CN100370994C - Ointment with clindamycin and metronidazole and method for preparing the same - Google Patents
Ointment with clindamycin and metronidazole and method for preparing the same Download PDFInfo
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- CN100370994C CN100370994C CNB200510093283XA CN200510093283A CN100370994C CN 100370994 C CN100370994 C CN 100370994C CN B200510093283X A CNB200510093283X A CN B200510093283XA CN 200510093283 A CN200510093283 A CN 200510093283A CN 100370994 C CN100370994 C CN 100370994C
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- Prior art keywords
- clindamycin
- ointment
- metronidazole
- water
- layering
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- KDLRVYVGXIQJDK-AWPVFWJPSA-N clindamycin Chemical compound CN1C[C@H](CCC)C[C@H]1C(=O)N[C@H]([C@H](C)Cl)[C@@H]1[C@H](O)[C@H](O)[C@@H](O)[C@@H](SC)O1 KDLRVYVGXIQJDK-AWPVFWJPSA-N 0.000 title claims abstract description 58
- 229960002227 clindamycin Drugs 0.000 title claims abstract description 56
- VAOCPAMSLUNLGC-UHFFFAOYSA-N metronidazole Chemical compound CC1=NC=C([N+]([O-])=O)N1CCO VAOCPAMSLUNLGC-UHFFFAOYSA-N 0.000 title claims abstract description 56
- 229960000282 metronidazole Drugs 0.000 title claims abstract description 56
- 239000002674 ointment Substances 0.000 title claims abstract description 40
- 238000000034 method Methods 0.000 title claims description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims abstract description 48
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 claims abstract description 22
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 20
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims abstract description 14
- 229940057995 liquid paraffin Drugs 0.000 claims abstract description 14
- 235000019333 sodium laurylsulphate Nutrition 0.000 claims abstract description 14
- 239000003871 white petrolatum Substances 0.000 claims abstract description 14
- 229940075507 glyceryl monostearate Drugs 0.000 claims abstract description 11
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 claims abstract description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 10
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 claims abstract description 6
- 238000003756 stirring Methods 0.000 claims description 15
- 239000000203 mixture Substances 0.000 claims description 14
- 239000004141 Sodium laurylsulphate Substances 0.000 claims description 13
- 229960001617 ethyl hydroxybenzoate Drugs 0.000 claims description 12
- NUVBSKCKDOMJSU-UHFFFAOYSA-N ethylparaben Chemical compound CCOC(=O)C1=CC=C(O)C=C1 NUVBSKCKDOMJSU-UHFFFAOYSA-N 0.000 claims description 12
- GYCKQBWUSACYIF-UHFFFAOYSA-N o-hydroxybenzoic acid ethyl ester Natural products CCOC(=O)C1=CC=CC=C1O GYCKQBWUSACYIF-UHFFFAOYSA-N 0.000 claims description 11
- 239000012153 distilled water Substances 0.000 claims description 9
- 235000021355 Stearic acid Nutrition 0.000 claims description 7
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 7
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 claims description 7
- 239000008117 stearic acid Substances 0.000 claims description 7
- HVUMOYIDDBPOLL-XWVZOOPGSA-N Sorbitan monostearate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O HVUMOYIDDBPOLL-XWVZOOPGSA-N 0.000 claims description 5
- 238000001816 cooling Methods 0.000 claims description 5
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims description 5
- 229920000053 polysorbate 80 Polymers 0.000 claims description 5
- 230000004927 fusion Effects 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 abstract description 15
- 235000011187 glycerol Nutrition 0.000 abstract description 11
- 150000002148 esters Chemical class 0.000 abstract description 9
- 150000003839 salts Chemical class 0.000 abstract description 9
- -1 liquid paraffin Substances 0.000 abstract description 7
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 abstract description 6
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 abstract description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 abstract description 4
- 239000002202 Polyethylene glycol Substances 0.000 abstract description 3
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 abstract description 3
- 239000000470 constituent Substances 0.000 abstract description 3
- 238000005516 engineering process Methods 0.000 abstract description 3
- 150000002334 glycols Chemical class 0.000 abstract description 3
- 238000004519 manufacturing process Methods 0.000 abstract description 3
