CN112516074A - 一种苯佐卡因药物制剂及其制备方法 - Google Patents
一种苯佐卡因药物制剂及其制备方法 Download PDFInfo
- Publication number
- CN112516074A CN112516074A CN202011437119.7A CN202011437119A CN112516074A CN 112516074 A CN112516074 A CN 112516074A CN 202011437119 A CN202011437119 A CN 202011437119A CN 112516074 A CN112516074 A CN 112516074A
- Authority
- CN
- China
- Prior art keywords
- preparation
- benzocaine
- solution
- gel
- stirring
- 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
- BLFLLBZGZJTVJG-UHFFFAOYSA-N benzocaine Chemical compound CCOC(=O)C1=CC=C(N)C=C1 BLFLLBZGZJTVJG-UHFFFAOYSA-N 0.000 title claims abstract description 149
- 229960005274 benzocaine Drugs 0.000 title claims abstract description 75
- 238000002360 preparation method Methods 0.000 title claims abstract description 49
- 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 claims abstract description 50
- 239000002202 Polyethylene glycol Substances 0.000 claims abstract description 27
- 229920001223 polyethylene glycol Polymers 0.000 claims abstract description 27
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims abstract description 25
- 229920002125 Sokalan® Polymers 0.000 claims abstract description 25
- 229930003427 Vitamin E Natural products 0.000 claims abstract description 25
- 229960001631 carbomer Drugs 0.000 claims abstract description 25
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 claims abstract description 25
- 239000011709 vitamin E Substances 0.000 claims abstract description 25
- 235000019165 vitamin E Nutrition 0.000 claims abstract description 25
- 229940046009 vitamin E Drugs 0.000 claims abstract description 25
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 claims abstract description 24
- 239000000463 material Substances 0.000 claims abstract description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 51
- 238000003756 stirring Methods 0.000 claims description 44
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 33
- 235000010228 ethyl p-hydroxybenzoate Nutrition 0.000 claims description 17
- 239000004403 ethyl p-hydroxybenzoate Substances 0.000 claims description 17
- NUVBSKCKDOMJSU-UHFFFAOYSA-N ethylparaben Chemical compound CCOC(=O)C1=CC=C(O)C=C1 NUVBSKCKDOMJSU-UHFFFAOYSA-N 0.000 claims description 17
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 claims description 15
- 229940043351 ethyl-p-hydroxybenzoate Drugs 0.000 claims description 14
- 238000010438 heat treatment Methods 0.000 claims description 14
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 10
- 238000002156 mixing Methods 0.000 claims description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 8
- 239000000203 mixture Substances 0.000 claims description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- 108010011485 Aspartame Proteins 0.000 claims description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 6
- 239000000605 aspartame Substances 0.000 claims description 6
