CN1257715C - Clindamycin metronidazole vagina effervescent tablet and its preparing method and use - Google Patents
Clindamycin metronidazole vagina effervescent tablet and its preparing method and use Download PDFInfo
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- CN1257715C CN1257715C CN 200410070111 CN200410070111A CN1257715C CN 1257715 C CN1257715 C CN 1257715C CN 200410070111 CN200410070111 CN 200410070111 CN 200410070111 A CN200410070111 A CN 200410070111A CN 1257715 C CN1257715 C CN 1257715C
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- clindamycin
- metronidazole
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- microcrystalline cellulose
- lauryl sulphate
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Abstract
The present invention discloses a clindamycin metronidazole vagina effervescent tablet, a preparation method thereof and an application thereof. The vagina effervescent tablet uses the salt or the ester of clindamycin and metronidazole as an active ingredient, and is prepared by a processing method of the conventional tablet. The present invention is characterized in that the effervescent tablet contains hydroxypropyl methyl cellulose used as an adhesive, and compared with the conventional effervescent tablet, the present invention has the advantages of large foaming amount, fine, abundant and lasting foam, long storing time, high therapeutic effect of medicine, simple technology and stable finished products; the present invention is favorable to sufficiently distribute the active ingredient of the medicine, and is suitable for industrial scale production.
Description
Technical field:
The present invention relates to a kind of clindamycin compounds and clindamycin metronidazole vagina effervescent tablet and preparation method thereof and the application in medical treatment.
Background technology:
Clindamycin is the lincomycin antibiotics, antibacterial activity is strong, has a broad antifungal spectrum, aerobic leather Lan Shi positive bacteria such as Streptococcus, staphylococcus (comprising the penicillin resistant bacterial strain), diphtheria corynebacterium, anthrax bacillus etc. are had obvious antibacterial action, most of anaerobe, chlamydia, mycoplasma, Plasmodium falciparum and toxoplasma are also had bactericidal action.This product acts on the ribosomal 50S subunit of sensitive organism, stops the prolongation of peptide chain, thereby suppresses the protein synthesis of bacterial cell.Clindamycin generally is a bacteriostatic, but under high concentration extremely sensitive antibacterial is also had bactericidal action.Be widely used in clinically and infect due to treatment aerobic leather Lan Shi positive bacteria and the various anaerobe.
Metronidazole is the first nitro glyoxaline compound, is anaerobe resistant, anti-trichomonal and anti-ameba medicine.Most of anaerobe had the strong antibiotic effect, be applicable to various anaerobic infections clinically, as septicemia, endocarditis, empyema, pulmonary abscess, abdominal cavity infection, gynecological infection, bone and the infection of joint, meninges, brain abscess etc., also applicable to amebiasis, trichomonal vaginitis, balantidiosis outside treatment intestinal and the intestinal, dracunculiasis etc.
Trichomonal vaginitis and bacterial vaginitis are the commonly encountered diseases and the frequently-occurring diseases of gynecological, account for the female reproductive system infection rate and reach 60%～80%, and great majority are the mixed infection of aerobe and anaerobe.Be many with single the treatment clinically at present with clindamycin or metronidazole.Clindamycin is generally antibacterial, can suppress the breeding of antibacterial under low concentration, and its antibacterial activity is strong 4～8 times than lincomycin; And the metronidazole bactericidal action is stronger, and both have certain synergism clinical proof on antibacterial action.Therefore, both are share, list is used one, and curative effect is more definite.Described this compositions patent among the U.S. Pat P5849776, but it is mainly used in the topical treatment of skin disease; Also described this compositions in the Chinese patent of application number 03123920.X, it is mainly used in quick and a large amount of drug administration by injection and infects with the degree of depth of treatment as septicemia, abdominal cavity infection etc., and dosage form is an injection.In addition, about the topical application preparation of the two compound recipe, as liniment, application is arranged also clinically, active component was Clindamycin Hydrochloride and metronidazole during its prescription was formed, and specification is that every ml contains clindamycin 10mg; Every ml contains metronidazole 8mg, and two medicines share the treatment that is used for acne, otitis media, sinusitis, folliculitis and other various bacterial skin infections in this ratio.But the preparation of relevant clindamycin and metronidazole compound recipe vagina administration, not report and application still at present.