- 229920001223 polyethylene glycol Polymers 0.000 abstract description 3
- 229920000136 polysorbate Polymers 0.000 abstract description 3
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 abstract description 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 abstract description 2
- 241001465754 Metazoa Species 0.000 abstract description 2
- 229940056211 paraffin Drugs 0.000 abstract description 2
- 239000012188 paraffin wax Substances 0.000 abstract description 2
- 239000000600 sorbitol Substances 0.000 abstract description 2
- 239000002253 acid Substances 0.000 abstract 1
- 235000013871 bee wax Nutrition 0.000 abstract 1
- 229960000541 cetyl alcohol Drugs 0.000 abstract 1
- 229940083575 sodium dodecyl sulfate Drugs 0.000 abstract 1
- 238000012360 testing method Methods 0.000 description 26
- 239000000126 substance Substances 0.000 description 7
- 230000002421 anti-septic effect Effects 0.000 description 4
- 238000007710 freezing Methods 0.000 description 4
- 230000008014 freezing Effects 0.000 description 4
- 239000003883 ointment base Substances 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- 238000011282 treatment Methods 0.000 description 4
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 239000006072 paste Substances 0.000 description 3
- 206010040872 skin infection Diseases 0.000 description 3
- 238000013112 stability test Methods 0.000 description 3
- 229960004274 stearic acid Drugs 0.000 description 3
- HOVAGTYPODGVJG-UVSYOFPXSA-N (3s,5r)-2-(hydroxymethyl)-6-methoxyoxane-3,4,5-triol Chemical compound COC1OC(CO)[C@@H](O)C(O)[C@H]1O HOVAGTYPODGVJG-UVSYOFPXSA-N 0.000 description 2
- CFKMVGJGLGKFKI-UHFFFAOYSA-N 4-chloro-m-cresol Chemical compound CC1=CC(O)=CC=C1Cl CFKMVGJGLGKFKI-UHFFFAOYSA-N 0.000 description 2
- 208000002874 Acne Vulgaris Diseases 0.000 description 2
- 206010016936 Folliculitis Diseases 0.000 description 2
- 206010033078 Otitis media Diseases 0.000 description 2
- 229920002565 Polyethylene Glycol 400 Polymers 0.000 description 2
- 206010000496 acne Diseases 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000000890 drug combination Substances 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 229940040145 liniment Drugs 0.000 description 2
- 239000000865 liniment Substances 0.000 description 2
- HOVAGTYPODGVJG-UHFFFAOYSA-N methyl beta-galactoside Natural products COC1OC(CO)C(O)C(O)C1O HOVAGTYPODGVJG-UHFFFAOYSA-N 0.000 description 2
- TZBAVQKIEKDGFH-UHFFFAOYSA-N n-[2-(diethylamino)ethyl]-1-benzothiophene-2-carboxamide;hydrochloride Chemical compound [Cl-].C1=CC=C2SC(C(=O)NCC[NH+](CC)CC)=CC2=C1 TZBAVQKIEKDGFH-UHFFFAOYSA-N 0.000 description 2
- JLFNLZLINWHATN-UHFFFAOYSA-N pentaethylene glycol Chemical compound OCCOCCOCCOCCOCCO JLFNLZLINWHATN-UHFFFAOYSA-N 0.000 description 2
- 229940093430 polyethylene glycol 1500 Drugs 0.000 description 2
- 238000009781 safety test method Methods 0.000 description 2
- 201000009890 sinusitis Diseases 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 231100000041 toxicology testing Toxicity 0.000 description 2
- 210000001215 vagina Anatomy 0.000 description 2
- IQXJCCZJOIKIAD-UHFFFAOYSA-N 1-(2-methoxyethoxy)hexadecane Chemical compound CCCCCCCCCCCCCCCCOCCOC IQXJCCZJOIKIAD-UHFFFAOYSA-N 0.000 description 1
- 206010002198 Anaphylactic reaction Diseases 0.000 description 1
- 241000186427 Cutibacterium acnes Species 0.000 description 1
- 241000193880 Demodex folliculorum Species 0.000 description 1
- 239000004593 Epoxy Substances 0.000 description 1
- 206010015150 Erythema Diseases 0.000 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- 239000004367 Lipase Substances 0.000 description 1
- 102000004882 Lipase Human genes 0.000 description 1
- 108090001060 Lipase Proteins 0.000 description 1
- 206010065764 Mucosal infection Diseases 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 239000005662 Paraffin oil Substances 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- IYFATESGLOUGBX-YVNJGZBMSA-N Sorbitan monopalmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O IYFATESGLOUGBX-YVNJGZBMSA-N 0.000 description 1
- 206010046914 Vaginal infection Diseases 0.000 description 1
- 201000008100 Vaginitis Diseases 0.000 description 1
- LWZFANDGMFTDAV-BURFUSLBSA-N [(2r)-2-[(2r,3r,4s)-3,4-dihydroxyoxolan-2-yl]-2-hydroxyethyl] dodecanoate Chemical compound CCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O LWZFANDGMFTDAV-BURFUSLBSA-N 0.000 description 1