- 235000010357 aspartame Nutrition 0.000 claims description 6
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 claims description 6
- 229960003438 aspartame Drugs 0.000 claims description 6
- 235000003599 food sweetener Nutrition 0.000 claims description 5
- 239000002904 solvent Substances 0.000 claims description 5
- 239000000126 substance Substances 0.000 claims description 5
- 239000003765 sweetening agent Substances 0.000 claims description 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 4
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 claims description 4
- 239000003755 preservative agent Substances 0.000 claims description 4
- 230000002335 preservative effect Effects 0.000 claims description 4
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 claims description 4
- 239000003381 stabilizer Substances 0.000 claims description 4
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 3
- 229960001617 ethyl hydroxybenzoate Drugs 0.000 claims description 3
- 238000000034 method Methods 0.000 claims description 3
- 229940068918 polyethylene glycol 400 Drugs 0.000 claims description 3
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims description 2
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 claims description 2
- 229960000686 benzalkonium chloride Drugs 0.000 claims description 2
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 claims description 2
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 claims description 2
- 229910000397 disodium phosphate Inorganic materials 0.000 claims description 2
- 235000019800 disodium phosphate Nutrition 0.000 claims description 2
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 claims description 2
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 claims description 2
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 claims description 2
- 229960002216 methylparaben Drugs 0.000 claims description 2
- 229910000403 monosodium phosphate Inorganic materials 0.000 claims description 2
- 235000019799 monosodium phosphate Nutrition 0.000 claims description 2
- 229960003742 phenol Drugs 0.000 claims description 2
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 claims description 2
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 claims description 2
- 229960003415 propylparaben Drugs 0.000 claims description 2
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 claims description 2
- 235000011121 sodium hydroxide Nutrition 0.000 claims description 2
- 239000000811 xylitol Substances 0.000 claims description 2
- 235000010447 xylitol Nutrition 0.000 claims description 2
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 claims description 2
- 229960002675 xylitol Drugs 0.000 claims description 2
- -1 and the like Substances 0.000 claims 2
- 238000004806 packaging method and process Methods 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 claims 1
