CN114432398A - Dendrobium nobile pharmaceutical composition and application thereof in toothpaste - Google Patents
Dendrobium nobile pharmaceutical composition and application thereof in toothpaste Download PDFInfo
- Publication number
- CN114432398A CN114432398A CN202011233744.XA CN202011233744A CN114432398A CN 114432398 A CN114432398 A CN 114432398A CN 202011233744 A CN202011233744 A CN 202011233744A CN 114432398 A CN114432398 A CN 114432398A
- Authority
- CN
- China
- Prior art keywords
- dendrobium
- parts
- total
- pharmaceutical composition
- dendrobium total
- 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.)
- Pending
Links
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 70
- 239000000606 toothpaste Substances 0.000 title abstract description 40
- 229940034610 toothpaste Drugs 0.000 title abstract description 36
- 240000004638 Dendrobium nobile Species 0.000 title abstract description 19
- 241001523681 Dendrobium Species 0.000 claims abstract description 168
- 229920001282 polysaccharide Polymers 0.000 claims abstract description 86
- 239000005017 polysaccharide Substances 0.000 claims abstract description 86
- 239000000203 mixture Substances 0.000 claims abstract description 70
- 150000004676 glycans Chemical class 0.000 claims abstract description 65
- 229930013930 alkaloid Natural products 0.000 claims abstract description 62
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 43
- QWUWMCYKGHVNAV-UHFFFAOYSA-N 1,2-dihydrostilbene Chemical group C=1C=CC=CC=1CCC1=CC=CC=C1 QWUWMCYKGHVNAV-UHFFFAOYSA-N 0.000 claims description 33
- 239000003814 drug Substances 0.000 claims description 32
- -1 polysaccharide compounds Chemical class 0.000 claims description 32
- 239000000706 filtrate Substances 0.000 claims description 29
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 27
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 21
- 238000001914 filtration Methods 0.000 claims description 20
- 239000002904 solvent Substances 0.000 claims description 19
- UXDFUVFNIAJEGM-UHFFFAOYSA-N 2-methoxy-5-[2-(3,4,5-trimethoxyphenyl)ethyl]phenol Chemical compound C1=C(O)C(OC)=CC=C1CCC1=CC(OC)=C(OC)C(OC)=C1 UXDFUVFNIAJEGM-UHFFFAOYSA-N 0.000 claims description 18
- 238000000034 method Methods 0.000 claims description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 17
- 238000002156 mixing Methods 0.000 claims description 16
- 239000012453 solvate Substances 0.000 claims description 16
- RYAHJFGVOCZDEI-UFFNCVEVSA-N Dendrobine Chemical compound C([C@H]1CC[C@@H]2[C@@]31C)N(C)[C@@H]3[C@H]1[C@@H](C(C)C)[C@@H]2C(=O)O1 RYAHJFGVOCZDEI-UFFNCVEVSA-N 0.000 claims description 15
- RYAHJFGVOCZDEI-CZKZLRAZSA-N dendrobine Natural products O=C1O[C@@H]2[C@H](C(C)C)[C@H]1[C@H]1[C@@]3(C)[C@@H]2N(C)C[C@H]3CC1 RYAHJFGVOCZDEI-CZKZLRAZSA-N 0.000 claims description 15
- 208000025157 Oral disease Diseases 0.000 claims description 14
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 14
- 208000030194 mouth disease Diseases 0.000 claims description 14
- WQZGKKKJIJFFOK-SVZMEOIVSA-N (+)-Galactose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-SVZMEOIVSA-N 0.000 claims description 12
- QUSGGAWWVBQNLE-UHFFFAOYSA-N 3,4-dihydroxy-5,4'-dimethoxybibenzyl Natural products C1=CC(OC)=CC=C1CCC1=CC(O)=C(O)C(OC)=C1 QUSGGAWWVBQNLE-UHFFFAOYSA-N 0.000 claims description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 12
- MTZQAGJQAFMTAQ-UHFFFAOYSA-N ethyl benzoate Chemical compound CCOC(=O)C1=CC=CC=C1 MTZQAGJQAFMTAQ-UHFFFAOYSA-N 0.000 claims description 12
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 12
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 claims description 12
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 12
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 10
- 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 claims description 10
- 150000003797 alkaloid derivatives Chemical class 0.000 claims description 10
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 10
- 150000003839 salts Chemical class 0.000 claims description 10
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims description 10
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims description 10
- 239000000463 material Substances 0.000 claims description 9
- 229940124531 pharmaceutical excipient Drugs 0.000 claims description 8
- 239000002244 precipitate Substances 0.000 claims description 8
- 235000010418 carrageenan Nutrition 0.000 claims description 7
- 239000000679 carrageenan Substances 0.000 claims description 7
- 229920001525 carrageenan Polymers 0.000 claims description 7
- 229940113118 carrageenan Drugs 0.000 claims description 7
- 239000000377 silicon dioxide Substances 0.000 claims description 7
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 claims description 7
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 6
- HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 claims description 6
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 claims description 6
- 239000004376 Sucralose Substances 0.000 claims description 6
- AEMOLEFTQBMNLQ-WAXACMCWSA-N alpha-D-glucuronic acid Chemical compound O[C@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-WAXACMCWSA-N 0.000 claims description 6
- GVGUFUZHNYFZLC-UHFFFAOYSA-N dodecyl benzenesulfonate;sodium Chemical compound [Na].CCCCCCCCCCCCOS(=O)(=O)C1=CC=CC=C1 GVGUFUZHNYFZLC-UHFFFAOYSA-N 0.000 claims description 6
- 235000019253 formic acid Nutrition 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 claims description 6
- 229920001223 polyethylene glycol Polymers 0.000 claims description 6
- 229920001296 polysiloxane Polymers 0.000 claims description 6
- 235000012239 silicon dioxide Nutrition 0.000 claims description 6
- 229940080264 sodium dodecylbenzenesulfonate Drugs 0.000 claims description 6
- 235000019408 sucralose Nutrition 0.000 claims description 6
- BAQAVOSOZGMPRM-QBMZZYIRSA-N sucralose Chemical compound O[C@@H]1[C@@H](O)[C@@H](Cl)[C@@H](CO)O[C@@H]1O[C@@]1(CCl)[C@@H](O)[C@H](O)[C@@H](CCl)O1 BAQAVOSOZGMPRM-QBMZZYIRSA-N 0.000 claims description 6
- 239000002202 Polyethylene glycol Substances 0.000 claims description 5
- 239000003513 alkali Substances 0.000 claims description 5
- 238000000605 extraction Methods 0.000 claims description 5
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 claims description 5
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 claims description 4
- 229920002125 Sokalan® Polymers 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 4
- 238000010828 elution Methods 0.000 claims description 4
- 239000011347 resin Substances 0.000 claims description 4
- 229920005989 resin Polymers 0.000 claims description 4
- 235000010413 sodium alginate Nutrition 0.000 claims description 4
- 239000000661 sodium alginate Substances 0.000 claims description 4
- 229940005550 sodium alginate Drugs 0.000 claims description 4
- 239000000230 xanthan gum Substances 0.000 claims description 4
- 235000010493 xanthan gum Nutrition 0.000 claims description 4
- 229920001285 xanthan gum Polymers 0.000 claims description 4
- 229940082509 xanthan gum Drugs 0.000 claims description 4
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 claims description 3
- LKAPTZKZHMOIRE-KVTDHHQDSA-N (2s,3s,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolane-2-carbaldehyde Chemical compound OC[C@H]1O[C@H](C=O)[C@@H](O)[C@@H]1O LKAPTZKZHMOIRE-KVTDHHQDSA-N 0.000 claims description 3
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims description 3
- 229920001817 Agar Polymers 0.000 claims description 3
- 229920002101 Chitin Polymers 0.000 claims description 3
- 239000001856 Ethyl cellulose Substances 0.000 claims description 3
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 claims description 3
- 239000004354 Hydroxyethyl cellulose Substances 0.000 claims description 3
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 claims description 3
- 229920001479 Hydroxyethyl methyl cellulose Polymers 0.000 claims description 3
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 3
- 235000010643 Leucaena leucocephala Nutrition 0.000 claims description 3
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 3
- 239000008272 agar Substances 0.000 claims description 3
- 235000010419 agar Nutrition 0.000 claims description 3
- 235000013871 bee wax Nutrition 0.000 claims description 3
- 239000012166 beeswax Substances 0.000 claims description 3
- 229960001631 carbomer Drugs 0.000 claims description 3
- 239000005018 casein Substances 0.000 claims description 3
- BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound 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 claims description 3
- 235000021240 caseins Nutrition 0.000 claims description 3
- LKAPTZKZHMOIRE-UHFFFAOYSA-N chitose Natural products OCC1OC(C=O)C(O)C1O LKAPTZKZHMOIRE-UHFFFAOYSA-N 0.000 claims description 3
- 238000004440 column chromatography Methods 0.000 claims description 3
- 235000019325 ethyl cellulose Nutrition 0.000 claims description 3
- 229920001249 ethyl cellulose Polymers 0.000 claims description 3
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 claims description 3
- 229940071826 hydroxyethyl cellulose Drugs 0.000 claims description 3
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 3
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims description 3
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 3
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 3
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 3
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 claims description 3
- 229920000609 methyl cellulose Polymers 0.000 claims description 3
- 235000010981 methylcellulose Nutrition 0.000 claims description 3
- 239000001923 methylcellulose Substances 0.000 claims description 3
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 3
- 229940068984 polyvinyl alcohol Drugs 0.000 claims description 3
- 235000019422 polyvinyl alcohol Nutrition 0.000 claims description 3
- 150000001298 alcohols Chemical class 0.000 claims description 2
- 241000220479 Acacia Species 0.000 claims 1
- 150000002170 ethers Chemical class 0.000 claims 1
- 150000002334 glycols Chemical class 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 21
- 206010018276 Gingival bleeding Diseases 0.000 abstract description 13
- 230000003110 anti-inflammatory effect Effects 0.000 abstract description 8
- 231100000331 toxic Toxicity 0.000 abstract description 7
- 230000002588 toxic effect Effects 0.000 abstract description 7
- 210000004400 mucous membrane Anatomy 0.000 abstract description 4
- 241000282414 Homo sapiens Species 0.000 abstract description 3
- 230000001194 anti-hemostatic effect Effects 0.000 abstract description 3
- 230000007794 irritation Effects 0.000 abstract description 3
- 238000009472 formulation Methods 0.000 description 19
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 16
- 230000008961 swelling Effects 0.000 description 13
- 239000000243 solution Substances 0.000 description 12
- 239000003795 chemical substances by application Substances 0.000 description 10
- 230000005764 inhibitory process Effects 0.000 description 10
- 238000002360 preparation method Methods 0.000 description 9
- 239000000843 powder Substances 0.000 description 8
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 239000004480 active ingredient Substances 0.000 description 6
- 238000005303 weighing Methods 0.000 description 6
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 5