- UFUVLHLTWXBHGZ-MGZQPHGTSA-N [(2r,3r,4s,5r,6r)-6-[(1s,2s)-2-chloro-1-[[(2s,4r)-1-methyl-4-propylpyrrolidine-2-carbonyl]amino]propyl]-4,5-dihydroxy-2-methylsulfanyloxan-3-yl] dihydrogen phosphate Chemical compound CN1C[C@H](CCC)C[C@H]1C(=O)N[C@H]([C@H](C)Cl)[C@@H]1[C@H](O)[C@H](O)[C@@H](OP(O)(O)=O)[C@@H](SC)O1 UFUVLHLTWXBHGZ-MGZQPHGTSA-N 0.000 description 1
- 210000000683 abdominal cavity Anatomy 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000036783 anaphylactic response Effects 0.000 description 1
- 208000003455 anaphylaxis Diseases 0.000 description 1
- 229960002233 benzalkonium bromide Drugs 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- KHSLHYAUZSPBIU-UHFFFAOYSA-M benzododecinium bromide Chemical compound [Br-].CCCCCCCCCCCC[N+](C)(C)CC1=CC=CC=C1 KHSLHYAUZSPBIU-UHFFFAOYSA-M 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- 239000007766 cera flava Substances 0.000 description 1
- 229950009789 cetomacrogol 1000 Drugs 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- 229960002242 chlorocresol Drugs 0.000 description 1
- 229960001200 clindamycin hydrochloride Drugs 0.000 description 1
- 229960002291 clindamycin phosphate Drugs 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 238000007598 dipping method Methods 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 239000007938 effervescent tablet Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 231100000321 erythema Toxicity 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- 235000010228 ethyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004403 ethyl p-hydroxybenzoate Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 238000003475 lamination Methods 0.000 description 1
- 235000019421 lipase Nutrition 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 229960003511 macrogol Drugs 0.000 description 1
- GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 1
- 229940051841 polyoxyethylene ether Drugs 0.000 description 1
- 229920000056 polyoxyethylene ether Polymers 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 229940055019 propionibacterium acne Drugs 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 208000013223 septicemia Diseases 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- DCXXMTOCNZCJGO-UHFFFAOYSA-N tristearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCCCCCCCC)COC(=O)CCCCCCCCCCCCCCCCC DCXXMTOCNZCJGO-UHFFFAOYSA-N 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
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- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention relates to an ointment using clindamycin or pharmaceutical salt or ester of clindamycin and metronidazole as active constituents. The ointment is prepared from 0.25 to 5 wt% of clindamycin or pharmaceutical salt or ester of clindamycin, 0.2 to 4 wt% of metronidazole, 10 to 40 wt% of greasy base, 5 to 50 wt% of water-soluble base, and water as the rest, and the sum of the weight percentages of the constituents is 100%, wherein the greasy base is selected from at least one of stearinic acid, glyceryl monostearate, paraffin, liquid paraffin, white vaseline, lanoline, cetanol, octadecanol, span series, bee wax and animal and plant fat and oil; the water-soluble base is selected from at least one of glycerine, propylene glycol, sorbitol, polyethylene glycol series, tween series, sodium dodecylsulfate, dimethyl sulfoxide, triethanolamine and ethanol. The ointment of the present invention is prepared by selecting the greasy base and the water-soluble base and using common equipment, has the advantages of simple preparation technology and stable product quality, and is suitable for industrialization production.
Description
Technical field:
The invention belongs to field of medicaments, relate to a kind of clindamycin compounds and clindamycin and metronidazole ointment and preparation method thereof.
Background technology:
The present Cuo health king who uses clinically is the preparation that Clindamycin Hydrochloride and metronidazole share, and promptly the clindamycin and metronidazole liniment is used for the treatment of acne, otitis media, sinusitis, folliculitis and other various bacterial skin infections.Clinical practice has proved that both share and can suppress, kill propionibacterium acnes, pityrosporum furfur and some other responsive strains effectively, suppresses the growth of demodex folliculorum, thereby reduces the generation of lipase, prevents that triacylglycerol is hydrolyzed into free fatty.