- 239000012528 membrane Substances 0.000 abstract description 10
- 239000000499 gel Substances 0.000 description 55
- 239000000243 solution Substances 0.000 description 42
- 229960004063 propylene glycol Drugs 0.000 description 15
- FTLYMKDSHNWQKD-UHFFFAOYSA-N (2,4,5-trichlorophenyl)boronic acid Chemical compound OB(O)C1=CC(Cl)=C(Cl)C=C1Cl FTLYMKDSHNWQKD-UHFFFAOYSA-N 0.000 description 12
- 229940085605 saccharin sodium Drugs 0.000 description 12
- 230000000052 comparative effect Effects 0.000 description 11
- 239000003814 drug Substances 0.000 description 11
- 210000004379 membrane Anatomy 0.000 description 9
- 239000011159 matrix material Substances 0.000 description 8
- 210000000214 mouth Anatomy 0.000 description 8
- 238000012360 testing method Methods 0.000 description 8
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 208000002193 Pain Diseases 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 210000004877 mucosa Anatomy 0.000 description 5
- 230000036407 pain Effects 0.000 description 5
- 229960000502 poloxamer Drugs 0.000 description 5
- 229920001983 poloxamer Polymers 0.000 description 5
- 239000004094 surface-active agent Substances 0.000 description 5
- 238000009792 diffusion process Methods 0.000 description 4
- 230000035515 penetration Effects 0.000 description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 208000027418 Wounds and injury Diseases 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 230000000857 drug effect Effects 0.000 description 3
- 239000002674 ointment Substances 0.000 description 3
- 235000000346 sugar Nutrition 0.000 description 3
- 239000001856 Ethyl cellulose Substances 0.000 description 2
- 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 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 239000006189 buccal tablet Substances 0.000 description 2
- 229920002301 cellulose acetate Polymers 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 229960004756 ethanol Drugs 0.000 description 2
- 235000019325 ethyl cellulose Nutrition 0.000 description 2
- 229920001249 ethyl cellulose Polymers 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- 238000005286 illumination Methods 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 239000003589 local anesthetic agent Substances 0.000 description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
- 229920000053 polysorbate 80 Polymers 0.000 description 2
- 239000008213 purified water Substances 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 230000035807 sensation Effects 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000005063 solubilization Methods 0.000 description 2
- 230000007928 solubilization Effects 0.000 description 2
- 239000007921 spray Substances 0.000 description 2
- 238000013112 stability test Methods 0.000 description 2
- 150000008163 sugars Chemical class 0.000 description 2