- 241000699670 Mus sp. Species 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 230000004054 inflammatory process Effects 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- 239000002562 thickening agent Substances 0.000 description 5
- 229930003231 vitamin Natural products 0.000 description 5
- 239000011782 vitamin Substances 0.000 description 5
- 235000013343 vitamin Nutrition 0.000 description 5
- 229940088594 vitamin Drugs 0.000 description 5
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 4
- 238000005160 1H NMR spectroscopy Methods 0.000 description 4
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
- 206010061218 Inflammation Diseases 0.000 description 4
- 241000699666 Mus <mouse, genus> Species 0.000 description 4
- 239000011230 binding agent Substances 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 230000007547 defect Effects 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 239000000314 lubricant Substances 0.000 description 4
- 231100000017 mucous membrane irritation Toxicity 0.000 description 4
- 239000002674 ointment Substances 0.000 description 4
- 239000003755 preservative agent Substances 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 230000000395 remineralizing effect Effects 0.000 description 4
- 239000004094 surface-active agent Substances 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 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 3
- CCEAFOJVRQZWQC-UHFFFAOYSA-N Ddendroxine Natural products CC12C3CCC2CN2CCOC12C1C(C(C)C)C3C(=O)O1 CCEAFOJVRQZWQC-UHFFFAOYSA-N 0.000 description 3
- CCEAFOJVRQZWQC-KFYGABLUSA-N Dendroxine Natural products O=C1O[C@@H]2[C@@H](C(C)C)[C@@H]1[C@H]1[C@]3(C)[C@@H](CN4[C@]23OCC4)CC1 CCEAFOJVRQZWQC-KFYGABLUSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 208000025865 Ulcer Diseases 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 230000001580 bacterial effect Effects 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 239000003086 colorant Substances 0.000 description 3
- 239000006071 cream Substances 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 230000008105 immune reaction Effects 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 210000002200 mouth mucosa Anatomy 0.000 description 3
- 230000002335 preservative effect Effects 0.000 description 3
- 239000008213 purified water Substances 0.000 description 3
- 239000000600 sorbitol Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 230000000699 topical effect Effects 0.000 description 3
- 231100000397 ulcer Toxicity 0.000 description 3
- JWAZRIHNYRIHIV-UHFFFAOYSA-N 2-naphthol Chemical compound C1=CC=CC2=CC(O)=CC=C21 JWAZRIHNYRIHIV-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- GHOKWGTUZJEAQD-UHFFFAOYSA-N Chick antidermatitis factor Natural products OCC(C)(C)C(O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-UHFFFAOYSA-N 0.000 description 2
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 2
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- 208000032843 Hemorrhage Diseases 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- 240000007472 Leucaena leucocephala Species 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 208000002193 Pain Diseases 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
- 229930003571 Vitamin B5 Natural products 0.000 description 2
- 229930003268 Vitamin C Natural products 0.000 description 2
- 229930003427 Vitamin E Natural products 0.000 description 2
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 229960001138 acetylsalicylic acid Drugs 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 230000002146 bilateral effect Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000000740 bleeding effect Effects 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- FAPWYRCQGJNNSJ-UBKPKTQASA-L calcium D-pantothenic acid Chemical compound [Ca+2].OCC(C)(C)[C@@H](O)C(=O)NCCC([O-])=O.OCC(C)(C)[C@@H](O)C(=O)NCCC([O-])=O FAPWYRCQGJNNSJ-UBKPKTQASA-L 0.000 description 2
- 229960002079 calcium pantothenate Drugs 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 239000000625 cyclamic acid and its Na and Ca salt Substances 0.000 description 2
- 230000006378 damage Effects 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
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 229940091249 fluoride supplement Drugs 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- 239000003205 fragrance Substances 0.000 description 2
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 208000007565 gingivitis Diseases 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 238000000227 grinding Methods 0.000 description 2
- 238000004192 high performance gel permeation chromatography Methods 0.000 description 2
- 239000003906 humectant Substances 0.000 description 2
- 230000028993 immune response Effects 0.000 description 2
- 210000000987 immune system Anatomy 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 230000003902 lesion Effects 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
- 210000000214 mouth Anatomy 0.000 description 2
- 239000002324 mouth wash Substances 0.000 description 2
- 229940051866 mouthwash Drugs 0.000 description 2
- 230000000474 nursing effect Effects 0.000 description 2
- 230000036407 pain Effects 0.000 description 2
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 239000012488 sample solution Substances 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- 229910052710 silicon Inorganic materials 0.000 description 2
- 239000010703 silicon Substances 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- PUZPDOWCWNUUKD-UHFFFAOYSA-M sodium fluoride Chemical compound [F-].[Na+] PUZPDOWCWNUUKD-UHFFFAOYSA-M 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000011550 stock solution Substances 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 230000002195 synergetic effect Effects 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 239000003826 tablet 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
- GYDJEQRTZSCIOI-LJGSYFOKSA-N tranexamic acid Chemical compound NC[C@H]1CC[C@H](C(O)=O)CC1 GYDJEQRTZSCIOI-LJGSYFOKSA-N 0.000 description 2
- 229960000401 tranexamic acid Drugs 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 239000011675 vitamin B5 Substances 0.000 description 2
- 235000009492 vitamin B5 Nutrition 0.000 description 2
- 239000011718 vitamin C Substances 0.000 description 2
- 235000019154 vitamin C Nutrition 0.000 description 2
- 239000011709 vitamin E Substances 0.000 description 2
- 235000019165 vitamin E Nutrition 0.000 description 2
- 229940046009 vitamin E Drugs 0.000 description 2
- 229940045997 vitamin a Drugs 0.000 description 2
- 239000000811 xylitol Substances 0.000 description 2
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 2
- 235000010447 xylitol Nutrition 0.000 description 2
- 229960002675 xylitol Drugs 0.000 description 2
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 description 1
- IOHPVZBSOKLVMN-UHFFFAOYSA-N 2-(2-phenylethyl)benzoic acid Chemical compound OC(=O)C1=CC=CC=C1CCC1=CC=CC=C1 IOHPVZBSOKLVMN-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
- WFJIVOKAWHGMBH-UHFFFAOYSA-N 4-hexylbenzene-1,3-diol Chemical compound CCCCCCC1=CC=C(O)C=C1O WFJIVOKAWHGMBH-UHFFFAOYSA-N 0.000 description 1
- 241000186046 Actinomyces Species 0.000 description 1
- 241000186044 Actinomyces viscosus Species 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 206010006326 Breath odour Diseases 0.000 description 1
- SGHZXLIDFTYFHQ-UHFFFAOYSA-L Brilliant Blue Chemical compound [Na+].[Na+].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 SGHZXLIDFTYFHQ-UHFFFAOYSA-L 0.000 description 1
- 241000222122 Candida albicans Species 0.000 description 1
- 244000025254 Cannabis sativa 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
- 241000193403 Clostridium Species 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- UDIPTWFVPPPURJ-UHFFFAOYSA-M Cyclamate Chemical compound [Na+].[O-]S(=O)(=O)NC1CCCCC1 UDIPTWFVPPPURJ-UHFFFAOYSA-M 0.000 description 1
- SNPLKNRPJHDVJA-ZETCQYMHSA-N D-panthenol Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCCO SNPLKNRPJHDVJA-ZETCQYMHSA-N 0.000 description 1
- 239000011703 D-panthenol Substances 0.000 description 1
- 235000004866 D-panthenol Nutrition 0.000 description 1
- 208000006558 Dental Calculus Diseases 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 206010014025 Ear swelling Diseases 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- 208000034619 Gingival inflammation Diseases 0.000 description 1
- 208000032139 Halitosis Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 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 description 1
- 235000006679 Mentha X verticillata Nutrition 0.000 description 1
- 235000002899 Mentha suaveolens Nutrition 0.000 description 1
- 235000001636 Mentha x rotundifolia Nutrition 0.000 description 1
- 241001646834 Mesona Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 239000004909 Moisturizer Substances 0.000 description 1
- 240000001307 Myosotis scorpioides Species 0.000 description 1
- DAOANAATJZWTSJ-UHFFFAOYSA-N N-Decanoylmorpholine Chemical compound CCCCCCCCCC(=O)N1CCOCC1 DAOANAATJZWTSJ-UHFFFAOYSA-N 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 208000007117 Oral Ulcer Diseases 0.000 description 1
- 241000233855 Orchidaceae Species 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 235000003181 Panax pseudoginseng Nutrition 0.000 description 1
- 244000131316 Panax pseudoginseng Species 0.000 description 1
- 241000605862 Porphyromonas gingivalis Species 0.000 description 1
- 241001426527 Rhaponticum Species 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 241000194019 Streptococcus mutans Species 0.000 description 1
- 241000194025 Streptococcus oralis Species 0.000 description 1
- 241000194023 Streptococcus sanguinis Species 0.000 description 1
- 239000005844 Thymol Substances 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- FPIPGXGPPPQFEQ-BOOMUCAASA-N Vitamin A Natural products OC/C=C(/C)\C=C\C=C(\C)/C=C/C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-BOOMUCAASA-N 0.000 description 1
- 208000005946 Xerostomia Diseases 0.000 description 1
- 239000003082 abrasive agent Substances 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 238000000862 absorption spectrum Methods 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 229910000318 alkali metal phosphate Inorganic materials 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- DNEHKUCSURWDGO-UHFFFAOYSA-N aluminum sodium Chemical compound [Na].[Al] DNEHKUCSURWDGO-UHFFFAOYSA-N 0.000 description 1
- 239000003945 anionic surfactant Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 208000002399 aphthous stomatitis Diseases 0.000 description 1
- 229950011260 betanaphthol Drugs 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 235000010216 calcium carbonate Nutrition 0.000 description 1
- JUNWLZAGQLJVLR-UHFFFAOYSA-J calcium diphosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])(=O)OP([O-])([O-])=O JUNWLZAGQLJVLR-UHFFFAOYSA-J 0.000 description 1
- 229940043256 calcium pyrophosphate Drugs 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 229940095731 candida albicans Drugs 0.000 description 1
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 229920003086 cellulose ether Polymers 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 235000019504 cigarettes Nutrition 0.000 description 1
