CN101455663A - Preparation process of butoconazole nitrate vagina plug and use thereof - Google Patents
Preparation process of butoconazole nitrate vagina plug and use thereof Download PDFInfo
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- CN101455663A CN101455663A CNA200710179503XA CN200710179503A CN101455663A CN 101455663 A CN101455663 A CN 101455663A CN A200710179503X A CNA200710179503X A CN A200710179503XA CN 200710179503 A CN200710179503 A CN 200710179503A CN 101455663 A CN101455663 A CN 101455663A
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Abstract
The invention discloses a preparation method for vaginal suppository having butoconazole nitrate and application therefor. The invention belongs to the field of new technology of drug, relating to a suppository of butoconazole nitrate, pharmaceutical preparation for treating candida vaginitis and preparation method thereof.
Description
Technical field
The invention belongs to the medicine new technical field, relate to a kind of novel form of Nitric acid butoconazole, be used for the treatment of pharmaceutical preparation of monilial vaginitis and preparation method thereof, specifically a kind of preparation method of butoconazole nitrate vagina plug and application thereof.
Background technology
According to the incomplete statistics of World Health Organization (WHO), various gynaecopathia sickness rate are more than 65% among the women.China's interrelated data investigation shows that gynaecological disease is rejuvenation trend, becomes " killer " that threaten China's female body health.Women of child-bearing age's gynaecopathia sickness rate is more than 70%, and the women is 100% vaginitis of suffering from various degree almost in life, has wherein more than 5% due to illness that feelings have had a strong impact on normal work and life, and gynecological inflammation also has the characteristics of outbreak repeatedly simultaneously.The big country of our vast 1,300,000,000 populations, tentatively women's ratio calculation are 50%, and wherein 1/4 is immature children, and that also has the women more than 400,000,000 will relate to Amino-Cerv, so Amino-Cerv should not be underestimated.In the Amino-Cerv, the proportion of medicine for external use constantly rises.Wherein more influential is miconazole, Confort Pessaries, Gyno Canesten vaginal tablet, Nystatin vagina effervescence, JIEERYIN XIYE etc., first three kind sales volume is bigger, account for half of gynecological external use Western medicine, and wherein miconazole is the most outstanding, considerably beyond other kind, monopolize three/the last one.Miconazole accounts for 42.1% of the market share in the gynecological external use medicine of market, Shanghai in October, 2004, ranks first, and Confort Pessaries (Compound Zedoary Turmeric Oil Suppositories) accounts for 12.27% and occupies second, 3,4,5 of JIEERYIN XIYE, Gyno Canesten vaginal tablet and FUYINJIE washing liquid apportions.
Nitric acid butoconazole is the imidazoles antifungal drug, is mainly used in the treatment monilial vaginitis.This product is by the exploitation of U.S. Syntex company, and 1986 in U.S.'s listing, at present mainly by the production and sales of U.S. KV drugmaker, trade name Gynazole-
, subsequently in Switzerland, France's listing; And, now recorded by American Pharmacopeia 28 editions (USP28) in a plurality of national applications registrations such as Britain, Italy, Japan, Canada, Mexico, Brazil, Spain, Portugal.In August, 2005, Gynazole-sells in Singapore in permission Pan Malayan company of KV drugmaker
, Pan Malayan company will sell Gynazole-1 (R) in other the Five countries in Asia simultaneously.In JIUYUE, 2005, permission GedeonRichter company of KV drugmaker is newly selling Gynazole-1 (R) 15 East European countries.Gynazole-
Also will enter more than 50 market in Europe, Latin America, the Middle East and Asia.Since nineteen ninety-two, the U.S. classifies the external Nitric acid butoconazole as the OTC (over-the-counter) antifungal agent.In the recommendation therapeutic scheme by U.S. CDC (CDC) formulation, 2% Nitric acid butoconazole vaginal cream is the choice drug that CDC recommends treatment vulvovaginal candidiasis scheme.
This Products Development belongs to domestic initiation, an alternative effective product is provided not only for patient's medication, has also filled up the domestic blank of this kind product.The medicine that is used for vulvovaginal candidiasis on the domestic market at present seldom, and sickness rate is higher.This product will have broader market, bigger economic benefit as the choice drug of treatment vulvovaginal candidiasis.The now Chinese import drugs registration of carrying out Nitric acid butoconazole vagina ointment of U.S. KV drugmaker is declared, and does not take clinical official written reply as yet.If external formulation products is ratified at home, a higher price will be arranged, homemade by contrast medicine is owing to be the first among the whole country, and state fixed price will be lower than imported product, so home made article and imported product also will have bigger competitive advantage in the market share.This product has more competitive advantage than miconazole: this product curative effect is better, and consumption is littler: dosage form is more excellent: safe: this product is a topical preparation, and absorbance is extremely low, can not cause systemic adverse reactions.Because its safe, better tolerance, determined curative effect was the OTC medicine by U.S.'s approval in 1996.This product raw material is cheap and easy to get, and preparation process is stable, is suitable for suitability for industrialized production.There is not Intellectual Property Rights Issues.