Disclosed a kind of vagina effervescence and preparation method thereof in the patent application of application number 94110780.9.This vagina effervescence is that active constituents of medicine is mixed with selected adjuvant, perhaps sour agent or alkaline agent is mixed respectively, adds hydroxypropyl methylcellulose (HPMC) then or polyvinylpyrrolidone (PVP) is granulated as binding agent.Resulting vagina effervescence, its disintegrate is quick, foam is many, but has the unabiding defective of foam, and medicine can not fully arrive the gauffer position of vagina well, thereby influences the therapeutic effect of medicine.
Summary of the invention:
At above-mentioned prior art defective, and consider that clindamycin has tangible bacteriostasis to aerobic leather Lan Shi positive bacteria and most of anaerobe, metronidazole has the strong antibiotic effect to most of anaerobe and trichomonas vaginitis, and the synergetic antibacterial effect of clindamycin and metronidazole, in addition, oral or drug administration by injection also can add heavy patient's Liver and kidney burden, the present invention proposes to utilize clindamycin and metronidazole and make a kind of novel clindamycin and metronidazole compound recipe vagina effervescence at the characteristics of gynaecopathia especially, realize topical, farthest bring into play drug effect, thereby finish the present invention.
One of purpose of the present invention provides a kind of clindamycin metronidazole vagina effervescent tablet.
Two of purpose of the present invention provides the preparation method of described clindamycin metronidazole vagina effervescent tablet.
Three of purpose of the present invention provides described clindamycin metronidazole vagina effervescent tablet and is used for vagina administration with gynaecopathias such as treatment vaginitiss.
For realizing above-mentioned goal of the invention, the present invention adopts following technical scheme:
A kind of clindamycin compounds and medicinal salt or ester thereof of following formula structure:
Vagina effervescence agent of the present invention, its with clindamycin or its pharmaceutical salts or its ester and metronidazole as active component, the binding agent that adds in it is characterized in that containing in this effervescent tablet; Preferred this binding agent is hydroxypropyl methylcellulose (HPMC).
Above-mentioned vagina effervescence, the weight ratio of wherein said clindamycin or its pharmaceutical salts or its ester and metronidazole is 8～12: 6～10; Preferred weight ratio is 10: 8.
Vagina effervescence of the present invention, it also can contain the binding agent that adds; Preferred this binding agent is polyvinylpyrrolidone (PVP).
Vagina effervescence of the present invention, it also contains adjuvants such as sodium bicarbonate, microcrystalline Cellulose, tartaric acid, starch, sodium lauryl sulphate, magnesium stearate, wherein the weight percentage of each composition is: clindamycin 15-30%, metronidazole 12-25%, tartaric acid 15-25%, sodium bicarbonate 15-25%, microcrystalline Cellulose 5-15%, starch 5-10%, sodium lauryl sulphate 1-3%, hydroxypropyl methylcellulose 1-5%, magnesium stearate 0.5-5%.Granulate and adopt the alcoholic solution of PVP, its weight percentage is 3-5%, alcoholic solution (greater than 95%) 95-98%.
The preparation method of vagina effervescence of the present invention, it comprises following steps: (a) with described clindamycin or its pharmaceutical salts or its ester and metronidazole and alkaline agent, binding agent auxiliary materials and mixing, system granule; (b) with described clindamycin or its pharmaceutical salts or its ester and metronidazole and sour agent, binding agent auxiliary materials and mixing, system granule; (c) with (a) prepared granule and (b) prepared granule mixing, add magnesium stearate, granulate, tabletting.
Wherein, described granulation is to granulate with the alcoholic solution of 5% polyvinylpyrrolidone.
