CN1149977C - 用于预防和治疗放射性粘膜炎和化学性粘膜炎的药物组合物 - Google Patents
用于预防和治疗放射性粘膜炎和化学性粘膜炎的药物组合物 Download PDFInfo
- Publication number
- CN1149977C CN1149977C CNB998088935A CN99808893A CN1149977C CN 1149977 C CN1149977 C CN 1149977C CN B998088935 A CNB998088935 A CN B998088935A CN 99808893 A CN99808893 A CN 99808893A CN 1149977 C CN1149977 C CN 1149977C
- Authority
- CN
- China
- Prior art keywords
- viscosity
- mucosa
- weight
- radiotherapy
- compositions
- 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.)
- Expired - Fee Related
Links
- 238000001959 radiotherapy Methods 0.000 title claims abstract description 22
- 206010028116 Mucosal inflammation Diseases 0.000 title claims abstract description 12
- 201000010927 Mucositis Diseases 0.000 title claims abstract description 12
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 7
- 238000002512 chemotherapy Methods 0.000 title abstract description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 10
- 239000007788 liquid Substances 0.000 claims abstract description 8
- 239000000203 mixture Substances 0.000 claims description 32
- 210000004877 mucosa Anatomy 0.000 claims description 25
- 239000000463 material Substances 0.000 claims description 17
- 229960004555 rutoside Drugs 0.000 claims description 15
- JMGZEFIQIZZSBH-UHFFFAOYSA-N Bioquercetin Natural products CC1OC(OCC(O)C2OC(OC3=C(Oc4cc(O)cc(O)c4C3=O)c5ccc(O)c(O)c5)C(O)C2O)C(O)C(O)C1O JMGZEFIQIZZSBH-UHFFFAOYSA-N 0.000 claims description 14
- IKGXIBQEEMLURG-BKUODXTLSA-N rutin Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@@H]1OC[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](OC=2C(C3=C(O)C=C(O)C=C3OC=2C=2C=C(O)C(O)=CC=2)=O)O1 IKGXIBQEEMLURG-BKUODXTLSA-N 0.000 claims description 13
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical group C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 claims description 12
- IVTMALDHFAHOGL-UHFFFAOYSA-N eriodictyol 7-O-rutinoside Natural products OC1C(O)C(O)C(C)OC1OCC1C(O)C(O)C(O)C(OC=2C=C3C(C(C(O)=C(O3)C=3C=C(O)C(O)=CC=3)=O)=C(O)C=2)O1 IVTMALDHFAHOGL-UHFFFAOYSA-N 0.000 claims description 12
- FDRQPMVGJOQVTL-UHFFFAOYSA-N quercetin rutinoside Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC=2C(C3=C(O)C=C(O)C=C3OC=2C=2C=C(O)C(O)=CC=2)=O)O1 FDRQPMVGJOQVTL-UHFFFAOYSA-N 0.000 claims description 12
- ALABRVAAKCSLSC-UHFFFAOYSA-N rutin Natural products CC1OC(OCC2OC(O)C(O)C(O)C2O)C(O)C(O)C1OC3=C(Oc4cc(O)cc(O)c4C3=O)c5ccc(O)c(O)c5 ALABRVAAKCSLSC-UHFFFAOYSA-N 0.000 claims description 12
- 235000005493 rutin Nutrition 0.000 claims description 12
- 230000008859 change Effects 0.000 claims description 7
- 239000000126 substance Substances 0.000 claims description 7
- -1 divinylbenzene glucitol compounds Chemical class 0.000 claims description 6
- 229930003935 flavonoid Natural products 0.000 claims description 6
- 150000002215 flavonoids Chemical group 0.000 claims description 6
- 235000017173 flavonoids Nutrition 0.000 claims description 6
- 229960004352 diosmin Drugs 0.000 claims description 5
- VUYDGVRIQRPHFX-UHFFFAOYSA-N hesperidin Natural products COc1cc(ccc1O)C2CC(=O)c3c(O)cc(OC4OC(COC5OC(O)C(O)C(O)C5O)C(O)C(O)C4O)cc3O2 VUYDGVRIQRPHFX-UHFFFAOYSA-N 0.000 claims description 5
- GZSOSUNBTXMUFQ-YFAPSIMESA-N diosmin Chemical compound C1=C(O)C(OC)=CC=C1C(OC1=C2)=CC(=O)C1=C(O)C=C2O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO[C@H]2[C@@H]([C@H](O)[C@@H](O)[C@H](C)O2)O)O1 GZSOSUNBTXMUFQ-YFAPSIMESA-N 0.000 claims description 4
- MYRTYDVEIRVNKP-UHFFFAOYSA-N divinylbenzene Substances C=CC1=CC=CC=C1C=C MYRTYDVEIRVNKP-UHFFFAOYSA-N 0.000 claims description 4
- ZCOLJUOHXJRHDI-CMWLGVBASA-N genistein 7-O-beta-D-glucoside Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=C2C(=O)C(C=3C=CC(O)=CC=3)=COC2=C1 ZCOLJUOHXJRHDI-CMWLGVBASA-N 0.000 claims description 4
- 229920001983 poloxamer Polymers 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- 239000001100 (2S)-5,7-dihydroxy-2-(3-hydroxy-4-methoxyphenyl)chroman-4-one Substances 0.000 claims description 3
- 239000001828 Gelatine Substances 0.000 claims description 3
- ZCOLJUOHXJRHDI-FZHKGVQDSA-N Genistein 7-O-glucoside Natural products O([C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](CO)O1)c1cc(O)c2C(=O)C(c3ccc(O)cc3)=COc2c1 ZCOLJUOHXJRHDI-FZHKGVQDSA-N 0.000 claims description 3
- QUQPHWDTPGMPEX-UHFFFAOYSA-N Hesperidine Natural products C1=C(O)C(OC)=CC=C1C1OC2=CC(OC3C(C(O)C(O)C(COC4C(C(O)C(O)C(C)O4)O)O3)O)=CC(O)=C2C(=O)C1 QUQPHWDTPGMPEX-UHFFFAOYSA-N 0.000 claims description 3
- QUQPHWDTPGMPEX-UTWYECKDSA-N aurantiamarin Natural products COc1ccc(cc1O)[C@H]1CC(=O)c2c(O)cc(O[C@@H]3O[C@H](CO[C@@H]4O[C@@H](C)[C@H](O)[C@@H](O)[C@H]4O)[C@@H](O)[C@H](O)[C@H]3O)cc2O1 QUQPHWDTPGMPEX-UTWYECKDSA-N 0.000 claims description 3
- APSNPMVGBGZYAJ-GLOOOPAXSA-N clematine Natural products COc1cc(ccc1O)[C@@H]2CC(=O)c3c(O)cc(O[C@@H]4O[C@H](CO[C@H]5O[C@@H](C)[C@H](O)[C@@H](O)[C@H]5O)[C@@H](O)[C@H](O)[C@H]4O)cc3O2 APSNPMVGBGZYAJ-GLOOOPAXSA-N 0.000 claims description 3
- 229920000159 gelatin Polymers 0.000 claims description 3
- 235000019322 gelatine Nutrition 0.000 claims description 3
- NNUVCMKMNCKPKN-UHFFFAOYSA-N glycitein Natural products COc1c(O)ccc2OC=C(C(=O)c12)c3ccc(O)cc3 NNUVCMKMNCKPKN-UHFFFAOYSA-N 0.000 claims description 3
- 235000008466 glycitein Nutrition 0.000 claims description 3
- DXYUAIFZCFRPTH-UHFFFAOYSA-N glycitein Chemical compound C1=C(O)C(OC)=CC(C2=O)=C1OC=C2C1=CC=C(O)C=C1 DXYUAIFZCFRPTH-UHFFFAOYSA-N 0.000 claims description 3
- 229940025878 hesperidin Drugs 0.000 claims description 3
- QUQPHWDTPGMPEX-QJBIFVCTSA-N hesperidin Chemical compound C1=C(O)C(OC)=CC=C1[C@H]1OC2=CC(O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@@H](CO[C@H]4[C@@H]([C@H](O)[C@@H](O)[C@H](C)O4)O)O3)O)=CC(O)=C2C(=O)C1 QUQPHWDTPGMPEX-QJBIFVCTSA-N 0.000 claims description 3
- ARGKVCXINMKCAZ-UHFFFAOYSA-N neohesperidine Natural products C1=C(O)C(OC)=CC=C1C1OC2=CC(OC3C(C(O)C(O)C(CO)O3)OC3C(C(O)C(O)C(C)O3)O)=CC(O)=C2C(=O)C1 ARGKVCXINMKCAZ-UHFFFAOYSA-N 0.000 claims description 3
- 229960000502 poloxamer Drugs 0.000 claims description 3
- 229920001987 poloxamine Polymers 0.000 claims description 3
- OXGUCUVFOIWWQJ-HQBVPOQASA-N quercitrin Chemical compound O[C@@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@H]1OC1=C(C=2C=C(O)C(O)=CC=2)OC2=CC(O)=CC(O)=C2C1=O OXGUCUVFOIWWQJ-HQBVPOQASA-N 0.000 claims description 3
- DCTLJGWMHPGCOS-UHFFFAOYSA-N Osajin Chemical compound C1=2C=CC(C)(C)OC=2C(CC=C(C)C)=C(O)C(C2=O)=C1OC=C2C1=CC=C(O)C=C1 DCTLJGWMHPGCOS-UHFFFAOYSA-N 0.000 claims 4
- OUZCFMSJGDEXRT-UHFFFAOYSA-N Scandinone Natural products O=C1C=2C(OC)=C(CC=C(C)C)C=3OC(C)(C)C=CC=3C=2OC=C1C1=CC=C(O)C=C1 OUZCFMSJGDEXRT-UHFFFAOYSA-N 0.000 claims 4
- CJPNHKPXZYYCME-UHFFFAOYSA-N Genistin Natural products OCC1OC(Oc2ccc(O)c3OC(=CC(=O)c23)c4ccc(O)cc4)C(O)C(O)C1O CJPNHKPXZYYCME-UHFFFAOYSA-N 0.000 claims 2
- YCUNGEJJOMKCGZ-UHFFFAOYSA-N Pallidiflorin Natural products C1=CC(OC)=CC=C1C1=COC2=CC=CC(O)=C2C1=O YCUNGEJJOMKCGZ-UHFFFAOYSA-N 0.000 claims 2
- 239000008365 aqueous carrier Substances 0.000 claims 2
- 210000004400 mucous membrane Anatomy 0.000 abstract description 5
- 230000002225 anti-radical effect Effects 0.000 abstract 1
- 239000000499 gel Substances 0.000 abstract 1
- 238000011127 radiochemotherapy Methods 0.000 abstract 1
- 241001597008 Nomeidae Species 0.000 description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- 238000011282 treatment Methods 0.000 description 11
- 206010028980 Neoplasm Diseases 0.000 description 10
- 229920001992 poloxamer 407 Polymers 0.000 description 9
- 229940044476 poloxamer 407 Drugs 0.000 description 9
- 201000011510 cancer Diseases 0.000 description 8
- 206010025482 malaise Diseases 0.000 description 8
- 239000003814 drug Substances 0.000 description 6
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 5
- 229930182478 glucoside Natural products 0.000 description 5
- 210000003128 head Anatomy 0.000 description 5
- 230000036541 health Effects 0.000 description 5
- 230000002265 prevention Effects 0.000 description 5
- KJGPBYUQZLUKLL-UHFFFAOYSA-N afrormosin Chemical compound C1=CC(OC)=CC=C1C1=COC2=CC(O)=C(OC)C=C2C1=O KJGPBYUQZLUKLL-UHFFFAOYSA-N 0.000 description 4