The patent that clindamycin and metronidazole share the aspect also has: the drug combination that has disclosed clindamycin and metronidazole among the U.S. Pat P5849776A, be mainly used in skin and mucosal infections, mention the pharmaceutical dosage forms such as ointment, emulsifiable paste, Emulsion, powder, dipping tablet, solution, gel, spray, lotion or suspension of clindamycin and metronidazole compositions very generally, and specifically disclosed following ointment and preparation thereof:
Metronidazole 0.75g
Clindamycin phosphate 1.18g
Methyl glucoside 1.0g
Stearyl alcohol 0.5g
Paraffin oil 6g
Polyoxyethylene 400 2g
Methyl glucoside sesquistearate 5g
The polyoxyethylene ether carbopol 9810.4g that forms by 20 moles oxireme
Glycerol 7g
Epoxy methylsiloxane 4g
It is 5 that sodium hydroxide is regulated pH value in right amount
Antiseptic is an amount of
Demineralized water adds to 100g
The ointment of being mentioned among the USP5849776A, prescription constituent is very complicated, and most of adjuvants are not the emulsifiable paste matrixes of domestic routine, and prepared cream products exists heat resistance and the bad shortcoming of cold tolerance, are difficult to be fit to suitability for industrialized production and clinical practice.
Also described the drug combination of clindamycin and metronidazole among the Chinese patent application 03123920.X, dosage form is an injection, is mainly used in the degree of depth infection of quick and a large amount of drug administration by injection treatments as septicemia, abdominal cavity infection etc.; Disclosed clindamycin metronidazole vagina effervescent tablet in the Chinese patent application numbers 200410070111.6, be mainly used in vagina administration with gynaecopathias such as treatment vaginitiss.
Summary of the invention:
Defective at the prior art existence, the present invention selects domestic conventional ointment base commonly used for use, with common ointment preparation method, prescription design by novelty, through screening repeatedly and testing, invented a kind of new clindamycin and metronidazole ointment, and be surprisingly found out that it has excellent cold tolerance and heat resistance, has good stability.
An object of the present invention is to provide a kind of clindamycin and metronidazole ointment, form by active component clindamycin or its pharmaceutical salts or its esters and metronidazole and ointment base.
Another object of the present invention provides a kind of preparation method of described clindamycin and metronidazole ointment.
For realizing above-mentioned goal of the invention, technical scheme of the present invention is:
A kind of clindamycin and metronidazole ointment, its with clindamycin or its pharmaceutical salts or its esters and metronidazole as active component, form with ointment base, wherein to account for the weight of ointment be 0.45%～9% for active component clindamycin or its pharmaceutical salts or its esters and metronidazole, and the weight that ointment base accounts for ointment is 91%～99.55%.
Preferably, in the clindamycin and metronidazole ointment of the present invention, weight based on ointment, the weight of clindamycin or its pharmaceutical salts or its esters is 0.25%～5%, the weight of metronidazole is 0.2%～4%, and the weight of greasing base is 10%～40%, and the weight of water-soluble base is 5%～50%, distilled water is an amount of, and each components contents percentage ratio sum is 100%.
Preferably, in the clindamycin and metronidazole ointment of the present invention, the weight ratio of clindamycin or its pharmaceutical salts or its ester and metronidazole is 8～12: 6～10; More preferably, the weight ratio of clindamycin or its pharmaceutical salts or its ester and metronidazole is 10: 8.
Described greasing base is preferably one or more in stearic acid, glyceryl monostearate, paraffin, liquid paraffin, white vaseline, lanoline, hexadecanol, octadecanol, span series, Cera Flava, the animal and plant fat.
Described water-soluble base is preferably one or more in glycerol, propylene glycol, sorbitol, Polyethylene Glycol series, tween series, sodium lauryl sulphate, dimethyl sulfoxide, triethanolamine, the ethanol.
Described span series is preferably Arlacel-60, Arlacel-40 or Arlacel-20.
Described Polyethylene Glycol series is preferably PEG400, cetomacrogol 1000, polyethylene glycol 1500, Macrogol 3000 or Macrogol 4000.
Described tween series is preferably tween 80, Tween-65, Tween-40 or tween 20.
In the clindamycin and metronidazole ointment of the present invention, also can contain an amount of antiseptic.Antiseptic can be parabens, chlorocresol, chlorobutanol, sorbic acid, benzalkonium chloride or benzalkonium bromide.
Described greasing base, more preferably one or more in stearic acid, glyceryl monostearate, liquid paraffin, white vaseline, hexadecanol, the Arlacel-60.
Described water-soluble base, more preferably one or more in glycerol, tween 80, sodium lauryl sulphate, PEG400, polyethylene glycol 1500, Macrogol 4000, the triethanolamine.
Described antiseptic, more preferably ethyl hydroxybenzoate.
More preferably, clindamycin and metronidazole ointment of the present invention is: based on the weight of ointment, the percentage by weight of each component is in the ointment: clindamycin or its pharmaceutical salts or its esters 0.25%～5%, metronidazole 0.2%～4%, stearic acid 2%～10%, liquid paraffin 2%～10%, white vaseline 2%～10%, glyceryl monostearate 5%～15%, glycerol 10%～20%, sodium lauryl sulphate 0.25%～1%, ethyl hydroxybenzoate 0.05%～0.1%, distilled water is an amount of, and each components contents percentage ratio sum is 100%.
