组合物;以及JP62051613涉及一种牙膏组合物,含有0.001~0.1wt%的选自黄酮醇、白杨素、橙皮素和橙皮苷类黄酮化合物。没有哪个在先技术的配方公开过一种生物类黄酮(其本身包含一种水溶性类黄酮的具体组合)与一种或多种水溶性果酸的组合物,该组合物在数量和形式上都适合以溶液口用、并具有抗菌活性。
从严格的生物化学和生理学这两者的观点来看,透明质酸是结缔组织基本物质中最重要的粘多糖。在人体中,透明质酸不仅存在于结缔组织还存在于重要的生物流体中,例如玻璃状体、水状体等,还存在于脐带中。它实际上没有毒性,也未发现对于人使用的特别禁忌征候。
与其它天然物质的组分一样的情况,透明质酸可从相对天然的物质提取得到,例如,它可从鸡冠提取,或可用生物技术生产。透明质酸具有非常宽的分子量范围,根据生产工艺的不同,分子量可以从30,000至超过15,000,000变化。有时,透明质酸还能以钠盐形式用于人的治疗和化妆处理。
在这方面,透明质酸的外部施用在改善结缔组织方面具有有利的效果,且能对抗由透明质酸酶生成菌引起的发炎过程;它有利于引起炎症的成分的分解,减低反常的毛细渗透,加速组织修复过程,并且它通过代谢性将游离水结合至它的分子结构,而进行抗水肿形成行为。透明质酸的治疗适应症很多,包括摩擦脱屑皮肤病,由动脉硬化血管病变、曲张性溃疡、结瘢延迟和外科切除引起的溃疡。
EP0444492A1中可知,分子量为800,000~4,000,000,优选为1,000,000~2,000,000的钠盐形式的透明质酸在药物组合物的制备中可用作活性成分,所述药物组合物用于治疗和预防口腔炎性感染的局部施用,并用于化妆处理和口腔卫生。
制备包括透明质酸和其它抗菌剂例如氯己定的制剂,具体是口腔制剂,的努力已经失败,这是因为所得到的制剂不稳定。在有些组合物中,需使用醇以制备制剂,通常不希望这样。盐形式的透明质酸与类黄酮的组合物可配制成局部用,优选是口用,且具体地,该组合物无需醇。不希望受任何具体理论的束缚,类黄酮混合物被认为可杀死细菌和病毒为透明质酸创造理想的环境,以提高和促进粘性或其它发炎组织的愈合速率。有利的是,所有配料来自天然,且在制备时没有使用危害性或合成的化学品。
发明内容
因此,本发明提供一种组合物,其pH范围为3至8.5,以3.5至8为佳,4至7更佳,5至6.5还更佳,包含:
(a)基于组合物的总重量,范围为0.1%至<10%w/w的原液,所述原液包含生物类黄酮的混合物和果酸或其盐;
(b)透明质酸纳;和
(c)水;以及任选的
(d)制药学上可接受的载体;
其中所述透明质酸钠的平均分子量为800,000~4,000,000,
且其自身可包含在制药学上或药理学上可接受的适合于口用的另一或其它配料。
优选地,透明质酸纳的分子量为800,000~4,000,000,最好为1,000,000~2,000,000,例如1,500,000。本发明的组合物通常包含所述组合物总重量的0.005至10%的所述透明质酸钠。
用于治疗用途的本发明组合物通常含有所述组合物总重量的0.2至10%w/w的透明质酸钠,优选为0.2至1%w/w的透明质酸钠,例如0.4、0.6或0.8%。
口腔疾病预防、化妆和护理用途的本发明组合物包含所述口用组合物总重量的0.005至0.1%w/w的透明质酸钠,例如0.01、0.02或0.08%,最好包含0.1%w/w的透明质酸钠。
所述组合物,以包含范围为0.1至5%w/w的原液为佳,0.1至2%w/w更佳,例如约为1%。所述组合物以包含范围为20至80%w/w的水为佳,该范围的低端适合于牙膏的情况,该范围的高端适合于液体组合物,如洗/冲/喷口药水的情况。例如,牙膏可以包含范围为20至45%w/w的水,例如20至30%w/w,特别是在组分(d)中如果包含二氧化硅的情况下;液体配方可以包含范围为60至80%w/w水(所有w/w,均基于组合物的总重量)。
特别首选的是当所述原液可从水溶性生物类黄酮与果酸,如柠檬酸、苹果酸和抗坏血酸组合来制备的时候。一种或多种酸,最好用合适的碱,如季铵碱来中和,例如胆碱,如胆碱碳酸盐、胆碱碳酸氢盐,或者,优选为氢氧化物。当柠檬酸、苹果酸和抗坏血酸都用于制备所述组合物时还更好,尤其是当它们被完全中和以形成柠檬酸盐、苹果酸盐和/或抗坏血酸盐的时候最好。特别首选的是胆碱抗坏血酸盐。因此,首选的是所述原液基本没有果酸,这就意味着其pH在中性范围内。作为示例,原液的pH范围为3至8.5、3.5至8.5、3.5至8、4至8、4至7.5、4.5至7.5、4.5至7、5至7、5至6.5、5.5至6.5和5.5至6,例如,pH为约5、约5.5、约6、约6.5或约7。
具体实施方式
本发明人不想受任何具体理论的约束,认为,所述果酸既对硬水具有螯合效应,还与活性剂的生物活性起协同作用,例如,生物类黄酮和胆碱抗坏血酸盐。因此,优选的原液包含水溶性生物类黄酮和胆碱抗坏血酸盐(以胆碱(如氢氧化物)和抗坏血酸形式,或以其本身的盐形式存在)。
优选地,所述原液还包含无毒性溶剂,例如易与水混合的或亲水的溶剂,且更优选地,包含水和易与水混合的助溶剂,如甘油、多元醇等。所述溶剂尤以包含水/甘油混合物为佳,其混合比例以2∶1~1∶2(水∶助溶剂)为佳。更优选地,组分(c)和(d)(余量包含水、一种或多种助溶剂和赋形剂和/或载体)是不含醇,具体地不含乙醇。
因此,所述原液,最好从下表所列配料制备:
配料 | %(w/w)在原液中的配料 |
生物类黄酮混合物(生物质45%) | 1~20,以2至15为佳,3至15更佳,如3,4或15,最佳为3.3 |
柠檬酸 | 1~20,以4至15为佳,如4,5,10或15,最佳为4.5 |
苹果酸 | 1~20,以4至15为佳,如4,5,10或15,最佳为4.5 |
抗坏血酸(维生素C)<sup>*</sup> | 1~20,以1至5为佳<sup>*</sup>,如1,2,3,4,或5,最佳为1.5 |
氢氧化胆碱溶液(45%的水溶液)<sup>*</sup> | 1~45,以4至20为佳<sup>*</sup>,如5,8,10,12,15或18. |
甘油/水或其他溶剂 | 余量,补足至100%,以5至50为佳<sup>*</sup>,如7,10或15,最佳为7.5 |
*抗坏血酸和氢氧化胆碱(或其他胆碱)可用胆碱抗坏血酸盐替代,并同时适当增加甘油和水(或替代溶剂)的量。首选的是,溶剂包含大约等百分比的甘油和水两者,如各5至25%,如15%的甘油和20%的水(当胆碱是以氢氧化溶液存在时),或如25%的甘油和25%的水(当胆碱和抗坏血酸以5%胆碱抗坏血酸盐存在时)。
因此,优选地,本发明的组合物如以下所述制备(基于组合物的重量):
(a)(i)范围为0.0002~1.5%w/w的生物类黄酮[不包括生物质,以另贡献0.00024~1.83%w/w为宜];
(ii)范围为0.001~2.0%w/w的柠檬酸;
(iii)范围为0.001~2.0%w/w的苹果酸;
(iv)范围为0.001~2.0%w/w的抗坏血酸;
(v)范围为0.00045~2.03%w/w的胆碱;和
(b)、(c)和(d)余量,包含水、一种或多种助溶剂和赋形剂和/或载体。
更优选地,本发明的组合物按如下所述制备(基于组合物的重量):
(a)(i)范围为0.00045~0.9%w/w的生物类黄酮[不包括生物质,以另贡献0.00055~1.1%w/w为宜];
(ii)范围为0.001~2.0%w/w的柠檬酸;
(iii)范围为0.001~2.0%w/w的苹果酸;
(iv)范围为0.001~2.0%w/w的抗坏血酸;
(v)范围为0.00045~2.03%w/w的胆碱;和
(b)、(c)和(d)余量,包含水、一种或多种助溶剂和赋形剂和/或载体。
由于本发明的原液,更优选地是按上述表格中给出的百分数制备,所以更优选地,本发明的组合物可按如下述制备:
(a)(i)范围为0.000675~0.675%w/w的生物类黄酮[不包括生物质];
(ii)范围为0.015~1.5%w/w的柠檬酸;
(iii)范围为0.015~1.5%w/w的苹果酸;
(iv)范围为0.005~0.5%w/w的抗坏血酸;
(v)范围为0.015~0.9%w/w的胆碱;和
(b)、(c)和(d)余量,包含水、一种或多种助溶剂和赋形剂和/或载体。
由于本发明优选的组合物,包含大约1%w/w的原液,在一个实施例中,本发明优选的口用组合物可按如下所述制备:
(a)(i)大约0.0675%w/w的生物类黄酮[不包括生物质];
(ii)大约0.15%w/w的柠檬酸;
(iii)大约0.15%w/w的苹果酸;
(iv)大约为0.05%w/w的抗坏血酸;
(v)大约为0.09%w/w的胆碱;和
(b)、(c)和(d)余量,包含水、一种或多种助溶剂和赋形剂和/或载体。
在另一个实施例中,本发明最佳的组合物可按如下所述制备:
(a)(i)大约0.01485%w/w的生物类黄酮[不包括生物质];
(ii)大约0.045%w/w的柠檬酸;
(iii)大约0.045%w/w的苹果酸;
(iv)大约0.015%w/w的抗坏血酸;和
(b)、(c)和(d)余量,包含水、一种或多种助溶剂和赋形剂和/或载体。
优选地,本发明的组合物为局部用组合物。本文所指的所有组合物最好是适合局部施用的形式。
更优选地,本发明的组合物为口用组合物。更优选地,本文所指的所有组合物为适合口用的形式。
在另一个实施例中,本发明最佳的口用组合物可按如下所述制备:
(a)(i)大约0.01485%w/w的生物类黄酮[不包括生物质];
(ii)大约0.045%w/w的柠檬酸;
(iii)大约0.045%w/w的苹果酸;
(iv)大约0.06%w/w胆碱抗坏血酸盐;和
(b)和(c)余量,包含水、一种或多种助溶剂和赋形剂和/或载体。