- 230000008961 swelling Effects 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- 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
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 229920002101 Chitin Polymers 0.000 description 1
- IELOKBJPULMYRW-NJQVLOCASA-N D-alpha-Tocopheryl Acid Succinate Chemical compound OC(=O)CCC(=O)OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C IELOKBJPULMYRW-NJQVLOCASA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 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 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 208000007117 Oral Ulcer Diseases 0.000 description 1
- 208000025157 Oral disease Diseases 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- 208000003251 Pruritus Diseases 0.000 description 1
- 206010039424 Salivary hypersecretion Diseases 0.000 description 1
- UEDUENGHJMELGK-HYDKPPNVSA-N Stevioside Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O UEDUENGHJMELGK-HYDKPPNVSA-N 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 206010042496 Sunburn Diseases 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 230000036592 analgesia Effects 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 208000002399 aphthous stomatitis Diseases 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 229940046011 buccal tablet Drugs 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 230000007012 clinical effect Effects 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 239000003431 cross linking reagent Substances 0.000 description 1
- 229940099418 d- alpha-tocopherol succinate Drugs 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 208000002925 dental caries Diseases 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000004945 emulsification Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000012374 esterification agent Substances 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 210000001508 eye Anatomy 0.000 description 1
- 239000010685 fatty oil Substances 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229960005150 glycerol Drugs 0.000 description 1
- 208000014617 hemorrhoid Diseases 0.000 description 1
- 230000010224 hepatic metabolism Effects 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 229920013821 hydroxy alkyl cellulose Polymers 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 229960004592 isopropanol Drugs 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 229960005015 local anesthetics Drugs 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 208000030194 mouth disease Diseases 0.000 description 1
- 210000002200 mouth mucosa Anatomy 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 210000003928 nasal cavity Anatomy 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 229940100688 oral solution Drugs 0.000 description 1
- 229940041678 oral spray Drugs 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000003002 pH adjusting agent Substances 0.000 description 1
