CN100364520C - Tebinaifen hydrochloride suppository and its preparation method - Google Patents
Tebinaifen hydrochloride suppository and its preparation method Download PDFInfo
- Publication number
- CN100364520C CN100364520C CNB2006100126202A CN200610012620A CN100364520C CN 100364520 C CN100364520 C CN 100364520C CN B2006100126202 A CNB2006100126202 A CN B2006100126202A CN 200610012620 A CN200610012620 A CN 200610012620A CN 100364520 C CN100364520 C CN 100364520C
- Authority
- CN
- China
- Prior art keywords
- suppository
- semi
- fatty acid
- tween
- preparation
- 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.)
- Active
Links
Landscapes
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The present invention relates to a Tebinaifen hydrochloride suppository for treating women genital tract fungous infection and a preparation method thereof. The suppository disclosed by the present invention contains terbinafine hydrochloride, substrates and leaching accelerating agents. The present invention has the advantages of high concentration of partial medicines, slow and persistent therapeutic effects on partial parts, and avoidance of stimulation on mucosae caused by fast and centralized release.
Description
Technical field:
The present invention relates to a kind of suppository its preparation method, more properly, the present invention relates to Tebinaifen hydrochloride suppository that is used for the treatment of the female genital fungal infection and preparation method thereof.
Background technology:
The female genital fungal infection is a kind of common mucosa infection, is mainly in gravid woman and diabetics.In recent years, this disease has the situation that increases gradually.This sick medicine of treatment mainly contains local application and oral administration dual mode at present.
Terbinafine HCl, its chemical name is (E)-N-(6.6-dimethyl-2-heptene-4-alkynes)-N-methyl isophthalic acid-naphthalene methylamine hydrochloric salt, it is a kind of propylamine antifungal agent, its mechanism of action is for disturbing the early stage biosynthesis of mycosterol specifically, the activity that optionally suppresses fungus Squalene Cycloxygenase, Squalene epoxidation reaction in the fungal cell membrane forming process is obstructed, thereby reaches the effect of killing or suppressing fungus.Terbinafine HCl is white or off-white color crystalline powder, and little have the spy smelly, easily molten in ethanol, and slightly soluble in water is almost insoluble in ether.Terbinafine HCl is at first succeeded in developing by Britain Sandoz drugmaker, and China also was used for clinical in 1994 in U.S.'s listing in 1996 in Britain's listing in 1991.Terbinafine HCl is not only can be oral but also propylene amine antifungal drug that can external, and drug susceptibility studies show that terbinafine has stronger antibacterial activity in vitro to multiple pathomycete.Preparation has tablet, presses down agent, cream, ointment, solution, gel, vagina effervescence etc.
Though terbinafine HCl is used for the treatment of the female genital fungal infection already, but owing to take oral formulations such as terbinafine HCl tablet, medicine is difficult to come together in a large number the reproductive tract mucosa, must heavy dose ofly use and could produce curative effect, thereby produce bigger toxic and side effects; Use inconvenience and press down dosage forms such as agent, cream, gel, nor reach effect preferably easily.Though the vagina effervescence listing is arranged at present, and vagina effervescence is big because of zest, patient's toleration is poor, is difficult to reach ideal effect too.
Summary of the invention:
The present inventor is in order to solve the shortcoming of the above-mentioned preparation of terbinafine HCl, and the experiment through a large amount of has prepared the Tebinaifen hydrochloride suppository that is used for the treatment of the female genital fungal infection.Tebinaifen hydrochloride suppository disclosed by the invention contains terbinafine HCl, substrate and stripping promoter; Its mesostroma can be one of semi-synthetic fatty acid ester or semi-synthetic cocos nucifera oil fat, and semi-synthetic fatty acid ester can be semi-synthetic fatty acid ester 34 types, semi-synthetic fatty acid ester 36 types, semi-synthetic fatty acid ester 38 types, preferred semi-synthetic fatty acid ester 36 types; Stripping promoter can be Tweens or spans, and Tweens can be one of tween 20, Tween-40, Tween-60, tween 80, and spans can be one of Arlacel-20, Arlacel-40, Arlacel-60, Arlacel-80, preferred tween 80.The ratio of each component (by weight) terbinafine HCl among the present invention: substrate: stripping promoter 1: 20～50: 0.2～0.6, preferred 1: 30～40: 0.3～0.5.Tebinaifen hydrochloride suppository disclosed by the invention, also contain freshener, can be one of menthol or Mentholum, wherein terbinafine HCl, substrate, stripping promoter, freshener are 1: 20～50: 0.2～0.6: 0.005～0.3 by weight, and optimum is 1: 33: 0.36: 0.18.