- 239000010630 cinnamon oil Substances 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 239000010634 clove oil Substances 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- HCAJEUSONLESMK-UHFFFAOYSA-N cyclohexylsulfamic acid Chemical compound OS(=O)(=O)NC1CCCCC1 HCAJEUSONLESMK-UHFFFAOYSA-N 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 208000002925 dental caries Diseases 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 229960003949 dexpanthenol Drugs 0.000 description 1
- 235000019821 dicalcium diphosphate Nutrition 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- GPLRAVKSCUXZTP-UHFFFAOYSA-N diglycerol Chemical compound OCC(O)COCC(O)CO GPLRAVKSCUXZTP-UHFFFAOYSA-N 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 239000004205 dimethyl polysiloxane Substances 0.000 description 1
- 235000013870 dimethyl polysiloxane Nutrition 0.000 description 1
- 230000003467 diminishing effect Effects 0.000 description 1
- LRCFXGAMWKDGLA-UHFFFAOYSA-N dioxosilane;hydrate Chemical compound O.O=[Si]=O LRCFXGAMWKDGLA-UHFFFAOYSA-N 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 229940000406 drug candidate Drugs 0.000 description 1
- 206010013781 dry mouth Diseases 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 210000005069 ears Anatomy 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 239000002662 enteric coated tablet Substances 0.000 description 1
- 239000003344 environmental pollutant Substances 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 239000003777 experimental drug Substances 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 150000002222 fluorine compounds Chemical class 0.000 description 1
- 230000000855 fungicidal effect Effects 0.000 description 1
- 230000007661 gastrointestinal function Effects 0.000 description 1
- 230000005176 gastrointestinal motility Effects 0.000 description 1
- 238000005227 gel permeation chromatography Methods 0.000 description 1
- 210000004195 gingiva Anatomy 0.000 description 1
- 208000011759 gum bleeding Diseases 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000002439 hemostatic effect Effects 0.000 description 1
- 241000411851 herbal medicine Species 0.000 description 1
- IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 1
- 229960003258 hexylresorcinol Drugs 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000036046 immunoreaction Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000037456 inflammatory mechanism Effects 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000002085 irritant Substances 0.000 description 1
- 231100000021 irritant Toxicity 0.000 description 1
- 235000020061 kirsch Nutrition 0.000 description 1
- 230000003859 lipid peroxidation Effects 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000001525 mentha piperita l. herb oil Substances 0.000 description 1
- 239000001683 mentha spicata herb oil Substances 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 230000001333 moisturizer Effects 0.000 description 1
- 230000003020 moisturizing effect Effects 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 230000009854 mucosal lesion Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000003605 opacifier Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 230000000149 penetrating effect Effects 0.000 description 1
- HWGNBUXHKFFFIH-UHFFFAOYSA-I pentasodium;[oxido(phosphonatooxy)phosphoryl] phosphate Chemical compound [Na+].[Na+].[Na+].[Na+].[Na+].[O-]P([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O HWGNBUXHKFFFIH-UHFFFAOYSA-I 0.000 description 1
- 235000019477 peppermint oil Nutrition 0.000 description 1
- 201000001245 periodontitis Diseases 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- 210000001539 phagocyte Anatomy 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- OQUKIQWCVTZJAF-UHFFFAOYSA-N phenol;sulfuric acid Chemical compound OS(O)(=O)=O.OC1=CC=CC=C1 OQUKIQWCVTZJAF-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 229940057847 polyethylene glycol 600 Drugs 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229910001414 potassium ion Inorganic materials 0.000 description 1
- 239000000955 prescription drug Substances 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- JUJWROOIHBZHMG-RALIUCGRSA-N pyridine-d5 Chemical compound [2H]C1=NC([2H])=C([2H])C([2H])=C1[2H] JUJWROOIHBZHMG-RALIUCGRSA-N 0.000 description 1
- 150000003856 quaternary ammonium compounds Chemical class 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000000518 rheometry 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
- 108700004121 sarkosyl Proteins 0.000 description 1
- 231100000241 scar Toxicity 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 230000001624 sedative effect Effects 0.000 description 1
- 239000000779 smoke Substances 0.000 description 1
- 238000002791 soaking Methods 0.000 description 1
- 235000015424 sodium Nutrition 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229940083542 sodium Drugs 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 229960001462 sodium cyclamate Drugs 0.000 description 1
- FQENQNTWSFEDLI-UHFFFAOYSA-J sodium diphosphate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]P([O-])(=O)OP([O-])([O-])=O FQENQNTWSFEDLI-UHFFFAOYSA-J 0.000 description 1
- 239000011775 sodium fluoride Substances 0.000 description 1
- 235000013024 sodium fluoride Nutrition 0.000 description 1
- 229940075560 sodium lauryl sulfoacetate Drugs 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 229960004711 sodium monofluorophosphate Drugs 0.000 description 1
- 235000019832 sodium triphosphate Nutrition 0.000 description 1
- ADWNFGORSPBALY-UHFFFAOYSA-M sodium;2-[dodecyl(methyl)amino]acetate Chemical compound [Na+].CCCCCCCCCCCCN(C)CC([O-])=O ADWNFGORSPBALY-UHFFFAOYSA-M 0.000 description 1
- UAJTZZNRJCKXJN-UHFFFAOYSA-M sodium;2-dodecoxy-2-oxoethanesulfonate Chemical compound [Na+].CCCCCCCCCCCCOC(=O)CS([O-])(=O)=O UAJTZZNRJCKXJN-UHFFFAOYSA-M 0.000 description 1
- 235000019721 spearmint oil Nutrition 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 208000003265 stomatitis Diseases 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 239000012085 test solution Substances 0.000 description 1
- 235000019818 tetrasodium diphosphate Nutrition 0.000 description 1
- 230000009974 thixotropic effect Effects 0.000 description 1
- 229960000790 thymol Drugs 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 230000000472 traumatic effect Effects 0.000 description 1
- WGIWBXUNRXCYRA-UHFFFAOYSA-H trizinc;2-hydroxypropane-1,2,3-tricarboxylate Chemical compound [Zn+2].[Zn+2].[Zn+2].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O WGIWBXUNRXCYRA-UHFFFAOYSA-H 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
- 239000011719 vitamin A Substances 0.000 description 1
- 235000019155 vitamin A Nutrition 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 239000000341 volatile oil Substances 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 239000011746 zinc citrate Substances 0.000 description 1
- 235000006076 zinc citrate Nutrition 0.000 description 1
- 229940068475 zinc citrate Drugs 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/898—Orchidaceae (Orchid family)
- A61K36/8984—Dendrobium
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
- A61K8/73—Polysaccharides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/96—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]
- A61K8/9794—Liliopsida [monocotyledons]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Epidemiology (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Botany (AREA)
- Biotechnology (AREA)
- Birds (AREA)
- Mycology (AREA)
- Microbiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Diabetes (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Hematology (AREA)
- General Chemical & Material Sciences (AREA)
- Alternative & Traditional Medicine (AREA)
- Medical Informatics (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Cosmetics (AREA)
Abstract
The invention provides a dendrobium nobile pharmaceutical composition and application thereof in toothpaste. The pharmaceutical composition comprises the following components in parts by weight: 1-10 parts of dendrobium total alkaloids, 1-10 parts of dendrobium total polysaccharides and 1-10 parts of dendrobium total bibenzyls. The pharmaceutical composition is safe and reliable to human body, has no toxic or side effect, has no irritation to mucous membrane, has obvious anti-inflammatory and hemostatic effects, can be used in oral care compositions such as toothpaste and the like, and is used for preventing and treating gingival bleeding and the like.
Description
Technical Field
The invention relates to the technical field of natural medicines, and particularly relates to a dendrobium stem medicinal composition and application thereof in toothpaste.
Background
At present, with the continuous improvement of living standard of people, the oral cavity and teeth problems such as gum bleeding, pain, swelling and the like caused by refined diet are frequent. People pay more and more attention to the nursing of oral teeth, and the ordinary toothpaste gradually develops to the Chinese herbal medicine toothpaste with the nursing effect.
The traditional Chinese medicine Dendrobium nobile (Dendrobium nobile Lindl), also called flat yellow grass, Royle rhaponticum etc., is a Dendrobium plant in the family of Orchidaceae, is a traditional famous and precious medicinal plant in China, is listed as the top quality in the book Shen nong Ben Cao Jing as early as possible, and is known as one of the Jiuda Mesona. The medicinal part is fresh or dry stem, and has effects of nourishing yin, replenishing vital essence, improving gastrointestinal function, reducing weight and prolonging life. Modern pharmacological studies show that the main active ingredients of dendrobium nobile lindl are alkaloids and polysaccharide compounds, and the dendrobium nobile lindl has multiple effects of resisting tumors, oxidation and aging, enhancing immunity, regulating gastrointestinal motility, reducing blood sugar, reducing blood fat and the like. The dendrobium total polysaccharide has a good moisturizing effect.
The prior art oral care compositions for treating oral diseases are mainly deficient in the following respects:
defect one: and (4) immune reaction. In order to improve the efficacy of preventing and treating gingival bleeding, a plurality of Chinese herbal toothpastes on the market at present are often added with tranexamic acid which is a hemostatic prescription drug, and long-term excessive use of the tranexamic acid can cause gingiva to generate antibodies, so that the use risk of consumers is increased. Therefore, the search for purely natural active ingredients with antibacterial, anti-inflammatory and hemostatic effects has wide application prospect.
And defect two: irritation of mucous membrane. The irritant toothpaste is used for irritating mucous membrane, so that oral ulcer is easily caused.
And a third defect: the process is complicated and the cost is high.
And a fourth defect: low safety and reliability, and certain toxic and side effect.
For the above reasons, further research on oral care compositions for treating oral diseases is needed to solve the problems that the common oral care compositions are easy to generate immune response and mucosal irritation, and have complex process, high cost, low safety and reliability and certain toxic and side effects.
