CN101721353B - Stable thermosensitive gelatin composition - Google Patents
Stable thermosensitive gelatin composition Download PDFInfo
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- CN101721353B CN101721353B CN2009102227521A CN200910222752A CN101721353B CN 101721353 B CN101721353 B CN 101721353B CN 2009102227521 A CN2009102227521 A CN 2009102227521A CN 200910222752 A CN200910222752 A CN 200910222752A CN 101721353 B CN101721353 B CN 101721353B
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Abstract
The invention relates to a stable thermosensitive gelatin composite, which comprises the following components in percentage by weight: 0.5 to 15 percent of active medicament for treating colpitis, 7 percent to 30 percent of poloxamer, 0.1 to 5 percent of hydroxypropyl methylcellulose, 0.01 to 2 percent of carbomer, 0 to 40 percent of additive and the balance of aqueous carriers. The thermosensitive gelatin composite has good physical stability without accumulating and demixing phenomena of the hydroxypropyl methylcellulose, and ensures the uniformity of the content of preparations, the uniformity of the release speed of the medicament, and the uniformity of the distribution of the preparations at the medicament applying part after the composition is used.
Description
Technical field
The present invention relates to technical field of medicine, be specifically related to a kind of stable thermosensitive gelatin composite.
Background technology
In recent years, carried out much to the research of heat-sensitive gel, also obtained certain substantial progress, using more is reverse heat-sensitive gel.Generally speaking; With the rising of temperature, fluidic flowability is better, and viscosity is lower; And reverse heat-sensitive gel exists with flowable fluid state when being lower than uniform temperature; And when temperature was elevated to certain value (phase transition temperature), this fluid then changed not flowable semi-solid state into, became gel.Reverse heat-sensitive gel is called heat-sensitive gel usually for short, and heat-sensitive gel adds medicine and other adjuvants and can make heat-sensitive gel preparation generally by heat sensitive macromolecular material is made.The phase transition temperature of heat-sensitive gel preparation can change immobilising semi-solid gel into usually a little less than human temperature under the effect of body temperature after being applied to human body, discharge medicine, the performance curative effect.
This special nature of heat-sensitive gel impels it to be used widely in field of pharmaceutical preparations, particularly mucosa delivery and cavity/canal drug administration.When being lower than phase transition temperature, its flowable helps commercial production, and tool has great advantage in technical processs such as preparation, fill; Simultaneously, this flowable helps preparation application back sprawling at medicine-feeding part.With not flowable common gel phase ratio, heat-sensitive gel preparation is with the obvious advantage.
As everyone knows, compare with oral administration, cavity/canal drug administration or mucosa delivery have advantages such as absorbing fast, bioavailability height, and for topical therapeutic, also have advantages such as good effect, untoward reaction are little, so cavity/canal drug administration are used widely.At present, cavity/canal drug administration mainly contains: ophthalmic preparation, like eye drop; Nasal formulations is like nasal drop, nasal spray; Oral mucosa is used preparation, like oral spray; Rectum is used preparation, like suppository; Vaginal preparation is like ointment, emulsifiable paste, gel, suppository, vaginal tablet, effervescent tablet, vaginal capsule, soft capsule etc.Above-mentioned preparation all belongs to ordinary preparation, and there are problems such as drug wastage, leakage, administration number of times be frequent in relative cavity/canal drug administration, causes curative effect to be difficult to problems such as assurance, patient's poor compliance.Therefore, how cavity/canal drug administration reaches slow release effect, is one of emphasis direction of pharmacy worker concern.
In up-to-date research, heat-sensitive gel is applied to the tract sustained-release administration, in heat-sensitive gel, adds biomembrane adhesion material and slow-release material, processes the slow release heat-sensitive gel.After being applied to medicine-feeding part; The slow release heat-sensitive gel has flow regime to change semi-solid state into rapidly; The bioadhesive material makes gel adhere to biofilm surface, prolongs the holdup time, reduces to run off and leakage; Slow-release material is then controlled drug slow and is discharged, thereby realizes the therapeutic purposes of slow release long-acting.