Clindamycin and metronidazole ointment of the present invention, its preparation process comprises following processing step:
(a) greasing base is become to split under 70～75 ℃ the temperature, fusion also stirs;
(b) water-soluble base is become to split under 70～75 ℃ the temperature, stir and make dissolving, and stir;
(c) described active component is added in (b), stir and make dissolving and mix homogeneously;
(d) (a) joined in synthermal (c), stir, natural cooling.
Clindamycin and metronidazole ointment of the present invention can be used for the treatment of acne, otitis media, sinusitis, folliculitis and other various bacterial skin infections, by external, realizes topical, farthest brings into play drug effect.Compare with the clindamycin and metronidazole liniment (being Cuo health king) of extensive use clinically, medicine is formed novel, use and carry convenient, especially to skin nonirritant, advantages such as preparation more stable.
Clindamycin and metronidazole ointment of the present invention, its production technology is easy, the finished product uniform and smooth, stability is very good, high safety, the curative effect height is easy to washing after the external.
The specific embodiment:
By the following examples, the excellent effect that inventive concept that the present invention may be better understood and invention obtain.The embodiment that is provided just in order to help to understand the present invention, rather than constitutes protection domain of the present invention is played restrictive effect, under design prerequisite of the present invention the present invention is simply changed, and all belongs to the scope of protection of present invention.
Embodiment 1:
Prescription is formed:
Clindamycin 10g
Metronidazole 8g
Stearic acid 100g
Liquid paraffin 80g
Glyceryl monostearate 70g
White vaseline 90g
Glycerol 100g
Sodium lauryl sulphate 5g
Ethyl hydroxybenzoate 1g
Ethanol 10ml
Distilled water adds to 1000g
Preparation method: taking ethylparaben, put in the container, behind the adding dissolve with ethanol, add water-soluble base glycerol, sodium lauryl sulphate and distilled water, water-bath is stirred down for 70～75 ℃ and is made dissolving, and clindamycin, metronidazole are added, stirring makes dissolving, and mix homogeneously; Greasing base stearic acid, liquid paraffin, glyceryl monostearate, white vaseline are put in another container 70～75 ℃ of following fusions of water-bath and mix homogeneously; The greasing base of mixing is joined in the synthermal water-soluble base, under same temperature conditions, stir in the same direction, make its fully emulsified, mix homogeneously, natural cooling.
Embodiment 2:
Prescription is formed:
Clindamycin 10g
Metronidazole 8g
Hexadecanol 120g
Liquid paraffin 60g
White vaseline 150g
Glycerol 60g
Sodium lauryl sulphate 5g
Ethyl hydroxybenzoate 1g
Distilled water adds to 1000g
Preparation method: water intaking dissolubility substrate glycerol, sodium lauryl sulphate, ethyl hydroxybenzoate and distilled water are put in the container, and water-bath is stirred down for 70～75 ℃ and made dissolving, and clindamycin, metronidazole are added, and stirs and makes dissolving and mix homogeneously; Greasing base hexadecanol, liquid paraffin, white vaseline are put in another container 70～75 ℃ of following fusions of water-bath and mix homogeneously; The greasing base of mixing is joined in the synthermal water-soluble base, under same temperature conditions, stir in the same direction, make its fully emulsified, mix homogeneously, natural cooling.
Embodiment 3:
Prescription is formed:
Clindamycin 10g
Metronidazole 8g
Glyceryl monostearate 120g
White vaseline 90g
Liquid Paraffin 90g
Arlacel-60 30g
Glycerol 100g
Ethyl hydroxybenzoate 1g
Tween 80 35g
Sodium lauryl sulphate 2.5g
Distilled water adds to 1000g
Preparation method: water intaking dissolubility substrate glycerol, ethyl hydroxybenzoate, tween 80, sodium lauryl sulphate and distilled water are put in the container, and water-bath is stirred down for 70～75 ℃ and made dissolving, and clindamycin, metronidazole are added, and stirs and makes dissolving and mix homogeneously; Greasing base glyceryl monostearate, white vaseline, liquid paraffin, Arlacel-60 are put in another container, and water-bath is dissolved down and mix homogeneously for 70～75 ℃; The greasing base of mixing is joined in the synthermal water-soluble base, under same temperature conditions, stir in the same direction, make its fully emulsified, mix homogeneously, natural cooling.