- 230000008058 pain sensation Effects 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 239000012466 permeate Substances 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 229920001993 poloxamer 188 Polymers 0.000 description 1
- 229940044519 poloxamer 188 Drugs 0.000 description 1
- 229940113115 polyethylene glycol 200 Drugs 0.000 description 1
- 229940068886 polyethylene glycol 300 Drugs 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 239000004800 polyvinyl chloride Substances 0.000 description 1
- 229920000915 polyvinyl chloride Polymers 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 208000026451 salivation Diseases 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 239000000344 soap Substances 0.000 description 1
- 230000003381 solubilizing effect Effects 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 229940013618 stevioside Drugs 0.000 description 1
- OHHNJQXIOPOJSC-UHFFFAOYSA-N stevioside Natural products CC1(CCCC2(C)C3(C)CCC4(CC3(CCC12C)CC4=C)OC5OC(CO)C(O)C(O)C5OC6OC(CO)C(O)C(O)C6O)C(=O)OC7OC(CO)C(O)C(O)C7O OHHNJQXIOPOJSC-UHFFFAOYSA-N 0.000 description 1
- 235000019202 steviosides Nutrition 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 210000000515 tooth Anatomy 0.000 description 1
- 208000004371 toothache Diseases 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 210000001215 vagina Anatomy 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Images
Classifications
-
- 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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/235—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group
- A61K31/24—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group having an amino or nitro group
- A61K31/245—Amino benzoic acid types, e.g. procaine, novocaine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
-
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P23/00—Anaesthetics
- A61P23/02—Local anaesthetics
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Anesthesiology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Inorganic Chemistry (AREA)
- Emergency Medicine (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Nutrition Science (AREA)
- Physiology (AREA)
- Medicinal Preparation (AREA)
Abstract
本发明提供了一种苯佐卡因药物制剂及其制备方法，该制剂成分包括：苯佐卡因，卡波姆，维生素E聚乙二醇琥珀酸酯及其它辅料。其中苯佐卡因，卡波姆，维生素E聚乙二醇琥珀酸酯在制剂中的重量百分比分别为：苯佐卡因5‑30%，卡波姆0.3‑5%，维生素E聚乙二醇琥珀酸酯0.05‑5%。本发明提供了苯佐卡因凝胶剂的制备方法，制备工艺简单，产品稳定性好，透膜速率高。
Description
技术领域
本发明属于制药技术领域，具体地，涉及包含苯佐卡因的一种药物制剂及其制备方法。
背景技术
凝胶剂是由药物、基质及其他辅料制成，具有凝胶特性的半固体或稠厚液体，可从口腔、鼻腔、眼黏膜、消化道粘膜、阴道、直肠、皮肤等多种途径给药。凝胶剂具有良好的生物相容性，外形美观，易于涂布使用，无油腻性，容易洗除，使用舒适感高等特点。凝胶剂可分为水性凝胶剂与油性凝胶剂，水性凝胶剂基质通常包括纤维素衍生物、卡波姆、泊洛沙姆、海藻酸盐、壳多糖、聚乙烯醇、明胶等，油性凝胶基质通常由液状石蜡与聚氯乙烯或脂肪油与铝皂构成，不同基质组成的制剂产生不同的临床作用，根据作用特点及主药的性质选择适宜的基质。
局部麻醉药是指能可逆性地阻断神经冲动的感觉传导，使患者局部痛觉暂时消失，但触压、温度觉等仍存在的药物。苯佐卡因(benzocaine)，又名氨苯甲酸乙酯，对各种原因引起的浅表性局部疼痛具有明显的镇痛作用，可用于缓解由于轻微刺激、疼痛或口腔和粘膜损伤引起的疼痛，用于皮肤和粘膜创面、溃疡面及痔疮的麻醉镇痛，可缓解晒伤、瘙痒和轻度烧伤，具有毒副作用小，作用时间持久等特点，但由于极微溶于水，吸收差，起效慢，且容易氧化变色而失效，含有苯佐卡因的上市产品有溶液、含片、喷雾剂、软膏、凝胶剂等剂型。