- 125000003118 aryl group Chemical group 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 230000002496 gastric effect Effects 0.000 description 4
- AGBQKNBQESQNJD-UHFFFAOYSA-N lipoic acid Chemical compound OC(=O)CCCCC1CCSS1 AGBQKNBQESQNJD-UHFFFAOYSA-N 0.000 description 4
- 230000005855 radiation Effects 0.000 description 4
- 150000003254 radicals Chemical class 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 4
- 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 description 3
- APKFDSVGJQXUKY-KKGHZKTASA-N Amphotericin-B Natural products O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1C=CC=CC=CC=CC=CC=CC=C[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-KKGHZKTASA-N 0.000 description 3
- 206010009944 Colon cancer Diseases 0.000 description 3
- SNPLKNRPJHDVJA-ZETCQYMHSA-N D-panthenol Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCCO SNPLKNRPJHDVJA-ZETCQYMHSA-N 0.000 description 3
- 206010061218 Inflammation Diseases 0.000 description 3
- NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 description 3
- 229920003102 Methocel™ E4M Polymers 0.000 description 3
- 206010039424 Salivary hypersecretion Diseases 0.000 description 3
- 229920002125 Sokalan® Polymers 0.000 description 3
- NUCLJNSWZCHRKL-UHFFFAOYSA-N allantoic acid Chemical compound NC(=O)NC(C(O)=O)NC(N)=O NUCLJNSWZCHRKL-UHFFFAOYSA-N 0.000 description 3
- POJWUDADGALRAB-UHFFFAOYSA-N allantoin Chemical compound NC(=O)NC1NC(=O)NC1=O POJWUDADGALRAB-UHFFFAOYSA-N 0.000 description 3
- APKFDSVGJQXUKY-INPOYWNPSA-N amphotericin B Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-INPOYWNPSA-N 0.000 description 3
- 229960003942 amphotericin b Drugs 0.000 description 3
- 235000020958 biotin Nutrition 0.000 description 3
- 229960002685 biotin Drugs 0.000 description 3
- 239000011616 biotin Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 150000008131 glucosides Chemical class 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- MWDZOUNAPSSOEL-UHFFFAOYSA-N kaempferol Natural products OC1=C(C(=O)c2cc(O)cc(O)c2O1)c3ccc(O)cc3 MWDZOUNAPSSOEL-UHFFFAOYSA-N 0.000 description 3
- 229960004194 lidocaine Drugs 0.000 description 3
- 239000011976 maleic acid Substances 0.000 description 3
- 210000003300 oropharynx Anatomy 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 210000000664 rectum Anatomy 0.000 description 3
- 208000026451 salivation Diseases 0.000 description 3
- 235000010413 sodium alginate Nutrition 0.000 description 3
- 239000000661 sodium alginate Substances 0.000 description 3
- 229940005550 sodium alginate Drugs 0.000 description 3
- QCHFTSOMWOSFHM-WPRPVWTQSA-N (+)-Pilocarpine Chemical compound C1OC(=O)[C@@H](CC)[C@H]1CC1=CN=CN1C QCHFTSOMWOSFHM-WPRPVWTQSA-N 0.000 description 2
- GHOKWGTUZJEAQD-ZETCQYMHSA-N (D)-(+)-Pantothenic acid Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-ZETCQYMHSA-N 0.000 description 2
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 2
- GZSOSUNBTXMUFQ-NJGQXECBSA-N 5,7,3'-Trihydroxy-4'-methoxyflavone 7-O-rutinoside Natural products O(C[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@H](Oc2cc(O)c3C(=O)C=C(c4cc(O)c(OC)cc4)Oc3c2)O1)[C@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@H](C)O1 GZSOSUNBTXMUFQ-NJGQXECBSA-N 0.000 description 2
- DANYIYRPLHHOCZ-UHFFFAOYSA-N 5,7-dihydroxy-4'-methoxyflavone Chemical compound C1=CC(OC)=CC=C1C1=CC(=O)C2=C(O)C=C(O)C=C2O1 DANYIYRPLHHOCZ-UHFFFAOYSA-N 0.000 description 2
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 2
- POJWUDADGALRAB-PVQJCKRUSA-N Allantoin Natural products NC(=O)N[C@@H]1NC(=O)NC1=O POJWUDADGALRAB-PVQJCKRUSA-N 0.000 description 2
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 2
- 239000004255 Butylated hydroxyanisole Substances 0.000 description 2
- 239000004322 Butylated hydroxytoluene Substances 0.000 description 2
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
- ZTDFZLVUIVPZDU-QGNHJMHWSA-N Cnicin Chemical compound OC[C@H](O)C(=C)C(=O)O[C@H]1CC(/C)=C/CC\C(CO)=C\[C@H]2OC(=O)C(=C)[C@@H]21 ZTDFZLVUIVPZDU-QGNHJMHWSA-N 0.000 description 2
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 2
- 235000004866 D-panthenol Nutrition 0.000 description 2
- 239000011703 D-panthenol Substances 0.000 description 2
- 206010015150 Erythema Diseases 0.000 description 2
- FVQOMEDMFUMIMO-UHFFFAOYSA-N Hyperosid Natural products OC1C(O)C(O)C(CO)OC1OC1C(=O)C2=C(O)C=C(O)C=C2OC1C1=CC=C(O)C(O)=C1 FVQOMEDMFUMIMO-UHFFFAOYSA-N 0.000 description 2
- VTAJIXDZFCRWBR-UHFFFAOYSA-N Licoricesaponin B2 Natural products C1C(C2C(C3(CCC4(C)CCC(C)(CC4C3=CC2)C(O)=O)C)(C)CC2)(C)C2C(C)(C)CC1OC1OC(C(O)=O)C(O)C(O)C1OC1OC(C(O)=O)C(O)C(O)C1O VTAJIXDZFCRWBR-UHFFFAOYSA-N 0.000 description 2
- 206010067352 Osteoradionecrosis Diseases 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
- REFJWTPEDVJJIY-UHFFFAOYSA-N Quercetin Chemical compound C=1C(O)=CC(O)=C(C(C=2O)=O)C=1OC=2C1=CC=C(O)C(O)=C1 REFJWTPEDVJJIY-UHFFFAOYSA-N 0.000 description 2
- QCHFTSOMWOSFHM-UHFFFAOYSA-N SJ000285536 Natural products C1OC(=O)C(CC)C1CC1=CN=CN1C QCHFTSOMWOSFHM-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 description 2
- 208000005946 Xerostomia Diseases 0.000 description 2
- 229960001138 acetylsalicylic acid Drugs 0.000 description 2
- ZRNARVWAJZIBTH-UHFFFAOYSA-N afromosin Natural products O1C=CC(=O)C2=C1C=C(O)C(OC)=C2 ZRNARVWAJZIBTH-UHFFFAOYSA-N 0.000 description 2
- 235000010443 alginic acid Nutrition 0.000 description 2
- 229920000615 alginic acid Polymers 0.000 description 2
- 229960000458 allantoin Drugs 0.000 description 2
- 229940087168 alpha tocopherol Drugs 0.000 description 2
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 2
- 229910021502 aluminium hydroxide Inorganic materials 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 230000001387 anti-histamine Effects 0.000 description 2
- 239000000739 antihistaminic agent Substances 0.000 description 2
- KZNIFHPLKGYRTM-UHFFFAOYSA-N apigenin Chemical compound C1=CC(O)=CC=C1C1=CC(=O)C2=C(O)C=C(O)C=C2O1 KZNIFHPLKGYRTM-UHFFFAOYSA-N 0.000 description 2
- 210000000988 bone and bone Anatomy 0.000 description 2
- BEWYHVAWEKZDPP-UHFFFAOYSA-N bornane Chemical compound C1CC2(C)CCC1C2(C)C BEWYHVAWEKZDPP-UHFFFAOYSA-N 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- SWLMUYACZKCSHZ-UHFFFAOYSA-N butoconazole Chemical compound C1=CC(Cl)=CC=C1CCC(SC=1C(=CC=CC=1Cl)Cl)CN1C=NC=C1 SWLMUYACZKCSHZ-UHFFFAOYSA-N 0.000 description 2
- 229960005074 butoconazole Drugs 0.000 description 2
- 235000010354 butylated hydroxytoluene Nutrition 0.000 description 2
- 229940095259 butylated hydroxytoluene Drugs 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 235000001465 calcium Nutrition 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- OROGSEYTTFOCAN-DNJOTXNNSA-N codeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC OROGSEYTTFOCAN-DNJOTXNNSA-N 0.000 description 2
- 201000010989 colorectal carcinoma Diseases 0.000 description 2
- 238000009096 combination chemotherapy Methods 0.000 description 2
- 208000002925 dental caries Diseases 0.000 description 2
- 229960003949 dexpanthenol Drugs 0.000 description 2
- IGBKNLGEMMEWKD-UHFFFAOYSA-N diosmin Natural products COc1ccc(cc1)C2=C(O)C(=O)c3c(O)cc(OC4OC(COC5OC(C)C(O)C(O)C5O)C(O)C(O)C4O)cc3O2 IGBKNLGEMMEWKD-UHFFFAOYSA-N 0.000 description 2
- 206010013781 dry mouth Diseases 0.000 description 2
- 231100000321 erythema Toxicity 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 229940045109 genistein Drugs 0.000 description 2
- 229930182470 glycoside Natural products 0.000 description 2
- 150000002338 glycosides Chemical class 0.000 description 2
- LPLVUJXQOOQHMX-UHFFFAOYSA-N glycyrrhetinic acid glycoside Natural products C1CC(C2C(C3(CCC4(C)CCC(C)(CC4C3=CC2=O)C(O)=O)C)(C)CC2)(C)C2C(C)(C)C1OC1OC(C(O)=O)C(O)C(O)C1OC1OC(C(O)=O)C(O)C(O)C1O LPLVUJXQOOQHMX-UHFFFAOYSA-N 0.000 description 2
- 239000001685 glycyrrhizic acid Substances 0.000 description 2
- 229960004949 glycyrrhizic acid Drugs 0.000 description 2
- UYRUBYNTXSDKQT-UHFFFAOYSA-N glycyrrhizic acid Natural products CC1(C)C(CCC2(C)C1CCC3(C)C2C(=O)C=C4C5CC(C)(CCC5(C)CCC34C)C(=O)O)OC6OC(C(O)C(O)C6OC7OC(O)C(O)C(O)C7C(=O)O)C(=O)O UYRUBYNTXSDKQT-UHFFFAOYSA-N 0.000 description 2
- 235000019410 glycyrrhizin Nutrition 0.000 description 2