Disclosure of Invention
Based on the above, the main purpose of the present invention is to provide a dendrobe pharmaceutical composition, so as to solve the problems that the common oral care composition in the prior art is easy to generate immune reaction and mucosal irritation, has a complex process, a high cost, low safety and reliability, and has a certain toxic and side effect.
In order to achieve the above object, according to one aspect of the present invention, there is provided a pharmaceutical composition comprising the following components in parts by weight: 1-10 parts of dendrobium total alkaloids, 1-10 parts of dendrobium total polysaccharides and 1-10 parts of dendrobium total bibenzyls.
Further, the dendrobium total alkaloids comprise dendrobine or pharmaceutically acceptable salt or solvate thereof, and/or dendrolether alkali or pharmaceutically acceptable salt or solvate thereof.
Further, the dendrobium total polysaccharide comprises dendrobium polysaccharide compound with D-glucuronic acid and D-galactose, the molar ratio of the D-glucuronic acid to the D-galactose is 5:1 to 0.5:1, and the molecular weight of the dendrobium polysaccharide compound is in the range of 2000Da to 3000 Da.
Further, the dendrobium total bibenzyl comprises erianin or a pharmaceutically acceptable solvate thereof, and/or 3,4-dihydroxy-5, 4' -dimethoxy bibenzyl or a pharmaceutically acceptable solvate thereof.
Further, the dendrobium polysaccharide compound has the following structure:
wherein n is 6, 7 or 8.
Further, the pharmaceutical composition comprises the following components in parts by weight: 5-10 parts of dendrobium total alkaloids, 1-10 parts of dendrobium total polysaccharides and 1-10 parts of dendrobium total bibenzyls.
Further, the pharmaceutical composition comprises the following components in parts by weight: 1-10 parts of dendrobium total alkaloids, 5-10 parts of dendrobium total polysaccharides and 1-10 parts of dendrobium total bibenzyls.
Further, the pharmaceutical composition comprises the following components in parts by weight: 1 part of dendrobium total alkaloids, 10 parts of dendrobium total polysaccharides and 1-10 parts of dendrobium total bibenzyls.
Further, the pharmaceutical composition comprises the following components in parts by weight: 1 part of dendrobium total alkaloids, 10 parts of dendrobium total polysaccharides and 2-5 parts of dendrobium total bibenzyls.
Further, the pharmaceutical composition comprises the following components in parts by weight: 1 part of dendrobium total alkaloids, 10 parts of dendrobium total polysaccharides and 2 parts of dendrobium total bibenzyls.
Further, the pharmaceutical composition comprises the following components in parts by weight: 1 part of dendrobium total alkaloids, 10 parts of dendrobium total polysaccharides and 5 parts of dendrobium total bibenzyl.
Further, the pharmaceutical composition comprises the following components in parts by weight: 1 part of dendrobium total alkaloids, 10 parts of dendrobium total polysaccharides and 10 parts of dendrobium total bibenzyls.
Further, the pharmaceutical composition comprises the following components in parts by weight: 10 parts of dendrobium total alkaloids, 1 part of dendrobium polysaccharide compound and 1 part of dendrobium total bibenzyl.
Further, the pharmaceutical composition comprises the following components in parts by weight: 1 part of dendrobium total alkaloids, 5 parts of dendrobium total polysaccharides and 5 parts of dendrobium total bibenzyls.
According to another aspect of the present invention, there is provided an oral care composition comprising the above pharmaceutical composition.
Further, the oral care composition is a toothpaste.
Further, the oral care composition also comprises pharmaceutically acceptable pharmaceutic adjuvants.
Further, the pharmaceutical adjuvant is selected from one or more of sodium carboxymethylcellulose, carbomer, polyvinyl alcohol, hydroxyethyl cellulose, sodium alginate, chitin, chitose, hydroxypropyl methylcellulose, ethyl cellulose, agar, hydroxyethyl methylcellulose, hydroxypropyl cellulose, beeswax, xanthan gum, acacia, casein, sucralose, ethyl benzoate, polyethylene glycol, carrageenan, silicon dioxide, sodium carboxymethylcellulose, methyl silicone, stearyl alcohol, sodium dodecylbenzene sulfonate, isopropyl myristate, glycerol and methylcellulose.
According to another aspect of the present invention there is provided the use of a pharmaceutical composition as described above or an oral care composition as described above in the manufacture of a medicament for the treatment of an oral disease.
Further, the oral care composition is a toothpaste.
According to another aspect of the present invention, there is provided a method of preparing a pharmaceutical composition, the method comprising the steps of:
1) taking a proper amount of dendrobium medicinal material, adding a first solvent for decoction and filtering to obtain first medicine residue and first filtrate, adding alcohol into the first filtrate to reach 70-90% of alcohol concentration, and filtering to obtain precipitate which is dendrobium total polysaccharide;
2) taking a proper amount of the first medicine residue, adding acid to dissolve and filter the first medicine residue to obtain second medicine residue and second filtrate, adding alkali to the second filtrate until the pH value is 8-10, and filtering the second filtrate to obtain precipitate which is the dendrobium total alkaloid;
3) taking a proper amount of the second medicine residue, adding a second solvent for extraction, filtering to obtain a third medicine residue and a third filtrate, carrying out macroporous resin column chromatography on the third filtrate, and collecting 60-80% alcohol elution fraction to obtain the dendrobium total bibenzyl; and
4) mixing the dendrobium total polysaccharide, the dendrobium total alkaloid and the dendrobium total bibenzyl to obtain a pharmaceutical composition, wherein the pharmaceutical composition comprises the following components in parts by weight: 1-10 parts of dendrobium total alkaloids, 1-10 parts of dendrobium total polysaccharides and 1-10 parts of dendrobium total bibenzyls.
Further, the first solvent and the second solvent are the same or different.
Further, the first solvent is selected from C1～C4Alcohol, glycol, ether, waterOne or more of formic acid and acetic acid.
Further, the second solvent is selected from C1～C4One or more of alcohol, glycol, ether, water, formic acid and acetic acid.
According to another aspect of the present invention, there is provided a process for preparing an oral care composition comprising mixing the above pharmaceutical composition with a pharmaceutically acceptable pharmaceutical excipient.
By applying the technical scheme of the invention, the pharmaceutical composition comprises the following components in parts by weight: 1-10 parts of dendrobium total alkaloids, 1-10 parts of dendrobium total polysaccharides and 1-10 parts of dendrobium total bibenzyls. The pharmaceutical composition is safe and reliable to a human body, has no toxic or side effect, has no irritation to mucous membrane, has obvious inflammation diminishing and bleeding stopping effects, can be used in oral care compositions such as toothpaste and the like, and can prevent and treat gingival bleeding and the like, so that the problems that common oral care compositions are easy to generate immunoreaction and mucous membrane irritation, complex in process, high in cost, low in safety and reliability and have certain toxic and side effects can be well solved.
Drawings
In order to more clearly illustrate the technical solutions in the embodiments of the present application, the drawings needed to be used in the description of the embodiments are briefly introduced below, and it is obvious that the drawings in the following description are only some embodiments of the present application, and it is obvious for a person skilled in the art to obtain other drawings based on these drawings without exceeding the protection scope of the present application.
FIG. 1 is an HPGPC chromatogram of a dendrobe polysaccharide compound involved in the present invention.
FIG. 2 is an infrared absorption spectrum of a dendrobe polysaccharide compound involved in the present invention.
Detailed Description
The technical solutions in the embodiments of the present application will be clearly and completely described below with reference to the drawings in the embodiments of the present application, and it is obvious that the described embodiments are some, but not all, embodiments of the present application. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present application.
It should be noted that the embodiments and features of the embodiments in the present application may be combined with each other without conflict. The present invention will be described in detail with reference to examples.
The present invention is described in further detail below with reference to specific examples, which should not be construed as limiting the scope of the invention as claimed herein.
As described in the background section, the existing oral care compositions are prone to immune reactions, mucosal irritation, complex process and high cost, and have problems of low safety and reliability, and certain toxic and side effects. In order to solve the problems, the invention provides a pharmaceutical composition, which comprises the following components in parts by weight: 1-10 parts of dendrobium total alkaloids, 1-10 parts of dendrobium total polysaccharides and 1-10 parts of dendrobium total bibenzyl. The medicinal composition has the effects of resisting inflammation, eliminating swelling and stopping bleeding, has the effect superior to that of dendrobium nobile medicinal materials and independent dendrobium nobile total alkaloids, dendrobium nobile total polysaccharides and dendrobium nobile total bibenzyl, and has good development and application prospects of oral care products such as toothpaste and the like.
In a preferred embodiment, the dendrobe total alkaloids comprise dendrobine or a pharmaceutically acceptable salt or solvate thereof, and/or dendrolether base or a pharmaceutically acceptable salt or solvate thereof.
Other alkaloid compounds in Dendrobine (Dendrobine) and Dendrobine (Dendroxine) and dendrobii total alkaloids can be converted into pharmaceutically acceptable salts or solvates thereof, preferably acid addition salts such as hydrochloride, hydrobromide, phosphate, acetate, fumarate, maleate, tartrate, citrate, oxalate, mesylate or p-toluenesulfonate.
Dendrobine (Dendrobine) has the following structural formula:
the dendrobine (Dendroxine) has the following structural formula:
in a preferred embodiment, the dendrobe total polysaccharide comprises dendrobe polysaccharide compounds having D-glucuronic acid and D-galactose in a molar ratio of D-glucuronic acid to D-galactose of 5:1 to 0.5:1, the dendrobe polysaccharide compounds having a molecular weight in the range of 2000Da to 3000 Da.
In a preferred embodiment, the dendrobium total bibenzyl comprises erianin or a pharmaceutically acceptable solvate thereof, and/or 3,4-dihydroxy-5, 4' -dimethoxybibenzyl or a pharmaceutically acceptable solvate thereof.
Erianin and 3,4-dihydroxy-5,4 '-dimethoxy bibenzyl (3,4-dihydroxy-5, 4' -dimethoxy bibenzyl) and other bibenzyl compounds in dendrobe total bibenzyl can be converted into pharmaceutically acceptable solvates.