Preferred manufacturing procedure: (a) half sodium bicarbonate of measuring clindamycin, metronidazole, microcrystalline Cellulose, starch, hypromellose, sodium lauryl sulphate and recipe quantity by recipe quantity is mixed together evenly, alcoholic solution with 5% polyvinylpyrrolidone is granulated, 50～60 ℃ of dryings make granule; (b) press the tartaric acid mix homogeneously of half amount of recipe quantity with clindamycin, metronidazole, microcrystalline Cellulose, starch, hypromellose, sodium lauryl sulphate and recipe quantity, alcoholic solution with 5% polyvinylpyrrolidone is granulated, 50～60 ℃ of dryings make granule; (c) with above-mentioned (a) and (b) prepared granule mixing, press recipe quantity and add magnesium stearate, granulate, tabletting.The heavily about 0.67g/ sheet of sheet.
Vagina effervescence of the present invention is suitable for vagina administration, in order to the treatment vaginitis, as gynaecopathias such as trichomonal vaginitis, bacterial vaginitiss.
The research of antibacterial activity in vitro test, the result shows that clindamycin and metronidazole two medicines share has increased antibacterial action and the range of application of medicine to leather Lan Shi aerobe and the microbial gynecological infection of anaerobism, the side effect that has reduced independent use simultaneously is with not enough, can bring into play maximum drug effect, gynaecopathias such as trichomonal vaginitis, bacterial vaginitis are had better curative effect.
Clindamycin of the present invention or its pharmaceutical salts or its esters for example can be materials such as Clindamycin Hydrochloride, clindamycin phosphate; The effective dose that clindamycin contains is 80～250mg, and the consumption of metronidazole is 64～200mg, and preferred dosage is: clindamycin 125mg, metronidazole 100mg; Perhaps clindamycin 100mg, metronidazole 80mg.
The pH value that vagina effervescence need be controlled in its aqueous solution usually is a faintly acid.It is sodium bicarbonate and tartaric acid that the present invention selects the low effervescent of toxicity for use, and by adjusting both proportionings, making its pH value in aqueous solution is 4.0～6.5, satisfies the physiological requirement of vagina medicinal.
Clindamycin metronidazole vagina effervescent tablet of the present invention, by the interior binding agent that adds, it is prescription science, novelty not only, and compares with existing effervescent tablet, has beyond thought effect, behind the effervescent tablet vagina administration particularly of the present invention, gas release is big, and foam is fine and closely woven, abundant, lasting, it is abundant to help drug distribution, the local drug concentration height, and store up and stay the time long, the curative effect of medicine obviously improved.
Contrast test:
Embodiment 1 prepared sample (sample 1); According to the described vagina effervescence prepared of the Chinese invention patent application sample (sample 2, sample 3) of application number 94110780.9, wherein active constituents of medicine is clindamycin and metronidazole.Investigate three kinds of sample gas releases, method is with reference to two appendix of Chinese Pharmacopoeia version in 2000.
Get 10 in 25ml tool plug scale test tube (internal diameter 1.5cm), each precision adds water 2ml, puts in 37 ℃ ± 1 ℃ water-bath after 5 minutes, drops into 1 of this product in each pipe respectively, and close plug is observed the volume (ml) of maximum gas release in 20 minutes.The result is as follows:
Three kinds of sample gas releases (ml) are investigated
| Sample | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 |
| Sample 1 | 19.7 | 21.2 | 20.5 | 19.8 | 22.3 | 21.6 | 20.8 | 22.4 | 22.4 | 20.9 |
| Sample 2 | 11.3 | 9.8 | 8.9 | 11.7 | 9.5 | 10.2 | 10.6 | 9.9 | 11.4 | 10.0 |
| Sample 3 | 12.2 | 13.4 | 14.0 | 13.4 | 14.2 | 11.9 | 12.4 | 12.7 | 13.6 | 13.5 |
The average gas release of three kinds of samples is respectively: sample 1,21.16ml; Sample 2,10.33ml; Sample 3,13.13ml.By above-mentioned contrast test, the result shows that vagina effervescence of the present invention (sample 1) is compared with the vagina effervescence of sample 3 with sample 2, and gas release increases significantly, and by the interior binding agent that adds, has produced the beyond thought effect of those skilled in the art.