- LPLVUJXQOOQHMX-QWBHMCJMSA-N glycyrrhizinic acid Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@@H]1C([C@H]2[C@]([C@@H]3[C@@]([C@@]4(CC[C@@]5(C)CC[C@@](C)(C[C@H]5C4=CC3=O)C(O)=O)C)(C)CC2)(C)CC1)(C)C)C(O)=O)[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O LPLVUJXQOOQHMX-QWBHMCJMSA-N 0.000 description 2
- 208000014829 head and neck neoplasm Diseases 0.000 description 2
- 229960001915 hexamidine Drugs 0.000 description 2
- OQLKNTOKMBVBKV-UHFFFAOYSA-N hexamidine Chemical compound C1=CC(C(=N)N)=CC=C1OCCCCCCOC1=CC=C(C(N)=N)C=C1 OQLKNTOKMBVBKV-UHFFFAOYSA-N 0.000 description 2
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 230000000968 intestinal effect Effects 0.000 description 2
- 230000005865 ionizing radiation Effects 0.000 description 2
- GXMWXESSGGEWEM-UHFFFAOYSA-N isoquercitrin Natural products OCC(O)C1OC(OC2C(Oc3cc(O)cc(O)c3C2=O)c4ccc(O)c(O)c4)C(O)C1O GXMWXESSGGEWEM-UHFFFAOYSA-N 0.000 description 2
- IYRMWMYZSQPJKC-UHFFFAOYSA-N kaempferol Chemical compound C1=CC(O)=CC=C1C1=C(O)C(=O)C2=C(O)C=C(O)C=C2O1 IYRMWMYZSQPJKC-UHFFFAOYSA-N 0.000 description 2
- 230000002045 lasting effect Effects 0.000 description 2
- 235000019136 lipoic acid Nutrition 0.000 description 2
- RDOIQAHITMMDAJ-UHFFFAOYSA-N loperamide Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(C(=O)N(C)C)CCN(CC1)CCC1(O)C1=CC=C(Cl)C=C1 RDOIQAHITMMDAJ-UHFFFAOYSA-N 0.000 description 2
- 229960001571 loperamide Drugs 0.000 description 2
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 2
- 239000000347 magnesium hydroxide Substances 0.000 description 2
- 229910001862 magnesium hydroxide Inorganic materials 0.000 description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
- 208000026037 malignant tumor of neck Diseases 0.000 description 2
- 229960002509 miconazole Drugs 0.000 description 2
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 2
- RTATXGUCZHCSNG-UHFFFAOYSA-N nicotiflorine Natural products OC1C(O)C(O)C(C)OC1OCC1C(O)C(O)C(O)C(OC=2C(C3=C(O)C=C(O)C=C3OC=2C=2C=CC(O)=CC=2)=O)O1 RTATXGUCZHCSNG-UHFFFAOYSA-N 0.000 description 2
- 230000008520 organization Effects 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 239000001814 pectin Substances 0.000 description 2
- 235000010987 pectin Nutrition 0.000 description 2
- 229920001277 pectin Polymers 0.000 description 2
- 229960001416 pilocarpine Drugs 0.000 description 2
- 239000000419 plant extract Substances 0.000 description 2
- 150000008442 polyphenolic compounds Chemical class 0.000 description 2
- 235000013824 polyphenols Nutrition 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000008213 purified water Substances 0.000 description 2
- OVSQVDMCBVZWGM-QSOFNFLRSA-N quercetin 3-O-beta-D-glucopyranoside Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=C(C=2C=C(O)C(O)=CC=2)OC2=CC(O)=CC(O)=C2C1=O OVSQVDMCBVZWGM-QSOFNFLRSA-N 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 150000008265 rhamnosides Chemical class 0.000 description 2
- JVXZRQGOGOXCEC-UHFFFAOYSA-N scutellarein Chemical compound C1=CC(O)=CC=C1C1=CC(=O)C2=C(O)C(O)=C(O)C=C2O1 JVXZRQGOGOXCEC-UHFFFAOYSA-N 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 230000004206 stomach function Effects 0.000 description 2
- 238000005728 strengthening Methods 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- ULSUXBXHSYSGDT-UHFFFAOYSA-N tangeretin Chemical compound C1=CC(OC)=CC=C1C1=CC(=O)C2=C(OC)C(OC)=C(OC)C(OC)=C2O1 ULSUXBXHSYSGDT-UHFFFAOYSA-N 0.000 description 2
- 229960002663 thioctic acid Drugs 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
- 229960000984 tocofersolan 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
- 210000004291 uterus Anatomy 0.000 description 2
- 229940088594 vitamin Drugs 0.000 description 2
- 239000011782 vitamin Substances 0.000 description 2
- 229920001285 xanthan gum Polymers 0.000 description 2
- 235000010493 xanthan gum Nutrition 0.000 description 2
- 239000000230 xanthan gum Substances 0.000 description 2
- 229940082509 xanthan gum Drugs 0.000 description 2
- 235000004835 α-tocopherol Nutrition 0.000 description 2
- 239000002076 α-tocopherol Substances 0.000 description 2
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 1
- OMDQUFIYNPYJFM-XKDAHURESA-N (2r,3r,4s,5r,6s)-2-(hydroxymethyl)-6-[[(2r,3s,4r,5s,6r)-4,5,6-trihydroxy-3-[(2s,3s,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoxan-2-yl]methoxy]oxane-3,4,5-triol Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O[C@H]2[C@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)[C@H](O)[C@H](O)[C@H](O)O1 OMDQUFIYNPYJFM-XKDAHURESA-N 0.000 description 1
- 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 description 1
- 229920002818 (Hydroxyethyl)methacrylate Polymers 0.000 description 1
- FTVWIRXFELQLPI-ZDUSSCGKSA-N (S)-naringenin Chemical compound C1=CC(O)=CC=C1[C@H]1OC2=CC(O)=CC(O)=C2C(=O)C1 FTVWIRXFELQLPI-ZDUSSCGKSA-N 0.000 description 1
- 239000001074 1-methoxy-4-[(E)-prop-1-enyl]benzene Substances 0.000 description 1
- LEZWWPYKPKIXLL-UHFFFAOYSA-N 1-{2-(4-chlorobenzyloxy)-2-(2,4-dichlorophenyl)ethyl}imidazole Chemical compound C1=CC(Cl)=CC=C1COC(C=1C(=CC(Cl)=CC=1)Cl)CN1C=NC=C1 LEZWWPYKPKIXLL-UHFFFAOYSA-N 0.000 description 1
- QXHHHPZILQDDPS-UHFFFAOYSA-N 1-{2-[(2-chloro-3-thienyl)methoxy]-2-(2,4-dichlorophenyl)ethyl}imidazole Chemical compound S1C=CC(COC(CN2C=NC=C2)C=2C(=CC(Cl)=CC=2)Cl)=C1Cl QXHHHPZILQDDPS-UHFFFAOYSA-N 0.000 description 1
- 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
- KBGKQZVCLWKUDQ-QNDFHXLGSA-N 2-(3,4-dihydroxyphenyl)-7-hydroxy-5-[(2s,3r,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxychromen-4-one Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC2=C1C(=O)C=C(C=1C=C(O)C(O)=CC=1)O2 KBGKQZVCLWKUDQ-QNDFHXLGSA-N 0.000 description 1
- VHVPQPYKVGDNFY-DFMJLFEVSA-N 2-[(2r)-butan-2-yl]-4-[4-[4-[4-[[(2r,4s)-2-(2,4-dichlorophenyl)-2-(1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-1,2,4-triazol-3-one Chemical compound O=C1N([C@H](C)CC)N=CN1C1=CC=C(N2CCN(CC2)C=2C=CC(OC[C@@H]3O[C@](CN4N=CN=C4)(OC3)C=3C(=CC(Cl)=CC=3)Cl)=CC=2)C=C1 VHVPQPYKVGDNFY-DFMJLFEVSA-N 0.000 description 1
- RFRMMZAKBNXNHE-UHFFFAOYSA-N 6-[4,6-dihydroxy-5-(2-hydroxyethoxy)-2-(hydroxymethyl)oxan-3-yl]oxy-2-(hydroxymethyl)-5-(2-hydroxypropoxy)oxane-3,4-diol Chemical compound CC(O)COC1C(O)C(O)C(CO)OC1OC1C(O)C(OCCO)C(O)OC1CO RFRMMZAKBNXNHE-UHFFFAOYSA-N 0.000 description 1
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- 239000001606 7-[(2S,3R,4S,5S,6R)-4,5-dihydroxy-6-(hydroxymethyl)-3-[(2S,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxyoxan-2-yl]oxy-5-hydroxy-2-(4-hydroxyphenyl)chroman-4-one Substances 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- 208000007848 Alcoholism Diseases 0.000 description 1
- 208000007860 Anus Neoplasms Diseases 0.000 description 1
- SMDOOINVMJSDPS-UHFFFAOYSA-N Astragaloside Natural products C1=C(O)C(OC)=CC(C2=C(C(=O)C3=C(O)C=C(O)C=C3O2)OC2C(C(OC3C(C(O)C(O)C(CO)O3)O)C(O)C(CO)O2)O)=C1 SMDOOINVMJSDPS-UHFFFAOYSA-N 0.000 description 1
- 229930003347 Atropine Natural products 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- CCZHKEJGAJVDRC-UHFFFAOYSA-N Belamcanidin Natural products C1=C(OC)C(OC)=CC=C1C1=COC2=CC(OC)=C(OC)C(O)=C2C1=O CCZHKEJGAJVDRC-UHFFFAOYSA-N 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 235000007627 Caesalpinia Nutrition 0.000 description 1
- 241000522234 Caesalpinia Species 0.000 description 1
- 208000017897 Carcinoma of esophagus Diseases 0.000 description 1
- 102100035882 Catalase Human genes 0.000 description 1
- 108010053835 Catalase Proteins 0.000 description 1
- 244000146462 Centella asiatica Species 0.000 description 1
- 235000004032 Centella asiatica Nutrition 0.000 description 1
- 235000013912 Ceratonia siliqua Nutrition 0.000 description 1
- 240000008886 Ceratonia siliqua Species 0.000 description 1
- 235000007866 Chamaemelum nobile Nutrition 0.000 description 1
- GHOKWGTUZJEAQD-UHFFFAOYSA-N Chick antidermatitis factor Natural products OCC(C)(C)C(O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-UHFFFAOYSA-N 0.000 description 1
- 229920002101 Chitin Polymers 0.000 description 1
- 229920001661 Chitosan Polymers 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- SHZGCJCMOBCMKK-UHFFFAOYSA-N D-mannomethylose Natural products CC1OC(O)C(O)C(O)C1O SHZGCJCMOBCMKK-UHFFFAOYSA-N 0.000 description 1