Summary of the invention
The most frequently used temperature-sensitive polymers material of preparation slow release heat-sensitive gel is a poloxamer, mainly is poloxamer 188 and poloxamer 407, through adjusting the phase transition temperature that consumption can obtain to suit.Biomembrane adhesion material commonly used has Polycarbophil, chitosan, sodium carboxymethyl cellulose hypromellose etc.Slow-release material commonly used has cellulose family, acrylic resin etc., and that the most commonly used is hypromellose (HPMC).HPMC is the plain derivant of neutral fibre; Neutral, stable in properties is seldom with medicine generation compatibility reaction; Viscosity remains unchanged basically before and after the heating; Its aqueous solution has the antienzyme effect, in the long term storage process, keeps viscosity stability preferably, has the sustained release performance that biomembrane adhesiveness and blocking medicine discharge simultaneously.Therefore, HPMC can be used as the slow-release material and the bioadhesive material of slow release heat-sensitive gel.
The combined preparation slow release heat-sensitive gel that can adopt poloxamer, HPMC, active medicine, other additives to form has slow release long-acting, advantage that the vaginal mucosa adhesiveness is good according to the slow release heat-sensitive gel of this art scheme preparation.For the stability that guarantees principal agent when using the slow release heat-sensitive gel in the effect of sprawling of medicine-feeding part; The slow release heat-sensitive gel should be preserved being lower than under the condition of phase transition temperature; And under this temperature; The flowable of slow release heat-sensitive gel is prone to cause the gathering of HPMC, and therefore lamination takes place in long-term put procedure easily.
Generally solve lamination problem through the viscosity that increases preparation; But as far as this preparation; The increase of viscosity can cause the mobile variation of slow release heat-sensitive gel, can not obtain ideal phase transition temperature, also is unfavorable for preparation sprawling in vaginal mucosa; Affect the treatment, can't adopt common means to solve lamination problem.
The present invention has carried out a large amount of tests; Adopt high speed (4000 rev/mins) centrifuging commonly used to quicken the layering of compositions, estimate the layering situation of different components, the unexpected adding of finding carbomer; Can improve centrifugal layering situation greatly; Select suitable carbomer consumption can stop the gathering of HPMC, solve lamination problem, form stable compositions.
Technical scheme of the present invention is following:
Stable thermosensitive gelatin composite of the present invention, percentage by weight is formed as follows: treat colpitic active medicine 0.5～15%, poloxamer 7%～30%, hypromellose 0.1%～5%, carbomer 0.01%～2%, additives 0～40%, aqueous carrier surplus.
Stable thermosensitive gelatin composite of the present invention, pH value are 3.5～7.5, preferred 4.0～7.0.
Treat colpitic active medicine and be meant the medicine that vaginal infection is had therapeutic effect; As treat the medicine of colpitis mycotica, bacterial vaginitis, trichomonal vaginitis, can be selected from salt, matrine and derivant thereof, other efficacious therapy medicines one of them or the two or more combination of salt, tioconazole or tioconazole of salt, miconazole or miconazole of salt, terconazole (triaconazole), secnidazole, ketoconazole or bifonazole, butoconazole or butoconazole of salt, tinidazole, isoconazole or isoconazole of salt or ester, clotrimazole, ornidazole, econazole nitrate, itraconazole or the itraconazole of metronidazole, clindamycin or clindamycin.Consumption is 0.5%～25%, and is preferred 0.5%～20%, percentage by weight.
Poloxamer mainly is meant poloxamer 188 and poloxamer 407, can use poloxamer 407 separately, also can use poloxamer 188 and poloxamer 407 simultaneously.Poloxamer consumption preferred 8%～25%.
Hypromellose is meant hypromellose K4M, hypromellose K15M, hypromellose K100M, can use wherein a kind ofly separately, also can use their combination.Hypromellose consumption preferred 0.3%～4%.
Carbomer is carbomer 934, Acritamer 940, Carbopol 941, carbomer 971, carbomer 974, carbomer 980, carbomer 1342, carbomer 1382, can use wherein a kind ofly separately, also can use their combination.The carbomer consumption is preferred 0.01%～1%, percentage by weight.
Aqueous carrier is meant water or buffer solution, and buffer solution is selected from phosphate buffer, acetate buffer, citrate buffer or phthalate buffer.