所述原液是按本领域技术人员熟知的工艺制备的。较合适的是,所述助溶剂在常温下与水混合,然后将中和过程涉及的酸,如抗坏血酸,在升温的情况下与所述溶剂一起混合,该温度保持在足以确保任何配料都不降解的低温。对于抗坏血酸的情况,其热降解温度大约在55℃以上,上述升温范围保持在约25℃至55℃以下,最好在大约在50℃左右。较合适的是,所述中和反应包括将氢氧化胆碱添加到混合物(初始pH=1.2;最终pH=5.5~6.0)的抗坏血酸中,或者添加胆碱抗坏血酸盐(即,其中抗坏血酸已被中和)本身。
然后,加入剩余的酸(以柠檬酸和苹果酸为佳),接着加入生物类黄酮,以得到一种pH范围为约2.0至6.5,通常在2.2至3.5,尤其是在2.3至3.0的溶液。其余未中和的酸也例如用氢氧化胆碱基本上中和,以得到一种基本上中和的溶液,其pH范围为例如5至8.5,其中以5.5至7为佳,以5.5至6.5更佳。
包含生物类黄酮的在先技术配方的所述抗菌作用依赖于生物类黄酮对微生物细胞质膜中必需氨基酸摄取的抑制,例如通过抑制病毒神经酰胺酶(neuroamidase)。然而,本发明的配方被认为是有效的,因为所选择的可溶的生物类黄酮与胆碱抗坏血酸盐的组合物,会引起微生物的包裹,二氢黄酮和葡糖苷成分分解成独立的片段,以及随后由二氢黄酮片段和胆碱抗坏血盐导致的微生物失活。
较好的是,所述生物类黄酮混合物包含由萃取工艺产生的与生物质结合的水溶性生物类黄酮;因此,所述生物类黄酮混合物,可能与高达40~60%w/w,最好是约55%w/w的生物质(基于该生物类黄酮混合物的重量)结合。所述生物类黄酮以葡糖苷为佳,尤以选自异克奥索姆(isocriocirm)、异柚皮苷、柚皮苷(narangin)、橙皮苷(hesperidin)、新橙皮苷(neohesperidin)、新地奥明(neodiomin)、柚皮素(naringenin)、枸橘苷(poncirin)和野漆树苷(rhiofolen)为佳,而且以上述各种以混合物形态存在为更佳。特别首选的是,生物类黄酮混合物的主要部分包含柚皮苷和新橙皮苷,例如超过75%的生物类黄酮组分(不包含生物质)由它们组成。合适的是,所述生物类黄酮混合物中基本不存在其他生物类黄酮(如黄酮醇、白杨素,橙皮苷),因此所述生物类黄酮组分基本上就由上文所列的水溶性生物类黄酮组成,尽管也可能存在痕量的其他生物类黄酮。特别合适的是,水溶性的生物类黄酮包含以下百分比(按总生物类黄酮组分中的生物类黄酮重量计):
生物类黄酮 | 总生物类黄酮组分的% |
异克奥索姆 | 2.4 |
异柚皮苷 | 2.7 |
柚皮苷 | 52.0 |
橙皮苷 | 3.1 |
新橙皮苷 | 27.8 |
新地奥明 | 3.1 |
柚皮素 | 3.4 |
枸橘苷 | 4.4 |
野漆树苷 | 1.1 |
合计 | 100% |
这种水溶性生物类黄酮混合物的合适来源在此称作“HPLC45”,其中(HPLC45的总组分的)约45%为所述生物类黄酮,余量(约55%)包含生物质,如果胶、糖和少量有机酸。如前所述,特别合适的是,生物类黄酮混合物主要部分包含柚皮苷和新橙皮苷,例如,它们作为生物类黄酮在带有生物质的混合物如HPLC45中超过35%。因此,按HPLC45总组分重量计算,最好有下面的生物类黄酮:
生物类黄酮 | %,在HPLC45中(生物类黄酮组分+生物质) |
异克奥索姆 | 1.1 |
异柚皮苷 | 1.2 |
柚皮苷 | 23.4 |
橙皮苷 | 1.4 |
新橙皮苷 | 12.5 |
新地奥明 | 1.4 |
柚皮素 | 1.5 |
枸橘苷 | 2.0 |
野漆树苷 | 0.5 |
合计 | HPLC45的45% |
作为柑橘属生物类黄酮复合物(Citrus Bioflavonoid Complex)45%HPLC,HPLC45可从Exquim(Grupo Ferrer的食品分支机构)获得。它源自于包含未长熟苦(血/红)橙中果皮的起始原料,例如塞维利亚柑橘,这种柑橘被归类为“不适于食用的”,其果核、果肉和油性皮已基本去除或仍未充分发育。该起始原料在亲水的离子性溶剂中压榨,例如在水/醇混合物中,最好是比例约为1∶10~20(溶剂∶起始原料)的水/乙醇中。由此得到的混合物经过滤分离水溶性生物质(被保留)和不溶性生物质(废弃)。然后对水溶性生物质作进一步精过滤,再经闪蒸而留下一种棕色的吸湿性粉末(HPLC45)。
较好的是,用于本发明组合物的生物类黄酮混合物包含水溶性葡糖苷,这有别于从包含水不溶性类黄酮的柚子或其他柑橘类水果或其他植物来源得到的混合物;还更好的是,它还有别于从那些含有大量籽、果肉和/或鲜果,具体是包含水不溶性成分的起始原料得到的混合物;此外,在先技术的发育更全/成熟的起始原料,更可能经受过杀虫剂和/或合成肥料,因此,其来源不如本发明溶液的生物类黄酮混合物来得“有机”或纯净。
较好的是,所述原液包含1~20%w/w的HPLC45,其中以2至15%为佳,以3至15%更佳,例如3、4、或15,最佳是3.3%。因此,所述原液包含0.45~9%的生物类黄酮混合物,其中以0.9至6.75%为佳,以1.35至6.75%更佳,例如1.35、1.8、或6.75,最佳是1.485%。
较好的是,本发明组合物,特别是除了水没有其他配料的情况下,以及所述原液,具有3至约8.5的pH,其中以约3至8.5%为佳,以约4至7.5%更佳,例如约5至7;尤其好的是pH在约5.5至6.5。因此,最好的是,所述组合物基本没有氢离子,例如没有果酸的氢离子;因此,最好如上所述,通过往原液中添加碱的方法,充分中和用于制备原液和/或组合物的所述果酸。另一方面,当组合物还包含缓冲剂的情况下,假设缓冲剂的存在量能有效地使组合物的pH在这些范围内,那么该原液的pH可以变动超过这些范围。
因此,本发明组合物的组分(d),可以包含一种调节或调整最后组合物的pH的缓冲剂,例如碱金属氢氧化物或氢氧化铵,或一元、二元或三元磷酸盐,如三(碱金属)磷酸盐。由于氢氧化物的量,比二元磷酸盐难以测定,所以最好使用一元磷酸盐和二元磷酸盐。另一供选方法,是使用正磷酸和二元或三元磷酸盐,如三(碱金属)磷酸盐的组合物。所述磷酸盐以钠盐、钾盐或铵盐的形式为佳;尤以采用钠盐更佳。然而,当担心钠离子对高血压影响的情况下,可采用单钾和二钾磷酸盐。当缓冲剂是磷酸二钠的时候,例如,它在组合物中可以高达约5%w/w,尤以在0至0.5%,例如在约0.05%w/w为佳。
另一可选配料,组分(d),可以包含氟化物源,例如氟化钠和单氟磷酸钠,其含量可高达本发明组合物的大约0.5%w/w。氟化物源以在0至0.15%的范围为佳,例如在液体组合物的情况下,约为0.05%w/w,但在牙膏的情况下,要更高些,其在0至0.3%之间,例如约为0.24%w/w,或者在0至1500ppm(以氟离子计)的范围之内为佳。
本发明组合物中,可以存在其他添加剂,例如调味剂、甜味剂或着色剂,或防腐剂。例如取自椒薄荷(peppermint)或荷兰薄荷(spearmint)的薄荷、桂皮(cinnamon)、桉树(eucalyptus),柑橘(citrus)、肉桂(cassia)、茴香(anise)、薄荷脑(menthol)等,都是合适的调味剂的实施例。调味剂在所述组合物中的存在量在0至3%的范围之内为佳;以高至2%为佳,例如高至0.5%,在液体组合物情况下,以0.2%左右为佳;对于牙膏的情况,可任选地多些,以0.5至2%为佳,在1%w/w左右更佳。甜味剂包含人工甜味剂或天然甜味剂,例如糖精钠,其存在量的范围可在0至2%,以高至1%w/w为佳,例如为组合物的0.05至0.3%w/w。着色剂是适宜的天然或合成色素,如二氧化钛或CI42090,或其混合物。在所述组合物中最好存在着色剂,其范围为0至3%之间;以高至0.1%为佳,例如高至0.05%,在液体组合物的情况下,以在0.005~0.0005%左右为佳;但对于牙膏的情况,可任选地多些,以高至1%为佳,在约0.5%w/w左右更佳。常用的防腐剂中,苯甲酸钠的浓度,以不足以达到改变所述组合物pH的大小为宜,否则,需要调节缓冲剂的用量,以到达所希望的pH。
组分(d)的其他可选配料,可以包含其他的活性作用剂,如抗菌斑剂和/或抗微生物剂。合适的作用剂包括季铵盐化合物,如度米芬(Domiphenbromide)、氯化十六烷基吡啶(CPC)、酚类化合物、乙醇以及上述的防腐剂。这些活性作用剂的存在量的浓度范围为0至4%w/w之间,但对于乙醇的情况,可高达70%,例如高达30%。例如,尤其是在本发明的液体组合物中,氯化十六烷基吡啶(CPC)等以高至2%为佳,例如约0.05%w/w左右。在本发明的液体组合物中,乙醇可含多达70%,以0至30%w/w为佳,如在喷口药水中约为15%w/w,但本发明组合物,具体为口用组合物,最好基本不存在乙醇或任何其他的醇。
组分(d)的其他可选配料,可以包含保湿剂、表面活性剂(非离子、阳离子或两性)、增稠剂、胶体和粘结剂。合适的保湿剂包括甘油、木糖醇、丙三醇和二醇,如丙二醇,其存在量各可高达50%w/w,但所述组合物的总保湿剂最好不超过约60~80%w/w。例如,液体组合物可包含多达约30%的甘油,外加高达约5%,最好是约2%w/w的木糖醇。表面活性剂最好不是阴离子性的,并且还可包括聚山梨醇酯20或可可酰胺甜菜碱(cocoamidobetaine)等,其含量高至为所述组合物的约6%,尤以约1.5至3%w/w为佳。
当本发明的口用组合物未喷口水形式时,所述口用组合物最好包括高至3%w/w左右的成薄膜剂,例如在0至0.1%的范围内,尤以约0.001至0.01%为佳,例如为所述口用组合物的约0.005%w/w。适合的成膜剂包括透明质酸钠以及以Gantrez商标出售的那些成膜剂。