- UBSCDKPKWHYZNX-UHFFFAOYSA-N Demethoxycapillarisin Natural products C1=CC(O)=CC=C1OC1=CC(=O)C2=C(O)C=C(O)C=C2O1 UBSCDKPKWHYZNX-UHFFFAOYSA-N 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- QAGGICSUEVNSGH-UHFFFAOYSA-N Diosmetin Natural products C1=C(O)C(OC)=CC=C1C1=CC(=O)C2=CC=C(O)C=C2O1 QAGGICSUEVNSGH-UHFFFAOYSA-N 0.000 description 1
- 206010013082 Discomfort Diseases 0.000 description 1
- 206010013886 Dysaesthesia Diseases 0.000 description 1
- 102000016942 Elastin Human genes 0.000 description 1
- 108010014258 Elastin Proteins 0.000 description 1
- 102100031780 Endonuclease Human genes 0.000 description 1
- 108010042407 Endonucleases Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- WEEGYLXZBRQIMU-UHFFFAOYSA-N Eucalyptol Chemical compound C1CC2CCC1(C)OC2(C)C WEEGYLXZBRQIMU-UHFFFAOYSA-N 0.000 description 1
- 102100026535 Fibronectin type III domain-containing protein 5 Human genes 0.000 description 1
- 206010017533 Fungal infection Diseases 0.000 description 1
- 229920000926 Galactomannan Polymers 0.000 description 1
- 229920002907 Guar gum Polymers 0.000 description 1
- 239000004705 High-molecular-weight polyethylene Substances 0.000 description 1
- OVSQVDMCBVZWGM-IDRAQACASA-N Hirsutrin Natural products O([C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1)C1=C(c2cc(O)c(O)cc2)Oc2c(c(O)cc(O)c2)C1=O OVSQVDMCBVZWGM-IDRAQACASA-N 0.000 description 1
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- RKUNBYITZUJHSG-UHFFFAOYSA-N Hyosciamin-hydrochlorid Natural products CN1C(C2)CCC1CC2OC(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-UHFFFAOYSA-N 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
- 101800001026 Irisin Proteins 0.000 description 1
- XETQTCAMTVHYPO-UHFFFAOYSA-N Isocamphan von ungewisser Konfiguration Natural products C1CC2C(C)(C)C(C)C1C2 XETQTCAMTVHYPO-UHFFFAOYSA-N 0.000 description 1
- RTATXGUCZHCSNG-TYSPDFDMSA-N Kaempferol-3-O-rutinoside Natural products OC1[C@H](O)[C@@H](O)C(C)O[C@H]1OCC1[C@@H](O)[C@@H](O)C(O)[C@H](OC=2C(C3=C(O)C=C(O)C=C3OC=2C=2C=CC(O)=CC=2)=O)O1 RTATXGUCZHCSNG-TYSPDFDMSA-N 0.000 description 1
- 241000218652 Larix Species 0.000 description 1
- 235000005590 Larix decidua Nutrition 0.000 description 1
- 241000325845 Leontopodium leontopodioides Species 0.000 description 1
- DEMKZLAVQYISIA-UHFFFAOYSA-N Liquirtin Natural products OC1C(O)C(O)C(CO)OC1OC1=CC=C(C2OC3=CC(O)=CC=C3C(=O)C2)C=C1 DEMKZLAVQYISIA-UHFFFAOYSA-N 0.000 description 1
- 208000008771 Lymphadenopathy Diseases 0.000 description 1
- 244000042664 Matricaria chamomilla Species 0.000 description 1
- 235000007232 Matricaria chamomilla Nutrition 0.000 description 1
- MZSGWZGPESCJAN-MOBFUUNNSA-N Melitric acid A Natural products O([C@@H](C(=O)O)Cc1cc(O)c(O)cc1)C(=O)/C=C/c1cc(O)c(O/C(/C(=O)O)=C/c2cc(O)c(O)cc2)cc1 MZSGWZGPESCJAN-MOBFUUNNSA-N 0.000 description 1
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 description 1
- BYBLEWFAAKGYCD-UHFFFAOYSA-N Miconazole Chemical compound ClC1=CC(Cl)=CC=C1COC(C=1C(=CC(Cl)=CC=1)Cl)CN1C=NC=C1 BYBLEWFAAKGYCD-UHFFFAOYSA-N 0.000 description 1
- 206010061297 Mucosal erosion Diseases 0.000 description 1
- RTATXGUCZHCSNG-QHWHWDPRSA-N Nicotiflorin Chemical compound O[C@@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@H](OC=2C(C3=C(O)C=C(O)C=C3OC=2C=2C=CC(O)=CC=2)=O)O1 RTATXGUCZHCSNG-QHWHWDPRSA-N 0.000 description 1
- 206010057852 Nicotine dependence Diseases 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- HDVDLQFPDLTOSI-UHFFFAOYSA-L O[AlH]O Chemical compound O[AlH]O HDVDLQFPDLTOSI-UHFFFAOYSA-L 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 206010030155 Oesophageal carcinoma Diseases 0.000 description 1
- MGJLSBDCWOSMHL-WFMNFSIZSA-N Ononin Natural products O(C)c1ccc(C=2C(=O)c3c(OC=2)cc(O[C@H]2[C@@H](O)[C@@H](O)[C@H](O)[C@H](CO)O2)cc3)cc1 MGJLSBDCWOSMHL-WFMNFSIZSA-N 0.000 description 1
- IQPSEEYGBUAQFF-UHFFFAOYSA-N Pantoprazole Chemical compound COC1=CC=NC(CS(=O)C=2NC3=CC=C(OC(F)F)C=C3N=2)=C1OC IQPSEEYGBUAQFF-UHFFFAOYSA-N 0.000 description 1
- JPYHHZQJCSQRJY-UHFFFAOYSA-N Phloroglucinol Natural products CCC=CCC=CCC=CCC=CCCCCC(=O)C1=C(O)C=C(O)C=C1O JPYHHZQJCSQRJY-UHFFFAOYSA-N 0.000 description 1
- 108010040201 Polymyxins Proteins 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- ZVOLCUVKHLEPEV-UHFFFAOYSA-N Quercetagetin Natural products C1=C(O)C(O)=CC=C1C1=C(O)C(=O)C2=C(O)C(O)=C(O)C=C2O1 ZVOLCUVKHLEPEV-UHFFFAOYSA-N 0.000 description 1
- QJTYCCFDQWFJHU-UHFFFAOYSA-N Quercetin-5-O-beta-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1=CC(O)=CC2=C1C(=O)C(O)=C(C=1C=C(O)C(O)=CC=1)O2 QJTYCCFDQWFJHU-UHFFFAOYSA-N 0.000 description 1
- 208000019155 Radiation injury Diseases 0.000 description 1
- 208000015634 Rectal Neoplasms Diseases 0.000 description 1
- HWTZYBCRDDUBJY-UHFFFAOYSA-N Rhynchosin Natural products C1=C(O)C(O)=CC=C1C1=C(O)C(=O)C2=CC(O)=C(O)C=C2O1 HWTZYBCRDDUBJY-UHFFFAOYSA-N 0.000 description 1
- ZONYXWQDUYMKFB-UHFFFAOYSA-N SJ000286395 Natural products O1C2=CC=CC=C2C(=O)CC1C1=CC=CC=C1 ZONYXWQDUYMKFB-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- IECRXMSGDFIOEY-UHFFFAOYSA-N Tangeretin Natural products COC=1C(OC)=C(OC)C(OC)=C(C(C=2)=O)C=1OC=2C1=CC=C(O)C=C1 IECRXMSGDFIOEY-UHFFFAOYSA-N 0.000 description 1
- 244000269722 Thea sinensis Species 0.000 description 1
- GAMYVSCDDLXAQW-AOIWZFSPSA-N Thermopsosid Natural products O(C)c1c(O)ccc(C=2Oc3c(c(O)cc(O[C@H]4[C@H](O)[C@@H](O)[C@H](O)[C@H](CO)O4)c3)C(=O)C=2)c1 GAMYVSCDDLXAQW-AOIWZFSPSA-N 0.000 description 1
- 239000005844 Thymol Substances 0.000 description 1
- 208000025569 Tobacco Use disease Diseases 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- XTXRWKRVRITETP-UHFFFAOYSA-N Vinyl acetate Chemical compound CC(=O)OC=C XTXRWKRVRITETP-UHFFFAOYSA-N 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
- 229930003270 Vitamin B Natural products 0.000 description 1
- 235000009392 Vitis Nutrition 0.000 description 1
- 241000219095 Vitis Species 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 244000042312 Wisteria floribunda Species 0.000 description 1
- 235000010724 Wisteria floribunda Nutrition 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- 230000003187 abdominal effect Effects 0.000 description 1
- 235000009962 acacetin Nutrition 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000001785 acacia senegal l. willd gum Substances 0.000 description 1
- VIUCZAYKDLEBOL-UHFFFAOYSA-N acetic acid phthalic acid Chemical compound CC(O)=O.OC(=O)C1=CC=CC=C1C(O)=O.OC(=O)C1=CC=CC=C1C(O)=O.OC(=O)C1=CC=CC=C1C(O)=O.OC(=O)C1=CC=CC=C1C(O)=O VIUCZAYKDLEBOL-UHFFFAOYSA-N 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 229960004150 aciclovir Drugs 0.000 description 1
- MKUXAQIIEYXACX-UHFFFAOYSA-N aciclovir Chemical compound N1C(N)=NC(=O)C2=C1N(COCCO)C=N2 MKUXAQIIEYXACX-UHFFFAOYSA-N 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 208000013228 adenopathy Diseases 0.000 description 1
- 201000007930 alcohol dependence Diseases 0.000 description 1
- 229940015825 aldioxa Drugs 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 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
- ILRRQNADMUWWFW-UHFFFAOYSA-K aluminium phosphate Chemical compound O1[Al]2OP1(=O)O2 ILRRQNADMUWWFW-UHFFFAOYSA-K 0.000 description 1
- 229940126575 aminoglycoside Drugs 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 229940069428 antacid Drugs 0.000 description 1
- 239000003159 antacid agent Substances 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 230000001028 anti-proliverative effect Effects 0.000 description 1
- 230000002421 anti-septic effect Effects 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 201000011165 anus cancer Diseases 0.000 description 1
- QMNWISYXSJWHRY-XWJCTJPOSA-N astragaloside Chemical compound O1[C@H](C(C)(O)C)CC[C@]1(C)[C@@H]1[C@@]2(C)CC[C@]34C[C@]4(CC[C@H](O[C@H]4[C@@H]([C@@H](O)[C@H](O)CO4)O)C4(C)C)C4[C@@H](O[C@H]4[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O4)O)CC3[C@]2(C)C[C@@H]1O QMNWISYXSJWHRY-XWJCTJPOSA-N 0.000 description 1
- RKUNBYITZUJHSG-SPUOUPEWSA-N atropine Chemical compound O([C@H]1C[C@H]2CC[C@@H](C1)N2C)C(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-SPUOUPEWSA-N 0.000 description 1