This product is a vagina medicinal, and be administered once every day, and used three days continuously each course of treatment, be in the treatment colpitis mycotica external used medicine course of treatment very short medicine.It can constitute with miconazole, and strong competitive advantage---1. curative effect is better: oidiomycetic effect is better than the similar medicine that miconazole etc. has gone on the market to this product to white in vivo; 2. consumption is littler: miconazole was respectively 3 days or 7 days the course of treatment, and the single-dose amount of 3 day course of treatment is 400mg, is 1 times of 7 day course of treatment, was 4 times of this product consumption; 3. dosage form is more excellent: vagina medicinal is to be excellent with emulsifiable paste, gel, and they are longer in the affected part time of staying, help thoroughly killing pathogen; And the daktarin vaginal preparation has only suppository, and this product has then been developed vaginal suppository, vagina effervescence, vaginal gel series of products, more helps marketing.
This product characteristics:
Drug release rapidly, evenly, local drug concentration height, long action time,, the not characteristics of pollution clothes little to local mucosa irritation have not only improved curative effect, and have improved the compliance of patient's medication.
The chemical structural formula of Nitric acid butoconazole is:
Molecular formula: C
19H
17C
13N
2S HNO
3
Molecular weight: 474.79
Pharmacological action and clinical practice
1. pharmacological toxicology
The imidazoles antifungal agent.It is equal to or is better than other imidazole derivatives such as clotrimazole, miconazole and nystatin to the oidiomycetic bacteriostasis of white, the cure rate of its clinical application 3 days and 8 days is respectively 80% and 95%, obviously is better than clotrimazole, and its short treating period, side effect is little, well-tolerated.
2. clinical practice
In a randomized, double-blind research, Jan B.Jacobson etc. has compared 1%, 2% Nitric acid butoconazole vaginal cream and the 2% miconazole nitrate for vagina emulsifiable paste effect of totally 6 days treatment candidiasis vaginal infection once a day.Treated back 8 days, 1% Nitric acid butoconazole group, 2% Nitric acid butoconazole group and 2% miconazole nitrate group mycology cure rate are respectively 91%, 98% and 83%, and clinical cure rate is respectively 75%, 78% and 68%.Treated back 28 days, 1% Nitric acid butoconazole group, 2% Nitric acid butoconazole group and 2% miconazole nitrate group mycology cure rate are respectively 80%, 82% and 68%, and clinical cure rate is respectively 67%, 73% and 66%.The result shows that 2% Nitric acid butoconazole treatment candidiasis vaginal infection effect is best, and relapse rate is low, and adverse reaction rate is low.
William Droegemueller etc. have compared the effect and the safety of 2% Nitric acid butoconazole emulsifiable paste and 200mg Mycoporin vaginal sheet medication treatment in 3 days vulvovaginal candidiasis in the multi-center clinical trial that 274 patient participates in.Treated back 8 days, Nitric acid butoconazole and clotrimazole group vagina are cultivated the Candida albicans negative rate and are respectively 95% and 81%, treat and are respectively 80% and 64% in back 30 days.Treated back 8 days, medicine does not cause any systemic side effect.The result shows that the therapeutic effect of 2% Nitric acid butoconazole vaginal cream is higher than 200mg Mycoporin vaginal sheet, and adverse reaction rate is all lower.
Walter A.Van Dyck compared the application of 1% and 2% Nitric acid butoconazole vaginal cream 3 or 6 days and 2% miconazole nitrate for vagina emulsifiable paste is used the effect for the treatment of vulvovaginal candidiasis in 6 days.Placebo treatment 6 days, 1% Nitric acid butoconazole vaginal cream treatment 3 days, 1% Nitric acid butoconazole vaginal cream treatment 6 days, 2% Nitric acid butoconazole emulsifiable paste treatment 3 days, 2% Nitric acid butoconazole emulsifiable paste treatment 6 days and 6 days microbiology cure rate of 2% Miconazole Nitrate Cream treatment are respectively 37%, 71%, 65%, 63%, 79% and 72%, and clinical cure rate is respectively 36%, 64%, 56%, 67%, 67% and 63%.The above results can see, the therapeutic effect of 1%, 2% Nitric acid butoconazole emulsifiable paste 3 or 6 days is similar to 2% Miconazole Nitrate Cream treatment 6 days at least, and 6 days therapeutic effect of 2% Nitric acid butoconazole emulsifiable paste treatment is best.
