CN103830162A

CN103830162A - Preparation method of doxycycline gel

Info

Publication number: CN103830162A
Application number: CN201210479289.0A
Authority: CN
Inventors: 沈巍; 郝智慧; 贺倩倩
Original assignee: QINGDAO CONLINENT ANIMAL PHARMACEUTICAL CO Ltd
Current assignee: QINGDAO CONLINENT ANIMAL PHARMACEUTICAL CO Ltd
Priority date: 2012-11-23
Filing date: 2012-11-23
Publication date: 2014-06-04

Abstract

The invention discloses a preparation method of a doxycycline gel. The method uses doxycycline as a main component, and NMP, polylactic acid-glycolic acid copolymer (PLGA) as auxiliary materials, wherein the mass ratio of doxycycline to NMP to polylactic acid-glycolic acid copolymer (PLGA) is 1.1:9:1. After complete release of gel, the polymer is also completely degraded in vivo, and the carrier does not need to be removed. The doxycycline gel is efficient and convenient, and is a novel efficient dental medicine. Through gingival administration of doxycycline hydrochloride sustained-release gel on rabbit, the sustained-release gel is proved to have the effect of treating periodontitis, and especially has better effect than an oral tablet on chronic periodontitis.

Description

A kind of preparation method of doxycycline gel

Technical field

The invention belongs to antibiotic formulations for animals field, relate to a kind of preparation method of doxycycline gel.

Background technology

Doxycycline (doxycycline), has another name called doxycycline, doxycycline, is second filial generation tetracycline medication, within 1963, is synthesized by Stohpens etc., and 1971 start to put into production in China.Tetracycline antibiotics has similar physicochemical property, owing to containing phenolic hydroxyl group, enol base and dimethylamino in molecule, belongs to soda acid amphiprotic substance, is soluble in acidity or alkaline solution, clinically its hydrochlorate of half.

This medicine had both had antibacterial action, be used for the treatment of mycoplasma, colibacillosis, salmonellosis, Bacillus pasteurii disease and the psittacosis etc. of poultry, many rickettsiaes, chlamydiaceae, anonymous mycobacteria genus, spirillum are to this product sensitivity, and other are if actinomyces, anthrax bacillus, listerisa monocytogenes in mjme, clostridium, Brucella, Campylobacter are also to this product sensitivity.Also find in recent years the effect of its some non-antibiosis, can suppress the matrix metalloproteinases such as collagenase, gelatinase, stromelysin ^[8]and stop pathologic connective tissue damage, also can reduce diabetics bone bed amount lost, and promoting bone growing, and can promote fibroblast adhere to and expand.Relevant research also shows, such medicine has elimination and suppress neutrophilic granulocyte the effect that produces oxygen-derived free radicals, and the effects such as antiinflammatory action and antithyroid, antiretroviral, antiulcer, therefore have considerable meaning to the exploitation of this medicine.

The common dosage forms of doxycycline mostly is oral tablet and capsule, along with companion animals dog cat quantity is more and more, the oral disease of dog cat comes into one's own all the more, along with the progress to the physiological deeply understanding of periodontitis pathology and pharmacotherapeutics, think that local sustained release antibacterial drug therapy periodontitis is more rational medication, the antibacterial activity of doxycycline is stronger 2～10 times than tetracycline, most of Periodontal Pathogens are had to obvious inhibitory action, and bacterial drug resistance is rare.The more important thing is, doxycycline can significantly suppress the activity of collagenase in periodontal tissue, effectively improves every periodontal index, improves the success rate of periodontitis treatment, is the medicine that can effectively treat periodontitis of generally acknowledging at present.The present invention has prepared the doxycycline gel of giving topical.。

Gel is a kind of special form, and because doxycycline is met photo-labile, preparation process is answered lucifuge operation, shading storage.Hydroxypropyl methylcellulose is a kind of biodegradable polymers, forms gel skeleton after meeting water-soluble liquid in periodontal tissue, attaches in periodontal pocket, and medicine can discharge by gel skeleton.Said preparation has very wide market prospect.

Summary of the invention

The object of invention is to develop a kind of novel form of doxycycline, effectively improves the bioavailability of medicine, delays the release of medicine, strengthens drug effect, reduces toxic and side effects, reaches the object of slow release, long-acting, targeting.

For achieving the above object, the invention provides a kind of doxycycline gel, this gel is taking doxycycline as main component, and taking NMP, polylactic acid-co-glycolic acid (PLGA) as adjuvant, the mass ratio of three kinds of constituents is 1.1:9:1..

NMP is efficient selective solvent, avirulence, and high boiling point, corrosivity is little, dissolubility is large, and viscosity is low, and volatility is low, good stability, the advantages such as easy recovery, are often applied to the solvent that medicine is produced.

The field that polylactic acid is carried out application is the earliest biological medicine industry.Polylactic acid has tight security and can be absorbed by tissue human body, and its technical value added is high, is the macromolecular material of medical industry development prospect.

Detailed description of the invention

In the present invention, the preparation method step of gel is as follows:

1, getting a certain proportion of PLGA and NMP is solvent preparation PLGA solution;

2, add doxycycline hydrochloride raw material;

3, mix, obtain doxycycline gel.

Further illustrate the present invention below in conjunction with instantiation.

embodiment 1

Get the about 0.5g of PLGA7:3, taking containing the NMP4.5g of 30% glycerol triacetate (GTA) as the PLGA solution of solvent compound concentration as 10%;

2, add doxycycline hydrochloride raw material 0.55g;

3, mix, obtain doxycycline gel.

Doxycycline gel prepared by said method is faint yellow translucent gels preparation.Relatively doxycycline hydrochloride sustained-release gel gingiva administration in rabbit, when rabbit gingiva drug administration by injection, saliva blood drug level is 4.5 μ g/mL to the maximum, far above oral administration (being 1.7 μ g/mL to the maximum), when oral administration, blood drug level is higher than gingiva drug administration by injection, drug level while indicating local periodontal pocket drug administration by injection in periodontal pocket will be apparently higher than oral administration, and medicine can concentrate and in periodontal pocket, produce bacteriostasis.And more than the drug level in 7 d in saliva all maintains 1 μ g/mL, more than maintaining minimal inhibitory concentration MIC=6 μ g/mL in expectation periodontal pocket.Gel discharges complete post polymerization thing and is also degraded in vivo completely, without taking out carrier, efficiently but also convenient, has been not only new and effective materia dentica again.By this experimental result can predict doxycycline hydrochloride inject treat periodontitis with sustained-release gel, especially the effect of chronic periodontitis is better than oral tablet.

Claims

1. the novel form of poultry antimicrobial drug a---gel preparation, this gel is taking doxycycline as main component, and taking N-Methyl pyrrolidone (NMP), polylactic acid-co-glycolic acid (PLGA) as adjuvant, the mass ratio of three kinds of constituents is 1.1:9:1.

2. method according to claim 1, is characterized in that: taking N-Methyl pyrrolidone as solvent.

3. method according to claim 1 and 2, is characterized in that: taking polylactic acid-co-glycolic acid (PLGA) as adjuvant.

4. according to the method described in claim 2 and 3, it is characterized in that: the mass ratio of doxycycline, NMP, tri-kinds of constituents of PLGA is 1.1:9:1.