- 229960000396 atropine Drugs 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 229960003321 baicalin Drugs 0.000 description 1
- 229940054066 benzamide antipsychotics Drugs 0.000 description 1
- 150000003936 benzamides Chemical class 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 229930006742 bornane Natural products 0.000 description 1
- 201000008275 breast carcinoma Diseases 0.000 description 1
- 210000005178 buccal mucosa Anatomy 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 235000019282 butylated hydroxyanisole Nutrition 0.000 description 1
- 229940043253 butylated hydroxyanisole Drugs 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 229960001631 carbomer Drugs 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 235000021466 carotenoid Nutrition 0.000 description 1
- 150000001747 carotenoids Chemical class 0.000 description 1
- 235000010418 carrageenan Nutrition 0.000 description 1
- 229920001525 carrageenan Polymers 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229940059958 centella asiatica extract Drugs 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000000812 cholinergic antagonist Substances 0.000 description 1
- 229960005233 cineole Drugs 0.000 description 1
- RFFOTVCVTJUTAD-UHFFFAOYSA-N cineole Natural products C1CC2(C)CCC1(C(C)C)O2 RFFOTVCVTJUTAD-UHFFFAOYSA-N 0.000 description 1
- DCSUBABJRXZOMT-IRLDBZIGSA-N cisapride Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(=CC(N)=C(Cl)C=2)OC)OC)N1CCCOC1=CC=C(F)C=C1 DCSUBABJRXZOMT-IRLDBZIGSA-N 0.000 description 1
- 229960005132 cisapride Drugs 0.000 description 1
- DCSUBABJRXZOMT-UHFFFAOYSA-N cisapride Natural products C1CC(NC(=O)C=2C(=CC(N)=C(Cl)C=2)OC)C(OC)CN1CCCOC1=CC=C(F)C=C1 DCSUBABJRXZOMT-UHFFFAOYSA-N 0.000 description 1
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
- 229960004316 cisplatin Drugs 0.000 description 1
- 239000004927 clay Substances 0.000 description 1
- 229910052570 clay Inorganic materials 0.000 description 1
- 229960004126 codeine Drugs 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- GUJOJGAPFQRJSV-UHFFFAOYSA-N dialuminum;dioxosilane;oxygen(2-);hydrate Chemical compound O.[O-2].[O-2].[O-2].[Al+3].[Al+3].O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O GUJOJGAPFQRJSV-UHFFFAOYSA-N 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 230000001079 digestive effect Effects 0.000 description 1
- 229940106018 diosmectite Drugs 0.000 description 1
- 229910000285 diosmectite Inorganic materials 0.000 description 1
- 235000015428 diosmetin Nutrition 0.000 description 1
- MBNGWHIJMBWFHU-UHFFFAOYSA-N diosmetin Chemical compound C1=C(O)C(OC)=CC=C1C1=CC(=O)C2=C(O)C=C(O)C=C2O1 MBNGWHIJMBWFHU-UHFFFAOYSA-N 0.000 description 1
- 229960001876 diosmetin Drugs 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 229960003913 econazole Drugs 0.000 description 1
- 229960003645 econazole nitrate Drugs 0.000 description 1
- 229920002549 elastin Polymers 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000008378 epithelial damage Effects 0.000 description 1
- TUJPOVKMHCLXEL-UHFFFAOYSA-N eriodictyol Natural products C1C(=O)C2=CC(O)=CC(O)=C2OC1C1=CC=C(O)C(O)=C1 TUJPOVKMHCLXEL-UHFFFAOYSA-N 0.000 description 1
- SBHXYTNGIZCORC-ZDUSSCGKSA-N eriodictyol Chemical compound C1([C@@H]2CC(=O)C3=C(O)C=C(C=C3O2)O)=CC=C(O)C(O)=C1 SBHXYTNGIZCORC-ZDUSSCGKSA-N 0.000 description 1
- 235000011797 eriodictyol Nutrition 0.000 description 1
- SBHXYTNGIZCORC-UHFFFAOYSA-N eriodyctiol Natural products O1C2=CC(O)=CC(O)=C2C(=O)CC1C1=CC=C(O)C(O)=C1 SBHXYTNGIZCORC-UHFFFAOYSA-N 0.000 description 1
- 201000005619 esophageal carcinoma Diseases 0.000 description 1
- 210000003238 esophagus Anatomy 0.000 description 1
- 229930003949 flavanone Natural products 0.000 description 1
- 150000002208 flavanones Chemical class 0.000 description 1
- 235000011981 flavanones Nutrition 0.000 description 1
- 229930003944 flavone Natural products 0.000 description 1
- 150000002212 flavone derivatives Chemical class 0.000 description 1
- 235000011949 flavones Nutrition 0.000 description 1
- HVQAJTFOCKOKIN-UHFFFAOYSA-N flavonol Natural products O1C2=CC=CC=C2C(=O)C(O)=C1C1=CC=CC=C1 HVQAJTFOCKOKIN-UHFFFAOYSA-N 0.000 description 1
- 150000002216 flavonol derivatives Chemical class 0.000 description 1
- 235000011957 flavonols Nutrition 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 208000024386 fungal infectious disease Diseases 0.000 description 1
- 230000000855 fungicidal effect Effects 0.000 description 1
- 239000000417 fungicide Substances 0.000 description 1
- 210000001156 gastric mucosa Anatomy 0.000 description 1
- 208000021302 gastroesophageal reflux disease Diseases 0.000 description 1
- 239000003349 gelling agent Substances 0.000 description 1
- 235000006539 genistein Nutrition 0.000 description 1
- TZBJGXHYKVUXJN-UHFFFAOYSA-N genistein Natural products C1=CC(O)=CC=C1C1=COC2=CC(O)=CC(O)=C2C1=O TZBJGXHYKVUXJN-UHFFFAOYSA-N 0.000 description 1
- 239000003292 glue Substances 0.000 description 1
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 1
- 235000003969 glutathione Nutrition 0.000 description 1
- 229960003180 glutathione Drugs 0.000 description 1
- 235000010417 guar gum Nutrition 0.000 description 1
- 239000000665 guar gum Substances 0.000 description 1
- 229960002154 guar gum Drugs 0.000 description 1
- 229920002674 hyaluronan Polymers 0.000 description 1
- 229960003160 hyaluronic acid Drugs 0.000 description 1
- OROGSEYTTFOCAN-UHFFFAOYSA-N hydrocodone Natural products C1C(N(CCC234)C)C2C=CC(O)C3OC2=C4C1=CC=C2OC OROGSEYTTFOCAN-UHFFFAOYSA-N 0.000 description 1
- 239000000416 hydrocolloid Substances 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 229940071826 hydroxyethyl cellulose Drugs 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 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 description 1
- 230000006872 improvement Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 210000004347 intestinal mucosa Anatomy 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- LNQCUTNLHUQZLR-OZJWLQQPSA-N iridin Chemical compound OC1=C(OC)C(OC)=CC(C=2C(C3=C(O)C(OC)=C(O[C@H]4[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O4)O)C=C3OC=2)=O)=C1 LNQCUTNLHUQZLR-OZJWLQQPSA-N 0.000 description 1
- GOMNOOKGLZYEJT-UHFFFAOYSA-N isoflavone Chemical compound C=1OC2=CC=CC=C2C(=O)C=1C1=CC=CC=C1 GOMNOOKGLZYEJT-UHFFFAOYSA-N 0.000 description 1
- CJWQYWQDLBZGPD-UHFFFAOYSA-N isoflavone Natural products C1=C(OC)C(OC)=CC(OC)=C1C1=COC2=C(C=CC(C)(C)O3)C3=C(OC)C=C2C1=O CJWQYWQDLBZGPD-UHFFFAOYSA-N 0.000 description 1
- 235000008696 isoflavones Nutrition 0.000 description 1
- 229960004130 itraconazole Drugs 0.000 description 1
- 235000008777 kaempferol Nutrition 0.000 description 1
- 229940059939 kayexalate Drugs 0.000 description 1
- 229960003174 lansoprazole Drugs 0.000 description 1
- SIXIIKVOZAGHPV-UHFFFAOYSA-N lansoprazole Chemical compound CC1=C(OCC(F)(F)F)C=CN=C1CS(=O)C1=NC2=CC=C[CH]C2=N1 SIXIIKVOZAGHPV-UHFFFAOYSA-N 0.000 description 1
- 210000002429 large intestine Anatomy 0.000 description 1
- 201000005264 laryngeal carcinoma Diseases 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- LRDGATPGVJTWLJ-UHFFFAOYSA-N luteolin Natural products OC1=CC(O)=CC(C=2OC3=CC(O)=CC(O)=C3C(=O)C=2)=C1 LRDGATPGVJTWLJ-UHFFFAOYSA-N 0.000 description 1
- 235000009498 luteolin Nutrition 0.000 description 1
- IQPNAANSBPBGFQ-UHFFFAOYSA-N luteolin Chemical compound C=1C(O)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(O)C(O)=C1 IQPNAANSBPBGFQ-UHFFFAOYSA-N 0.000 description 1
- KBGKQZVCLWKUDQ-UHFFFAOYSA-N luteolin-glucoside Natural products OC1C(O)C(O)C(CO)OC1OC1=CC(O)=CC2=C1C(=O)C=C(C=1C=C(O)C(O)=CC=1)O2 KBGKQZVCLWKUDQ-UHFFFAOYSA-N 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- TTWJBBZEZQICBI-UHFFFAOYSA-N metoclopramide Chemical compound CCN(CC)CCNC(=O)C1=CC(Cl)=C(N)C=C1OC TTWJBBZEZQICBI-UHFFFAOYSA-N 0.000 description 1
- 229960004503 metoclopramide Drugs 0.000 description 1
- 230000011278 mitosis Effects 0.000 description 1
- UXOUKMQIEVGVLY-UHFFFAOYSA-N morin Natural products OC1=CC(O)=CC(C2=C(C(=O)C3=C(O)C=C(O)C=C3O2)O)=C1 UXOUKMQIEVGVLY-UHFFFAOYSA-N 0.000 description 1
- 229960005181 morphine Drugs 0.000 description 1
- 210000000214 mouth Anatomy 0.000 description 1