A.J.Hajman compared the application of 2% Nitric acid butoconazole emulsifiable paste 3 days in a single at random blind parallel test and 1% clotrimazole cream is used the oidiomycotic effect of vagina outside the treatment in 6 days.Nitric acid butoconazole group and clotrimazole group clinical cure rate are respectively 53.3% and 38.7%.Not having the relevant side effect of treatment takes place.In the treatment of vaginal candidiasis, 2% Nitric acid butoconazole emulsifiable paste medication was much better than 1% clotrimazole cream medication 6 days in 3 days in curative effect and safety.The clinical research result shows that the therapeutic effect of 2% Nitric acid butoconazole emulsifiable paste will be higher than other several drugses such as clotrimazole, miconazole and econazole.
Above-mentioned result of study shows that Nitric acid butoconazole can effectively suppress Candida, trichophyton, Microsporon and Epidermophyton.The vaginal infection height that Candida albicans, Oidium tropicale and this other kinds of genus are caused is effective clinically.The Nitric acid butoconazole short term therapy can significantly be removed the infection of above-mentioned fungus, and is difficult for recurrence, and adverse reaction rate is low, is a good antifungal drug.
This product has following characteristics:
1. dosage form advanced person, rapid-action, the effect more abundant, unique novel form effervescent tablet and suppository is relatively: characteristics such as have in local application of gynecological that disintegration rate is fast, rapid-action, mucosa fully, is not hindered in absorption, clean hygiene, storage are easy have overcome the weak point of traditional suppository.
2. curative effect is better: oidiomycetic effect is better than the own similar medicines that go on the market such as miconazole to this product to white in vivo.
3. consumption is littler: miconazole was respectively 3 days or 7 days the course of treatment, and the single-dose amount of 3 day course of treatment is 400mg, is 1 times of 7 day course of treatment, was 4 times of this product consumption.
4. safe: this product is a topical preparation, and absorbance is extremely low, can not cause systemic adverse reactions.
5. raw material is cheap and easy to get, and preparation process is stable, is suitable for suitability for industrialized production.
Summary of the invention
It is tablet of making of principal agent and preparation method thereof with the Nitric acid butoconazole that the object of the invention is to provide a kind of good stability, quality height, evident in efficacy, untoward reaction little.
A kind of vagina effervescence that contains Nitric acid butoconazole of the present invention is made up of following component:
100 parts of Nitric acid butoconazoles
571 parts of Polyethylene Glycol-4000
342.6 parts of Polyethylene Glycol-1000
171.3 parts of mixed fatty glycerides
57.1 parts of propylene glycol
A kind of vagina effervescence that contains Nitric acid butoconazole of the present invention is achieved through the following technical solutions:
1. Nitric acid butoconazole is crossed 100 mesh sieves.
2. the water-bath fusing about 65 ℃ of the Polyethylene Glycol of recipe quantity-1000, Polyethylene Glycol-4000, mixed fatty glycerides, propylene glycol, stir.
4. add the Nitric acid butoconazole of recipe quantity, stir.
5. impouring is cooled off and is scribbled in the model of liquid paraffin under molten condition.
6. put cold, after treating to solidify fully both.
7. product inspection, packing.
A kind of vagina effervescence that contains Nitric acid butoconazole that the present invention obtains has that method is simple, the characteristics of good stability, quality.
Following example is used for illustrating the present invention but does not limit the present invention in any way.
Embodiment 1: 1000 of specifications
Prescription:
Nitric acid butoconazole 100g
Polyethylene Glycol-4000 571g
Polyethylene Glycol-1000 342.6g
Mixed fatty glycerides 171.3g
Propylene glycol 57.1g
Method for making:
1. Nitric acid butoconazole is crossed 100 mesh sieves.
2. the water-bath fusing about 65 ℃ of the Polyethylene Glycol of recipe quantity-1000, Polyethylene Glycol-4000, mixed fatty glycerides, propylene glycol, stir.
4. add the Nitric acid butoconazole of recipe quantity, stir.
5. impouring is cooled off and is scribbled in the model of liquid paraffin under molten condition.
6. put cold, after treating to solidify fully both.
7. product inspection, packing.