Vaginal suppository generally adopts water-soluble base or prepares with the miscible substrate of water, and substrate commonly used has semi-synthetic fatty acid glyceride, Polyethylene Glycol, glycerin gelatine, polyoxyethylene sorbitan aliphatic ester, Myrj 45 etc.The present inventor is by a series of experiments, selecting substrate at last for use is one of semi-synthetic fatty acid ester or semi-synthetic cocos nucifera oil fat, semi-synthetic fatty acid ester can be semi-synthetic fatty acid ester 34 types, semi-synthetic fatty acid ester 36 types, semi-synthetic fatty acid ester 38 types, preferred semi-synthetic fatty acid ester 36 types.
The terbinafine HCl lipotropy is strong, in order to increase the stripping of medicine in substrate, the present inventor adds stripping promoter in preparation, stripping promoter can be Tweens or spans, Tweens can be one of tween 20, Tween-40, Tween-60, tween 80, spans can be one of Arlacel-20, Arlacel-40, Arlacel-60, Arlacel-80, preferred tween 80.
Terbinafine HCl itself has certain zest, can cause burn feeling etc.Therefore the present inventor has added freshener in preparation, freshener can be one of Mentholum or menthol, in order to alleviate the burn feeling that terbinafine HCl causes, through test, 0.5% freshener has refrigerant effect, can offset the burn feeling that terbinafine HCl causes.Consumption increases, and effect no longer increases.
By a series of experiments, final selected terbinafine HCl: substrate: stripping promoter is 1: 20～50: 0.2～0.6 by weight, preferred 1: 30～40: 0.3～0.5, terbinafine HCl, substrate, stripping promoter, freshener are 1: 20～50: 0.2～0.6: 0.005～0.3 by weight, and optimum is 1: 33: 0.36: 0.18.
The invention also discloses a kind of method of producing above-mentioned preparation, comprising:
1. substrate fusing: get substrate, heat fused, temperature are reduced to 40-50 ℃;
2. drug treating: terbinafine HCl 100 order fine powders add stripping promoter, freshener (as needs) grinds well;
3. mix: substrate is added in the medicated powder and fast fast stir, stir;
4. molding: medicine is injected the bolt mould, survey loading amount, cooling, packing is promptly.
Preparation disclosed by the invention has carried out melting a series of experiments such as change time limit experiment, influence factor's test, stability experiment by the Pharmacopoeia of the People's Republic of China to the requirement of suppository, meet standards of pharmacopoeia.Since the poorly water-soluble of terbinafine HCl own, the local absorption difficulty, and preparation disclosed by the invention is tested through stripping, and the result who obtains is terbinafine HCl stripping lentamente in hour, dissolution rate is more than 80% after one hour.Thereby understand that furtherly preparation disclosed by the invention has the local drug concentration height, and can bring into play slow and persistent therapeutical effect in the part, can avoid again simultaneously concentrating fast discharging the advantage that causes the stimulation of mucosa.
The specific embodiment
The present invention is illustrated further that following examples and experimental example should not be construed as limitation of the present invention below in conjunction with embodiment and experimental example.
Terbinafine HCl: Hubei Pharmaceutical Co., Ltd.;
Semi-synthetic fatty acid glyceride: going up Hydron is medical technology company limited;
Menthol: Anhui group of huge nation;
Tween: Xinxiang Gao Jin Pharma Inc..
Other is commercially available pharmaceutic adjuvant rank as not explaining.