口腔给药可避免首过肝脏代谢以及胃肠道的蛋白酶水解，为局部或全身治疗提供了许多优势，具有独特的作用。对于口腔疾病用药，溶液剂、喷雾剂、含片、软膏剂、凝胶剂等制剂直接作用于患处，相比于全身吸收的药物制剂，更具有优势。苯佐卡因口腔给药制剂，可缓解口腔、牙齿或粘膜损伤引起的疼痛，用于口腔溃疡、牙痛、龋齿等疾病的治疗。
作为发挥局部麻醉作用的药物，苯佐卡因制成口服溶液、喷剂等制剂则无法长时间停留在作用部位，药物起效快，但效果持续时间短；制成含片等固体制剂，则因含化时间而起效慢，且存在颗粒异物感，流涎和舌头运动也无法较长时间滞留患处，药效无法长期维持。而软膏剂、凝胶制剂为半固体制剂，起效快，可黏附在黏膜上而作用时间较长，具有明显的制剂优势。相较于软膏，凝胶剂外观美观，不油腻，易清除，则是更佳的选择。苯佐卡因凝胶剂，可快速起效镇痛，又可在口腔中较长时间维持药效，广泛应用于临床。
专利CN1891300B中公开了一种含苯佐卡因成膜凝胶组合物及其用途，此发明组合物成分包括苯佐卡因、羟烷基纤维素、交联剂等，采用乙基纤维素和醋酸纤维素为凝胶基质，以水杨酸为酯化剂，制成苯佐卡因成膜凝胶，此凝胶涂抹后在患处形成一层坚韧、耐磨、持久的疏水性附膜，在表面保留5个小时以上，有效延长药物的滞留时间。此专利采用了乙基纤维素和醋酸纤维素为水不溶性材料，使用有机溶剂制备得到，因其疏水性的特点不易降解，若在口腔中使用，因在患处较长时间滞留，口腔内硬化膜的一种异物感会严重影响患者的顺应性。
专利CN109833303A中公开了一种含有增强稳定性的苯佐卡因的药物组合物，赖氨酸可以减少苯佐卡因和糖发生美拉德反应(Maillard reaction)，增强苯佐卡因在贮存期间的稳定性。固体制剂常含有还原糖(如葡萄糖、乳糖、蔗糖)，此专利技术提供了一种方法，以减少苯佐卡因与还原糖发生反应而增加稳定。
维生素E聚乙二醇琥珀酸酯是天然维生素E的水溶性衍生物(结构式如附图1)，可由亲水的聚乙二醇(PEG)与亲脂的生育酚琥珀酸酯(TAS)发生酯化反应而得，因此具有两亲性，具有PEG和TAS的生理活性。作为一种新颖的表面活性剂，维生素E聚乙二醇琥珀酸酯在已上市药物中的应用并不多见，但可见不少对药物的增溶、乳化、分散、促进药物渗透等方面的相关研究报道。
本发明人提供了一种含苯佐卡因的药物制剂及其制备方法，采用卡波姆为凝胶基质，维生素E聚乙二醇琥珀酸酯为稳定剂，制备的凝胶剂稳定性高，起效快。
发明内容
本发明提供一种含有苯佐卡因的凝胶剂及制备方法，发明人发现以卡波姆为基质，含有维生素E聚乙二醇琥珀酸酯为稳定剂。本发明人发现以卡波姆为基质，维生素E聚乙二醇琥珀酸酯为稳定剂的苯佐卡因凝胶，与其他凝胶基质及稳定剂的苯佐卡因凝胶剂相比，药物的降解速度慢，稳定性高，透膜速度快。
本发明为一种苯佐卡因凝胶剂及其制备方法，凝胶剂的成分包括苯佐卡因、卡波姆、维生素E聚乙二醇琥珀酸酯和pH调节剂、防腐剂、甜味剂、溶剂等。
上述本发明的凝胶剂，其中苯佐卡因是起到主要药效作用的药物，在凝胶中的重量占比可在5-30％，优选10-20％。
上述本发明的凝胶剂，以卡波姆为主要凝胶基质，制备的凝胶外观漂亮，长期放置不易变形，卡波姆在凝胶中的重量占比可在0.3-5％，优选1-3％。
上述本发明的凝胶剂，主要特征在于含有维生素E聚乙二醇琥珀酸酯，在凝胶中的重量占比可在0.05-5％，优选0.1-2％。维生素E聚乙二醇琥珀酸酯为表面活性剂，发挥增溶、增加稳定、促进渗透的作用，可增加苯佐卡因凝胶放置稳定性，促进药物的透膜吸收。
上述本发明的凝胶剂，其中pH调节剂不限于以下物质的一种或几种：氢氧化钠，碳酸氢钠，磷酸氢钠，磷酸二氢钠，三乙醇胺等，优选三乙醇胺。
上述本发明的凝胶剂，其中防腐剂不限于以下物质的一种或几种：对羟基苯甲酸甲酯，对羟基苯甲酸乙酯，对羟基苯甲酸丙酯，苯扎氯胺，苯酚等，优选对羟基苯甲酸乙酯。
上述本发明的凝胶剂，其中甜味剂不限于以下物质的一种或几种：糖精钠，蛋白糖，甜菊糖，阿斯巴甜，木糖醇等，优选糖精钠、阿斯巴甜。
上述本发明的凝胶剂，其中溶剂不限于以下物质的一种或几种：乙醇，丙二醇，丙三醇，聚乙二醇400，聚乙二醇300，聚乙二醇200，异丙醇，DMF，水，优选乙醇、丙二醇或聚乙二醇400和水。
上述本发明的苯佐卡因凝胶剂的制备方法包括以下步骤：
步骤一：将对羟基苯甲酸乙酯加入适量纯水中，加热溶解，加入卡波姆，静置使充分溶胀，得到溶液A；
步骤二：将苯佐卡因和维生素E聚乙二醇琥珀酸酯加入丙二醇中，搅拌溶液，得到溶液B；
步骤三：将甜味剂加入溶液A中，搅拌溶解，在搅拌下缓慢加入溶液B中，混合均匀得到溶液C；
步骤四：将三乙醇胺加入适量水中，加入溶液C，并补加纯水至足量，搅拌均匀得到最终制剂。
卡波姆为高分子材料，加入水溶液后无需搅拌，静置保证充分溶胀。完全溶胀后，可以电动搅拌桨缓慢搅拌，可避免出现泡沫影响产品外观性状。
本发明的实施例中苯佐卡因在凝胶中的重量占比优选在5-20％，但不限于此浓度范围。都以卡波姆为凝胶基质，维生素E聚乙二醇琥珀酸酯作为表面活性剂，起增溶稳定作用。对照例1不含表面活性剂，对照例2采用吐温80替代维生素E聚乙二醇琥珀酸酯作为表面活性剂，对照例3采用泊洛沙姆为凝胶基质。
附图说明
附图1维生素E聚乙二醇琥珀酸酯结构
具体实施方式
下面详细描述本发明的实施例。下面描述的实施例仅用于解释本发明，而不是对本发明的限制。
实施例1苯佐卡因凝胶剂的制备
处方：苯佐卡因5g，卡波姆9403g，三乙醇胺适量，丙二醇5g，维生素E聚乙二醇琥珀酸酯0.2g，对羟基苯甲酸乙酯0.1g，糖精钠0.15g，纯水加至100ml。制备方法：
(1)将0.1g对羟基苯甲酸乙酯加入至约70ml纯水中，加热搅拌使溶解，加入3g卡波姆，静置使充分溶胀，得到溶液A；
(2)将5g苯佐卡因和0.2g维生素E聚乙二醇琥珀酸酯加入5g丙二醇中，加热搅拌使溶解，得到溶液B；
(3)将溶液A与溶液B混合，搅拌均匀，加入0.15g糖精钠，搅拌使溶解，得到溶液C；
(4)取三乙醇胺加入适量水中，加入溶液C中，搅拌使成凝胶，补加纯水至足量，搅拌均匀得到最终制剂。
实施例2
处方：苯佐卡因20g，卡波姆9402g，三乙醇胺适量，丙二醇20g，维生素E聚乙二醇琥珀酸酯1g，对羟基苯甲酸乙酯0.1g，阿斯巴甜0.1g，纯水加至100ml。
(1)将0.1g对羟基苯甲酸乙酯加入至约70ml纯水中，加热搅拌使溶解，加入2g卡波姆，静置使充分溶胀，得到溶液A；
(2)将20g苯佐卡因和1g维生素E聚乙二醇琥珀酸酯加入20g丙二醇中，加热搅拌使溶解，得到溶液B；
(3)将溶液A与溶液B混合，搅拌均匀，加入0.1g阿斯巴甜，搅拌使溶解，得到溶液C；
(4)取三乙醇胺加入适量水中，缓慢加入溶液C中，搅拌使成凝胶，补加纯水至足量，搅拌均匀得到最终制剂。
实施例3