当本发明的所述口用组合物是以牙膏形式存在时,最好包括胶体、粘结剂和/或增稠剂,如胶体二氧化硅、卡拉胶和纤维素衍生物,如羧甲基纤维素钠。这些配料在所述口用组合物的含量可高至3%w/w左右,如高至约2%,尤以约0.5至1%w/w为佳。
本发明的牙膏组合物还可包含研磨剂,如水合二氧化硅、磷酸氢钙、或水不溶性碱金属偏磷酸盐,其在所述口用组合物可高至约25%w/w,尤以约10至15%w/w左右为佳。
本发明组合物可局部施用,且可以是霜剂、凝胶、膏体、牙膏和洗口药水形式。对此,本发明的药物组合物通常包含常规的赋形剂,例如,如山梨醇和/或麦芽糖醇之类的多元醇,如聚乙二醇之类的二元醇,如羧甲基纤维素之类的增稠剂,如对羟基苯甲酸甲酯或丙酯的防腐剂,如辣椒素之类的调味剂,如糖精之类的甜味剂,以及着色剂。
本发明组合物可以采用本技术领域中已知的用于制备类似组合物(如牙膏、洗口药水或冲口药水、喷口药水等)的任何方法制备。所有这些方法,都包括将组分(a)、(b)以及,如果存在的话,还有(d),均匀地物理混合在一起。
所述组合物最好采用合适的包装,如带有使用说明书的、具有或没有喷头或其他敷抹装置的塑料管或金属管,塑料或玻璃的透明瓶、半透明或不透明的瓶子,罐或分配器。这种包装本身还可以进一步包装到一个硬纸板箱或其他合适的容器中,相同的或进一步的使用说明书可附在其内或写在其上;这种说明书写在附带的小纸盒或散页上也很合适。包装上最好列出组合物的活性成分、主要成份或全部成分。该说明书可包含组合物领域的技术人员已知的内容,特别是有关抗菌使用的内容。于是,他们可建议按规定的时间间隔,每天2~3次,将豌豆大小的牙膏施用于牙齿;每天至少一次,最好是在饭后,用满口的洗口药水或冲口药水冲洗口腔周围;等等。
因此,本发明的所述口用组合物,可用于:治疗、预防或改善口腔中的微生物尤其是细菌性感染或其他牙周疾病的影响;清洁口腔,消毒口腔或从口腔清除碎渣;清爽、清新、消除或改善口气或口味;以及常规护理口腔的卫生、外观和感觉。因此,本发明进一步提供了一种包含与高分子量透明质酸钠组合的生物类黄酮混合物(如上文所述的混合物)和果酸的原液,该原液用于制备治疗口腔中微生物尤其是细菌感染的药剂;特别地,所述药物包含0.1%至10%w/w(基于所述口用组合物的总重量)的原液。较好的是,本发明提供(a)包含生物类黄酮和果酸混合物的原液,以及(b)透明质酸钠,其中所述透明质酸钠的平均分子量为800,000~4,000,000,和(d)其他制药学或药理学上可接受的适合口用的配料(如上文所述),用于制备微生物尤其是细菌性口腔感染的治疗的药剂;特别地,其中所述药物包含0.1%至10%w/w(基于所述口用组合物的总重量)的原液。
治疗用途的本发明组合物可有利地用于治疗齿龈感染,该感染表现为齿龈组织的炎性症状,例如,齿龈炎、口腔炎、由如固定或移动修补物或外科手术之类的机械原因引起的疼痛。本发明组合物的牙龈膏可在儿童长牙阶段使用。本发明的所述口用组合物可用于治疗粘膜炎、阿弗他溃疡、扁平苔藓、口腔念珠菌病、齿龈炎、牙周炎或干槽症。本发明组合物可用于治疗已感染的、或潜在地感染的、和/或红肿的皮肤,例如粉刺、灼伤和创伤。
本发明组合物对治疗或预防由下列细菌引起的感染、疾病或病征是有用的:龋齿放线菌(Actinomyces odontolyticus)、粘性放线菌(Actinomycesviscosus)、牙龈卟啉单胞菌(Porphyromonas gingivalis)、中间普雷沃菌(Prevotella intermedia)、颊普雷沃菌(Prevotella buccae)、牙普雷沃菌(Prevotella dentalis)、格登链球菌(Streptococcusgordonii)、血链球菌(Streptococcus sanguinis)、口腔链球菌(S oralis)、远缘链球菌(Ssobrinus)、变形链球菌(S mutans)、中间链球菌(S intermedius)、嗜酸乳杆菌(Lactobacillus acidophilus)、缠结优杆菌(Eubacterium nodatum)、衣氏放线菌(Actinomyces israelii)、奈斯隆迪放线菌(Actinomyces naeslundii)、白假丝酵母(Calbicans)和热带假丝酵母(C tropicalis)。
在生物试验中,用于制备本发明组合物的原液(参见实施例1)稀释成1/10时可抑制上述所有细菌,且稀释成1/100时也可抑制上述链球菌属细菌。其他生物学数据在本文下述实施例中给出。现将通过下面的实施例阐明本发明。
实施例1:原液的制备
(a)HPLC45的制备
起始原料包含未长熟的苦(血/红)橙,例如塞维利亚柑橘的中果皮,这种柑橘被归类为“不适于食用”,并其果核、果肉和油性皮已被基本去除。起始原料被碾碎后以1∶10~20的比例(溶剂∶起始原料)在水/乙醇中压榨到。所得混合物经过滤,保留水溶性生物质,丢弃不溶性的生物质。然后进一步精滤水溶性生物质,在经闪蒸后,得到棕色的吸湿性粉末(HPLC45)。或者,可从Exquim(Grupo Ferrer)获得HPLC45。
(b)HPLC45的生物类黄酮组合物
对在步骤(a)所得HPLC45的分析表明,HPLC45总成分的45%为生物类黄酮,其余量(55%)包含果胶、糖和低级有机酸。下列生物类黄酮所占的百分比(以HPLC45中的生物类黄酮重量计)为:
生物类黄酮 | %,HPLC45中的生物类黄酮 |
异克奥索姆 | 2.4 |
异柚皮苷 | 2.7 |
柚皮苷 | 52.0 |
橘皮苷 | 3.1 |
新橘皮苷 | 27.8 |
新地奥明 | 3.1 |
柚皮素 | 3.4 |
枸橘苷 | 4.4 |
野漆树苷 | 1.1 |
合计 | 100% |
因此,以HPLC45总成分的重量计,存在下列生物类黄酮:
生物类黄酮 | %HPLC45 |
异克奥索姆 | 1.1 |
异柚皮苷 | 1.2 |
柚皮苷 | 23.4 |
橘皮苷 | 1.4 |
新橘皮苷 | 12.5 |
新地奥明 | 1.4 |
柚皮素 | 1.5 |
枸橘苷 | 2.0 |
野漆树苷 | 2.8 |
(c)原液的制备
配料 | %原液 |
HPLC45 | 15 |
柠檬酸 | 15 |
苹果酸 | 15 |
抗坏血酸(维生素C)<sup>*</sup> | 5<sup>*</sup> |
氢氧化胆碱溶液(45%的水溶液) | 15<sup>*</sup> |
甘油 | 15<sup>*</sup> |
水 | 20<sup>*</sup> |
合计 | 100% |
水、甘油和抗坏血酸是在常温下混合在一起的,然后升温至50℃。加入氢氧化胆碱,以中和抗坏血酸(开始pH=1.2;最终pH=5.5~6.0)。
[*抗坏血酸和氢氧化胆碱可用5%的胆碱抗坏血酸盐替代,而甘油和水的量各提高至25%]
然后,加入剩余的酸(柠檬酸和苹果酸),随后加入HPLC45,得到原液,其pH为6.2至7.2,并包含6.75%(原液的w/w)的生物类黄酮。
实施例2A:喷口药水
配料 | 百分比 |
甘油 | 10.000 |
乙醇 | 15.000 |
木糖醇 | 2.000 |
聚山梨醇酯20 | 1.500 |
原液,pH调至6.44 | 1.000 |
调味剂 | 0.200 |
糖精钠 | 0.080 |
氯化十六烷基吡啶 | 0.050 |
磷酸氢二钠·12H<sub>2</sub>O | 0.075 |
透明质酸钠 | 0.005 |
水 | 补足至.100% |
A.实验室样品:一种基于本发明的喷口药水,使用上述配料按如下方法制备:在容器(A)中,边搅拌边将透明质酸钠分散在水中,得到没有结块的溶液。添加糖精钠、氯化十六烷基吡啶、磷酸氢二钠、木糖醇和原液,搅拌至所有配料完全溶解。添加甘油,混合均匀。在另一容器(B)中,使聚山梨醇酯20、调味剂和乙醇混合。混合至调味剂完全分散。将容器(B)的内容物加至容器(A),搅拌得到均质液体。
B.替代(生产)方法:一种基于本发明的喷口药水,使用上述配料按如下方法制备:在容器(A)中,将透明质酸钠分散在甘油中。搅拌并加水得到没有结块的溶液。添加木糖醇、原液、糖精钠、氯化十六烷基吡啶和磷酸氢二钠,搅拌至所有配料完全溶解。在另一容器(B)中,使聚山梨醇酯20、调味剂和乙醇混合。混合至调味剂完全分散。将容器(B)的内容物加至容器(A),搅拌得到均质液体。
实施例2B:喷口药水
配料 | 百分比 |
甘油 | 10.000 |
乙醇 | 15.000 |
木糖醇 | 2.000 |
聚山梨醇酯20 | 1.500 |
原液,pH调节至6.44 | 1.000 |
调味剂 | 0.200 |
糖精钠 | 0.080 |
氯化十六烷基吡啶 | 0.050 |
磷酸氢二钠·12H<sub>2</sub>O | 0.075 |
透明质酸钠(平均分子量1,500,000) | 0.01 |
水 | 补足至100% |
本发明的喷口药水可用上述配料以上面的方法制备。
实施例3:冲口药水
配料 | 百分比 |
甘油 | 25.000 |
乙醇 | 0.000 |
木糖醇 | 2.000 |
聚山梨醇酯20 | 1.500 |
原液(pH=6.23,在室温下放置6个月后) | 0.500 |
调味剂 | 0.200 |
糖精钠 | 0.050 |
氟化钠 | 0.050 |
磷酸氢二钠·12H<sub>2</sub>O | 0.050 |
CI 18965(黄2G)CI 42051(专利蓝V) | 0.00090.0003 |
透明质酸钠(平均分子量1,500,000) | 0.01 |
水,补足至100% | 70.53 |