Simultaneously, by the interior binding agent that adds, compare with the vagina effervescence of routine, it is easier, convenient to granulate, and preparation section is simplified, and preparation process is simple, and steady quality is more suitable in industrial-scale production.
Clindamycin metronidazole vagina effervescent tablet of the present invention; compare with preparations such as traditional oral, the injection of clindamycin, metronidazole, externals; both overcome drug-induced gastrointestinal upset; pollution clothes not; do not hinder patient's normal activity and easily be accepted; make things convenient for patient's medication, also improved the curative effect of medicine, reduced toxic and side effects.Brought very big convenience for clinical treatment trichomonal vaginitis, bacterial vaginitis.
The specific embodiment:
Below further set forth the present invention by the specific embodiment, but it does not constitute the restricted effect to the present invention.
Embodiment 1
Clindamycin 1250g
Metronidazole 1000g
Tartaric acid 1240g
Sodium bicarbonate 1350g
Microcrystalline Cellulose 600g
Hypromellose 140g
Starch 500g
Sodium lauryl sulphate 120g
Magnesium stearate 120g
It is an amount of with the alcoholic solution of 5% polyvinylpyrrolidone to granulate.Be made into 10000.
Preparation method: will partly measure clindamycin, metronidazole, microcrystalline Cellulose, starch, hypromellose, sodium lauryl sulphate and sodium bicarbonate by recipe quantity and be mixed together evenly, and granulate 50～60 ℃ of dryings with the alcoholic solution of 5% polyvinylpyrrolidone; To partly measure clindamycin, metronidazole, microcrystalline Cellulose, starch, hypromellose, sodium lauryl sulphate and tartaric acid mix homogeneously by recipe quantity, granulate 50～60 ℃ of dryings with the alcoholic solution of 5% polyvinylpyrrolidone; With the magnesium stearate that above-mentioned two kinds of granules mix and add recipe quantity, granulate, the heavily about 0.67g/ sheet of tabletting, sheet.
Embodiment 2
2500 parts of clindamycins
2000 parts of metronidazoles
1380 parts in tartaric acid
1500 parts of sodium bicarbonate
800 parts of microcrystalline Cellulose
150 parts of hypromelloses
600 parts of starch
200 parts of sodium lauryl sulphates
180 parts of magnesium stearate
It is an amount of with the alcoholic solution of 5% polyvinylpyrrolidone to granulate.Be made into 10000.
Preparation method: adopt embodiment 1 identical method to prepare.The heavily about 0.98g/ sheet of the sheet of the vagina effervescence that obtains.
Claims (11)
1. vagina effervescence agent, its with clindamycin or its pharmaceutical salts or its ester and metronidazole as active component, the binding agent that adds in it is characterized in that containing in this effervescent tablet, described binding agent is a hydroxypropyl methylcellulose.
2. the described vagina effervescence of claim 1, the weight ratio of wherein said clindamycin or its pharmaceutical salts or its ester and metronidazole is 8～12: 6～10.
3. the described vagina effervescence of claim 2, the weight ratio of wherein said clindamycin or its pharmaceutical salts or its ester and metronidazole is 10: 8.
4. each described vagina effervescence of claim 1-3, it also contains the binding agent that adds, and described binding agent is a polyvinylpyrrolidone.
5. each described vagina effervescence of claim 1-3, it also contains sodium bicarbonate, microcrystalline Cellulose, tartaric acid, starch, sodium lauryl sulphate, magnesium stearate.
6. the described vagina effervescence of claim 4, it also contains sodium bicarbonate, microcrystalline Cellulose, tartaric acid, starch, sodium lauryl sulphate, magnesium stearate.