- DCYOADKBABEMIQ-OWMUPTOHSA-N myricitrin Chemical compound O[C@@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@H]1OC1=C(C=2C=C(O)C(O)=C(O)C=2)OC2=CC(O)=CC(O)=C2C1=O DCYOADKBABEMIQ-OWMUPTOHSA-N 0.000 description 1
- DCYOADKBABEMIQ-FLCVNNLFSA-N myricitrin Natural products O([C@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@H](C)O1)C1=C(c2cc(O)c(O)c(O)c2)Oc2c(c(O)cc(O)c2)C1=O DCYOADKBABEMIQ-FLCVNNLFSA-N 0.000 description 1
- WGEYAGZBLYNDFV-UHFFFAOYSA-N naringenin Natural products C1(=O)C2=C(O)C=C(O)C=C2OC(C1)C1=CC=C(CC1)O WGEYAGZBLYNDFV-UHFFFAOYSA-N 0.000 description 1
- 235000007625 naringenin Nutrition 0.000 description 1
- 229940117954 naringenin Drugs 0.000 description 1
- 229930019673 naringin Natural products 0.000 description 1
- DFPMSGMNTNDNHN-ZPHOTFPESA-N naringin Chemical compound O[C@@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@H]1O[C@H]1[C@H](OC=2C=C3O[C@@H](CC(=O)C3=C(O)C=2)C=2C=CC(O)=CC=2)O[C@H](CO)[C@@H](O)[C@@H]1O DFPMSGMNTNDNHN-ZPHOTFPESA-N 0.000 description 1
- 229940052490 naringin Drugs 0.000 description 1
- RTATXGUCZHCSNG-ZFDPGQBLSA-N nicotiflorin Natural products O(C[C@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@H](OC2=C(c3ccc(O)cc3)Oc3c(c(O)cc(O)c3)C2=O)O1)[C@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@H](C)O1 RTATXGUCZHCSNG-ZFDPGQBLSA-N 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 229960000988 nystatin Drugs 0.000 description 1
- VQOXZBDYSJBXMA-NQTDYLQESA-N nystatin A1 Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/CC/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 VQOXZBDYSJBXMA-NQTDYLQESA-N 0.000 description 1
- 229960000381 omeprazole Drugs 0.000 description 1
- SBQLYHNEIUGQKH-UHFFFAOYSA-N omeprazole Chemical compound N1=C2[CH]C(OC)=CC=C2N=C1S(=O)CC1=NC=C(C)C(OC)=C1C SBQLYHNEIUGQKH-UHFFFAOYSA-N 0.000 description 1
- MGJLSBDCWOSMHL-MIUGBVLSSA-N ononin Chemical compound C1=CC(OC)=CC=C1C1=COC2=CC(O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O3)O)=CC=C2C1=O MGJLSBDCWOSMHL-MIUGBVLSSA-N 0.000 description 1
- MGJLSBDCWOSMHL-UHFFFAOYSA-N ononoside Natural products C1=CC(OC)=CC=C1C1=COC2=CC(OC3C(C(O)C(O)C(CO)O3)O)=CC=C2C1=O MGJLSBDCWOSMHL-UHFFFAOYSA-N 0.000 description 1
- 230000010355 oscillation Effects 0.000 description 1
- 229960005019 pantoprazole Drugs 0.000 description 1
- 229940055726 pantothenic acid Drugs 0.000 description 1
- 235000019161 pantothenic acid Nutrition 0.000 description 1
- 239000011713 pantothenic acid Substances 0.000 description 1
- RUVINXPYWBROJD-UHFFFAOYSA-N para-methoxyphenyl Natural products COC1=CC=C(C=CC)C=C1 RUVINXPYWBROJD-UHFFFAOYSA-N 0.000 description 1
- 229960005489 paracetamol Drugs 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000002688 persistence Effects 0.000 description 1
- QCDYQQDYXPDABM-UHFFFAOYSA-N phloroglucinol Chemical compound OC1=CC(O)=CC(O)=C1 QCDYQQDYXPDABM-UHFFFAOYSA-N 0.000 description 1
- 229960001553 phloroglucinol Drugs 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- QYSPLQLAKJAUJT-UHFFFAOYSA-N piroxicam Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=CC=CC=N1 QYSPLQLAKJAUJT-UHFFFAOYSA-N 0.000 description 1
- 229960002702 piroxicam Drugs 0.000 description 1
- 229920001993 poloxamer 188 Polymers 0.000 description 1
- 229940044519 poloxamer 188 Drugs 0.000 description 1
- 229920001467 poly(styrenesulfonates) Polymers 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000193 polymethacrylate Polymers 0.000 description 1
- 229940041153 polymyxins Drugs 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 150000004804 polysaccharides Chemical class 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229960005205 prednisolone Drugs 0.000 description 1
- OIGNJSKKLXVSLS-VWUMJDOOSA-N prednisolone Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OIGNJSKKLXVSLS-VWUMJDOOSA-N 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 229940126409 proton pump inhibitor Drugs 0.000 description 1
- 239000000612 proton pump inhibitor Substances 0.000 description 1
- 238000002661 proton therapy Methods 0.000 description 1
- 235000005875 quercetin Nutrition 0.000 description 1
- 229960001285 quercetin Drugs 0.000 description 1
- SZDMSNWMQAMVTJ-UHFFFAOYSA-N quercetin-3-O-glucoside Natural products OC1OC(COC2=C(C(=O)c3cc(O)cc(O)c3O2)c4ccc(O)c(O)c4)C(O)C(O)C1O SZDMSNWMQAMVTJ-UHFFFAOYSA-N 0.000 description 1
- FZKBNCDAGYDHTP-UHFFFAOYSA-N quercetin-3-O-glycoside Natural products OC1C(O)C(O)C(O)OC1COC1=C(C=2C=C(O)C(O)=CC=2)OC2=CC(O)=CC(O)=C2C1=O FZKBNCDAGYDHTP-UHFFFAOYSA-N 0.000 description 1
- 206010038038 rectal cancer Diseases 0.000 description 1
- 201000001275 rectum cancer Diseases 0.000 description 1
- 210000003296 saliva Anatomy 0.000 description 1
- 210000003079 salivary gland Anatomy 0.000 description 1
- 150000004760 silicates Chemical class 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 229960001407 sodium bicarbonate Drugs 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000002048 spasmolytic effect Effects 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 229960002607 sulconazole Drugs 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000009747 swallowing Effects 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 235000013616 tea Nutrition 0.000 description 1
- FHFSSMDJUNVMNY-UHFFFAOYSA-N tectoridin Natural products COc1c(O)c2C(=O)C(=COc2cc1OC3OC(CO)C(O)C(O)C3O)c4cccc(O)c4 FHFSSMDJUNVMNY-UHFFFAOYSA-N 0.000 description 1
- CNOURESJATUGPN-UDEBZQQRSA-N tectoridin Chemical compound C1=C2OC=C(C=3C=CC(O)=CC=3)C(=O)C2=C(O)C(OC)=C1O[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O CNOURESJATUGPN-UDEBZQQRSA-N 0.000 description 1
- 229960000790 thymol Drugs 0.000 description 1
- 229960004214 tioconazole Drugs 0.000 description 1
- 239000011732 tocopherol Substances 0.000 description 1
- 229960001295 tocopherol Drugs 0.000 description 1
- 238000003325 tomography Methods 0.000 description 1
- RUVINXPYWBROJD-ONEGZZNKSA-N trans-anethole Chemical compound COC1=CC=C(\C=C\C)C=C1 RUVINXPYWBROJD-ONEGZZNKSA-N 0.000 description 1
- 229960005294 triamcinolone Drugs 0.000 description 1
- GFNANZIMVAIWHM-OBYCQNJPSA-N triamcinolone Chemical compound O=C1C=C[C@]2(C)[C@@]3(F)[C@@H](O)C[C@](C)([C@@]([C@H](O)C4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 GFNANZIMVAIWHM-OBYCQNJPSA-N 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 208000012991 uterine carcinoma Diseases 0.000 description 1
- 210000001215 vagina Anatomy 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 235000019155 vitamin A Nutrition 0.000 description 1
- 239000011719 vitamin A Substances 0.000 description 1
- 235000019156 vitamin B Nutrition 0.000 description 1
- 239000011720 vitamin B Substances 0.000 description 1
- 229940045997 vitamin a Drugs 0.000 description 1
- VHBFFQKBGNRLFZ-UHFFFAOYSA-N vitamin p Natural products O1C2=CC=CC=C2C(=O)C=C1C1=CC=CC=C1 VHBFFQKBGNRLFZ-UHFFFAOYSA-N 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
- A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0031—Rectum, anus
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0034—Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/006—Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/06—Free radical scavengers or antioxidants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/02—Suppositories; Bougies; Bases therefor; Ovules
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4858—Organic compounds
Abstract
本发明涉及用于粘着在粘膜上、特别是用于预防或治疗由放疗或联合放化疗引起的与放疗和化疗有关粘膜炎的药物组合物，该组合物含有与室温为液态、而在粘膜温度下胶凝化并因呈胶态能够粘着在粘膜上的载体混合的有效量抗自由基化合物。
Description
本发明涉及用于预防和治疗放射性粘膜炎和由抗癌综合化学疗法引起的粘膜炎的药物组合物。
从1987-1992年在其多个成员国中采集的数据，世界卫生组织(WHO)按性别计算出1994年全球范围内癌症的大约发病率(世界卫生组织：世界卫生统计年报，1987-1992-瑞士日内瓦，WHO)为：男性发病率最高的部位是前列腺(32％)；女性发病率最高的是乳腺癌(32％)。在男性中，头、颈癌以及口咽腔癌的发病率接近6％，而结肠直肠癌的发病率为12％。在女性中，头、颈癌以及口咽腔癌的发病率是5％，而结肠直肠癌的发病率为13％，同时子宫癌的发病率为8％。这些数字除本身意义外直接表明考虑抗有丝分裂治疗、特别是抗增殖的综合化学疗法和放疗引起的副作用的问题广泛性。
根据其部位，癌症治疗经常涉及中能或高能放射治疗，可以是首先治疗，也可以是手术和化疗的辅助治疗。放射治疗尤其广泛地用于某些部位的治疗：头和颈；脑；口咽腔；食管和胃；大肠和直肠；子宫。在1994年，国家癌症研究院(NCI)对美国人群在这些部位新的癌症发病情况进行了评估：
-头和颈，脑 17,500新病例
-口咽腔 29,600新病例
-喉 12,500新病例
-食管和胃 35,000新病例
-结肠和直肠 150,000新病例
-子宫 46,000新病例。
由于计算化轴向X线断层摄影术的发展，照射场的测定、照射动力学以及辐射速度均有不断的改进。因此，对于“头、颈”癌，目前已知手术和放疗之间的期间应不超过6周，并且任何放疗的中断-甚至当副作用严重引起的中断-都将损害其功效。再者，已知对某些肿瘤需要加速放疗(剂量增强)以更为有效地到达处于分裂期的较大量肿瘤细胞：超分次(hyperfractionated)放疗。同样，对加强疗效的持续研究导致交替放疗和质子疗法的出现，这使得照射可以非常精细地聚焦。
食管癌或喉癌的放疗照射由于因电离辐射攻击粘膜，是导致吞咽痛苦、强烈的功能障碍之源(这可以引起显著的体重减轻)。同样，腹部腺病或肿瘤的照射引起胃部的并发症。恶心和呕吐是最常见的症状。然而，会出现早期上皮损伤以及特别是痛苦的溃疡，它们经常是非常严重的，并且可以持续到放疗结束以后。
无论如何，颈颜面放疗的颊并发症是最典型的。该治疗最初明显有强度不同的粘膜反应-口咽粘膜炎-这与长期暴露于太阳光下(在非常炎热的夏季或热带国家)受强紫外线照射所引起的严重灼伤后产生的严重皮疹非常类似。放射性粘膜炎、特别是口咽粘膜炎的特异性与粘膜的特异性及其脆弱性有关。不象皮肤那样覆盖有厚厚的组织，粘膜(颊、龈、胃、肠、子宫、阴道和肛门直肠)非常脆弱，因为它们是由缺乏在水和血管中富含的角蛋白的细胞结构组成的。在这些组织中，由于高能辐射引起的分子振荡使细胞组织结构被极为迅速地破坏，这是粘膜受到破坏的根源。与皮肤组织不同，这些粘膜不能抵御这种类型的侵袭，并且不具有有效地防御在每一照射周期中因接受能量引起的损伤的保护性生理系统(例如亲脂亲水性特征；更新速度等)。
口咽粘膜炎最具危害性的后果是功能性障碍，对其感觉因人而异可以极为不同，这种障碍与临床症状的强度没有关系。因此放射性粘膜炎具有高度破坏性，特别是当水肿后出现红斑、然后粘膜糜烂时尤其如此，这还会导致强烈的疼痛、严重妨碍进食。
此外，对涎腺进行目标量的照射引起口腔干燥，这通常是强烈的和持续性的，甚至是永久的。除了唾液分泌减少或口腔干燥(失去唾液)等不适之外，还可能造成极度感觉不良的是，多发性龋齿也迅速形成。在此阶段，牙齿损伤的主要危险除了掉牙之外，还需要拔掉接受辐射的、构成放射性骨坏死骨(通常是下颌骨)的牙齿。因此，放射后口腔干燥的并发症是霉菌病、反复细菌感染、多发性龋齿和放射性骨坏死，这些并发症常发生、特别是发生于上呼吸消化道的放疗过程中。
由于粘膜炎可以被几种辅因子(例如与化疗有关的[5-FU，顺铂]、尼古丁成瘾、酒精中毒、不良的牙颊卫生等)加重，因此放射性粘膜炎的出现引起的危险可能极为严重。由此证明需要研究有效预防因电离辐射造成的红斑粘膜反应的手段。
由于目前对放射性粘膜炎的预防或治疗的治疗手段不佳，因此本发明人对此问题感兴趣。实际上，这些手段基本上包括系统性反复施用止痛药(例如阿司匹林)、杀真菌药(例如两性霉素B、咪康唑)、接触性麻醉剂(如利多卡因)和漱口水(以洗必太和己脒定为基础)。
这就是开发一种如下组合物之想法的产生过程，该组合物在室温为液体，但是能够粘着在粘膜上，因为当温度达到粘膜的温度时它形成胶状，并且该组合物含有抗自由基活性物质、而同时不干扰每一剂量放疗发出的能量。预防“头、颈”癌放疗后颊咽粘膜炎的这一开发构思也适用于其他形式的粘膜炎，这些粘膜炎是由放疗和/或化疗或者联合放化疗治疗癌症(例如结肠、直肠和肛门癌)或者当这些治疗偶然达到阴道粘膜时引起的
因此，本发明的目的是提供一种特别是用于预防和治疗放射性粘膜炎和化学性粘膜炎的药物组合物，该组合物含有有效量的具有抗自由基活性的化合物，该化合物与室温为液态、而在粘膜温度为胶态并因呈胶态能够粘着在粘膜上的载体混合。
具有抗自由基活性的化合物尤其可以选自：
1-天然来源的类黄酮物质，例如：
i)黄酮醇类，其中有：
-芸香苷：芦丁(槲皮素3-O-芸香糖苷)、槲皮苷(槲皮素3-O-
鼠李糖苷)、异槲皮苷(槲皮素3-O-葡糖苷)，
-洋芫荽苷(地奥司明)(香叶木素7β-芸香糖苷)、黄芪苷(莰
非醇3-O-葡糖苷)、莰非醇3-O-芸香糖苷、杨酶苷(或杨梅
黄酮3-O-鼠李糖苷)，
-刺槐素(或莰非醇3-O-刺槐糖苷7-鼠李糖苷)，
-山奈苷(或者莰非醇3，7-O-二鼠李糖苷)，
-川皮苷，
-蜜桔素。
ii)黄酮类，其中有
-野漆树苷(或5，7，4’-三羟黄酮7-O-新橙皮糖苷)、木犀草素
7-O-葡糖苷，
-黄芩素(或黄芩配基5-O-葡糖苷)，
-柳穿鱼苷(或柳穿鱼素7-O-芸香苷)，
-木犀草苷(或木犀草素5-O-葡糖苷)，
-刺槐苷(或刺槐素7-O-鼠李葡糖苷)，
iii)黄烷酮类，其中有：
-甘草苷(或甘草苷4′-O-葡糖苷)、柚皮苷(或柚皮素7-O-新
橙皮糖苷)、桔皮苷(或桔皮素7-O-芸香糖苷)，
-圣草苷(或圣草素7-O-鼠李糖苷)，
2-天然来源的异黄酮类物质，例如：
-芒柄花素7-O-葡糖苷(或芒柄花苷)、阿佛洛莫生
(afromosin)7-O-葡糖苷(或多花紫藤苷)，
-染料木苷(或染料木黄酮7-O-葡糖苷)、大豆苷、黄豆黄素，
-染料木黄酮6-O-丙二酰基葡糖苷、大豆黄素6-O-丙二酰基葡
糖苷、染料木黄酮6-O-乙酰基葡糖苷，
-鸢尾苷(或鸢尾素7-O-葡糖苷)，
-尼鸢尾黄素，
-鸢尾苷(或鸢尾黄素7-O-葡糖苷)或射干苷。
3-生育酚；
4-多酚和含有多酚的植物提取物例如矢车菊苷配基
(procyanidolic)低聚物，millepertuis、Kallanchoe pinnata、
春黄菊、松树皮、茶、Centella asiatica、落叶松、火绒草的
提取物，
5-维生素：例如维生素A，类胡萝卜素，α-硫辛酸，
6-植物油的活性部分例如α-lupaline、hierogaline，
7-丁基羟基苯甲醚、丁基羟基甲苯。
室温为液态、而在粘膜温度为胶态的载体可以由特别是下列物质混合物的含水分散液或溶液构成：
a-0.05-5％(重量)(优选0.1-3％(重量))赋予粘性的物质；
b-1-20％(重量)(优选5-20％(重量))根据温度改变粘度的物质。
i)赋予粘性的物质可具体选自下列化合物：-胶体或水胶体(多糖物质及其相关物质)：
·半乳甘露聚糖及其衍生物：瓜尔胶、角豆胶和刺云实胶等
·淀粉及其衍生物
·阿拉伯胶、西黄蓍胶和刺梧桐胶等
·果胶和果胶的衍生物等
·藻酸类：藻酸、藻酸钠和藻酸钠/钙等
·角叉菜胶及其衍生物等
·纤维素及其衍生物：羧甲基纤维素(CMC)、羧甲基纤维素钠、CMC钙、甲基纤维素、羟丙基纤维素、羟丙甲基纤维素和羟乙基纤维素等
·高分子量葡聚糖
·黄原胶及其衍生物等
·透明质酸及其衍生物和壳多糖、脱乙酰壳多糖及它们的衍生物等-丙烯酸、甲基丙烯酸及其衍生物的聚合物：聚甲基丙烯酸酯、亲有机物的羧乙烯基聚合物(卡波普、卡波姆)、聚羟乙基甲基丙烯酸酯，-聚乙烯基衍生物、聚乙烯吡咯烷酮、聚(乙烯吡咯烷酮和乙酸乙烯酯)、聚乙酸苯二甲酸乙烯酯、聚乙烯醇，-高分子量聚乙二醇，-聚丙烯酰胺及其衍生物，-马来酸聚合物，例如聚乙烯基醚/马来酸共聚物、聚乙烯基醚/马来酸共聚复合物的钠/钙盐，-聚苯乙烯磺酸钠，-无机衍生物：二氧化硅和硅酸盐衍生物及硅氧烷等
ii)随温度变化改变粘度的物质实例，可例举：
·泊洛沙姆(如泊洛沙姆188和泊洛沙姆407等)和poloxamines
·二乙烯基苯山梨醇类化合物(disorbene)，它们溶于亲脂性溶媒。
在室温(20℃)下粘度低于200×10-3Pa.s并且在35-37℃下粘度高于2000×10-3Pa.s的组合物是优选的，粘度的测定用LV型Brookfield粘度计/LV4旋转仪，在0.5转/分的转速条件下，15秒钟后读取粘度数据。
例如，在温度升高时，包含赋予粘性的物质(c＝1.7％羟丙基甲基纤维素(HPMC))及5％芦丁和14％泊洛沙姆407的本发明溶液表现出下列行为：
| 温度(t℃) | 粘度(10-3Pa.s) |
| 253035 | 31414333027 |
可见，在25℃下，该溶液是流动的(粘度数量级在300×10-3Pa.s)，当温度升高到30℃时发生胶凝化，随后使温度升至35℃(从25℃升至35℃时，粘度增加到10倍)。
该水性组合物优选具有与粘膜相容的pH值(通常在pH7-8)。
本发明的主题物还可以是固体组合物，该组合物将用于与水混合以形成在室温是液体的溶液并且该溶液在与被保护的粘膜接触时能够形成凝胶。对于胃粘膜和/或肠道粘膜，本发明的主题物可以是固体形式的，例如粉末或颗粒，或者是在加入液体载体后可形成液体组合物的颗粒形式(例如，在临用前可配制成可饮用糖浆、悬浮液或溶液的粉末)。组合物还可呈在服用前溶于水的裸片或颗粒形式。
本发明的组合物可含有与抗自由基活性化合物联合应用的其它活性成分，它们优选是下列药物治疗成分：
-镇痛剂和解痉剂(对乙酰氨基酚、阿司匹林、可待因、吗啡、阿托品、洛派丁胺、间苯三酚等)、麻醉剂(塞罗卡因、利多卡因)和抗菌剂(洗必太、己脒定)，
-皮质激素类抗炎药(泼尼松龙和曲安西龙等)或昔康类(如炎痛喜康等)，
-抗溃疡药(抗组胺H2药、前列腺素及其衍生物、质子泵抑制剂，例如奥美拉唑、泮托拉唑、兰索拉唑)，
-抗酸剂和胃肠修饰剂(磷酸铝、氢氧化铝和氢氧化镁、粘土(diosmectite)、actapulgite等)，
-治疗胃食管反流药和消化动力药(藻酸钠、碳酸氢钠和甲氧氯普胺等)，
-止吐药(苯甲酰胺类、抗组胺H1药和setrons等)，
-止泻药(洛派丁胺等)，
-针对消化道的抗真菌剂(两性霉素B、制霉菌素、噻康唑、依曲康唑、益康唑和布康唑等)，
-治疗消化功能障碍的药物(如西沙比得)和针对肠道运输的药物，
-肠道抗菌剂(氨基糖苷类、硝基咪唑类和多粘菌素类等)和抗病毒剂(如阿昔洛韦)，
-被认为具有缓解和/或增强(上述活性)性质的产物：生物素、多酚类、甘草酸、百里酚和桉叶油素等，及富含甘草酸、泛醇、尿囊素及其衍生物的植物提取物，
-维生素：B族维生素(B1、B6、B12)、烟酰胺、生物素、泛酸，
-矫正唾液分泌减少和调节唾液分泌的产品：匹鲁卡品、茴三硫，
-肽和酶：弹性蛋白、胶原、谷胱甘肽、过氧化氢酶、内切核酸酶，它们可用于修复被放射损伤的组织。
下列实施例说明本发明。
I-
用于颊粘膜的组合物
以实施例的形式给出以下制剂，这些制剂用于说明本发明、而非限制性的：
| 百分数 | ||||
| 实施例 | 1 | 2 | 3 | 4 |
| 水溶性芸香苷 | 2-10 | 2-10 | 2-10 | 2-10 |
| 匹鲁卡品盐酸盐 | --- | 1-5 | --- | 1-5 |
| 泊洛沙姆407 | 14.0 | 5-20 | 5-20 | 5-20 |
| HPMC | 1-3 | 1-3 | 1-3 | 1-3 |
| 芳香剂 | 0.1-0.5 | 0.1-0.5 | 0.1-0.5 | 0.1-0.5 |
| α-生育酚 | --- | --- | 0.01-0.05 | 0.01-0.05 |
| 缓冲液pH7.8加至 | 100 | 100 | 100 | 100 |
这些组分构成具有热可逆性稠度的溶液，该溶液：在室温(20-25℃)呈液态，在生理腔的温度(35-37℃)为粘性。因此，含有5-20％泊洛沙姆407和1-3％HPMC聚合物(即6-23％的胶凝剂)的组合物在室温(25℃)的粘度低至足以将其容易地推进(经给药系统)(150-300×10-3Pa·S)，然后有效地在待保护粘膜上形成凝胶(例如，当温度增至30-35℃时，粘度达到2000-21,000×10-3Pa.s)。
II-
用于消化道粘膜的组合物
1-可胶凝的液体组合物
作为非限制性的实例，可以提及以下实施例：
| 百分数 | ||||
| 实施例 | 5 | 6 | 7 | 8 |
| 芸香苷 | 2-10 | 1-5 | 0-5 | 0-5 |
| 两性霉素B | --- | 1-2.5 | --- | --- |
| 咪康唑 | --- | --- | 1-5 | --- |
| 尿囊素 | 0-1 | 0-1 | 0-1 | --- |
| 生物素 | 0-0.050 | 0-0.050 | 0-0.050 | 0-0.050 |
| 右泛醇 | 0-1 | 0-1 | 0-1 | 0-1 |
| Millepertuis(水提物) | --- | --- | --- | 0-5 |
| Kallanchoe(水提物) | --- | --- | --- | 0-5 |
| HPMC(Methocel E4M) | 1-3 | 1-3 | 1-3 | 1-3 |
| 泊洛沙姆407(Lutrol F127) | 6-20 | 6-20 | 6-20 | 6-20 |
| 甜味剂/芳香剂 | 适量 | 适量 | 适量 | 适量 |
| 防腐剂 | 适量 | 适量 | 适量 | 适量 |
| 水加至 | 100 | 100 | 100 | 100 |
2-待分散于水中的颗粒
在胃肠道的温度下，该组合物形成凝胶，粘着在粘膜的绒毛上。
| mg | ||||
| 实施例 | 9 | 10 | 11 | 12 |
| 地奥司明 | 500 | 500 | 500 | 500 |
| Centella asiatica提取物 | --- | 20-50 | --- | --- |
| 羟丙基甲基纤维素(HPMC) | 150 | 150 | 150 | 150 |
| 黄原胶 | 250 | 250 | 250 | 250 |
| 碳酸钙 | 1000 | 1000 | 500 | --- |
| 尿囊素铝* | --- | --- | 900 | --- |
| 铅克洛沙** | --- | --- | 100 | --- |
| 泊洛沙姆407 | 1500 | 1500 | 1500 | 1500 |
| 氢氧化铝 | --- | --- | --- | 400 |
| 氢氧化镁 | --- | --- | --- | 400 |
| 芳香剂 | 适量 | 适量 | 适量 | 适量 |
| 木糖醇 | 1000 | 1000 | 1000 | 1000 |
*尿囊酸二羟基铝
**尿囊酸氯羟基铝
(每一袋分散在100-200毫升水中)。
实施例13-待分散在水中的颗粒(即配即用制剂)
使用时，将每袋以mg量分散在100ml水中，该组合物在胃肠道的温度下也形成凝胶，粘着在粘膜的绒毛上：
| OPC* | 200-500 |
| α-硫辛酸 | 0-20 |
| 聚维酮 | 200 |
| β-环糊精 | 1000-3000 |
| 羟丙基甲基纤维素 | 100 |
| 泊洛沙姆407 | 1000 |
| 芳香剂/甜味剂 | 适量 |
*矢车菊苷配基低聚物(葡萄核或松树皮的提取物)。
III-
用于直肠粘膜的组合物
以下给出可热胶凝的即用型的粘性溶液的两个实例：
| 实施例 | 18(％) | 19(％) |
| 芸香苷 | 2-10 | 1-5 |
| 右泛醇 | --- | 1-5 |
| 丁基羟基甲苯 | --- | 1-10 |
| α-生育酚 | --- | 0.01-0.05 |
| (HPMC)Methocel E4M | 1-3 | 1-3 |
| 泊洛沙姆407 | 5-20 | 5-20 |
| 纯化水加至 | 100 | 100 |
IV-
用于阴道粘膜的组合物
下面给出在粘膜温度胶凝的溶液的三个非限制性实例：
| 实施例 | 20(％) | 21(％) | 22(％) |
| 芸香苷 | 0.5-10 | 0.5-10 | 0.5-10 |
| 硝酸布康唑 | 1-5 | --- | --- |
| 硝酸益康唑 | --- | 1-3 | --- |
| 硫康唑(thioconazole) | --- | --- | 2-5 |
| 泊洛沙姆407 | 6-20 | 6-20 | 6-20 |
| Methocel E4M | 1-2 | 1-2 | 1-2 |
| 纯化水加至 | 100 | 100 | 100 |
Claims (14)
1.用于粘着在粘膜上用于预防和治疗由放疗和联合放化疗引起的放射性粘膜炎和化学性粘膜炎的药物组合物，该组合物含有有效量的选自类黄酮和异黄酮类的化合物，该化合物与室温为液态、而在粘膜温度胶凝化并因呈胶态能够粘着在粘膜上的载体混合。
2.权利要求1的组合物，其中载体是含水载体，并且含有0.05-5％(重量)赋予粘性的物质和1-20％(重量)根据温度改变粘度的物质的混合物。
3.权利要求2的组合物，其中载体含有0.1-3％(重量)赋予粘性的物质和5-20％(重量)根据温度改变粘度的物质的混合物。
4.权利要求2的组合物，其中根据温度改变粘度的物质选自泊洛沙姆、poloxamines和二乙烯基苯山梨醇化合物。
5.权利要求1的组合物，其中类黄酮选自芸香苷、洋芫荽苷、槲皮苷、蜜桔素和桔皮苷。
6.权利要求1的组合物，其中异黄酮类是染料木苷、大豆苷或黄豆黄素。
7.权利要求5的组合物，其中芸香苷是芦丁。
8.与室温为液态、而在粘膜温度下胶凝化并因呈胶态能够粘着在粘膜上的载体混合的、选自类黄酮和异黄酮类的化合物在制备预防和治疗放射性粘膜炎和化学性粘膜炎的药物组合物中的用途。
9.权利要求8的用途，其中载体是含水载体，并且含有0.05-5％(重量)赋予粘性的物质和1-20％(重量)根据温度改变粘度的物质的混合物。
10.权利要求9的用途，其中载体含有0.1-3％(重量)赋予粘性的物质和5-20％(重量)根据温度改变粘度的物质的混合物。
11.权利要求9的用途，其中根据温度改变粘度的物质选自泊洛沙姆、poloxamines和二乙烯基苯山梨醇化合物。
12.权利要求8的用途，其中类黄酮选自芸香苷、洋芫荽苷、槲皮苷、蜜桔素和桔皮苷。
13.权利要求8的用途，其中异黄酮类是染料木苷、大豆苷或黄豆黄素。
14.权利要求12的用途，其中芸香苷是芦丁。
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR98/09230 | 1998-07-20 | ||
| FR9809230A FR2781156B1 (fr) | 1998-07-20 | 1998-07-20 | Composition pharmaceutique destinee notamment a la prevention et au traitement des radiomucites et des chimiomucites |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1310610A CN1310610A (zh) | 2001-08-29 |
| CN1149977C true CN1149977C (zh) | 2004-05-19 |
Family
ID=9528788
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB998088935A Expired - Fee Related CN1149977C (zh) | 1998-07-20 | 1999-07-19 | 用于预防和治疗放射性粘膜炎和化学性粘膜炎的药物组合物 |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US7033606B1 (zh) |
| EP (1) | EP1098631B1 (zh) |
| JP (1) | JP2002521321A (zh) |
| CN (1) | CN1149977C (zh) |
| AT (1) | ATE235226T1 (zh) |