Additives are meant and are the safety that guarantees compositions, other components that effectiveness adds; Like dissolution accelerator, pH regulator agent, antioxidant, antiseptic, chelating agent, aromatic etc.; Additives selectively add one or more as required; Be not every kind and all must add, consumption can be adjusted according to prior art.
Dissolution accelerator refers to for the component of impelling the principal agent dissolving to add, like ethanol, propylene glycol, Polyethylene Glycol, glycerol, Tweens, spans, sodium alkyl sulfonate class, cholate, cyclodextrin derivative etc.
The pH regulator agent is selected from pharmaceutically acceptable acid or alkali, one or more in example hydrochloric acid, phosphoric acid, lactic acid, vitamin C, sorbic acid, citric acid, sodium hydroxide, sodium lactate, sodium phosphate, disodium-hydrogen or sodium dihydrogen phosphate, sodium carbonate, the sodium bicarbonate.
Antioxidant is selected from one or more in sodium sulfite, sodium sulfite, sodium pyrosulfite, sodium thiosulfate, organic sulfur compound class (like thioglycerol, sulfo-sorbic acid), vitamin C, vitamin E, amino acids (like glycine, methionine, cysteine), thiourea, ascorbyl palmitate, dibutyl cresols, toluene di-tert-butyl phenol, butylated hydroxyanisole, tartaric acid, the citric acid etc.
Antiseptic is selected from one or several in the salt of salt, benzoic acid or benzoic salt, benzalkonium chloride, benzalkonium bromide, ethanol, propylene glycol, benzyl alcohol, chlorobutanol, chlorhexidine or chlorhexidine of methyl hydroxybenzoate, ethyl hydroxybenzoate, propylparaben, sorbic acid or sorbic acid.
Chelating agent is selected from pharmaceutically acceptable complexing of metal ion agent, like disodium edetate, calcium disodium edetate etc.
Aromatic is selected from pharmaceutically acceptable essence or spice, like in jasmine flower essence, Oleum menthae, Fructus Citri tangerinae essence, honey peach essence, apple essence, flavoring banana essence or the flavoring pineapple essence one or more.
Preferably, the colpitic active medicine of described treatment is following, and consumption all is weight percentage:
I. the salt of butoconazole is Nitric acid butoconazole, consumption preferred 1%～6%.
Ii. the salt of miconazole is miconazole nitrate, consumption preferred 1%～12%.
Iii. tioconazole, consumption preferred 1%～6%.
Iv. clindamycin phosphate, consumption preferred 1%～5%.
The present invention also provides a kind of method of stabilisation thermosensitive gelatin composite; In the heat-sensitive gel that comprises poloxamer and hypromellose that the preparation compositions is used, add 0.01～2wt% carbomer; Preferred carbomer addition is 0.01～1wt%, reaches to stop the hypromellose generation to assemble and cause heat-sensitive gel layering purpose.
It is good to place physical stability for a long time according to the heat-sensitive gel of technical scheme of the present invention preparation; Place more than 12 months at normal temperatures; Hypromellose can not take place assemble and lamination, guarantee the content uniformity of preparation and the homogeneity of drug releasing rate, and preparation uses the homogeneity of back in the agents area distribution; Thereby, has significant advantage for the safety of medicine, effectiveness and quality controllability lay the foundation.
The specific embodiment
Below in conjunction with embodiment the present invention is done detailed elaboration, but be not limited to the embodiment of these concrete records.For excellent results of the present invention better is described, also comparative experimental research is enumerated for example.The each component consumption all is weight percentage.
Comparative Examples 1. gel components are following:
Poloxamer 407 15%
Hypromellose K15M 1.5%
Methyl hydroxybenzoate 0.15%
Water surplus
Method for preparing:
Get methyl hydroxybenzoate, poloxamer, hypromellose, make dispersion in the entry stirring to add simultaneously, in 4 ℃ of condition held; After treating abundant swelling, using the NaOH solution of 0.1N and the hydrochloric acid solution adjusting pH of 0.1N in case of necessity is 4～6, is sub-packed in the vaginal administration device; Every of 5g promptly gets.
Sample after the packing is in the room temperature held, the routine observation lamination, and the result finds in the time of 35 days, to observe tangible hypromellose clustering phenomena, gel layering.