The structural formula of Erianin (Erianin) is shown below:
the structural formula of 3,4-dihydroxy-5,4 '-dimethoxy bibenzyl (3,4-dihydroxy-5, 4' -dimethoxy bibenzyl) is shown as follows:
the alkaloid compound contained in the dendrobium total alkaloids and the bibenzyl compound contained in the dendrobium total bibenzyl can exist in a stereoisomer. It is to be understood that the present invention encompasses the use of all geometric and optical isomers of the above-described compounds and mixtures thereof, including racemic compounds. The use of tautomeric forms and mixtures thereof also form an aspect of the invention.
The alkaloid compound or its pharmaceutically acceptable salt or solvate, the bibenzyl compound or its pharmaceutically acceptable solvate and total dendrobium polysaccharides contained in total dendrobium alkaloids can be generally administered to mammals including human beings in the form of common pharmaceutical compositions, such as capsules, microcapsules, tablets, granules, powders, troches, syrups, aerosols, inhalations, solutions, injections, suspensions, ointments, creams, suppositories and the like, and the most suitable formulation form is ointment or cream.
The pharmaceutical composition containing herba Dendrobii total alkaloids, herba Dendrobii total bibenzyls and herba Dendrobii total polysaccharides can be applied topically, such as oral topical application, and can be in the form of solution, suspension, heptafluorocarbon aerosol and dry powder preparation; or systemically, e.g. orally, in the form of tablets, capsules, syrups, powders or granules, or parenterally, in the form of solutions or suspensions, or subcutaneously or rectally, or transdermally.
For topical application, the active substance is suitably applied in the form of an ointment, medicated liquor, emulsion, solution, lotion, spray, suspension, or the like. It is preferably in the form of ointment or cream. These agents for topical administration may be prepared by mixing the product as the active ingredient with non-toxic, inert, solid or liquid carriers conventionally used in such formulations and suitable for topical treatment.
In a preferred embodiment, the dendrobe polysaccharide compound has the following structure:
wherein n is 6, 7 or 8.
In order to further enhance the synergistic effect of the two components in the pharmaceutical composition, i.e. enhance the anti-inflammatory and hemostatic effects of the pharmaceutical composition, in a preferred embodiment, the pharmaceutical composition comprises the following components in parts by weight: 5-10 parts of dendrobium total alkaloids, 1-10 parts of dendrobium total polysaccharides and 1-10 parts of dendrobium total bibenzyl.
In a preferred embodiment, the pharmaceutical composition comprises the following components in parts by weight: 1-10 parts of dendrobium total alkaloids, 5-10 parts of dendrobium total polysaccharides and 1-10 parts of dendrobium total bibenzyls.
In a preferred embodiment, the pharmaceutical composition comprises the following components in parts by weight: 1 part of dendrobium total alkaloids, 10 parts of dendrobium total polysaccharides and 1-10 parts of dendrobium total bibenzyls.
In a preferred embodiment, the pharmaceutical composition comprises the following components in parts by weight: 1 part of dendrobium total alkaloids, 10 parts of dendrobium total polysaccharides and 2-5 parts of dendrobium total bibenzyls.
In a preferred embodiment, the pharmaceutical composition comprises the following components in parts by weight: 1 part of dendrobium total alkaloids, 10 parts of dendrobium total polysaccharides and 2 parts of dendrobium total bibenzyls.
In a preferred embodiment, the pharmaceutical composition comprises the following components in parts by weight: 1 part of dendrobium total alkaloids, 10 parts of dendrobium total polysaccharides and 5 parts of dendrobium total bibenzyl.
In a preferred embodiment, the pharmaceutical composition comprises the following components in parts by weight: 1 part of dendrobium total alkaloids, 10 parts of dendrobium total polysaccharides and 10 parts of dendrobium total bibenzyls.
In a preferred embodiment, the pharmaceutical composition comprises the following components in parts by weight: 10 parts of dendrobium total alkaloids, 1 part of dendrobium total polysaccharides and 1 part of dendrobium total bibenzyl.
In a preferred embodiment, the pharmaceutical composition comprises the following components in parts by weight: 1 part of dendrobium total alkaloids, 5 parts of dendrobium total polysaccharides and 5 parts of dendrobium total bibenzyls.
According to another aspect of the present invention, there is provided an oral care composition comprising the above pharmaceutical composition.
In a preferred embodiment, the oral care composition is a toothpaste.
The oral care composition of the present invention can be formulated, for example, into a toothpaste, a dental gel, or an aqueous or aqueous-alcoholic oral care composition (mouthwash) according to a method known per se.
The oral care compositions of the present invention contain at least one active ingredient of the present invention in a total amount of 0.00001 to 50 wt.%, 0.0001 to 10 wt.%, 0.0001 to 5 wt.%, 0.005 to 1 wt.%, or 0.1 to 20 wt.%, 0.5 to 15 wt.%, or 1 to 5 wt.%, calculated relative to the weight of the composition.
In a preferred embodiment, the oral care composition further comprises a pharmaceutically acceptable pharmaceutical excipient.
Oral care compositions, particularly toothpastes, may also contain abrasives such as silica hydrate, dicalcium phosphate dihydrate, calcium carbonate, sodium bicarbonate, calcium pyrophosphate and alumina. By way of example, a mixture of precipitated silicon and an abrasive of precipitated silicon having a tendency to stick may be used [ Handbook of Pharmaceutical Excipients (Handbook of Pharmaceutical Excipients), british institute of pharmacy, 1Lambeth High Street, london SE 17 JN, england, p.253-256 ]. The first of these is used because of its thixotropic properties and the second is used because of its ability to more effectively remove adherent substances from the tooth surface. The use of these products ensures a low abrasive action, since this is the case of amorphous solids with moderate hardness, which are at the same time totally and completely compatible with fluorides used as mineralizers, since they do not contain calcium salts, which would render them insoluble and reduce their bioavailability.
The formulations of the oral care compositions of the present invention, such as toothpastes, may also contain suitable additives and carriers to improve their properties and simplify preparation. They are selected, for example, from binders, thickeners, fragrances, dyes, preservatives, humectants or moisturizers, surfactants, lubricants, opacifiers, remineralizing agents, surfactants, buffers, alcohols, vitamins, water, other active ingredients, and mixtures thereof.
As the binder, any binder commonly used in these types of formulations, such as tragacanth, may be used. The binder may be present in the formulation in an amount of 0.5 to 1.5 wt.%, relative to the total amount.
Organic thickeners such as sodium carboxymethylcellulose, cellulose ethers, xanthan gum, carrageenan, sodium alginate and carbopol may also be incorporated in the oral care compositions. Inorganic thickeners such as silica thickeners, sodium aluminum silicate and clays can also be used to provide the corresponding rheology. The thickener may be included in the formulation in an amount of 0.5 to 5 wt.% of the total amount.
Toothpastes can be aromatized by the addition of suitable conventional aromatizers such as mint aroma. Essential oils, including clove oil, cinnamon oil, peppermint oil, and spearmint oil, may also be used. The fragrance may be present in the formulation in an amount of 0.5 to 1.5 wt.%, relative to the total amount.
As the colorant, any colorant commonly used in toothpaste formulations can be used, for example, FCF brilliant blue, ci.42090[ KIRSCH PHARMA ]. The colorant may be present in the formulation in an amount of 0.001 to 0.005 wt.%, relative to the total amount.
The preservative may be any conventional preservative, for example a benzoic acid derivative, such as methyl paraben. The preservative may be present in the formulation in an amount of 0.1 to 0.3 wt.%, relative to the total amount.
For example, as sweetening agent, sodium saccharin or cyclamic acid and its derivatives such as sodium cyclamate may be used. The sweetener may be present in the formulation in an amount of 0.08 to 0.15 wt.%, relative to the total amount.
The humectant used to prevent the toothpaste from drying and hardening is chosen in particular from glycerol, sorbitol, propylene glycol, xylitol and liquid polyethylene glycols, in particular mixtures of sorbitol, glycerol and xylitol, for example present in an amount of 1 to 60 wt.%, relative to the total amount.
As the lubricant, any lubricant commonly used in toothpaste formulations can be used, such as dimethicone (polymer of dimethylpolysiloxane), which is a surfactant that imparts good rheological properties to the toothpaste object of the present invention. The lubricant may be present in the formulation in an amount of 0.25 to 0.75 wt.%, relative to the total amount.
As the opacifying agent, any usual opacifying agent, such as titanium dioxide, can be used. The opacifying agent may be present in the formulation in an amount of 0.05 to 1 wt.%, relative to the total amount.
As remineralizing agents, fluoride sources such as sodium fluoride, tin (II) fluoride and sodium monofluorophosphate were used, since in this way 100% active fluoride was obtained as remineralizing agent for white damage caused by organic acids due to bacterial fermentation. The remineralizing agent may be present in the formulation in an amount of 0.2 to 0.4 wt.%, relative to the total amount.
Conventional ingredients, for example, anionic surfactants such as sodium lauryl sulfate, sodium N-lauryl sarcosinate, sodium lauryl sulfoacetate and sodium alkyl glyceryl ether sulfonate, may also be present, usually and additionally. The surfactant may be present in the formulation in an amount of 0.05 to 5 wt.%, relative to the total amount.
The toothpaste proposed by the present invention may also contain vitamins selected from the following, as appropriate: vitamin A, vitamin B5, vitamin C, vitamin E and mixtures thereof. If they are used, each vitamin may be present in the formulation in an amount of 0.1 to 5 wt.%, relative to the total amount. These vitamins can be used as such, as provitamins or in the form of pharmaceutically acceptable salts. Vitamin a is usually used in the form of palmitate, which promotes epithelialization of the oral mucosa and protects the gums. Vitamin B5, more particularly D-panthenol, has soothing, therapeutic, anti-inflammatory effects, protects the epithelial mucosa, promotes epithelialization of lesions, and softens scar tissue, and is suitable for treating lesions resulting from tooth extraction, gingivitis, stomatitis, pain resulting from denture placement, ulcers, traumatic mucosal lesions, and chronic and recurrent ulcers. Vitamin C regenerates the oral mucosal epithelium, stimulates collagen synthesis and the immune system (inflammatory mechanisms) and enhances the ability to protect phagocytic cells from bacterial damage. Vitamin E is commonly used in the form of acetate, which has sedative and anti-inflammatory effects, protects the oral mucosa from lipid peroxidation caused by free radical formation and from environmental pollutants (ozone, cigarette smoke, etc.), and facilitates wound healing. By incorporating all or some of the above vitamins, the present invention provides a toothpaste which has the above characteristics and anti-inflammatory properties and is an effective soothing agent and enhances the protective properties of the oral mucosa and reduces the occurrence of plaque and gum and bacterial contamination.