Embodiment 4 (contrast test):
Carried out detailed research from thermostability, freezing test, stability test and safety testing aspect respectively, and with compare according to the described clindamycin and metronidazole ointment of U.S. Pat P5849776A.
(1) thermostability, freezing test:
Get the sample of being developed, place respectively at 55 ℃ of constant temperature and reached-15 ℃ of placements 24 hours in 6 hours, should not have oil-water separation.
Show by result of the test, clindamycin and metronidazole ointment of the present invention, by thermostability, freezing test, sample does not all have the oil-water separation phenomenon; According to the clindamycin and metronidazole ointment of the described preparation of U.S. Pat P5849776A, after 55 ℃ of constant temperature were placed 6 hours, the sample emulsifiability reduced, and liquefaction phenomenon occurs.The result sees Table 1 and table 2 respectively.
Table 1 heat-resistance test result
| Classification | Sample | Liquefaction | Layering | Change color |
| Product of the present invention | Embodiment 1 | There is not liquefaction | No layering | Invariant color |
| Embodiment 2 | There is not liquefaction | No layering | Invariant color | |
| Embodiment 3 | There is not liquefaction | No layering | Invariant color | |
| Imitated patented product | 040425 | Liquefaction is arranged | Layering is arranged | Color burn |
Table 2 freezing test result
| Classification | Sample | Alligatoring | Dehydration | Variable color |
| Product of the present invention | Embodiment 1 | Do not have | Do not have | Invariant color |
| Embodiment 2 | Do not have | Do not have | Invariant color | |
| Embodiment 3 | Do not have | Do not have | Invariant color | |
| Imitated patented product | 040425 | Have | Have | Invariant color |
(2) stability test:
To the sample of being developed keep sample for a long time the test and accelerated test.
Sample thief, press commercially available back, long term test (places 25 ℃ ± 2 ℃, relative humidity 60% ± 10%) places under the condition, and respectively at 3,6,9,12,18,24 months sample analysis, and place under accelerated test (30 ℃ ± 2 ℃, relative humidity 75% ± 10%) condition, and respectively at 1,2,3,6 the end of month sample analysis.Aspects such as main character from sample, uniformity, oil-water separation phenomenon (having or not layering), content, related substance test are investigated.
In contrast, to also keep sample for a long time with method according to the sample of U.S. Pat P5849776A preparation and test and accelerated test, aspects such as main character from sample, uniformity, oil-water separation phenomenon (having or not layering), content, related substance test are investigated.
Table 3 and 4 is clindamycin and metronidazole ointment stability test result of the present invention.
Table 5 and 6 is the sample stability result of the test according to U.S. Pat P5849776A preparation.
Shown that by result of the test clindamycin and metronidazole ointment of the present invention is in keep sample for a long time test and accelerated test are investigated, sample is stable, the appearance character uniform and smooth, and no lamination, content, related substance have no significant change.According to the prepared sample of United States Patent (USP), its keep sample for a long time test and accelerated test are all defective, and color sample is deepened, and coarsening phenomenon is arranged, and metronidazole content also has to a certain degree decline.Therewith as seen, the stability of ointment of the present invention obviously is better than imitated proprietary articles emulsifiable paste.
The table 3 ointment of the present invention result of the test that keeps sample for a long time
| Sample | Time (moon) | Character | Uniformity | Have or not layering | Content (%) | Related substance (%) | ||
| Clindamycin | Metronidazole | Clindamycin | Metronidazole | |||||
| Embodiment 1 | 0 | Off-white color | Uniform and smooth | No layering | 99.6 | 98.9 | 5.46 | 0.011 |
| 3 | Off-white color | Uniform and smooth | No layering | 99.0 | 98.5 | 5.50 | 0.010 | |
| 6 | Off-white color | Uniform and smooth | No layering | 99.2 | 98.3 | 5.62 | 0.014 | |
| 9 | Off-white color | Uniform and smooth | No layering | 99.5 | 98.8 | 5.66 | 0.016 | |