处方：苯佐卡因10g，卡波姆9402g，三乙醇胺适量，丙二醇10g，维生素E聚乙二醇琥珀酸酯0.5g，对羟基苯甲酸乙酯0.1g，糖精钠0.1g，纯水加至100ml。制备方法：
(1)将0.1g对羟基苯甲酸乙酯加入至约70ml纯水中，加热搅拌使溶解，加入2g卡波姆，静置使充分溶胀，得到溶液A；
(2)将10g苯佐卡因和0.5g维生素E聚乙二醇琥珀酸酯加入20g丙二醇中，加热搅拌使溶解，得到溶液B；
(3)将溶液A与溶液B混合，搅拌均匀，加入0.1g糖精钠，搅拌使溶解，得到溶液C；
(4)取三乙醇胺加入适量水中，加入溶液C中，搅拌使成凝胶，补加纯水至足量，搅拌均匀得到最终制剂。
对照例1
处方：苯佐卡因10g，卡波姆9402g，三乙醇胺适量，丙二醇10g，对羟基苯甲酸乙酯0.1g，糖精钠0.1g，纯水加至100ml。
制备方法：
(1)将0.1g对羟基苯甲酸乙酯加入至约70ml纯化水中，加热搅拌使溶解，加入2g卡波姆，静置使充分溶胀，得到溶液A；
(2)将10g苯佐卡因加入10g丙二醇中，加热搅拌使溶解，得到溶液B；
(3)将溶液A与溶液B混合，搅拌均匀，加入0.1g糖精钠，搅拌使溶解，得到溶液C；
(4)取三乙醇胺加入适量水中，缓慢加入溶液C中，搅拌使成凝胶，补加纯水至足量，搅拌均匀得到最终制剂。
对照例2
处方：苯佐卡因10g，泊洛沙姆40724g，泊洛沙姆1886g，丙二醇10g，对羟基苯甲酸乙酯0.1g，糖精钠0.1g，纯水加至100ml。
制备方法：
(1)将0.1g对羟基苯甲酸乙酯加入至约80ml纯水中，加热搅拌使溶解，依次加入0.1g糖精钠、6g泊洛沙姆188、24g泊洛沙姆，搅拌使溶解，得到溶液A；
(2)将10g苯佐卡因加入10g丙二醇中，加热搅拌使溶解，得到溶液B；
(3)将溶液A与溶液B混合，搅拌均匀，补加纯水至足量，搅拌使溶解，得到最终制剂。
对照例3
处方：苯佐卡因10g，卡波姆9402g，三乙醇胺适量，丙二醇10g，吐温801g，对羟基苯甲酸乙酯0.1g，糖精钠0.1g，纯水加至100ml。
制备方法：
(1)将0.1g对羟基苯甲酸乙酯加入至约70ml纯化水中，加热搅拌使溶解，加入2g卡波姆，静置使充分溶胀，得到溶液A；
(2)将10g苯佐卡因、1g吐温80加入10g丙二醇中，加热搅拌使溶解，得到溶液B；
(3)将溶液A与溶液B混合，搅拌均匀，加入0.1g糖精钠，搅拌使溶解，得到溶液C；
(4)取三乙醇胺加入适量水中，缓慢加入溶液C中，搅拌使成凝胶，补加纯水至足量，搅拌均匀得到最终制剂。
试验例1 30天影响因素的稳定性试验
将本发明实施例1-3、对照例1-3制备的苯佐卡因凝胶剂放置于20ml西林瓶中，分别在60℃高温、5000LX光照下放置30天，于0天、30天取样，参照中国药典方法检查性状、含量，结果见下表1。
表1苯佐卡因凝胶稳定性试验结果
结果可见，在60℃和光照下放置30天，本发明实施例1-3制备得到的苯佐卡因凝胶剂外观性状没有发生变化，含量没有明显变化，而对照例的外观性状和含量变化较大，说明本发明的苯佐卡因凝胶剂稳定性好。
试验例2透膜试验
为考察苯佐卡因凝胶的透膜性能，在Franz扩散池中，采用猪颊膜，对本发明实施例3、对照例1和对照例2制备的苯佐卡因凝胶剂进行透膜试验。将预处理后的猪颊膜置于Franz扩散池的瓶口，在扩散池中注入pH6.8缓冲液，在透皮扩散试验仪中进行试验，定时取样检测苯佐卡因含量，试验结果见下表2。
表2苯佐卡因凝胶透膜试验结果
试验结果可见，相较于对照例1和对照例2，实施例3中的苯佐卡因更快透过粘膜，说明含有卡波姆和维生素E聚乙二醇琥珀酸酯的苯佐卡因凝胶透膜速率快，起效快。
Claims (11)
1.一种含有苯佐卡因的药物制剂及其制备方法，其特征在于所述药物制剂包括以下成分：苯佐卡因，卡波姆，稳定剂及其它辅料。
2.根据权利要求1所述的含有苯佐卡因的药物制剂及其制备方法，其特征在于稳定剂为维生素E聚乙二醇琥珀酸酯。
3.根据权利要求1所述的含有苯佐卡因的药物制剂及其制备方法，其特征在于其它辅料包括pH调节剂、防腐剂、溶剂等。
4.根据权利要求3所述的含有苯佐卡因的药物制剂及其制备方法，其特征在于所述的pH调节剂由以下物质组成：氢氧化钠，碳酸氢钠，磷酸氢钠，磷酸二氢钠，三乙醇胺等，或它们的混合物。
5.根据权利要求3所述的含有苯佐卡因的药物制剂及其制备方法，其特征在于所述的防腐剂由以下物质组成：对羟基苯甲酸甲酯，对羟基苯甲酸乙酯，对羟基苯甲酸丙酯，苯扎氯胺，苯酚等，或它们的混合物。
6.根据权利要求3所述的含有苯佐卡因的药物制剂及其制备方法，其特征在于所述的甜味剂由以下物质组成：糖精钠，蛋白糖，甜菊糖，阿斯巴甜，木糖醇等，或它们的混合物。
7.根据权利要求3所述的含有苯佐卡因的药物制剂及其制备方法，其特征在于所述的溶剂由以下物质组成：乙醇，丙二醇，聚乙二醇400，异丙醇，DMF，水等，或它们的混合物。
8.根据权利要求1所述的含有苯佐卡因的药物制剂及其制备方法，其特征在于以下几个成分构成按重量百分比为：苯佐卡因5-30%，卡波姆0.3-5%，维生素E聚乙二醇琥珀酸酯0.05-5%。
9.根据前述权利要求所述的含有苯佐卡因的药物制剂及其制备方法，其中所述药物制剂为凝胶剂。
10.根据权利要求1所述的含有苯佐卡因的药物制剂及其制备方法，其特征在于，制备方法包括以下步骤：
将对羟基苯甲酸乙酯加入适量纯水中，加热溶解，加入卡波姆，静置使充分溶胀，得到溶液A；
将苯佐卡因和维生素E聚乙二醇琥珀酸酯加入丙二醇中，搅拌溶液，得到溶液B；
将甜味剂加入溶液A中，搅拌溶解，在搅拌下缓慢加入溶液B中，混合均匀得到溶液C；
将三乙醇胺加入适量水中，加入溶液C，并补加纯水至足量，搅拌均匀得到最终制剂。
11.根据权利要求1所述的含有苯佐卡因的药物制剂及其制备方法，其特征在于，进一步包括：对所述的苯佐卡因凝胶剂进行灌装、包装。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011437119.7A CN112516074A (zh) | 2020-12-11 | 2020-12-11 | 一种苯佐卡因药物制剂及其制备方法 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011437119.7A CN112516074A (zh) | 2020-12-11 | 2020-12-11 | 一种苯佐卡因药物制剂及其制备方法 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN112516074A true CN112516074A (zh) | 2021-03-19 |
Family
ID=74999444
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202011437119.7A Pending CN112516074A (zh) | 2020-12-11 | 2020-12-11 | 一种苯佐卡因药物制剂及其制备方法 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN112516074A (zh) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2023242417A1 (en) * | 2022-06-17 | 2023-12-21 | Bertie International Ab | Long-lasting anaesthetic formulation |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20000017706A (ko) * | 1999-07-08 | 2000-04-06 | 이승하 | 국소마취제를함유한약용겔제조성물 |
| KR20020026402A (ko) * | 2000-10-02 | 2002-04-10 | 한상철 | 피부투과도가 향상된 국소마취용 외용제 조성물 |
-
2020
- 2020-12-11 CN CN202011437119.7A patent/CN112516074A/zh active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20000017706A (ko) * | 1999-07-08 | 2000-04-06 | 이승하 | 국소마취제를함유한약용겔제조성물 |
| KR20020026402A (ko) * | 2000-10-02 | 2002-04-10 | 한상철 | 피부투과도가 향상된 국소마취용 외용제 조성물 |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2023242417A1 (en) * | 2022-06-17 | 2023-12-21 | Bertie International Ab | Long-lasting anaesthetic formulation |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5118633B2 (ja) | 医療用デバイスおよび医薬製剤において有用な粘膜付着性キシログルカン含有製剤 | |
| AU2010317747B2 (en) | Use of bethanechol for treatment of xerostomia | |
| Guo et al. | Emerging strategies for enhancing buccal and sublingual administration of nutraceuticals and pharamaceuticals | |
| AU2007298814B2 (en) | Galenic form for the trans-mucosal delivery of active ingredients | |
| PT1510213E (pt) | Sistemas de melhoramento de penetração e reduzida irritação incluíndo testosterona | |
| JPH10287588A (ja) | 医薬製剤 | |
| Bharat et al. | A review: Novel advances in semisolid dosage forms & patented technology in semisolid dosage forms | |
| US8722744B2 (en) | Galenical form for the administration of paracetamol by transmucous means | |
| JP3207212B2 (ja) | 吸収促進剤およびこれを含有する外用剤 | |
| CN101474144A (zh) | 盐酸丁卡因脂质体凝胶及其制备方法 | |
| IL137559A (en) | A system for administering drugs through the skin | |
| WO2019161470A1 (pt) | Composição farmacêutica na forma de suspensão aquosa e uso de uma composição farmacêutica na forma de suspensão aquosa | |
| CN112516074A (zh) | 一种苯佐卡因药物制剂及其制备方法 | |
| JP2001199883A (ja) | 消炎鎮痛外用剤 | |
| US9662340B2 (en) | Testosterone gel compositions and related methods | |
| WO2011025792A1 (en) | Compositions for absorption and sustained action of leptin-related peptides | |
| JP5811404B2 (ja) | セトロンを頬側経粘膜投与するための処方物（ｆｏｒｍｕｌａｔｉｏｎ） | |
| CN113350266B (zh) | 一种具有抗菌作用的口腔黏膜修复原位温敏凝胶 | |
| US12070440B2 (en) | Topical formulations of nitroglycerin | |
| RU2814279C2 (ru) | Композиция для профилактики или лечения проктологических заболеваний | |
| Anu et al. | A review on mucoadhesive bilayer buccal patches | |
| CN110812332B (zh) | 一种双氯芬酸钠咽部滞留颗粒 | |
| Teja et al. | FORMULATION AND EVALUATION OF GLIBENCLAMIDE TRANSDERMAL PATCHES | |
| JP2001072605A (ja) | 経皮経粘膜吸収促進剤組成物 | |
| CN111481499A (zh) | 一种羟苯磺酸钙凝胶剂及其制备方法与应用 |
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 | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20210319 |