Other active ingredients are for example: antimicrobial plaque penetrating agents such as beta-naphthol, thymol and hexylresorcinol; or fungicidal compounds, such as quaternary ammonium compounds; tartar healants such as tetrasodium pyrophosphate, GANTREZ-polymer S-70, sodium triphosphate, and zinc citrate; peroxide compounds such as hydrogen peroxide and inorganic peroxides.
Optionally, a buffer may also be used, included at a suitable concentration to maintain the pH between about 6 and 8, such as an alkali metal phosphate buffer. The presence of potassium ions may also provide any allergy-reducing effect.
Water or alcohol may be included in a proportion of 1 to 20 wt.% of the total amount of the substance.
In combination with or instead of alcohol, it is also possible to use diol compounds, such as glycerol, sorbitol or propylene glycol.
The oral care substance of the invention can be readily prepared by mixing the appropriate amounts of the ingredients in, for example, a reactor provided with a stirring paddle.
In a preferred embodiment, the pharmaceutical excipients are selected from one or more of sodium carboxymethylcellulose, carbomer, polyvinyl alcohol, hydroxyethyl cellulose, sodium alginate, chitin, chitose, hydroxypropyl methylcellulose, ethylcellulose, agar, hydroxyethyl methylcellulose, hydroxypropyl cellulose, beeswax, xanthan gum, acacia, casein, sucralose, ethyl benzoate, polyethylene glycol, carrageenan, silicon dioxide, sodium carboxymethylcellulose, methyl silicone, stearyl alcohol, sodium dodecyl benzene sulfonate, isopropyl myristate, glycerol and methyl cellulose.
According to another aspect of the present invention there is provided the use of a pharmaceutical composition as described above or an oral care composition as described above in the manufacture of a medicament for the treatment of an oral disease.
In the present invention, the term "treatment" also includes "prevention" unless there is a specific statement to the contrary. The terms "treatment" and "treating" should be construed accordingly.
The term "prevention" as used herein refers to all actions of inhibiting or delaying the onset of an oral disease by administering a pharmaceutical composition of the invention to an individual.
The term "treatment" as used herein means all actions that alleviate or beneficially alter the symptoms of oral disease by administering a pharmaceutical composition of the present invention to an individual.
In the present invention, oral diseases are concepts covering all diseases occurring in the oral cavity regardless of symptoms thereof, and may include, for example, oral diseases mainly derived from oral microorganisms such as streptococcus mutans, streptococcus oralis, streptococcus sanguis, clostridium nucleatum, porphyromonas gingivalis, actinomyces viscosus, actinomyces companioni, candida albicans, and the like, or oral diseases caused by oral immune degeneration. Non-limiting examples of oral diseases include caries, gingivitis, periodontitis, oral mucosal ulcers, halitosis, and xerostomia.
The present invention also provides a method for treating an oral disease comprising administering to a subject in need thereof a pharmaceutically effective amount of a pharmaceutical composition for preventing or treating an oral disease.
As used herein, the term "subject" includes all animals including mammals, including mice, livestock, humans, and the like.
In the method for treating oral diseases of the present invention, the descriptions of the dose, administration route, administration mode and the like of the pharmaceutical composition are the same as those in connection with the pharmaceutical composition of the present invention.
The term "effective amount" refers to the amount required to at least partially achieve a desired immune response or to delay or completely halt the onset or progression of the particular disease to be treated. The amount depends on the health and physical condition of the subject to be treated, the taxonomic group of the subject, the ability of the subject's immune system to synthesize antibodies, the degree of protection desired, the vaccine formulation, the medical condition assessment, and other relevant factors. This amount will be within a relatively wide range that can be measured in normal attempts.
Of course, for the above therapeutic uses, the dosage varies depending on the compound used, the mode of administration, the treatment desired and the disease to be treated. The daily dosage of the dendrobium total alkaloids defined above can be 0.001mg/kg-100 mg/kg. The daily dose of the above-defined total polysaccharides of Dendrobium nobile may be 0.001mg/kg-100 mg/kg. The daily dosage of total bibenzyl of herba Dendrobii as defined above may be 0.001mg/kg-100 mg/kg.
In a preferred embodiment, the oral care composition is a toothpaste.
According to another aspect of the present invention, there is provided a method of preparing a pharmaceutical composition, the method comprising the steps of:
1) taking a proper amount of dendrobium medicinal material, adding a first solvent for decoction and filtering to obtain first medicine residue and first filtrate, adding alcohol into the first filtrate to reach 70-90% of alcohol concentration, and filtering to obtain precipitate which is dendrobium total polysaccharide;
2) taking a proper amount of the first medicine residue, adding acid to dissolve and filter the first medicine residue to obtain second medicine residue and second filtrate, adding alkali to the second filtrate until the pH value is 8-10, and filtering the second filtrate to obtain precipitate which is the dendrobium total alkaloid;
3) taking a proper amount of the second medicine residue, adding a second solvent for extraction, filtering to obtain a third medicine residue and a third filtrate, carrying out macroporous resin column chromatography on the third filtrate, and collecting 60-80% alcohol elution fraction to obtain the dendrobium total bibenzyl; and
4) mixing the dendrobium total polysaccharide, the dendrobium total alkaloid and the dendrobium total bibenzyl to obtain a pharmaceutical composition, wherein the pharmaceutical composition comprises the following components in parts by weight: 1-10 parts of dendrobium total alkaloids, 1-10 parts of dendrobium total polysaccharides and 1-10 parts of dendrobium total bibenzyls.
In a preferred embodiment, the first solvent and the second solvent are the same or different.
In a preferred embodiment, the first solvent is selected from C1～C4One or more of alcohol, glycol, ether, water, formic acid and acetic acid.
In a preferred embodiment, the second solvent is selected from C1～C4One or more of alcohol, glycol, ether, water, formic acid and acetic acid.
According to another aspect of the present invention, there is provided a process for preparing an oral care composition comprising mixing the above pharmaceutical composition with a pharmaceutically acceptable pharmaceutical excipient.
According to another aspect of the present invention, there is provided a method for preparing toothpaste, which comprises mixing the above-mentioned pharmaceutical composition with a pharmaceutically acceptable excipient.
In a preferred embodiment, the toothpaste formulation consists of the following components: 1-10 parts of dendrobium total alkaloid, 1-10 parts of dendrobium total polysaccharide, 1-10 parts of dendrobium total bibenzyl, 0.1-20 parts of sucralose, 0.1-20 parts of ethyl benzoate, 6000.1-20 parts of polyethylene glycol, 0.1-20 parts of carrageenan, 0.1-100 parts of silicon dioxide, 0.1-20 parts of sodium carboxymethylcellulose, 0.1-20 parts of methyl silicone, 0.1-20 parts of stearyl alcohol, 0.1-20 parts of sodium dodecyl benzene sulfonate, 0.1-20 parts of isopropyl myristate, 0.1-20 parts of glycerol and 100 parts of purified water.
In a preferred embodiment, the preparation of the toothpaste comprises the steps of:
(1) dissolving appropriate amount of herba Dendrobii total polysaccharide, appropriate amount of sucralose, appropriate amount of sodium carboxymethylcellulose, appropriate amount of sodium dodecylbenzenesulfonate, and appropriate amount of glycerol in water;
(2) grinding appropriate amount of herba Dendrobii total alkaloids, appropriate amount of herba Dendrobii bibenzyl, appropriate amount of ethyl benzoate, appropriate amount of silicon dioxide, appropriate amount of stearyl alcohol, appropriate amount of methyl silicone, and appropriate amount of isopropyl myristate into superfine powder;
(3) adding a proper amount of polyethylene glycol 600 and a proper amount of carrageenan into the solution obtained in the step (1) to be uniformly dispersed; and
(4) and (3) uniformly mixing the superfine powder in the step (2) and the solution in the step (3) to form paste, and subpackaging to obtain the toothpaste.
In a preferred embodiment, the dendrobium stem is dendrobium stem.
Examples
Preparation process of dendrobium total polysaccharide
Taking a proper amount of dendrobium nobile lindl, adding 20 times and 10 times of purified water, decocting for 1 hour respectively, filtering to obtain a first filtrate and first medicine residues, combining the first filtrate, concentrating to a concentration equivalent to 1g of dendrobium nobile lindl medicinal material per 1ml, refrigerating for 12 hours at 4 ℃, filtering, adding ethanol into the filtrate to 80% ethanol concentration, standing for 24 hours, filtering, and collecting precipitates to obtain the dendrobium nobile lindl total polysaccharide.
And (3) determining the content of the dendrobium total polysaccharide:
1. the dendrobium polysaccharide test solution:
weighing 20mg of dendrobium total polysaccharide powder, adding hot water to dissolve, and cooling to a constant volume of 10mL to obtain the dendrobium polysaccharide sample solution.
2. Configuration of the standard curve:
the glucose standard is precisely weighed and prepared into a glucose solution with the concentration of 180 mu g/mL, namely a stock solution. Diluting the stock solution, respectively preparing into 0, 30, 60, 90, 120, 150 and 180 μ g/mL, performing phenol-sulfuric acid color reaction according to the method of 3, and measuring absorbance at 480nm together with the dendrobium polysaccharide sample.
3. And (3) detecting the content of the dendrobium polysaccharide:
taking 1mL of dendrobium polysaccharide sample solution, adding 1mL of 5% phenol and 5mL of concentrated sulfuric acid, mixing uniformly, heating in boiling water for 20min, and stopping reaction in ice bath for 5 min. The absorbance was measured at 480nm together with a standard curve sample. And calculating the polysaccharide content in the dendrobium total polysaccharide to be 82.7 percent by a standard curve regression equation.
Preparation of dendrobium polysaccharide compound
Dissolving the above herba Dendrobii total polysaccharide 200g with 1.6L water, adding 0.5mol/L H in water bath at 30 deg.C2O24.0mmol/L acetic acid; and reacting for 4 hours, and after the reaction is finished, performing ultrafiltration treatment to obtain 130g of dendrobium polysaccharide compound.