| 12 | Off-white color | Uniform and smooth | No layering | 98.8 | 98.0 | 5.71 | 0.014 | |
| Embodiment 2 | 0 | Off-white color | Uniform and smooth | No layering | 99.0 | 97.9 | 5.49 | 0.015 |
| 3 | Off-white color | Uniform and smooth | No layering | 98.8 | 98.2 | 5.53 | 0.016 | |
| 6 | Off-white color | Uniform and smooth | No layering | 98.9 | 97.7 | 5.58 | 0.016 | |
| 9 | Off-white color | Uniform and smooth | No layering | 98.7 | 97.5 | 5.60 | 0.018 | |
| 12 | Off-white color | Uniform and smooth | No layering | 98.5 | 97.5 | 5.64 | 0.014 | |
| Embodiment 3 | 0 | Off-white color | Uniform and smooth | No layering | 98.4 | 98.5 | 5.51 | 0.012 |
| 3 | Off-white color | Uniform and smooth | No layering | 98.1 | 98.7 | 5.55 | 0.014 | |
| 6 | Off-white color | Uniform and smooth | No layering | 97.8 | 98.4 | 5.57 | 0.016 | |
| 9 | Off-white color | Uniform and smooth | No layering | 98.0 | 98.3 | 5.63 | 0.013 | |
| 12 | Off-white color | Uniform and smooth | No layering | 97.7 | 98.0 | 5.68 | 0.017 |
Table 4 ointment accelerated test of the present invention result
| Sample | Time (moon) | Character | Uniformity | Have or not layering | Content (%) | Related substance (%) | ||
| Clindamycin | Metronidazole | Clindamycin | Metronidazole | |||||
| Embodiment 1 | 0 | Off-white color | Uniform and smooth | No layering | 99.6 | 98.9 | 5.46 | 0.011 |
| 1 | Off-white color | Uniform and smooth | No layering | 99.2 | 98.6 | 5.53 | 0.013 | |
| 2 | Off-white color | Uniform and smooth | No layering | 99.4 | 98.7 | 5.55 | 0.014 | |
| 3 | Off-white color | Uniform and smooth | No layering | 99.1 | 98.4 | 5.61 | 0.014 | |
| 6 | Off-white color | Uniform and smooth | No layering | 99.1 | 98.3 | 5.64 | 0.017 | |
| Embodiment 2 | 0 | Off-white color | Uniform and smooth | No layering | 99.0 | 97.9 | 5.49 | 0.015 |
| 1 | Off-white color | Uniform and smooth | No layering | 98.9 | 97.6 | 5.57 | 0.013 | |
| 2 | Off-white color | Uniform and smooth | No layering | 98.4 | 97.7 | 5.62 | 0.016 | |
| 3 | Off-white color | Uniform and smooth | No layering | 98.3 | 97.4 | 5.64 | 0.017 | |
| 6 | Off-white color | Uniform and smooth | No layering | 98.0 | 97.0 | 5.69 | 0.019 | |
| Embodiment 3 | 0 | Off-white color | Uniform and smooth | No layering | 98.4 | 98.5 | 5.51 | 0.012 |
| 1 | Off-white color | Uniform and smooth | No layering | 98.2 | 98.3 | 5.54 | 0.014 | |
| 2 | Off-white color | Uniform and smooth | No layering | 97.9 | 98.4 | 5.58 | 0.016 | |
| 3 | Off-white color | Uniform and smooth | No layering | 97.8 | 98.0 | 5.65 | 0.018 | |
| 6 | Off-white color | Uniform and smooth | No layering | 97.6 | 97.6 | 5.70 | 0.015 | |
The imitated patented product of table 5 result of the test that keeps sample for a long time
| Time (moon) | Character | Uniformity | Have or not layering | Content (%) | Related substance (%) | ||
| Clindamycin | Metronidazole | Clindamycin | Metronidazole | ||||
| 0 | Off-white color | Uniform and smooth | No layering | 98.6 | 98.8 | 5.50 | 0.013 |
| 3 | Off-white color | Uniform and smooth | No layering | 98.2 | 97.8 | 5.61 | 0.015 |
| 6 | Off-white color | Uniform and smooth | No layering | 98.1 | 97.1 | 5.64 | 0.018 |
| 9 | Little yellow | The sample alligatoring | No layering | 97.8 | 96.3 | 5.62 | 0.021 |
| 12 | Little yellow | The sample alligatoring | No layering | 98.0 | 95.1 | 5.68 | 0.024 |
Table 6 is copied patented product accelerated test result
| Time (moon) | Character | Uniformity | Have or not layering | Content (%) | Related substance (%) | ||
| Clindamycin | Metronidazole | Clindamycin | Metronidazole | ||||
| 0 | Off-white color | Uniform and smooth | No layering | 98.6 | 98.8 | 5.50 | 0.013 |
| 1 | Off-white color | Uniform and smooth | No layering | 98.4 | 97.9 | 5.53 | 0.019 |
| 2 | Off-white color | Uniform and smooth | No layering | 98.0 | 97.1 | 5.57 | 0.024 |
| 3 | Little yellow | The sample alligatoring | No layering | 98.2 | 95.8 | 5.61 | 0.028 |
| 6 | Little yellow | The sample alligatoring | No layering | 97.8 | 94.6 | 5.64 | 0.030 |
(3) safety testing:
With the sample the developed skin bit of the complete sum breakage of partial smearing rat respectively, do not see that the part has erythema or edema to form, show that no obvious local irritation reacts and anaphylaxis.