| AU (1) | AU4629699A (zh) |
| CA (1) | CA2337152C (zh) |
| DE (1) | DE69906302T2 (zh) |
| DK (1) | DK1098631T3 (zh) |
| ES (1) | ES2196823T3 (zh) |
| FR (1) | FR2781156B1 (zh) |
| PT (1) | PT1098631E (zh) |
| WO (1) | WO2000004878A1 (zh) |
Families Citing this family (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7655694B2 (en) | 2000-06-14 | 2010-02-02 | The United States Of America As Represented By The Department Of Health And Human Services | Phytoestrogenic isoflavone compositions, their preparation and use thereof for protection against and treatment of radiation injury |
| US20020013331A1 (en) * | 2000-06-26 | 2002-01-31 | Williams Robert O. | Methods and compositions for treating pain of the mucous membrane |
| ES2254523T3 (es) * | 2000-11-22 | 2006-06-16 | Rxkinetix, Inc. | Tratamiento de mucositis. |
| EP1593127B1 (en) | 2003-02-14 | 2012-06-06 | Henry M. Jackson Foundation For The Advancement Of Military Medicine, Inc. | Radiation protection by gamma-tocotrienol, alpha-tocopherol succinate or gamma-tocopherol succinate |
| JP4898447B2 (ja) * | 2003-10-14 | 2012-03-14 | プルーロームド インコーポレイテッド | 結石破砕術の際の腎結石破片の閉じ込め |
| US20090042781A1 (en) * | 2004-06-28 | 2009-02-12 | Novo Nordisk A/S | Methods for Treating Diabetes |
| CA2635603C (en) * | 2005-11-30 | 2016-01-19 | Endo Pharmaceuticals Inc. | Treatment of xerostomia |
| CN100444847C (zh) * | 2006-01-11 | 2008-12-24 | 刘展欣 | 一种微粒化地奥司明和橙皮甙组合物栓剂 |
| EP2046359B1 (en) | 2006-06-20 | 2020-05-27 | Izun Pharmaceuticals Corporation | Anti-inflammatory dissolvable film |
| ES2539114T3 (es) * | 2006-07-20 | 2015-06-26 | Izun Pharmaceuticals Corporation | Enjuague formador de película |
| KR101017650B1 (ko) * | 2008-03-04 | 2011-02-25 | 한국원자력연구원 | 헤스페리딘 또는 이의 약학적으로 허용가능한 염을유효성분으로 함유하는 세포 보호용 조성물 |
| JP5376889B2 (ja) * | 2008-09-30 | 2013-12-25 | 小林製薬株式会社 | カンジダ症予防又は治療剤 |
| US9884082B2 (en) | 2008-11-13 | 2018-02-06 | David A. Hamlin | Compositions and methods for alleviating hyposalivation and for providing oral comfort |
| US9597278B2 (en) | 2008-11-13 | 2017-03-21 | David A. Hamlin | Compositions and methods for alleviating hyposalivation and for providing oral comfort |
| FR2940761B1 (fr) * | 2009-01-07 | 2012-12-28 | Polymerexpert Sa | Composition anti-ronflement contenant un polymere thermogelifiant |
| ES2742525T3 (es) | 2009-10-01 | 2020-02-14 | Adare Pharmaceuticals Us L P | Composiciones de corticosteroides administradas oralmente |
| EP2572713B1 (en) * | 2011-09-22 | 2014-08-13 | King Saud University | Extracts and isolated flavonoids from Euphorbia cuneata useful as anti-ulcer agents |
| FR2999934B1 (fr) * | 2012-12-21 | 2015-02-20 | Servier Lab | Composition pharmaceutique sous la forme d'une suspension orale comprenant une fraction flavonoique et de la gomme xanthane |
| CN103405482B (zh) * | 2013-01-25 | 2016-01-06 | 丽水同舟药食资源科技开发有限公司 | 柳叶腊梅提取物在制备治疗炎性肠病和减轻化疗药物引起的消化道损伤的药物中的应用 |
| WO2015034678A2 (en) | 2013-09-06 | 2015-03-12 | Aptalis Pharmatech, Inc. | Corticosteroid containing orally disintegrating tablet compositions for eosinophilic esophagitis |
| FR3023167B1 (fr) * | 2014-07-07 | 2018-01-12 | Laboratoires Rivadis Sas | Composition cosmetique ou pharmaceutique a application topique comprenant une association de pectine et d'un extrait de centella asiatica et applications |
| CN112915076B (zh) * | 2016-06-15 | 2022-11-08 | 南京简庄生物技术有限公司 | 一种外用皮肤组织保护及修复制剂 |
| TWI728172B (zh) | 2016-08-18 | 2021-05-21 | 美商愛戴爾製藥股份有限公司 | 治療嗜伊紅性食道炎之方法 |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4748022A (en) * | 1985-03-25 | 1988-05-31 | Busciglio John A | Topical composition |
| JPH0758963B2 (ja) | 1989-01-27 | 1995-06-21 | 日本電気株式会社 | セル交換装置 |
| US5032384A (en) * | 1989-01-27 | 1991-07-16 | Block Drug Company, Inc. | Compositions and method for the treatment of disease |
| CA2011423A1 (en) | 1989-03-07 | 1990-09-07 | Peter M. Taylor | Pharmaceutical compositions useful as drug delivery vehicles and/or as wound dressings |
| IT1250691B (it) * | 1991-07-22 | 1995-04-21 | Giancarlo Santus | Composizioni terapeutiche per somministrazione intranasale comprendenti ketorolac. |
| EP0648113A4 (en) * | 1992-04-23 | 1996-12-04 | Berlex Lab | BIOADHAESIVE FIXED MINERAL OIL EMULSION. |
| US5281196A (en) * | 1992-05-22 | 1994-01-25 | Sultenfuss Thomas J | Skin treatment composition and method of use |
| EP0577143B1 (de) * | 1992-07-03 | 1999-01-27 | ALFATEC-PHARMA GmbH | Feste und flüssige Lösungen von Flavonoiden |
| FR2695034B1 (fr) * | 1992-09-01 | 1994-10-07 | Oreal | Composition cosmétique ou pharmaceutique comprenant en association une peroxydase et un agent anti-oxygène singulet. |
| GB9321341D0 (en) * | 1993-10-15 | 1993-12-08 | Bristol Myers Squibb Co | Therapeutic compositions for use in the treatment of skin lesions and method of making same |
| DE4444238A1 (de) * | 1994-12-13 | 1996-06-20 | Beiersdorf Ag | Kosmetische oder dermatologische Wirkstoffkombinationen aus Zimtsäurederivaten und Flavonglycosiden |
| IN186803B (zh) * | 1997-02-05 | 2001-11-10 | Panacea Biotec Ltd |
-
1998
- 1998-07-20 FR FR9809230A patent/FR2781156B1/fr not_active Expired - Fee Related
-
1999
- 1999-07-19 JP JP2000560871A patent/JP2002521321A/ja active Pending
- 1999-07-19 DK DK99929503T patent/DK1098631T3/da active
- 1999-07-19 CA CA002337152A patent/CA2337152C/en not_active Expired - Fee Related
- 1999-07-19 AU AU46296/99A patent/AU4629699A/en not_active Abandoned
- 1999-07-19 PT PT99929503T patent/PT1098631E/pt unknown
- 1999-07-19 WO PCT/FR1999/001760 patent/WO2000004878A1/fr active IP Right Grant
- 1999-07-19 ES ES99929503T patent/ES2196823T3/es not_active Expired - Lifetime
- 1999-07-19 US US09/764,990 patent/US7033606B1/en not_active Expired - Fee Related
- 1999-07-19 CN CNB998088935A patent/CN1149977C/zh not_active Expired - Fee Related
- 1999-07-19 EP EP99929503A patent/EP1098631B1/fr not_active Expired - Lifetime
- 1999-07-19 DE DE69906302T patent/DE69906302T2/de not_active Expired - Fee Related
- 1999-07-19 AT AT99929503T patent/ATE235226T1/de not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| CA2337152C (en) | 2008-09-16 |
| DK1098631T3 (da) | 2003-07-21 |
| PT1098631E (pt) | 2003-06-30 |
| AU4629699A (en) | 2000-02-14 |
| JP2002521321A (ja) | 2002-07-16 |
| FR2781156B1 (fr) | 2001-06-29 |
| CA2337152A1 (en) | 2000-02-03 |
| DE69906302T2 (de) | 2003-11-27 |
| FR2781156A1 (fr) | 2000-01-21 |
| EP1098631A1 (fr) | 2001-05-16 |
| WO2000004878A1 (fr) | 2000-02-03 |
| ATE235226T1 (de) | 2003-04-15 |
| CN1310610A (zh) | 2001-08-29 |
| DE69906302D1 (de) | 2003-04-30 |
| EP1098631B1 (fr) | 2003-03-26 |
| US7033606B1 (en) | 2006-04-25 |
| ES2196823T3 (es) | 2003-12-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1149977C (zh) | 用于预防和治疗放射性粘膜炎和化学性粘膜炎的药物组合物 | |
| JP2007512336A (ja) | 可溶性結合剤を含む結腸下剤組成物 | |
| NO341742B1 (no) | Farmasøytisk sammensetning for anvendelse ved forebygging eller behandling av mukositt | |
| CN1599599A (zh) | 兽用药和人用药中活性物质给药的可崩解的粘膜粘性药物制剂 | |
| KR20040089628A (ko) | 생체내에서 상전이하는 액상 매트릭스 및 액상 경구 제제 | |
| ES2242939T3 (es) | Mejoras a composiciones o relacionadas con las mismas. | |
| CN100444847C (zh) | 一种微粒化地奥司明和橙皮甙组合物栓剂 | |
| CN108159024A (zh) | 一种治疗口腔溃疡的缓释贴膜及其制备方法 | |
| CN103249304B (zh) | 用于治疗瘀伤的组合物和方法 | |
| CN103211801A (zh) | 一种在口腔中快速溶解的膜剂及其制备方法 | |
| WO2003099297A1 (en) | Treatment of mucositis | |
| JP2004002320A (ja) | 生体内で相転移する液状マトリックスおよび液状経口製剤 | |
| CN109771395B (zh) | 一种含有槲皮素的口腔黏膜剂及其制备方法 | |
| CN101023961B (zh) | 一种含透明质酸钠和锌盐的药物组合物 | |
| JPH10218780A (ja) | 肛門直腸疾患および結腸疾患の制御および処置のための新規な薬学組成物およびその製造方法 | |
| CN102100789A (zh) | 一种治疗咽炎的中药组合物及其制备方法 | |
| CN112891448B (zh) | 用于治疗浅表性胃炎的胶体果胶铋制剂及其制备方法 | |
| CN1179726C (zh) | 柚皮苷在制备支持性治疗非典型性肺炎药物中的应用 | |
| CN1886137A (zh) | 脱氧鸭嘴花碱的口服制剂及其应用 | |
| CN1414847A (zh) | 含吡喹酮的缓释抗蠕虫组合物 | |
| CN1078468C (zh) | 叶绿素铜钠盐用于制造抗胃粘膜损伤的组合物的用途 | |
| CN103156816A (zh) | 经口腔粘膜吸收的阿莫曲坦药物 | |
| WO2018167655A1 (en) | Laxative syrup | |
| Ghildiyal et al. | Plantago Ovata Gum and Locust Bean as a Natural Polymer in Hydrodynamically Balanced Systems: A Review | |
| CN1682973A (zh) | 一种千金藤素口腔崩解片及其制备方法 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C17 | Cessation of patent right | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20040519 |