Identification of dendrobe polysaccharide compound
Collecting 20mg of the polysaccharide compound of herba Dendrobii, detecting by high performance gel chromatography (HPGPC), and separating with Sephax Mono GPC-10MP gel chromatographic column (4.6mm 300mm, 5 μm); taking 0.1mol/L sodium chloride as a mobile phase; the flow rate is 0.5 mL/min; the column temperature is 30 ℃; the difference detector detected as a dendron polysaccharide compound (shown in FIG. 1) with a molecular weight of 2500 Da.
Taking 3mg of the dendrobe polysaccharide compound, adding 500mg of KBr powder, grinding uniformly, tabletting, analyzing by an infrared spectrometer, and obtaining the infrared spectrum absorption shown in figure 2.
Dissolving 15mg of the polysaccharide compound in deuterated pyridine, and analyzing with nuclear magnetic resonance spectrometer1H/13The C-NMR data are shown in Table 1.
TABLE 1 Dendrobium polysaccharide Compounds1H/13C-NMR spectrum data and attribution
Preparation process of dendrobe total alkaloids, dendrobine and dendrobine ether
Taking a proper amount of the first medicine residue, adding 10 times of 0.1% hydrochloric acid solution, soaking for 24 hours, filtering to obtain a second filtrate and second medicine residue, adding NaOH into the second filtrate, adjusting the pH value to 8-9, concentrating to the concentration of 5g of dendrobium nobile medicinal material per 1ml, standing for 12 hours, filtering, adding the precipitate into 95% ethanol with equal weight volume for ultrasonic dissolution, filtering, and recovering ethanol from the filtrate to obtain the dendrobium nobile total alkaloid. Subjecting the total alkaloids to silica gel column chromatography, and eluting with n-hexane-ethyl acetate system (20:1, 10:1) in gradient manner to obtain dendrobine and dendroetherification alkali.
Identification of Dendrobine (Dendrobine)
1H-NMR(400MHz,CDCl3)δ:4.85(1H,dd,J＝5.4,3.1Hz),3.16(1H,t,J ＝8.7Hz),2.72(1H,t,J＝8.7Hz),2.66(1H,d,J＝3.1Hz),2.50(3H,s),2.46 (1H,t,J＝5.4Hz),2.38(1H,t,J＝8.7Hz),2.15(1H,m),2.13(1H,m),2.11(1H, m),2.06(1H,m),1.89(1H,m),1.85(1H,m),1.58(1H,m),1.41(3H,s),0.99 (3H,d,J＝2.9Hz),0.98(3H,d,J＝2.9Hz)；13C-NMR(100MHz,CDCl3)δ: 20.3,21.0,24.9,31.0,32.7,32.9,36.5,43.3,44.2,51.6,52.7,53.9,62.2,67.1, 79.6,179.3。
Identification of dendrobine (Dendroxine)
1H-NMR(400MHz,CDCl3)δ:4.26(1H,d,J＝4.8Hz,H-3),3.87(1H,m, H-17b),3.81(1H,m,H-17a),3.17(1H,m,H-4),3.00(2H,m,H-16),2.81(1H, dd,J＝9.8,7.2Hz,H-11b),2.46(1H,dd,J＝7.0,4.2Hz,H-5),2.21(1H,m, H-11a),2.08(2H,m,H-8),2.01(1H,m,H-6),1.86(1H,m,H-12),1.73(2H,m, H-7),1.51(1H,m,H-9),1.24(3H,s,H-10),1.01(3H,d,J＝6.1Hz,H-14),0.91 (3H,d,J＝6.4Hz,H-13)；13C-NMR(100MHz,CDCl3)δ:178.2,103.1,80.6, 77.1,64.6,55.7,53.8,53.4,51.5,43.1,42.1,31.5,30.7,27.6,24.2,21.1,21.0。
Preparation process of dendrobium total bibenzyl, erianin and 3,4-dihydroxy-5, 4' -dimethoxy bibenzyl
Taking a proper amount of the second medicine residues, adding 10 times of 85% ethanol for reflux extraction twice, each time for 1 hour, filtering to obtain a third medicine residue and a third filtrate, recovering the third filtrate until no alcohol smell exists, loading the third filtrate onto a macroporous resin chromatographic column with the weight equal to that of the dendrobium nobile medicinal material, eluting with 5 times of column volume of water, 20% ethanol and 70% ethanol respectively, collecting 70% ethanol elution fractions, and recovering ethanol to obtain the dendrobium nobile total bibenzyl. Subjecting the dendrobe total bibenzyl to silica gel column chromatography, and gradient eluting with n-hexane-ethyl acetate system (5:1, 2:1) to obtain erianin and 3,4-dihydroxy-5, 4' -dimethoxy bibenzyl.
Structural identification of Erianin
1H-NMR(400MHz,CDCl3)δ:6.80(1H,d,J＝2.0Hz,H-2),6.73(1H, d,J＝8.2Hz,H-5),6.64(1H,dd,J＝8.2,2.0Hz,H-6),6.36(2H,s, H-2',6'),3.85(3H,s,-OCH3-4),3.81(9H,s,-OCH3-3',4',5'),2.81 (4H,s,H-a,a'),5.63(1H,s,-OH)；13C-NMR(100MHz,CDCl3)δ: 153.1,145.4,144.8,137.5,136.3,135.1,119.6,114.5,110.5,105.2,60.7, 56.1,38.3,37.2。
Structural identification of 3,4-dihydroxy-5,4 '-dimethoxy bibenzyl (3,4-dihydroxy-5, 4' -dimethoxy bibenzyl)
1H-NMR(400MHz,CDCl3)δ:7.05(2H,d,J＝6.6Hz,H-2′,6′),6.80(2H, d,J＝6.6Hz,H-3′,5′),6.28(1H,d,J＝1.8Hz,H-2),6.23(1H,d,J＝1.8Hz, H-6),3.75(3H,s,4′-OCH3),3.75(3H,s,5-OCH3),2.81(2H,dd,J＝8.7,6.2Hz, H-2a),2.73(2H,dd,J＝8.8,6.2Hz,H-2a′)；13C-NMR(100MHz,CDCl3)δ: 159.2,149.3,146.2,135.2,134.2,131.6,130.4,114.5,109.7,105.1,56.6,55.5, 39.1,38.5。
The pharmaceutical compositions claimed in the present invention are illustrated in further detail below by means of specific embodiments:
example 1: respectively weighing 1 part of total dendrobium alkaloids, 10 parts of total dendrobium polysaccharides and 10 parts of total dendrobium bibenzyl, and uniformly mixing to obtain the composition 1.
Example 2: respectively weighing 10 parts of total dendrobium alkaloids, 1 part of total dendrobium polysaccharides and 1 part of total dendrobium bibenzyl, and uniformly mixing to obtain the composition 2.
Example 3: respectively weighing 1 part of total dendrobium alkaloids, 5 parts of total dendrobium polysaccharides and 5 parts of total dendrobium bibenzyls, and uniformly mixing to obtain a composition 3.
Example 4: respectively weighing 1 part of total dendrobium alkaloids, 10 parts of total dendrobium polysaccharides and 2 parts of total dendrobium bibenzyl, and uniformly mixing to obtain the composition 4.
Example 5: respectively weighing 1 part of total dendrobium alkaloids, 10 parts of total dendrobium polysaccharides and 5 parts of total dendrobium bibenzyl, and uniformly mixing to obtain the composition 5.
Anti-inflammatory activity of dendrobe pharmaceutical composition
Experimental drugs
Positive drugs: aspirin enteric-coated tablets, batch number: BJ10849, Bayer pharmaceuticals, Inc.
The test pharmaceutical compositions 1-5 are prepared according to the methods of examples 1-5; SHDT, SHSWJ, SHLB are short for herba Dendrobii total polysaccharide, herba Dendrobii total alkaloid and herba Dendrobii total bibenzyl respectively, and are prepared according to the above preparation method of herba Dendrobii total polysaccharide, herba Dendrobii total alkaloid and herba Dendrobii total bibenzyl respectively.
Experimental methods
100 ICR mice, half of the mice, are taken, after being bred adaptively for one week, the mice are randomly divided into 10 groups, 10 mice in each group, and the model group comprises: intragastric administration of a 0.5% CMC-Na solution in solvent; positive drug aspirin group: 0.2g/kg/d aspirin solution is administered by intragastric administration; the test drug components are respectively given 2g/kg/d of the compositions 1-5 and SHDT, SHSWJ and SHLB extracts. The above groups were administered continuously for 5 days, after 1 hour after the last administration, the mouse was sacrificed by cervical dislocation 1 hour after the inflammation, both ears were taken off along the auricle base line, one ear was taken off from the same site by a puncher and weighed by an electronic balance, the swelling degree was determined by subtracting the control side ear weight from the inflammation ear weight, and the inhibition ratio was calculated. Swelling degree is the weight difference (mg) of bilateral auricles; the inhibition rate is (swelling degree of model group-swelling degree of administration group)/swelling degree of model group x 100%
Results of the experiment
As shown in table 2, compared with the model group, the dendrobe pharmaceutical composition can significantly inhibit the mouse auricle swelling caused by xylene (P <0.001, P <0.01), and with the strongest effects of the composition 4 and the composition 5 (the inhibition rates are 65.58% and 63.65%, respectively), the dendrobe total alkaloids also have a certain inhibition effect on the mouse auricle swelling degree, but the inhibition effects of the dendrobe total polysaccharides and the dendrobe total bibenzyl group on the mouse auricle swelling degree are not obvious, which indicates that the dendrobe pharmaceutical composition has a certain synergistic effect.
TABLE 2 Effect of Dendrobium pharmaceutical compositions on mouse ear swelling caused by Dimethylbenzene
Note: p <0.05, P <0.01, P < 0.001; swelling degree is the weight difference (mg) of bilateral auricles;
inhibition rate (degree of swelling in model group-degree of swelling in administered group)/degree of swelling in model group × 100%
Dendrobium toothpaste gingival bleeding inhibition test
Experimental Material
And (3) adding the following auxiliary materials into the dendrobium extract of the composition 1-5, SHDT, SHSWJ, SHLB and the like respectively: 0.1 part of sucralose, 0.5 part of ethyl benzoate, 20 parts of polyethylene glycol 60020 parts, 1 part of carrageenan, 80 parts of silicon dioxide, 5 parts of sodium carboxymethylcellulose, 10 parts of methyl silicone, 5 parts of stearyl alcohol, 10 parts of sodium dodecyl benzene sulfonate, 5 parts of isopropyl myristate, 10 parts of glycerol and 100 parts of purified water, and preparing the toothpaste corresponding to each group according to the preparation steps of the toothpaste. The commercially available toothpaste is the Yunnan white drug powder pseudo-ginseng toothpaste purchased in the supermarket.