Embodiment: the preparation of terbinafine HCl bolt
Embodiment 1:
Prescription:
Terbinafine HCl 50g
Tween 80 18g
Menthol 9g
Semi-synthetic fatty acid glyceride 36 type 1655g
----------------------------------
1000
Preparation process:
1. get semi-synthetic fatty acid glyceride 36 types, heat fused, temperature are reduced to 40-50 ℃;
2. drug treating: terbinafine HCl 100 order fine powders add tween 80, menthol grinds well;
3. mix: semi-synthetic fatty acid glyceride is added in the medicated powder and fast fast stir, stir;
4. molding: medicine is injected the bolt mould, survey loading amount, cooling;
5. pack: packing, check gets product.
Embodiment 2
Prescription:
Terbinafine HCl 50g
Arlacel-60 10g
Mentholum 2.5g
Semi-synthetic cocos nucifera oil fat 1000g
----------------------------------
1000
Preparation method is with embodiment 1
Embodiment 3
Prescription:
Terbinafine HCl 50g
Tween-60 10g
Menthol 15g
Semi-synthetic cocos nucifera oil fat 2500g
----------------------------------
1000
Preparation method is with embodiment 1
Embodiment 4
Prescription
Terbinafine HCl 50g
Tween 80 18g
Semi-synthetic fatty acid glyceride 34 type 1655g
----------------------------------
1000
Preparation method is with embodiment 1
Embodiment 5
Prescription:
Terbinafine HCl 50g
Tween-60 30g
Menthol 5g
Semi-synthetic fatty acid glyceride 38 type 2000g
----------------------------------
1000
Preparation method is with embodiment 1
Experimental example
The dissolution test of experimental example 1. terbinafine HCl bolts
The sample of embodiment 1-5 preparation is contained in the filtration paper cylinder, changes blue laws by dissolution method first method and carry out stripping mensuration, dissolution medium is a 500ml water.Assay method adopts ultraviolet spectrophotometry, and promptly precision is measured dissolution fluid 5ml, filters, and precision is measured subsequent filtrate 1ml, puts in the 5ml measuring bottle, adds dehydrated alcohol and is diluted to scale, shakes up, as need testing solution; It is an amount of that other gets the terbinafine HCl reference substance, adds 80% alcoholic solution and make the solution that contains 20 μ g among every 1ml, in contrast product solution.According to spectrophotography, measure trap at 283nm wavelength place, calculate promptly.
(1) instrument
ZRS-8G type intelligence dissolution test instrument: Radio Factory of Tianjin Univ.
DU640 type ultraviolet spectrophotometer: BECKMAN company
(2) test specimen
A presses embodiment 1 preparation
B presses embodiment 2 preparations
C presses embodiment 3 preparations
D presses embodiment 4 preparations
E presses embodiment 5 preparations
(3) result of the test sees the following form
| Laboratory sample | A | B | C | D | E | |
| Stripping quantity (%) | 10 minutes | 36.5 | 24.1 | 32.6 | 36.3 | 35.6 |
| 20 minutes | 71.2 | 43.5 | 64.7 | 71.0 | 72.3 | |
| 30 minutes | 87.4 | 60.5 | 82.7 | 87.2 | 88.6 | |
| 45 minutes | 96.2 | 77.7 | 86.6 | 96.4 | 97.5 | |
| 60 minutes | 94.9 | 82.7 | 85.9 | 94.7 | 96.7 | |
Experimental example 2 crowds experiment
Preparation (the 50m g 1 time/day that utilizes the embodiment of the invention 1 to obtain, one week of logotype) with terbinafine oral (1 time/day 2 week of logotype of 250m g) contrast treatment vaginal candidiasis, matched group 2,4,8,16 all cure rates are respectively 93%, 81%, 63%, 42%.2 weeks of experimental group cure rate, 4 weeks, 8 weeks, 16 weeks are respectively 95%, 92.5%, 90%, 87.5%.Experimental group is better than the curative effect of matched group.Compare with matched group, the cure rate when 2,4 weeks does not have significant difference.8, then there were significant differences (P＜0.01) for the cure rate in 16 whens week.This shows terbinafine treatment vaginal candidiasis, intravaginal is placed curative effect and is better than oral effect, and short treating period.