Claims (5)
1. an ointment, is characterized in that as active component with clindamycin, the percentage by weight of each component is in the ointment: clindamycin 0.25%～5%, metronidazole 0.2%～4%, stearic acid 2%～10%, liquid paraffin 2%～10%, white vaseline 2%～10%, glyceryl monostearate 5%～15%, glycerol 10%～20%, sodium lauryl sulphate 0.25%～1%, ethyl hydroxybenzoate 0.05%～0.1%, surplus are distilled water, and each components contents percentage ratio sum is 100%.
2. an ointment is characterized in that: clindamycin 10g, metronidazole 8g, stearic acid 100g, liquid paraffin 80g, white vaseline 90g, glyceryl monostearate 70g, glycerol 100g, sodium lauryl sulphate 5g, ethyl hydroxybenzoate 1g, ethanol 10ml, adding distil water to total amount is 1000g.
3. ointment is characterized in that: clindamycin 10g, and metronidazole 8g, hexadecanol 120g, liquid paraffin 60g, white vaseline 150g, glycerol 60g, sodium lauryl sulphate 5g, ethyl hydroxybenzoate 1g, adding distil water to total amount is 1000g.
4. an ointment is characterized in that: clindamycin 10g, metronidazole 8g, glyceryl monostearate 120g, white vaseline 90g, liquid paraffin 90g, Arlacel-60 30g, glycerol 100g, tween 80 35g, sodium lauryl sulphate 2.5g, ethyl hydroxybenzoate 1g, adding distil water to total amount is 1000g.
5. method for preparing each described ointment of claim 1-4, it comprises following steps: (a) greasing base is become to split under 70～75 ℃ the temperature fusion and mix homogeneously; (b) water-soluble base is become to split under 70～75 ℃ the temperature, stir and make dissolving and mix homogeneously; (c) described active component is added in (b), stir and make dissolving and mix homogeneously; (d) (a) joined in synthermal (c), stirring makes fully emulsified, and stirs natural cooling.
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| CNB200510093283XA CN100370994C (en) | 2005-08-24 | 2005-08-24 | Ointment with clindamycin and metronidazole and method for preparing the same |
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| CN101120913B (en) * | 2006-08-11 | 2011-04-20 | 北京协和药厂 | Ftibamzone chrisma with PEG-200 as co-solvent |
| IT1400415B1 (en) * | 2010-05-26 | 2013-05-31 | Over S R L | COMPOSITIONS FOR THE TREATMENT OF THE HELICOBACTER PYLORI INFECTION. |
| CN101884642A (en) * | 2010-07-30 | 2010-11-17 | 哈尔滨乐泰药业有限公司 | Compound emulsifiable paste for treating acne and preparation method thereof |
| CN102688294A (en) * | 2012-06-13 | 2012-09-26 | 浙江农林大学 | Illicium henryi-contained anti-virus ointment for external use and preparation method and application thereof |
| CN103006681B (en) * | 2012-12-04 | 2014-07-09 | 哈尔滨乐泰药业有限公司 | Compound emulsifiable paste for treating acne and preparation method thereof |
| CN103933051B (en) * | 2014-05-12 | 2014-12-24 | 广东台城制药股份有限公司 | Triamcinolone acetonide acetat and preparation method thereof |
| CN105395473B (en) * | 2015-12-11 | 2018-04-20 | 上海上药新亚药业有限公司 | Clindamycin Hydrochloride emulsifiable paste and preparation method thereof |
| CN105748528A (en) * | 2016-03-13 | 2016-07-13 | 无锡南理工科技发展有限公司 | Acne cream and preparation method thereof |
| CN106727283B (en) * | 2016-12-26 | 2019-06-14 | 侯俊领 | A kind of metronidazole erythromycin compound ointment and preparation method thereof for treating face acnes |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5849776A (en) * | 1994-07-06 | 1998-12-15 | Centre International De Recherches Dermatologiques Galderma (C.I.R.D. Galderma) | Medicaments based on metronidazole or on a synergic mixture of metronidazole and clindamycin |
-
2005
- 2005-08-24 CN CNB200510093283XA patent/CN100370994C/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5849776A (en) * | 1994-07-06 | 1998-12-15 | Centre International De Recherches Dermatologiques Galderma (C.I.R.D. Galderma) | Medicaments based on metronidazole or on a synergic mixture of metronidazole and clindamycin |
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