Experimental methods
180 gingival bleeding subjects are selected and randomly divided into 9 groups, 20 persons are taken in each group, each group of subjects use each group to give toothpaste, the teeth are brushed for 1 time respectively in the morning and at the evening and are continuously used for 30 days, and gingival bleeding relieving results are recorded on the 10 th day, the 20 th day and the 30 th day from the beginning of the test respectively.
Results of the experiment
The results show (see table 3), the dendrobium medicinal composition toothpaste has a certain inhibition effect on gingival bleeding, the toothpaste prepared from the composition 4 and the composition 5 has a good effect on inhibiting gingival bleeding, and the toothpaste prepared from the dendrobium total polysaccharide, the dendrobium total alkaloid and the dendrobium total bibenzyl has a non-obvious effect on inhibiting gingival bleeding.
TABLE 3 inhibition rate of dendrobe toothpaste on gingival bleeding of subject
The above embodiments show that the dendrobium pharmaceutical composition of the present invention has significant anti-inflammatory and gingival bleeding inhibition effects, and can be used in oral cleaning products such as toothpaste, mouthwash, etc., to effectively prevent and treat gingival bleeding and inflammation.
The foregoing detailed description of the embodiments of the present application has been presented to illustrate the principles and implementations of the present application, and the above description of the embodiments is only provided to help understand the method and the core concept of the present application. Meanwhile, a person skilled in the art should, according to the idea of the present application, change or modify the embodiments and applications of the present application based on the application scope of the present application. In view of the above, the description should not be taken as limiting the application.
Claims (10)
1. The pharmaceutical composition is characterized by comprising the following components in parts by weight: 1-10 parts of dendrobium total alkaloids, 1-10 parts of dendrobium total polysaccharides and 1-10 parts of dendrobium total bibenzyls.
2. The pharmaceutical composition of claim 1, wherein the dendrobe total alkaloids comprise dendrobine or a pharmaceutically acceptable salt or solvate thereof, and/or dendrotherine or a pharmaceutically acceptable salt or solvate thereof; preferably, the dendrobium total polysaccharide comprises dendrobium polysaccharide compounds with D-glucuronic acid and D-galactose, the molar ratio of the D-glucuronic acid to the D-galactose is 5:1 to 0.5:1, and the molecular weight of the dendrobium polysaccharide compounds is in the range of 2000Da to 3000 Da; preferably, the dendrobium total bibenzyl comprises erianin or a pharmaceutically acceptable solvate thereof, and/or 3,4-dihydroxy-5, 4' -dimethoxy bibenzyl or a pharmaceutically acceptable solvate thereof.
3. The pharmaceutical composition of claim 1, wherein the dendrobe polysaccharide compound has the structure:
wherein n is 6, 7 or 8.
4. The pharmaceutical composition according to any one of claims 1 to 3, wherein the pharmaceutical composition comprises the following components in parts by weight: 1-10 parts of dendrobium total alkaloids, 5-10 parts of dendrobium total polysaccharides and 1-10 parts of dendrobium total bibenzyls; preferably, the pharmaceutical composition comprises the following components in parts by weight: 1 part of dendrobium total alkaloids, 10 parts of dendrobium total polysaccharides and 1-10 parts of dendrobium total bibenzyls; more preferably, the pharmaceutical composition comprises the following components in parts by weight: 1 part of dendrobium total alkaloids, 10 parts of dendrobium total polysaccharides and 2-5 parts of dendrobium total bibenzyls.
5. An oral care composition comprising the pharmaceutical composition of any one of claims 1 to 4.
6. The oral care composition of claim 5, further comprising a pharmaceutically acceptable pharmaceutical excipient; preferably, the pharmaceutical adjuvant is selected from one or more of sodium carboxymethylcellulose, carbomer, polyvinyl alcohol, hydroxyethyl cellulose, sodium alginate, chitin, chitose, hydroxypropyl methylcellulose, ethyl cellulose, agar, hydroxyethyl methylcellulose, hydroxypropyl cellulose, beeswax, xanthan gum, acacia, casein, sucralose, ethyl benzoate, polyethylene glycol, carrageenan, silicon dioxide, sodium carboxymethylcellulose, methyl silicone, stearyl alcohol, sodium dodecylbenzene sulfonate, isopropyl myristate, glycerol and methylcellulose.
7. Use of a pharmaceutical composition according to any one of claims 1 to 4 or an oral care composition according to claim 5 or 6 in the manufacture of a medicament for the treatment of an oral disease.
8. A method of preparing a pharmaceutical composition, comprising the steps of:
1) taking a proper amount of dendrobium medicinal material, adding a first solvent for decoction and filtering to obtain first medicine residue and first filtrate, adding alcohol into the first filtrate to reach 70-90% of alcohol concentration, and filtering to obtain precipitate which is dendrobium total polysaccharide;
2) taking a proper amount of the first medicine residue, adding acid to dissolve and filtering to obtain a second medicine residue and a second filtrate, adding alkali to the second filtrate until the pH value is 8-10, and filtering to obtain a precipitate which is the total dendrobium alkaloids;
3) taking a proper amount of the second medicine residue, adding a second solvent for extraction, filtering to obtain a third medicine residue and a third filtrate, carrying out macroporous resin column chromatography on the third filtrate, and collecting 60-80% alcohol elution fraction to obtain the dendrobium total bibenzyl; and
4) mixing the dendrobium total polysaccharide, the dendrobium total alkaloid and the dendrobium total bibenzyl to obtain a pharmaceutical composition, wherein the pharmaceutical composition comprises the following components in parts by weight: 1-10 parts of dendrobium total alkaloids, 1-10 parts of dendrobium total polysaccharides and 1-10 parts of dendrobium total bibenzyls.
9. The method according to claim 8, wherein the first solvent and the second solvent are the same or different, more preferably the first solvent is selected from C1～C4Is selected from one or more of alcohols, glycols, ethers, water, formic acid and acetic acid, more preferably the second solvent is selected from C1～C4One or more of alcohol, glycol, ether, water, formic acid and acetic acid.
10. A method of making an oral care composition comprising mixing the pharmaceutical composition of any one of claims 1 to 4 with a pharmaceutically acceptable pharmaceutical excipient.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011233744.XA CN114432398A (en) | 2020-11-06 | 2020-11-06 | Dendrobium nobile pharmaceutical composition and application thereof in toothpaste |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011233744.XA CN114432398A (en) | 2020-11-06 | 2020-11-06 | Dendrobium nobile pharmaceutical composition and application thereof in toothpaste |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN114432398A true CN114432398A (en) | 2022-05-06 |
Family
ID=81361031
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202011233744.XA Pending CN114432398A (en) | 2020-11-06 | 2020-11-06 | Dendrobium nobile pharmaceutical composition and application thereof in toothpaste |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN114432398A (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115368425A (en) * | 2021-08-06 | 2022-11-22 | 遵义医科大学 | Triterpenoid compound, preparation method and anti-inflammatory application thereof |
-
2020
- 2020-11-06 CN CN202011233744.XA patent/CN114432398A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115368425A (en) * | 2021-08-06 | 2022-11-22 | 遵义医科大学 | Triterpenoid compound, preparation method and anti-inflammatory application thereof |
Non-Patent Citations (1)
| Title |
|---|
| 任晓斌等: "云南白药牙膏对牙龈炎的临床研究" * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| RU2552322C2 (en) | Oral care compositions | |
| JP4828922B2 (en) | Antiallergic agent | |
| JP2015212274A (en) | Oral care composition | |
| EP1444984B1 (en) | Topical pharmaceutical compositions containing natural active constituents suitable for the prevention and treatment of mucosal inflammation processes | |
| JPH03220129A (en) | Sebum suppressant | |
| JPH09208484A (en) | Active oxygen-eliminator and composition containing the same | |
| KR20110131653A (en) | Composition for improving atopic dermatitis comprising hot water extract of green tea and ethanol extract of green tea | |
| KR20170141053A (en) | Composition for prevention or treatment of dental disease comprising an extract of Gardenia jasminoides | |
| KR102562835B1 (en) | Composition for prevention or treatment of oral disease comprising ROSAE LAEVIGATAE Extract | |
| CN114432398A (en) | Dendrobium nobile pharmaceutical composition and application thereof in toothpaste | |
| KR20070000675A (en) | Composition containing mung bean extract, bletillae tuber extract and black cohosh extract and use thereof | |
| KR101063147B1 (en) | Compositions containing ginsenosides Ｒｏ (ｇｉｎｓｅｎｏｓｉｄｅ Ｒｏ) | |
| KR20170141030A (en) | Composition for prevention or treatment of dental disease comprising cistanoside A | |
| JPS5855409A (en) | Medicinal composition for preventing and treating periodontoses | |
| KR102415612B1 (en) | Composition for prevention or treatment of oral disease comprising Melonis Pedicellus Extract | |
| JPS6388117A (en) | Composition for oral cavity | |
| KR102300090B1 (en) | Composition for prevention or treatment of oral disease comprising Viola mandshurica extract | |
| KR102496723B1 (en) | A composition for prevention, improvement or treatment of skin diseases containing a Ophiopogonin-D | |
| KR0138247B1 (en) | The oral cavity hygienic compositions | |
| KR102097387B1 (en) | A composition for preventing and treating oral disease comprising black rice | |
| KR20170134123A (en) | Composition for prevention or treatment of dental disease comprising astragaloside | |
| KR100587695B1 (en) | Compositions for treating acne comprising phytandiol amine | |
| US7129275B2 (en) | Compositions for treating acne comprising phytandiol amine | |
| KR102495895B1 (en) | Composition for prevention or treatment of oral disease comprising Zingiber officinale extract | |
| KR20050118820A (en) | The composition having the prevention of atopy |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20220506 |
|
| WD01 | Invention patent application deemed withdrawn after publication |