The effectiveness and the safety of Terbinafine hydrochloride vaginal bolt (preparation that the embodiment of the invention 1 obtains) treatment VVC (VVC) of having adopted multicenter randomized controlled observation.140 routine patients, test group 70 examples are used Terbinafine hydrochloride vaginal bolt 50mg/ days, matched group 70 example daktarin (miconazole nitrate) bolts, be 7 days two groups of courses of treatment.After the drug withdrawal 7 days, the variation of contrast symptom, sign, candidiasis smear and cultivation and biochemical indicator between organizing and in the group.The result shows all do not have biochemical indicator abnormal change and untoward reaction.ITT analyzes treatment back test group and two groups of candidiasis smears of matched group negative conversion rate is respectively 98.77% and 95.57% (P＞0.05).Two groups of general curative effect effective percentage are respectively 95.37% and 90.00%.
In addition, utilize the embodiment of the invention 1 preparation that obtains and the terbinafine HCl effervescent tablet contrast of having gone on the market to carry out the comfort level experiment of medicine to the patient, 40 routine patients, experimental group 20 examples Terbinafine hydrochloride vaginal bolt 50m g/d, matched group 20 examples are used the terbinafine HCl effervescent tablet, and be 7 days two groups of courses of treatment.Matched group has 14 routine patients to represent that all the local excitation sense is very heavy, and burn feeling is arranged, and uses the back uncomfortable, and experimental group has only 2 examples to show slight local excitation sense is arranged.
Claims (9)
1. Tebinaifen hydrochloride suppository that is used for the treatment of the female genital fungal infection, said preparation contains terbinafine HCl, substrate and stripping promoter, its mesostroma is semi-synthetic fatty acid ester or semi-synthetic cocos nucifera oil ester, stripping promoter is Tweens or spans, and terbinafine HCl, substrate, stripping promoter are 1: 20～50: 0.2～0.6 by weight.
2. the suppository of claim 1, its mesostroma is one of semi-synthetic fatty acid ester 34 types, semi-synthetic fatty acid ester 36 types, semi-synthetic fatty acid ester 38 types.
3. the suppository of claim 2, its mesostroma is semi-synthetic fatty acid ester 36 types.
4. the suppository of claim 1, wherein stripping promoter is one of tween 20, Tween-40, Tween-60, tween 80.
5. the suppository of claim 4, wherein stripping promoter is tween 80.
6. the suppository of claim 1 also contains freshener, and freshener is one of Mentholum, menthol.
7. the suppository of claim 6, wherein freshener is a menthol.
8. the arbitrary described suppository of claim 6-7, wherein terbinafine HCl, substrate, stripping promoter, freshener are 1: 20～50: 0.2～0.6: 0.005～0.3 by weight.