A.实验室样品:一种基于本发明的冲口药水,可使用上述配料按如下方法制备:在混合容器(A)中,通过搅拌将透明质酸钠分散水,得到无结块的溶液。将加入糖精钠、氟化钠、磷酸氢二钠、色素、木糖醇和原液,并混合至所有配料完全溶解。加入甘油,并混合至均匀。在另一容器(B)中,使聚山梨醇酯20、调味剂混合。混合至调味剂完全分散。将容器(B)的内容物加至容器(A),搅拌得到均质液体。
B.替代(生产)方法:一种基于本发明的冲口药水,可使用上述配料按如下方法制备:在混合容器(A)中,通过搅拌将透明质酸钠分散于水,得到无结块的溶液。加入保湿剂、原液、糖精钠,氟化钠、磷酸氢二钠和色素。混合至所有配料完全溶解。在另一容器(B)中,使聚山梨醇酯20、调味剂和乙醇混合。混合至调味剂完全分散。将容器(B)的内容物加至容器(A),搅拌得到均质液体。
实施例4:牙膏
配料 | 百分比 |
甘油 | 30.000 |
水合二氧化硅-研磨剂 | 12.000 |
水合二氧化硅-增稠剂 | 11.000 |
木糖醇 | 10.000 |
可可酰胺甜菜碱(30%) | 3.000 |
黄原胶 | 1.000 |
原液(pH=6.68,在常温 | 0.500 |
下放置6个月后) | |
透明质酸钠(平均分子量1,500,000) | 0.1 |
调味剂 | 1.000 |
糖精钠 | 0.260 |
氟化钠 | 0.240 |
二氧化钛 | 0.500 |
水 | 补至100% |
A.实验室样品:一种基于本发明的牙膏,可使用上述配料按如下所述制备:在容器A中,通过搅拌将透明质酸钠分散于水,得到无结块的溶液,并加入甘油。向其中加入糖精钠,氟化钠,原液和木糖醇,搅拌溶解。将容器(A)的内容物,转移至真空混合器(容器B)。将粉末(水合二氧化硅、黄原胶和二氧化钛)在容器C内进行预混合,然后加入到真空搅拌器(B)的液相中。在真空状态下混合均匀,以形成平滑的膏体。
实施例5:原液的制备
下述原液是按上述方法制备的:
生物类黄酮混合物 3.3%
苹果酸 4.5%
柠檬酸 4.5%
甘油 7.5%
抗坏血酸 1.5%
水 78.6%
溶液的pH 1.5~1.75
实施例6:原液的制备
下述原液是按上述方法制备的:
生物类黄酮混合物 3.3%
苹果酸 4.5%
柠檬酸 4.5%
胆碱抗坏血酸 6.0%
LFG61烷基糖苷 13.3%
丙二醇 7.5%
水 60.9%
溶液pH 1.5~1.75
判断本发明的组合物对一些与牙周病相关的厌氧菌和兼性细菌是否有抗菌活性的试验,按如下方法进行。
方法和材料
可采用的细菌包括:龋齿放线菌、粘性放线菌、牙龈卟啉单胞菌、中间普雷沃菌、颊普雷沃菌、牙普雷沃菌、格登链球菌和血链球菌,特别是ATCC菌株。所有厌氧菌均可在唐怀特利厌氧室(Don Whitely AnaerobicChamber)(可从UK,Don Whitely,Yorkshire得到)内,在严格厌氧培养基(Fastidious Anaerobic Broth(FAB))中,37℃下生长24小时。所述兼性细菌可在营养培养基中,在10%(v/v)二氧化碳的条件下,于37℃生长24小时。起始培养物为1mL约106cfu/mL的过夜生长物。所述培养物添加浓度最低至1/10,000(0.001%)的本发明组合物。所述稀释液就是适当的培养液。其生长情况可采用分光光度法以在650nm下的吸光度增加值进行评价。
可用5%(v/v)血琼脂平板上的生长来评估牙膏和洗口药水组合物。可在琼脂中切出直径约0.5厘米的孔,并填充各组合物的稀释液;该稀释剂就是适当的培养液。所述平板可用约0.2毫升106cfu/mL左右的培养液预先接种。未见生长抑制的孔浓度可视作最低抑菌浓度。
附加试验
试验了两种原液:实施例5和实施例6。使用血心浸液(Blood-HeartInfusion(BHI)或沙氏培养基(Sabouraud’s broth)作为稀释剂,每种配方都制备了一系列两倍稀释液,它们的pH分别为1.75和2.0,得到具有一组浓度范围(在8%~0.015625%v/v之间)的溶液。
获得一些细菌和假丝酵母的菌株(见表1),并在适当的条件下培养48h。在培养液(细菌用BHI,假丝酵母用沙氏培养基)中制备各种微生物的悬浮液,以达到约等于麦氏标准3.0(MacFarland3.0)的浊度水平。
表1本研究使用的微生物菌种
需氧细菌 | 厌氧细菌 | 酵母 |
格登链球菌血链球菌 | 龋齿放线菌粘性放线菌难辨梭菌(Clostridium difficile)牙龈卟啉单胞菌颊普雷沃菌中间普雷沃菌 | 白假丝酵母都柏林假丝酵母(Candida dubliniensis)光滑假丝酵母(Candida glabrata)克鲁斯假丝酵母(Candida krusei)近平滑假丝酵母(Candida parapsilosis)热带假丝酵母 |
将100μL体积的各微生物悬浮液,加入到微量滴定板的孔中。再往每个孔添加同等体积的实施例5或实施例6的溶液(含有匹配的培养液),以得到最终4%~0.0078125%(v/v)的原液浓度。还制备不含原液和/或微生物的孔,作为对照。每个微量滴定板都置于适当气氛下,37℃下,培养24小时。在培养之后,通过使用分光光度计在波长544纳米下吸光度读数,测定每个孔中的浊度,以估计各种微生物种的相对量。吸光度读数用不存在微生物的对照样进行背景扣除。
最小抑菌浓度(MIC)定义为与微生物是在无原液的情况下生长的对照样相比,导致微生物量显著下降(即下降>50%)的的最低原液浓度。试验进行3次,在存在各种微生物情况下确定实施例5和实施例6的配方的最小抑菌浓度。
结果:
观察所得到的实施例5和实施例6两配方对13种微生物的MIC值归纳于表2。
所研究的每种微生物的生长,除光滑假丝酵母外,都受到实施例5和实施例6两配方的抑制。该酵母菌的生长根本不受实施例6的抑制,甚至在本研究使用的最高浓度8%(v/v)下也存在生长。
对实施例5和实施例6的两配方的MIC值进行比较表明,在抑制微生物生长方面,实施例5比实施例6更为有效。除了对牙龈卟啉单胞菌两种配方具有相同的MIC值1%之外,对每种微生物的MIC值,实施例5的都比实施例6的更低。此外,实施例5在浓度为1%(v/v)时,抑制每种微生物的生长,虽然生长的降低没有完全大于50%(在本研究设定的用于定义MIC的标准)。这就支持使用1%(v/v)的实施例5原液作为今后产品和研究中的首选工作浓度。
表2就实施例5和实施例6两配方,本研究所观察到的对每种微生物的MIC值
*即使在本研究所用最高浓度的情况下,也没有明显的生长抑制。
Claims (23)
1.一种组合物,其pH范围为3至8.5,包含:
(a)基于组合物的总重量,范围为0.1%w/w至小于10%w/w的原液,所述原液包含:0.45-9%的生物类黄酮混合物,其中超过75%的生物类黄酮为柚皮苷和新橙皮苷;以及任选地0.001~2.0%w/w的柠檬酸、0.001~2.0%w/w的苹果酸、0.001~2.0%w/w的抗坏血酸和0.00045~2.03%w/w的胆碱;
(b)基于所述组合物总重量的0.005至10%w/w的透明质酸钠;和
(c)水,
其中所述透明质酸钠的平均分子量为800,000~4,000,000,
其特征在于,所述生物类黄酮混合物源自于未长熟苦橙的中果皮,且包括由萃取工艺产生的与生物质结合的水溶性生物类黄酮。
2.根据权利要求1的组合物,还包括制药学上可接受的载体。
3.根据权利要求1或2的组合物,其中所述透明质酸钠的分子量为1,000,000~2,000,000。
4.根据权利要求1的组合物,其包含所述组合物总重量的0.2至10%w/w的所述透明质酸钠。
5.根据权利要求1的组合物,其中,基于生物类黄酮混合物的重量,所述生物质的范围为40至60%w/w。
6.根据权利要求1的组合物,其中,所述组合物的pH范围为3.5至8。
7.根据权利要求1的组合物,包含:基于所述组合物的重量,范围为20至80%w/w的水。
8.根据权利要求7的组合物,其中,所述组合物是包含20至40%w/w水的牙膏,或者是包含60至80%w/w水的液体组合物。
9.根据权利要求1的组合物,包含:基于所述组合物重量,范围为0至30%w/w的醇。
10.根据权利要求9的组合物,其中所述醇是乙醇。
11.根据权利要求1的组合物,其中,所述生物类黄酮选自异克奥索姆、异柚皮苷、柚皮苷、橙皮苷、新橙皮苷、新地奥明,柚皮素,枸橘苷和野漆树苷。
12.根据权利要求2的组合物,其中,所述载体选自加氟剂、香味剂、甜味剂、色素、抗微生物剂、保湿剂、表面活性剂、增稠剂、粘结剂、研磨剂、成膜剂。
13.根据权利要求1的组合物,其为口用组合物。
14.根据权利要求1的组合物,其为牙膏或喷口药水的形式。
15.根据权利要求1的组合物,其用于治疗、预防或改善口腔中的微生物感染。
16.根据权利要求15的组合物,所述微生物感染为细菌感染。
17.根据权利要求16的组合物,其用于治疗粘膜炎、阿弗他溃疡、扁平苔藓、口腔念珠菌病、齿龈炎、牙周炎或干槽症,以及用于儿童长牙阶段。
18.根据权利要求1的组合物,其用于治疗已感染的、或潜在地感染的、和/或红肿的皮肤。
19.根据权利要求1的组合物,其中所述感染选自:龋齿放线菌(Actinomycesodontolyticus)、粘性放线菌(Actinomyces viscosus)、牙龈卟啉单胞菌(Porphyromonasgingivalis)、中间普雷沃菌(Prevotella intermedia)、颊普雷沃菌(Prevotellabuccae)、牙普雷沃菌(Prevotella dentalis)、格登链球菌(Streptococcus gordonii)、血链球菌(Streptococcus sanguinis)、口腔链球菌(S oralis)、远缘链球菌(S sobrinus)、变形链球菌(S mutans)、中间链球菌(S intermedius)、嗜酸乳杆菌(Lactobacillusacidophilus)、纠结优杆菌(Eubacterium nodatum)、衣氏放线菌(Actinomycesisraelii)、奈斯隆迪放线菌(Actinomyces naeslundii)、白假丝酵母(C albicans)和热带假丝酵母(C tropicalis)的感染。
20.根据权利要求6的组合物,其中所述组合物的pH范围为4至7。
21.根据权利要求6的组合物,其中所述组合物的pH范围为5至6.5。
22.权利要求1的组合物的制备方法,包括:对组分(a)、(b)、(c)进行均匀的物理混合。
23.权利要求2的组合物的制备方法,包括:对组分(a)、(b)、(c)和制药学上可接受的载体进行均匀的物理混合。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GBGB0614353.1A GB0614353D0 (en) | 2006-07-20 | 2006-07-20 | Oral compositions, their preparation and use |
GB0614353.1 | 2006-07-20 | ||
PCT/GB2007/002756 WO2008009956A1 (en) | 2006-07-20 | 2007-07-20 | Combinations for oral compositions, their preparation and use |
Publications (2)
Publication Number | Publication Date |
---|---|
CN101495089A CN101495089A (zh) | 2009-07-29 |
CN101495089B true CN101495089B (zh) | 2019-06-11 |
Family
ID=36998354
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN200780027438.7A Active - Reinstated CN101495090B (zh) | 2006-07-20 | 2007-07-20 | 口用组合物及其制备和应用 |
CN200780027437.2A Active CN101495089B (zh) | 2006-07-20 | 2007-07-20 | 用于口用组合物的组合物及其制备和应用 |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN200780027438.7A Active - Reinstated CN101495090B (zh) | 2006-07-20 | 2007-07-20 | 口用组合物及其制备和应用 |
Country Status (9)
Country | Link |
---|---|
US (3) | US20100068157A1 (zh) |
EP (2) | EP2043592B1 (zh) |
JP (3) | JP5508005B2 (zh) |
CN (2) | CN101495090B (zh) |
AT (2) | ATE548020T1 (zh) |
CA (2) | CA2658468C (zh) |
ES (2) | ES2384687T3 (zh) |
GB (2) | GB0614353D0 (zh) |
WO (2) | WO2008009956A1 (zh) |
Families Citing this family (44)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB0614353D0 (en) | 2006-07-20 | 2006-08-30 | Oraldent Ltd | Oral compositions, their preparation and use |
JP2011513291A (ja) * | 2008-02-26 | 2011-04-28 | スティーブンソン グループ リミテッド | 保存製品、および保存料組成物 |
GB0803473D0 (en) * | 2008-02-26 | 2008-04-02 | Stephenson Group Ltd | Sanitising composition |
US9056121B1 (en) * | 2008-06-30 | 2015-06-16 | Reyn Pharma, Llc | Method of administering hyaluronan formulation for the amelioration of osteophytes |
IT1396468B1 (it) * | 2008-11-11 | 2012-12-14 | Farma Derma Srl | Uso topico di acido ialuronico ad azione filmogena in preparati per il trattamento e profilassi di patologie delle vie respiratorie. |
EP2198862A1 (en) | 2008-12-18 | 2010-06-23 | Citrox Limited | Use of flavonoids to treat parasitic infection |
EP2394634B1 (en) | 2009-02-03 | 2018-11-21 | Sunstar Inc. | Hesperidin-containing composition |
GB2468836B (en) | 2009-02-05 | 2012-09-05 | Citrox Biosciences Ltd | Sterilisation with misting |
PL2418945T3 (pl) * | 2009-04-15 | 2019-05-31 | Bmg Pharma S P A | Kompozycje soli mineralnej - kwasu sulfonowego i sposoby ich stosowania |
JP2011073970A (ja) * | 2009-09-29 | 2011-04-14 | Sunstar Inc | 口腔用又は咽喉用組成物 |
PT2515646T (pt) | 2009-11-02 | 2017-03-28 | Meda Ab | Composições que compreendem extractos que contêm flavonóides de plantas do género citrus e/ou flavonóides citrus isolados e agentes surfactantes catiónicos especificos, e para utilizar a referida composição como um agente para tratar infestações com piolho da cabeça |
CA2847661A1 (en) * | 2010-08-06 | 2012-02-09 | Phyto Innovative Products Ltd. | Compositions comprising oleuropeins and flavanoids and their use |
CN102652712A (zh) * | 2011-03-04 | 2012-09-05 | 全球生技股份有限公司 | 具抗菌的口腔护理组成物及其制法 |
WO2012139146A1 (de) * | 2011-04-13 | 2012-10-18 | Technische Universität Wien | Verfahren zur bekämpfung von bakteriellen infektionen bei einer pflanze unter verwendung von flavonoiden |
US9387969B2 (en) * | 2011-04-14 | 2016-07-12 | Edward Schapiro | Toothpaste composition and method of applying a single serving of toothpaste to a toothbrush |
EP2717690B1 (en) | 2011-06-13 | 2020-04-15 | OralDent Limited | Ophthalmic compositions |
EP2681996A1 (en) * | 2012-07-03 | 2014-01-08 | CeBeC Group Ltd. | Biocidal compositions |
IN2015DN01286A (zh) | 2012-08-24 | 2015-07-03 | Citrox Biosciences Ltd | |
DE102013000699A1 (de) * | 2012-10-04 | 2014-04-10 | Maria Clementine Martin Klosterfrau Vertriebsgesellschaft Mbh | Zusammensetzung, insbesondere pharmazeutische Zusammensetzung, insbesondere zur Verabreichung bei Heiserkeit |
JP6118547B2 (ja) * | 2012-12-10 | 2017-04-19 | 花王株式会社 | 口腔用組成物 |
EP2934463B1 (en) * | 2012-12-20 | 2018-02-14 | Colgate-Palmolive Company | Oral care composition containing ionic liquids |
WO2014206690A1 (en) * | 2013-06-27 | 2014-12-31 | Firmenich Sa | Taste-modifying ingredient |
MX365970B (es) | 2013-12-27 | 2019-06-21 | Colgate Palmolive Co | Composiciones para cuidado oral prebioticas que contienen acidos carboxilicos. |
NO339503B1 (no) * | 2014-06-18 | 2016-12-19 | Meda Otc Ab | Sammensetning for forebygging eller behandling av dental erosjon |
CN106446599A (zh) * | 2015-08-11 | 2017-02-22 | 中国科学院青岛生物能源与过程研究所 | 一种筛选婴幼儿龋病的口腔致病性生物标记物的方法 |
RU2624502C2 (ru) * | 2015-11-17 | 2017-07-04 | Общество с ограниченной ответственностью "ДЖИ-Групп" | Лечебно-профилактический материал для стоматологии |
CN107028839A (zh) * | 2017-05-31 | 2017-08-11 | 易金阳 | 口腔护理组合物及其应用、牙膏组合物 |
GB201713362D0 (en) * | 2017-08-21 | 2017-10-04 | Givaudan Sa | Improvements in or relating to organic compounds |
US20190365629A1 (en) * | 2018-05-29 | 2019-12-05 | Mary Kay Inc. | Topical compositions and methods |
JP2020002019A (ja) * | 2018-06-25 | 2020-01-09 | ロート製薬株式会社 | 口腔用組成物 |
GB2578146A (en) | 2018-10-18 | 2020-04-22 | Citrox Biosciences Ltd | Bioflavonoid compositions and their use for water purification and food preservation |
GB2578147A (en) * | 2018-10-18 | 2020-04-22 | Oraldent Ltd | Bioflavonoid compositions and their use |
CN109369805A (zh) * | 2018-12-27 | 2019-02-22 | 广东工业大学 | 一种用于防治牙龈炎的卵黄抗体夹心含片及其制备方法 |
JP2020200245A (ja) * | 2019-06-06 | 2020-12-17 | ポッカサッポロフード&ビバレッジ株式会社 | 口臭抑制用組成物 |
BR112021024271A2 (pt) | 2019-06-14 | 2022-01-11 | Procter & Gamble | Composições para tratamento bucal sem enxágue |
BR112021024266A2 (pt) | 2019-06-14 | 2022-01-11 | Procter & Gamble | Composições para tratamento bucal sem enxágue |
CN114040742A (zh) | 2019-06-14 | 2022-02-11 | 宝洁公司 | 免洗型口腔护理组合物 |
WO2020248229A1 (en) * | 2019-06-14 | 2020-12-17 | The Procter & Gamble Company | Leave-on oral care compositions |
IT201900025483A1 (it) * | 2019-12-24 | 2021-06-24 | Adco S R L | Composizione per la disinfezione della cavità orale |
WO2022157314A1 (en) * | 2021-01-22 | 2022-07-28 | Dsm Ip Assets B.V. | Hyaluronic acid for use on the skin |
GB2605971A (en) | 2021-04-19 | 2022-10-26 | Citrox Biosciences Ltd | Nutritional supplement and uses |
GB2605972A (en) | 2021-04-19 | 2022-10-26 | Citrox Biosciences Ltd | Nutritional supplements for amelioration of respiratory tract infections |
WO2023104843A1 (de) | 2021-12-09 | 2023-06-15 | Beiersdorf Ag | Topisch applizierbare zubereitung zur verbesserung des hautzustandes |
CN115518004B (zh) * | 2022-01-13 | 2024-01-16 | 海尼达(江苏)医疗科技有限公司 | 一种辅助改善口腔健康的组合物及其应用 |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0444492B1 (en) * | 1990-02-21 | 1996-01-10 | RICERFARMA Srl | Topically administered compositions based on high molecular weight hyaluronic acid for treating inflammations of the oral cavity, and for oral cavity hygiene and cosmetic treatment |
EP1600143A1 (en) * | 2003-02-13 | 2005-11-30 | Kabushiki Kaisha Hayashibara Seibutsu Kagaku Kenkyujo | SKIN PREPARATION FOR EXTERNAL USE CHARACTERIZED BY CONTAINING SUGAR DERIVATIVE OF a,a-TREHALOSE |
Family Cites Families (41)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2823166A (en) * | 1954-11-17 | 1958-02-11 | Walter H Hoffman | Choline ascorbate, methods for producing same, and compositions thereof |
US2888381A (en) * | 1955-09-01 | 1959-05-26 | Us Vitamin Corp | Solutions of citrus bioflavonoids |
JPS55125840A (en) | 1979-03-19 | 1980-09-29 | Olympus Optical Co | Endoscope |
US4303676A (en) * | 1980-03-21 | 1981-12-01 | Balazs Endre A | Hyaluronate based compositions and cosmetic formulations containing same |
JPH0755895B2 (ja) | 1985-08-29 | 1995-06-14 | サンスター株式会社 | 歯磨組成物 |
JPH07187974A (ja) * | 1993-12-24 | 1995-07-25 | Lion Corp | 口腔用組成物 |
JP4010574B2 (ja) * | 1994-12-05 | 2007-11-21 | 電気化学工業株式会社 | 皮膚外用剤 |
US5571518A (en) * | 1995-10-30 | 1996-11-05 | Chesebrough-Pond's Usa Co., Division Of Conopco, Inc. | Cosmetic compositions containing tricholine citrate |
JPH10182390A (ja) * | 1996-12-25 | 1998-07-07 | Lion Corp | 口腔用組成物 |
US6120779A (en) * | 1998-01-29 | 2000-09-19 | Soma Technologies | Use of partial and complete salts of choline and carboxylic acids for the treatment of skin disorders |
DE19949575A1 (de) | 1999-10-14 | 2001-04-19 | Michael Hermann Hinz | Neuartige Wirkstoffkombination von biologisch hochwirksamen Fluoriden u. Flavonoiden zur Therapie und Prphylaxe von Zahnerkrankungen |
US20020155163A1 (en) | 1999-12-27 | 2002-10-24 | Samuel D. Benjamin | Integrated multi-vitamin and mineral combination |
JP4261744B2 (ja) * | 2000-07-05 | 2009-04-30 | 小林製薬株式会社 | 口腔用組成物 |
CA2327738A1 (en) | 2000-12-06 | 2002-06-06 | Darlene Jazzar | Lemon extract and treatment methods |
CA2431044A1 (en) * | 2000-12-13 | 2002-06-20 | University Of Rochester | Oral compositions and use thereof |
JP2002226386A (ja) * | 2001-01-30 | 2002-08-14 | Rohto Pharmaceut Co Ltd | 植物抽出物を含有する外皮用組成物 |
WO2002092028A2 (en) * | 2001-05-15 | 2002-11-21 | The Procter & Gamble Company | Oral care compositions |
US20030017219A1 (en) * | 2001-05-25 | 2003-01-23 | Frank Corsini | Carbohydrate modifying agent and drinks containing the modifying agent |
ITRM20010364A1 (it) * | 2001-06-25 | 2002-12-27 | Biosalts Srl | Ascorbil derivati di carnitine e composizioni cosmetiche contenenti tali derivati. |
JP2003055179A (ja) * | 2001-08-10 | 2003-02-26 | Hideaki Hanaki | 口腔スプレー用組成物 |
JP4846141B2 (ja) | 2001-08-31 | 2011-12-28 | 東洋精糖株式会社 | 即効性および持続性を有するフラボノイド配糖体を含有する経口栄養補給剤 |
US20030105027A1 (en) | 2001-11-06 | 2003-06-05 | Rosenbloom Richard A. | Nutritional supplements and methods for prevention, reduction and treatment of radiation injury |
US20030125264A1 (en) * | 2001-12-29 | 2003-07-03 | Kimberly-Clark Worldwide, Inc. | Methods For Treating Wounds |
EP1514540B1 (en) | 2002-05-01 | 2014-08-27 | Hayashibara Co., Ltd. | Calcium-containing tissue strengthening agents and use thereof |
AU2003239461A1 (en) | 2002-05-15 | 2003-12-02 | Zhishin Inc. | Nutraceutical compositions comprising citrus alkaloids and method |
US7545801B2 (en) * | 2002-12-02 | 2009-06-09 | Cedar Point Communications, Inc. | In-band control mechanism for switching architecture |
US20060172059A1 (en) * | 2002-12-19 | 2006-08-03 | Kanou Takeuchi | Method of inhibiting water content variation of composition and use thereof |
DE10323178A1 (de) * | 2003-05-22 | 2004-12-09 | Basf Ag | Mischung, umfassend ein Tensid und ein Cotensid |
WO2005025527A1 (de) | 2003-09-09 | 2005-03-24 | Dsm Ip Assets B.V. | Oral wirkendes im wesentlichen wasserfreies topisches mittel enthaltend ein oder mehrere oxidationsempfindliche stoffe |
JP2005132792A (ja) * | 2003-10-31 | 2005-05-26 | Univ Kinki | 抗掻痒剤 |
JP4030495B2 (ja) * | 2003-10-31 | 2008-01-09 | 学校法人近畿大学 | 抗アレルギー剤 |
JP2005170804A (ja) * | 2003-12-08 | 2005-06-30 | Univ Kinki | 抗アレルギー剤 |
FR2869229B1 (fr) * | 2004-04-26 | 2006-08-25 | Sederma Soc Par Actions Simpli | Utilisation d'un inducteur des ugt par voie topique |
US7877473B2 (en) | 2004-07-21 | 2011-01-25 | Sony Corporation | Mode detection of data transfer between a source device and a connected portable device |
EP1771149A1 (en) * | 2004-07-23 | 2007-04-11 | The Procter and Gamble Company | Skin care composition containing a flavonoid and vitamin b3 |
US20060034784A1 (en) * | 2004-08-12 | 2006-02-16 | The Procter & Gamble Company | Oral compositions and systems |
JP3665327B1 (ja) | 2004-09-24 | 2005-06-29 | 小林製薬株式会社 | 消臭剤 |
US20060140881A1 (en) | 2004-12-22 | 2006-06-29 | Guofeng Xu | Oral care compositions containing flavonoids and flavans |
JP4654060B2 (ja) * | 2005-03-29 | 2011-03-16 | 株式会社 ア・ファーマ近大 | ネオヘスペリジンの抗酸化作用に基づく美白剤または色素沈着症改善剤 |
US7629011B2 (en) * | 2005-08-22 | 2009-12-08 | Del Monte Corporation | Process for removing the peel from citrus fruit |
GB0614353D0 (en) * | 2006-07-20 | 2006-08-30 | Oraldent Ltd | Oral compositions, their preparation and use |
-
2006
- 2006-07-20 GB GBGB0614353.1A patent/GB0614353D0/en not_active Ceased
-
2007
- 2007-07-20 CN CN200780027438.7A patent/CN101495090B/zh active Active - Reinstated
- 2007-07-20 US US12/374,447 patent/US20100068157A1/en not_active Abandoned
- 2007-07-20 WO PCT/GB2007/002756 patent/WO2008009956A1/en active Application Filing
- 2007-07-20 GB GB0714228A patent/GB2440440A/en not_active Withdrawn
- 2007-07-20 EP EP07766319A patent/EP2043592B1/en active Active
- 2007-07-20 AT AT07766319T patent/ATE548020T1/de active
- 2007-07-20 CN CN200780027437.2A patent/CN101495089B/zh active Active
- 2007-07-20 JP JP2009520056A patent/JP5508005B2/ja active Active
- 2007-07-20 CA CA2658468A patent/CA2658468C/en active Active
- 2007-07-20 ES ES07766319T patent/ES2384687T3/es active Active
- 2007-07-20 JP JP2009520055A patent/JP5452221B2/ja active Active
- 2007-07-20 US US12/374,443 patent/US9532939B2/en active Active
- 2007-07-20 AT AT07766321T patent/ATE551988T1/de active
- 2007-07-20 EP EP07766321A patent/EP2043593B1/en active Active
- 2007-07-20 CA CA2658710A patent/CA2658710C/en active Active
- 2007-07-20 ES ES07766321T patent/ES2385405T3/es active Active
- 2007-07-20 WO PCT/GB2007/002758 patent/WO2008009958A1/en active Application Filing
-
2013
- 2013-12-27 JP JP2013270823A patent/JP5883428B2/ja active Active
-
2016
- 2016-08-25 US US15/247,806 patent/US9987214B2/en active Active
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0444492B1 (en) * | 1990-02-21 | 1996-01-10 | RICERFARMA Srl | Topically administered compositions based on high molecular weight hyaluronic acid for treating inflammations of the oral cavity, and for oral cavity hygiene and cosmetic treatment |
EP1600143A1 (en) * | 2003-02-13 | 2005-11-30 | Kabushiki Kaisha Hayashibara Seibutsu Kagaku Kenkyujo | SKIN PREPARATION FOR EXTERNAL USE CHARACTERIZED BY CONTAINING SUGAR DERIVATIVE OF a,a-TREHALOSE |
Also Published As
Publication number | Publication date |
---|---|
EP2043592A1 (en) | 2009-04-08 |
CA2658468C (en) | 2017-05-23 |
CA2658710C (en) | 2016-07-05 |
US20100068157A1 (en) | 2010-03-18 |
JP5508005B2 (ja) | 2014-05-28 |
US20160361346A1 (en) | 2016-12-15 |
JP2014074062A (ja) | 2014-04-24 |
EP2043593A1 (en) | 2009-04-08 |
CN101495090B (zh) | 2015-04-22 |
US9987214B2 (en) | 2018-06-05 |
WO2008009958A1 (en) | 2008-01-24 |
CN101495089A (zh) | 2009-07-29 |
ES2384687T3 (es) | 2012-07-11 |
GB2440440A (en) | 2008-01-30 |
CN101495090A (zh) | 2009-07-29 |
ATE548020T1 (de) | 2012-03-15 |
US9532939B2 (en) | 2017-01-03 |
ES2385405T3 (es) | 2012-07-24 |
EP2043592B1 (en) | 2012-03-07 |
WO2008009956A1 (en) | 2008-01-24 |
ATE551988T1 (de) | 2012-04-15 |
JP2009544603A (ja) | 2009-12-17 |
JP5883428B2 (ja) | 2016-03-15 |
GB0614353D0 (en) | 2006-08-30 |
JP5452221B2 (ja) | 2014-03-26 |
EP2043593B1 (en) | 2012-04-04 |
GB0714228D0 (en) | 2007-08-29 |
JP2009544604A (ja) | 2009-12-17 |
US20100055053A1 (en) | 2010-03-04 |
CA2658468A1 (en) | 2008-01-24 |
CA2658710A1 (en) | 2008-01-24 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN101495089B (zh) | 用于口用组合物的组合物及其制备和应用 | |
AU2005319183B2 (en) | Antibacterial and anti-inflammatory oral care composition | |
WO2004028519A1 (ja) | 防腐殺菌剤並びに該防腐殺菌剤を配合した化粧料、医薬品及び食品 | |
JP2011074082A (ja) | 防腐殺菌剤及び人体施用組成物 | |
KR101291216B1 (ko) | 포도근, 검은재나무 및 꽃싸리 추출물을 함유하는 항균용 조성물 | |
JP4734293B2 (ja) | 防腐殺菌剤及び人体施用組成物 | |
JP2005232125A (ja) | 防腐殺菌剤並びに該防腐殺菌剤を配合した化粧品、医薬品及び食品 | |
JP2019214538A (ja) | 歯肉組織細胞への歯周病菌の侵入抑制剤 | |
CN112587421A (zh) | 一种含植物提取物的免洗手消毒凝胶及其制备方法和应用 | |
JPH08231361A (ja) | 口腔用組成物 | |
KR20030009578A (ko) | 구취억제용 구강용 조성물 | |
KR20160084904A (ko) | 천연 약재 추출물을 유효 성분으로 함유하는 구강 위생 증진용 조성물 | |
KR102227751B1 (ko) | 오미자, 백리향 및 꽃향유의 추출 혼합물을 유효성분으로 함유하는 천연 방부대체제 및 이의 용도 | |
JP7393823B2 (ja) | 歯周病菌用口腔組成物 | |
KR100356697B1 (ko) | 여드름에효과가있는피부용조성물 | |
JP2005232012A (ja) | 防腐殺菌剤並びに該防腐殺菌剤を配合した化粧料、医薬品及び食品 | |
KR20240000763A (ko) | 플라즈마 라디칼 용액과 천연 유래 추출물이 함유된 항균제 조성물 | |
KR20220096916A (ko) | 세이지 추출물, 소목 추출물, 어성초 추출물, 로즈마리 추출물, 마늘 추출물, 및 황련 추출물을 유효성분으로 포함하는 항균용 화장료 조성물 | |
JP2001335459A (ja) | 皮膚組成物 | |
JP2005015361A (ja) | 防腐殺菌剤 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C12 | Rejection of a patent application after its publication | ||
RJ01 | Rejection of invention patent application after publication |
Application publication date: 20090729 |
|
GR01 | Patent grant | ||
GR01 | Patent grant |