Comparative Examples 2. gel components are following:
Poloxamer 407 17%
Hypromellose K100M 0.5%
Methyl hydroxybenzoate 0.15%
Water surplus
Method for preparing:
Get methyl hydroxybenzoate, poloxamer, hypromellose, make dispersion in the entry stirring to add simultaneously, in 4 ℃ of condition held; After treating abundant swelling, using the NaOH solution of 0.1N and the hydrochloric acid solution adjusting pH of 0.1N in case of necessity is 4～6, is sub-packed in the vaginal administration device; Every of 5g promptly gets.
Sample after the packing is in the room temperature held, the routine observation lamination, and the result finds in the time of 40 days, to observe tangible hypromellose clustering phenomena, gel layering.
Comparative Examples 3. gel components are following:
Poloxamer 407 14%
Poloxamer 188 14.5%
Hypromellose K100M 0.5%
Methyl hydroxybenzoate 0.15%
Water surplus
Method for preparing:
Get methyl hydroxybenzoate, poloxamer 407, poloxamer 188, hypromellose; Make dispersion in the entry stirring to add simultaneously, in 4 ℃ of condition held, treat abundant swelling after; Using the NaOH solution of 0.1N and the hydrochloric acid solution adjusting pH of 0.1N in case of necessity is 4～6; Be sub-packed in the vaginal administration device, every of 5g promptly gets.
Sample after the packing is in the room temperature held, the routine observation lamination, and the result finds in the time of 42 days, to observe tangible hypromellose clustering phenomena, gel layering.
Comparative Examples 4. components of pharmaceutical composition are following:
Nitric acid butoconazole 2%
HYDROXYPROPYL BETA-CYCLODEXTRIN 32%
Poloxamer 407 16%
Hypromellose K4M 1.5%
Methyl hydroxybenzoate 0.15%
Water surplus
Method for preparing:
Get Nitric acid butoconazole, HYDROXYPROPYL BETA-CYCLODEXTRIN, methyl hydroxybenzoate, add water and continue stirring and dissolving, add poloxamer, hypromellose simultaneously in stirring; In 4 ℃ of condition held; After treating abundant swelling, using the NaOH solution of 0.1mol/l and the hydrochloric acid solution adjusting pH of 0.1N in case of necessity is 4～6, is sub-packed in the vaginal administration device; Every of 5g promptly gets.
Sample after the packing is in the room temperature held, the routine observation lamination, and the result finds in the time of 38 days, to observe tangible hypromellose clustering phenomena, gel layering.
Comparative Examples 5. components of pharmaceutical composition are following:
Miconazole nitrate 2%
HYDROXYPROPYL BETA-CYCLODEXTRIN 34%
Poloxamer 407 15.5%
Hypromellose K100M 0.3%
Methyl hydroxybenzoate 0.1%
Propylparaben 0.1%
Disodium edetate 0.005%
Water surplus
Method for preparing:
Get miconazole nitrate, HYDROXYPROPYL BETA-CYCLODEXTRIN, methyl hydroxybenzoate, propylparaben, disodium edetate, add water and continue stirring and dissolving, add poloxamer, hypromellose simultaneously in stirring; In 4 ℃ of condition held; After treating abundant swelling, using the NaOH solution of 0.1mol/l and the hydrochloric acid solution adjusting pH of 0.1N in case of necessity is 4～6, is sub-packed in the vaginal administration device; Every of 5g promptly gets.
Sample after the packing is in the room temperature held, the routine observation lamination, and the result finds in the time of 40 days, to observe tangible hypromellose clustering phenomena, gel layering.
Comparative Examples 6. components of pharmaceutical composition are following:
Clindamycin phosphate 2.5%
Poloxamer 407 15.5%
Hypromellose K15M 4%
Tween 80 12%
Methyl hydroxybenzoate 0.15%
Disodium edetate 0.005%
PH5.8 phosphate buffer surplus
Method for preparing:
Get Tween 80, clindamycin phosphate, methyl hydroxybenzoate, disodium edetate, make dispersion stirring to add simultaneously in the pH5.8 phosphate buffer, continue to be stirred to dissolving fully; Add poloxamer, hypromellose simultaneously in stirring; In 4 ℃ of condition held, treat abundant swelling after, be sub-packed in the vaginal administration device; Every of 5g promptly gets.
Sample after the packing is in the room temperature held, the routine observation lamination, and the result finds in the time of 45 days, to observe tangible hypromellose clustering phenomena, gel layering.
It below is specific embodiment.
Embodiment 1. thermosensitive gelatin composite components are following:
Matrine 1%
Poloxamer 407 17%
Hypromellose K100M 0.5%
Carbomer 980 0.15%
Methyl hydroxybenzoate 0.15%
Water surplus
Method for preparing:
Get carbomer, make dispersion in the entry stirring to add simultaneously, continue to be stirred to dissolving fully; Add matrine, methyl hydroxybenzoate, poloxamer, hypromellose simultaneously stirring, to disperse the back in 4 ℃ of condition held, treat abundant swelling after; Using the NaOH solution of 0.1N and the hydrochloric acid solution adjusting pH of 0.1N in case of necessity is 4～6; Be sub-packed in the vaginal administration device, every of 5g promptly gets.
Sample after the packing is in the room temperature held, and routine observation lamination, result are found to place and do not observed tangible hypromellose clustering phenomena in 12 months as yet, and gel is layering not.
Embodiment 2. thermosensitive gelatin composite components are following:
Nitric acid butoconazole 2%
HYDROXYPROPYL BETA-CYCLODEXTRIN 32%
Poloxamer 407 16%
Hypromellose K4M 1.5%
Carbomer 974 0.1%
Methyl hydroxybenzoate 0.15%
Water surplus
Method for preparing:
Get carbomer, make dispersion in the entry stirring to add simultaneously, continue to be stirred to dissolving fully; Add Nitric acid butoconazole, HYDROXYPROPYL BETA-CYCLODEXTRIN, methyl hydroxybenzoate simultaneously in stirring, continue stirring until dissolving, add poloxamer, hypromellose simultaneously in stirring; In 4 ℃ of condition held, treat abundant swelling after, using the hydrochloric acid solution of NaOH solution and the 0.1N of 0.1mol/l to regulate pH in case of necessity is 4～6; Be sub-packed in the vaginal administration device, every of 5g promptly gets.
Sample after the packing is in the room temperature held, and routine observation lamination, result are found to place and do not observed tangible hypromellose clustering phenomena in 12 months as yet, and gel is layering not.
Embodiment 3. thermosensitive gelatin composite components are following:
Nitric acid butoconazole 1%
HYDROXYPROPYL BETA-CYCLODEXTRIN 28%
Poloxamer 407 16.5%
Hypromellose K100M 0.5%
Carbomer 0.15%
Methyl hydroxybenzoate 0.1%
Propylparaben 0.1%
Water surplus
Method for preparing:
Get carbomer, make dispersion in the entry stirring to add simultaneously, continue to be stirred to dissolving fully; Add Nitric acid butoconazole, HYDROXYPROPYL BETA-CYCLODEXTRIN, methyl hydroxybenzoate, propylparaben simultaneously in stirring, continue stirring until dissolving, add poloxamer, hypromellose simultaneously in stirring; In 4 ℃ of condition held, treat abundant swelling after, using the hydrochloric acid solution of NaOH solution and the 0.1N of 0.1mol/l to regulate pH in case of necessity is 4～6; Be sub-packed in the vaginal administration device, every of 10g promptly gets.
Sample after the packing is in the room temperature held, and routine observation lamination, result are found to place and do not observed tangible hypromellose clustering phenomena in 12 months as yet, and gel is layering not.
Embodiment 4. thermosensitive gelatin composite components are following:
Miconazole nitrate 2%
HYDROXYPROPYL BETA-CYCLODEXTRIN 34%
Poloxamer 407 15.5%
Hypromellose K100M 0.3%
Carbomer 0.2%
Methyl hydroxybenzoate 0.1%
Propylparaben 0.1%
Disodium edetate 0.005%
Water surplus
Method for preparing:
Get carbomer, make dispersion in the entry stirring to add simultaneously, continue to be stirred to dissolving fully; Add miconazole nitrate, HYDROXYPROPYL BETA-CYCLODEXTRIN, methyl hydroxybenzoate, propylparaben, disodium edetate simultaneously in stirring, continue stirring until dissolving, add poloxamer, hypromellose simultaneously in stirring; In 4 ℃ of condition held; After treating abundant swelling, using the NaOH solution of 0.1mol/l and the hydrochloric acid solution adjusting pH of 0.1N in case of necessity is 4～6, is sub-packed in the vaginal administration device; Every of 5g promptly gets.
Sample after the packing is in the room temperature held, and routine observation lamination, result are found to place and do not observed tangible hypromellose clustering phenomena in 12 months as yet, and gel is layering not.
Embodiment 5. thermosensitive gelatin composite components are following:
Clindamycin phosphate 2.5%
Poloxamer 407 15.5%
Hypromellose K15M 4%
Carbomer 0.1%
Tween 80 12%
Methyl hydroxybenzoate 0.15%
Disodium edetate 0.005%
PH5.8 phosphate buffer surplus
Method for preparing:
Get carbomer, make dispersion stirring to add simultaneously in the pH5.8 phosphate buffer, continue to be stirred to dissolving fully; Add Tween 80, clindamycin phosphate, methyl hydroxybenzoate, disodium edetate simultaneously in stirring, continue stirring until dissolving, add poloxamer, hypromellose simultaneously in stirring; In 4 ℃ of condition held, treat abundant swelling after, be sub-packed in the vaginal administration device; Every of 5g promptly gets.
Sample after the packing is in the room temperature held, and routine observation lamination, result are found to place and do not observed tangible hypromellose clustering phenomena in 12 months as yet, and gel is layering not.
Embodiment 6. thermosensitive gelatin composite components are following:
Clindamycin phosphate 2.5%
Poloxamer 407 16%
Hypromellose K100M 0.5%
Carbomer 0.1%
PEG400 10%
Methyl hydroxybenzoate 0.15%
Disodium edetate 0.005%
Water surplus
Method for preparing:
Get carbomer, make dispersion in the entry stirring to add simultaneously, continue to be stirred to dissolving fully; Add PEG400, clindamycin phosphate, methyl hydroxybenzoate, disodium edetate simultaneously in stirring, continue stirring until dissolving, add poloxamer, hypromellose simultaneously in stirring; In 4 ℃ of condition held, treat abundant swelling after, using the hydrochloric acid solution of NaOH solution and the 0.1N of 0.1mol/l to regulate pH in case of necessity is 5～7; Be sub-packed in the vaginal administration device, every of 5g promptly gets.
Sample after the packing is in the room temperature held, and routine observation lamination, result are found to place and do not observed tangible hypromellose clustering phenomena in 12 months as yet, and gel is layering not.
Embodiment 7. thermosensitive gelatin composite components are following:
Tioconazole 2%
HYDROXYPROPYL BETA-CYCLODEXTRIN 35%
Poloxamer 407 16%
Hypromellose K100M 0.5%
Carbomer 0.12%
Methyl hydroxybenzoate 0.1%
Propylparaben 0.1%
Disodium edetate 0.005%
Water surplus
Method for preparing:
Get carbomer, make dispersion in the entry stirring to add simultaneously, continue to be stirred to dissolving fully; Add tioconazole, HYDROXYPROPYL BETA-CYCLODEXTRIN, methyl hydroxybenzoate, propylparaben, disodium edetate simultaneously in stirring, continue stirring until dissolving, add poloxamer, hypromellose simultaneously in stirring; In 4 ℃ of condition held, treat abundant swelling after, using the hydrochloric acid solution of NaOH solution and the 0.1N of 0.1mol/l to regulate pH in case of necessity is 4～6; Be sub-packed in the vaginal administration device, every of 5g promptly gets.
Sample after the packing is in the room temperature held, and routine observation lamination, result are found to place and do not observed tangible hypromellose clustering phenomena in 12 months as yet, and gel is layering not.
Above embodiment and Comparative Examples effect analysis and conclusion are following:
With poloxamer and hypromellose is the heat-sensitive gel gel lamination that easy generation causes because of the hypromellose gathering in long-term put procedure of main matrix preparation, and heat-sensitive gel becomes heterodisperse system, influences heat-sensitive gel character; After adding the different activities medicine; Lamination still can take place in this heat-sensitive gel, and according to technical scheme of the present invention, add a certain amount of carbomer after; The lamination of thermosensitive gelatin composite is significantly improved; Place at ambient temperature more than 12 months, layering can not take place, the time of changing may be longer.Therefore, thermosensitive gelatin composite provided by the invention has good physical stability, helps improving safe, effective, the quality controllability of medicine, compared with prior art, has obvious improvement.
Claims (3)
1. stable thermosensitive gelatin composite, percentage by weight is formed as follows: treat colpitic active medicine 0.5～15%, poloxamer 4077%～30%, hypromellose 0.1%～5%, carbomer 0.01%～2%, additives≤40%, aqueous carrier surplus; The pH value of compositions is 3.5～7.5;
The colpitic active medicine of described treatment is selected from matrine, clindamycin phosphate, Nitric acid butoconazole, tioconazole or miconazole nitrate;
Described hypromellose is meant hypromellose K4M, hypromellose K15M or hypromellose K100M; Described carbomer is carbomer 974 or carbomer 980;
Described additives are one of dissolution accelerator, pH regulator agent, antioxidant, antiseptic, chelating agent, aromatic or combination; Wherein,
Dissolution accelerator is Polyethylene Glycol or Tween 80; The pH regulator agent is hydrochloric acid or sodium hydroxide;
Antiseptic is selected from methyl hydroxybenzoate, ethyl hydroxybenzoate or propylparaben; Chelating agent is selected from disodium edetate;
Aromatic is selected from a kind of in jasmine flower essence, Oleum menthae, Fructus Citri tangerinae essence, honey peach essence, apple essence, flavoring banana essence or the flavoring pineapple essence.
2. thermosensitive gelatin composite as claimed in claim 1 is characterized in that, the pH value of compositions is 4.0～7.0.
3. thermosensitive gelatin composite as claimed in claim 1 is characterized in that, described carbomer consumption 0.01%～1% percentage by weight.
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| CN102525877A (en) * | 2010-12-30 | 2012-07-04 | 国家人口计生委科学技术研究所 | Preparation of butoconazole nitrate in-situ gel |
| CN102525885B (en) * | 2011-11-21 | 2017-06-27 | 程雪翔 | A kind of Ketoconazole gel and preparation method thereof |
| CN103239389A (en) * | 2013-06-03 | 2013-08-14 | 南京泽恒医药技术开发有限公司 | Preparation method of progestin sustained-release gel for treating threatened abortion |
| CN105079405A (en) * | 2015-09-24 | 2015-11-25 | 青岛海之源智能技术有限公司 | Miconazole nitrate compound lotion and preparing method |
| CN106109398A (en) * | 2016-06-14 | 2016-11-16 | 上海通用药业股份有限公司 | A kind of vagina gel containing tioconazole |
| CN106038477A (en) * | 2016-06-14 | 2016-10-26 | 上海通用药业股份有限公司 | Method for preparing vagina gel containing tioconazole |
| CN106580981B (en) * | 2017-01-23 | 2019-04-23 | 牡丹江医学院 | A kind of pharmaceutical composition and its preparation method and application for treating gynaecological imflammation |
| CN107308104A (en) * | 2017-06-30 | 2017-11-03 | 江苏耐雀生物工程技术有限公司 | A kind of preparation method of gynecological gel |
| CN115837046A (en) * | 2022-11-23 | 2023-03-24 | 哈尔滨誉衡制药有限公司 | Ornidazole pessary and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1377706A (en) * | 2002-04-22 | 2002-11-06 | 沈阳药科大学 | Ocular in-situ gel preparatino with proper phase conversion temperature |
| CN1593386A (en) * | 2004-06-30 | 2005-03-16 | 上海复康医药科技发展有限公司 | Temperature sensitive gel formulation for in situ vagina uses |
| CN1814253A (en) * | 2005-11-23 | 2006-08-09 | 上海华拓医药科技发展有限公司 | Heat-sensitive gel preparation and preparing method |
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| CN101721353A (en) | 2010-06-09 |
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Inventor after: Gong Honggang Inventor after: Dai Zhijie Inventor after: Yang Shuhua Inventor after: Chang Jianhui Inventor after: Deng Wenjun Inventor after: Deng Shuhai Inventor before: Chang Jianhui Inventor before: Deng Wenjun Inventor before: Gong Honggang Inventor before: Deng Shuhai |
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