Embodiment 2: 10000 of specifications
Prescription:
Nitric acid butoconazole 1000g
Polyethylene Glycol-4000 5710g
Polyethylene Glycol-1000 3426g
Mixed fatty glycerides 1713g
Propylene glycol 571g
Method for making:
1. Nitric acid butoconazole is crossed 100 mesh sieves.
2. the water-bath fusing about 65 ℃ of the Polyethylene Glycol of recipe quantity-1000, Polyethylene Glycol-4000, mixed fatty glycerides, propylene glycol, stir.
4. add the Nitric acid butoconazole of recipe quantity, stir.
5. impouring is cooled off and is scribbled in the model of liquid paraffin under molten condition.
6. put cold, after treating to solidify fully both.
7. product inspection, packing.
Claims (7)
1. the preparation method of a butoconazole nitrate vagina plug and application thereof, the active ingredient that it is characterized in that this suppository are to be the suppository that principal agent is made with the Nitric acid butoconazole.
2. according to the preparation method and the application thereof of described a kind of butoconazole nitrate vagina plug of claim 1, it is characterized in that this bolt is the pharmaceutical preparation that is used for the treatment of monilial vaginitis.
3. according to the preparation method and the application thereof of described a kind of butoconazole nitrate vagina plug of claim 1, it is characterized in that forming including but not limited to following component:
100 parts of Nitric acid butoconazoles
571 parts of Polyethylene Glycol-4000
342.6 parts of Polyethylene Glycol-1000
171.3 parts of mixed fatty glycerides
57.1 parts of propylene glycol
4. according to the preparation method and the application thereof of described a kind of butoconazole nitrate vagina plug of claim 3, it is characterized in that described filler is Polyethylene Glycol-4000, Polyethylene Glycol-1000, mixed fatty glycerides, Polyethylene Glycol-6000 etc., but be not limited to these filleies.
5. according to the preparation method and the application thereof of described a kind of butoconazole nitrate vagina plug of claim 3, it is characterized in that described stabilizing agent or solubilizing agent are propylene glycol, Tween-80, glycerol, sorbitol etc., but be not limited to this stabilizing agent or solubilizing agent.
6. according to the preparation method and the application thereof of claim 3,4,5 described a kind of butoconazole nitrate vagina plugs, one of prescription that it is characterized in that this bolt is:
Nitric acid butoconazole 100g
Polyethylene Glycol-4000 571g
Polyethylene Glycol-1000 342.6g
Mixed fatty glycerides 171.3g
Propylene glycol 57.1g
7. the preparation method of the preparation method of a kind of butoconazole nitrate vagina plug according to claim 6 and application thereof is characterized in that may further comprise the steps:
1. Nitric acid butoconazole is crossed 100 mesh sieves.
2. the water-bath fusing about 65 ℃ of the Polyethylene Glycol of recipe quantity-1000, Polyethylene Glycol-4000, mixed fatty glycerides, propylene glycol, stir.
4. add the Nitric acid butoconazole of recipe quantity, stir.
5. impouring is cooled off and is scribbled in the model of liquid paraffin under molten condition.
6. put cold, after treating to solidify fully both.
7. product inspection, packing.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA200710179503XA CN101455663A (en) | 2007-12-14 | 2007-12-14 | Preparation process of butoconazole nitrate vagina plug and use thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA200710179503XA CN101455663A (en) | 2007-12-14 | 2007-12-14 | Preparation process of butoconazole nitrate vagina plug and use thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101455663A true CN101455663A (en) | 2009-06-17 |
Family
ID=40766961
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA200710179503XA Pending CN101455663A (en) | 2007-12-14 | 2007-12-14 | Preparation process of butoconazole nitrate vagina plug and use thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101455663A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101982167A (en) * | 2010-10-21 | 2011-03-02 | 孙福春 | Butoconazole nitrate suppository used in gynaecology, preparation method and application thereof |
| CN102028652A (en) * | 2010-11-29 | 2011-04-27 | 林凡友 | Method for preparing fenticonazole nitrate suppository |
| CN105796477A (en) * | 2014-12-29 | 2016-07-27 | 四川滇虹医药开发有限公司 | Butoconazole nitrate suppository and preparation method thereof |
-
2007
- 2007-12-14 CN CNA200710179503XA patent/CN101455663A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101982167A (en) * | 2010-10-21 | 2011-03-02 | 孙福春 | Butoconazole nitrate suppository used in gynaecology, preparation method and application thereof |
| CN102028652A (en) * | 2010-11-29 | 2011-04-27 | 林凡友 | Method for preparing fenticonazole nitrate suppository |
| CN105796477A (en) * | 2014-12-29 | 2016-07-27 | 四川滇虹医药开发有限公司 | Butoconazole nitrate suppository and preparation method thereof |
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| Date | Code | Title | Description |
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| C06 | Publication | ||
| PB01 | Publication | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Open date: 20090617 |