7. the described vagina effervescence of claim 5, wherein the weight percentage of each composition is: clindamycin 15-30%, metronidazole 12-25%, tartaric acid 15-25%, sodium bicarbonate 15-25%, microcrystalline Cellulose 5-15%, starch 5-10%, sodium lauryl sulphate 1-3%, hydroxypropyl methylcellulose 1-5%, magnesium stearate 0.5-5%.
8. method for preparing each described vagina effervescence of claim 5-7, it comprises following steps: (a) described clindamycin or its pharmaceutical salts or its ester and metronidazole and microcrystalline Cellulose, starch, hypromellose, sodium lauryl sulphate, sodium bicarbonate are mixed together evenly, make granule; (b) described clindamycin or its pharmaceutical salts or its ester and metronidazole and microcrystalline Cellulose, starch, hypromellose, sodium lauryl sulphate, tartaric acid are mixed together evenly, make granule; (c) with (a) prepared granule and (b) prepared granule mixing, add magnesium stearate, granulate, tabletting.
9. the described method of claim 8, wherein granulating is alcoholic solution granulation with 5% polyvinylpyrrolidone.
10. claim 8 or 9 described methods, wherein, (a) half sodium bicarbonate of measuring clindamycin, metronidazole, microcrystalline Cellulose, starch, hypromellose, sodium lauryl sulphate and recipe quantity by recipe quantity is mixed together evenly, alcoholic solution with 5% polyvinylpyrrolidone is granulated, 50～60 ℃ of dryings make granule; (b) press the tartaric acid mix homogeneously of half amount of recipe quantity with clindamycin, metronidazole, microcrystalline Cellulose, starch, hypromellose, sodium lauryl sulphate and recipe quantity, alcoholic solution with 5% polyvinylpyrrolidone is granulated, 50～60 ℃ of dryings make granule; (c) with above-mentioned (a) and (b) prepared granule mixing, press recipe quantity and add magnesium stearate, granulate, tabletting.
11. each described vagina effervescence of claim 1-7 is used for vagina administration to treat the application of colpitic medicine in preparation.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410070111 CN1257715C (en) | 2004-08-02 | 2004-08-02 | Clindamycin metronidazole vagina effervescent tablet and its preparing method and use |
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| Application Number | Priority Date | Filing Date | Title |
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| CN 200410070111 CN1257715C (en) | 2004-08-02 | 2004-08-02 | Clindamycin metronidazole vagina effervescent tablet and its preparing method and use |
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| CN1257715C true CN1257715C (en) | 2006-05-31 |
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Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100446774C (en) * | 2005-05-31 | 2008-12-31 | 黑龙江龙桂制药有限公司 | Clindamycin hydrochloride vaginal effervescent tablet and its preparing method |
| CN102335151B (en) * | 2010-07-20 | 2015-07-08 | 杭州赛利药物研究所有限公司 | Clindamycin phosphate vaginal mucosa tablet and preparation method thereof |
| CN102335152B (en) * | 2010-07-20 | 2015-07-08 | 杭州赛利药物研究所有限公司 | Terbinafine hydrochloride vagina sustained release tablet and its preparation method |
| EP2704694A4 (en) * | 2011-05-02 | 2014-11-19 | Aptalis Pharmatech Inc | Rapid dissolve tablet compositions for vaginal administration |
| CN102670646B (en) * | 2012-05-07 | 2014-01-22 | 河南省康星药业股份有限公司 | Cattle effervescent tablet taking lincomycin hydrochloride as main component and preparation process for effervescent tablet |
| CN102836139A (en) * | 2012-09-20 | 2012-12-26 | 山东方明药业集团股份有限公司 | Compound ketoconazole vaginal effervescent tablet and preparation method thereof |
| CN112569196B (en) * | 2020-12-30 | 2023-05-12 | 海南海神同洲制药有限公司 | Clindamycin phosphate vaginal tablet and preparation process thereof |
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