9. the described suppository of claim 8, wherein terbinafine HCl, substrate, stripping promoter, freshener are 1: 33: 0.36 by weight: 0.18.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2006100126202A CN100364520C (en) | 2006-04-24 | 2006-04-24 | Tebinaifen hydrochloride suppository and its preparation method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2006100126202A CN100364520C (en) | 2006-04-24 | 2006-04-24 | Tebinaifen hydrochloride suppository and its preparation method |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1830424A CN1830424A (en) | 2006-09-13 |
| CN100364520C true CN100364520C (en) | 2008-01-30 |
Family
ID=36993026
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB2006100126202A Active CN100364520C (en) | 2006-04-24 | 2006-04-24 | Tebinaifen hydrochloride suppository and its preparation method |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN100364520C (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108210449B (en) * | 2018-02-02 | 2021-01-26 | 佛山市南海东方澳龙制药有限公司 | Terbinafine hydrochloride cream for dogs and preparation method thereof |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1279944A (en) * | 1999-07-08 | 2001-01-17 | 齐鲁制药厂 | Effervescent tablets for curing vaginitis and its preparing method |
| CN1531430A (en) * | 2001-03-30 | 2004-09-22 | ŵ�����˹ɷ�����˾ | Local used composition containing antifungal agent |
| CN1552314A (en) * | 2003-05-27 | 2004-12-08 | 北京亚科希药物研究所 | Antibacterial medicinal composition |
| CN1579379A (en) * | 2003-08-08 | 2005-02-16 | 台湾东洋药品工业股份有限公司 | Allylamine derivative composition and its use |
| CN1634858A (en) * | 2004-11-03 | 2005-07-06 | 浙江海正药业股份有限公司 | Process for preparing terbinafine hydrochliride |
-
2006
- 2006-04-24 CN CNB2006100126202A patent/CN100364520C/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1279944A (en) * | 1999-07-08 | 2001-01-17 | 齐鲁制药厂 | Effervescent tablets for curing vaginitis and its preparing method |
| CN1531430A (en) * | 2001-03-30 | 2004-09-22 | ŵ�����˹ɷ�����˾ | Local used composition containing antifungal agent |
| CN1552314A (en) * | 2003-05-27 | 2004-12-08 | 北京亚科希药物研究所 | Antibacterial medicinal composition |
| CN1579379A (en) * | 2003-08-08 | 2005-02-16 | 台湾东洋药品工业股份有限公司 | Allylamine derivative composition and its use |
| CN1634858A (en) * | 2004-11-03 | 2005-07-06 | 浙江海正药业股份有限公司 | Process for preparing terbinafine hydrochliride |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1830424A (en) | 2006-09-13 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2006275232B2 (en) | Use of hydroxybenzoic acid ester and analogues for the manufacture of a mendicament for the prevention and treatment of virus infection | |
| TW201114766A (en) | Pharmaceutical composition for a hepatitis C viral protease inhibitor | |
| CN102078326A (en) | Topically applied composition containing povidone iodine and mometasone furoate | |
| CN101147735A (en) | Pharmaceutical composition for injection and its medicine box | |
| Vishvakarma | Design and development of montelukast sodium fast dissolving films for better therapeutic efficacy | |
| CN100364520C (en) | Tebinaifen hydrochloride suppository and its preparation method | |
| CN102429912B (en) | Pharmaceutical composition prepared with micronized prasterone or sodium prasterone sulfate and use thereof | |
| CN103284941A (en) | Expansion suppository of clotrimazole or salt thereof, preparation method and detection method | |
| CN103251636B (en) | Medicament for treating Candida infections and diseases caused by Candida, and preparation method thereof | |
| EP2851368B1 (en) | Complex compounds of germanium, methods for producing same, and drugs | |
| CN101584703A (en) | Pharmaceutical composition for treating colpitis and preparation method thereof | |
| CN115124532B (en) | Rhein and matrine eutectic crystal, preparation method, composition and application thereof | |
| CN105147827B (en) | A kind of antibacterial medicines and preparation method thereof | |
| CN102266285A (en) | Low excitant ibuprofen injection | |
| CN105030716B (en) | Caffeinum pharmaceutical combination and preparation method thereof | |
| CN102349935A (en) | Purpose of ginkgolic acid in preparing external preparation for treating venereal disease, gynopathy and perianal disease | |
| CN104042574B (en) | A kind of freeze-drying medicinal composition containing ganciclovir | |
| CN1850202A (en) | Vagina external-use medicine composition and its preparing method and use | |
| CN103284953A (en) | Bicyclol solid preparation and preparation method thereof | |
| CN102406890A (en) | Modified composition, preparation method and application thereof | |
| CN103751105A (en) | Application of ginkgolic acid nanometer liposome in treatment of gynecological diseases and venereal diseases | |
| CN103751230A (en) | Application of gingko extract nanometer liposome in gynecological disease treatment | |
| CN109364148A (en) | A kind of FUKE QIANJIN PIAN and preparation method thereof | |
| CN108379237A (en) | A kind of medicament microcapsule preparation for the treatment of of urinary tract infections and preparation method thereof | |
| RU2420281C2 (en) | Method of treating diseases caused by herpes virus |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant |