CN101502510B - Medicament composition for treating colpitis symptoms and preparation method thereof - Google Patents
Medicament composition for treating colpitis symptoms and preparation method thereof Download PDFInfo
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- CN101502510B CN101502510B CN2009100197235A CN200910019723A CN101502510B CN 101502510 B CN101502510 B CN 101502510B CN 2009100197235 A CN2009100197235 A CN 2009100197235A CN 200910019723 A CN200910019723 A CN 200910019723A CN 101502510 B CN101502510 B CN 101502510B
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Abstract
The invention relates to a drug combination for curing the inflammation of vagina, which adopts the form of a foaming agent, in particular to a foaming agent with the principle agents being metronidazole, clotrimazole and chlorhexidine acetate. The drug combination has the advantages of even distribution, wide coating area and better effect in the vagina by adopting the form, and meanwhile, the drug combination feels more comfortable and has stronger retention property than other forms. In the formula of the foaming agent, the drug combination can permeate into the mucosal folds of the vaginarapidly and effectively by dispersing atomizing particles with the particle diameter being a few micrometers in a foaming manner under the action of pressure; the drug combination has higher absorption rate than the spraying agent with water being the only solvent with the assistance from various fat-soluble auxiliary materials; the drug contamination and the cross contamination are avoided during the administration; the invention has the advantages that the curative effect is fully produced, the administration is sanitary, convenient, safe and reliable without causing the foreign body sensation, and the drug combination is easily accepted by patients; and the invention further has the advantages of drug stability, form stability and long effective duration.
Description
Technical field
The present invention relates to the reform of medicine conventional dosage forms, is that novel employing metronidazole, clotrimazole, chlorhexidine acetate is compound recipe foam of principal agent and preparation method thereof specifically.
Background technology
Bacterial vaginitis, colpitis mycotica, trichomonal vaginitis and antibacterial fungus infusorian mixed infective vaginitis are women's common frdquently encountered diseases, have had a strong impact on women's health.
Present useful metronidazole or can mould azoles, the chlorhexidine acetate one pack system is as the dosage form of anti-inflammation, but one pack system lacks synergism, particularly very poor to the mixed infection therapeutic effect.The metronidazole,clotrimazole and chlorhexidine acetate suppositories (recording) that makes by the medicinal composition of metronidazole, clotrimazole, three kinds of compositions of chlorhexidine acetate 2000 editions two ones of Chinese Pharmacopoeias, through clinical application for many years, prove that this compound preparation is evident in efficacy to treatment mixed infection, mycotic, trichomonal vaginitis.The safe dosage form of two azoles of present domestic list marketing has metronidazole,clotrimazole and chlorhexidine acetate suppositories, metronidazole effervescence patch, the safe ointment of two azoles.Chinese patent application CN03113292.8 has reported safe preparation of two azoles and preparation method thereof, CN93115777.3 has reported dithiazole ointment and preparation technology thereof, CN94113652.3 has reported metronidazole effervescence patch and preparation method thereof, CN200410104481.7 has reported a kind of metronidazole,clotrimazole and chlorhexidine acetate suppositories and preparation method thereof, and these patents have related to the different dosage form of metronidazole,clotrimazole and chlorhexidine acetate suppositories, effervescent tablet, cream.Weakness such as but above-mentioned listing dosage form and patent report dosage form and preparation method thereof ubiquity dosage form is backward, bioavailability is low, use inconvenience, plastid as bolt is harder, its preparation technology through cold contraction makes the very not regular slyness of its external form again, use winter, sends into regular meeting's damage vagina in the vagina process; Then easily melt, glue hands summer; And suppository is met the body temperature fusion and is easily run off, and affects the treatment, pollution clothes, and the patient has sense of discomfort, and suppository holdup time long (6-8 hour) and to absorb intravaginal moisture zest strong, for recurrence hides some dangers for, the destructible acid-base balance; Unguentum special device drug delivery, easily administration is inhomogeneous, and unguentum also runs off easily, makes focal zone can not get the medicine of therapeutic dose, also easy pollution clothes; Bioavailability reduced when the effervescent tablet disintegrate was incomplete, more than need during several dosage form medication manipulationly, both unhygienic, cross-contamination easily has foreign body sensation in patient's body again, brings discomfort to the patient.
Existing various dosage formulation does not all well solve the above problems, and therefore need provide a kind of and can make things convenient for the patient to use, and can effectively improve the medicine of the novel therapeutic treatment colpitis of therapeutic effect simultaneously again.
Summary of the invention
The present invention has overcome the shortcoming of solid preparations such as suppository and semi-solid preparation, has improved the defective of above dosage form, and research design has gone out new dosage form, adopted the form of foam.Foamy form can make medicine be evenly distributed in tract, be coated with wide, better effects if, the sensation of Shi Yonging is more comfortable than other dosage forms simultaneously, anelasticity is stronger than other dosage forms.In the prescription of the foam that adds propellant, because used propellant, not to promote by valve, but make particle diameter have only several microns droplet to become cystose to disperse by pressure, medicine can effectively arrive rapidly and infiltrate tract mucosa wrinkle wall, medicine is that the spray of unique solvent is faster at the auxiliary absorptance down of various fat-soluble adjuvants with water, use does not have drug contamination and cross-contamination, have curative effect fully, use hygienic and convenient, safe and reliable, no foreign body sensation, the patient is easy to accept and medicine is stablized, dosage form is stable, the advantage that effect duration is long.And in not adding the foam prescription of propellant, directly assembling produces foamy mechanical pump, and is simple to operation, and the foamy character that produces is consistent with the foam property that adds the propellant generation, has same advantage.
The present invention realizes by following means:
A kind of pharmaceutical composition that is used for the treatment of colpitis, this pharmaceutical composition adopt the dosage form of foam to make the compound recipe foam, the principal agent of this foam by weight percentage: metronidazole 3.0-15.0%; Clotrimazole 3.0-12.0%; Chlorhexidine acetate 0.1-0.7% and pharmaceutic adjuvant are that 73.0-93.8% is formulated, wherein optimum proportioning by weight percentage: metronidazole 6.0-12.0%; Clotrimazole 5.0-10.0%; Chlorhexidine acetate 0.2-0.55% and pharmaceutic adjuvant are 78.0-88.7%.
Metronidazole is to the effect of most of anaerobe tool strong antibiotic, but aerobe and facultative anaerobe are not had effect.Antimicrobial spectrum comprises bacteroides fragilis and other Bacteroidess, fusiform bacilarmature, aerogenesis clostridium, Eubacterium, Wei Rong coccus, dyspepsiacoccus and peptostreptococcus etc.In addition, ameba and infusorian also there is stronger killing action.The nitroreduction of this product becomes a kind of cell toxicant, thereby acts on the DNA metabolic process of antibacterial, impels cell death.The mechanism of anti-ameba ruptures the protozoacide nitrogen chain for suppressing its redox reaction; Clotrimazole: bacteriostasis is arranged, also can have bactericidal action when concentration is high.The biosynthesis that can suppress sterin such as fungus ergosterol; Its permeability of damage fungal cell membrane nuclear alteration causes important substance leakage in the cell; Also can suppress the triacylglycerol of fungus and the biosynthesis of phospholipid; Still but the activity of inhibited oxidation and peroxidase causes peroxide excessive buildup in born of the same parents, causes degeneration of fungus subcellular structure and necrosis; Chlorhexidine acetate: this product is an antibiosis anti-inflammatory drug, and some staphylococcus, Streptococcus mutans, streptococcus salivarius, Candida albicans, escherichia coli and anaerobism bacterium acidi propionici are extremely sensitive to this product; Bloodthirsty streptococcus medium sensitivity, Proteus, Pseudomonas, Klebsiella and Grain-negative coccus are then low responsive.Chlorhexidine is because of being with positive electric charge, and is adsorbable in mucomembranous surface, gradually from adsorption site disperse, release, produces the bacteriostasis that continues.Adsorbable in the permeability barrier of antibacterial endochylema film, cellular content is spilt, low concentration suppresses antibacterial, high concentration kill bacteria.Above-mentioned various drug regimens use and can play collaborative effect, thereby play better treatment colpitis.
Pharmaceutic adjuvant described in the prescription of this foam mainly comprises pH regulator agent, foaming agent, foam substrate, foam stabiliser, spice, solvent, propellant etc., also can comprise the pharmaceutic adjuvant that other are commonly used, can look different requirement and adjust the mixing operating position of various adjuvants.
PH value regulator amount ranges 0.000-3.000% (w/w) wherein: example hydrochloric acid, phosphoric acid, sodium hydroxide, sodium bicarbonate, sodium citrate etc.; Foaming agent adopts surfactant, its amount ranges 0.200-10.000% (by weight percentage), and preferred nonionic surfactants and anion surfactant, non-ionic surface active agent mainly contains: polysorbate60, Tween 80, Arlacel-85 etc.; Anion surfactant mainly contains: sodium lauryl sulphate etc.; Foam substrate is mainly foam substrates quantity scope 0-15% (w/w), be preferably higher fatty acids class, high fatty alcohol class, higher fatty acids lipid, higher fatty acids class wherein, as: stearic acid, Palmic acid etc., the high fatty alcohol class, as: octadecanol, hexadecanol etc., higher fatty acids lipid, as: lanoline, Cera Flava etc.; Foam stabiliser amount ranges 0.000-15.000% (w/w), as: tetrapotassium pyrophosphate, glycerol, agar, dioctyl sodium sulphosuccinate, Palmic acid trimethyl-ethylene amine, polyvinylpyrrolidone, triethanolamine etc.; Essence amount ranges 0.000-0.500% (w/w), as: all kinds of essence such as Herba Menthae essence, jasmin essence etc.; Solvent load 40.000-90.000% (w/w), as: distilled water, glycerol, propylene glycol, ethanol etc.; Propellant can be one or more blended chlorofluoromethane hydrocarbons and compressibility gas etc., its amount ranges 3.000-40.000% (w/w), as: the chlorofluoromethane hydro carbons, as: isceon, dichlorodifluoromethane, dichlorotetra-fluoroethane, monochlorodifluoromethane or the like, or the not chloride tetrafluoroethane of environmental protection more, Difluoroethane etc.; Hydrocarbon, as: iso-butane, propane etc.; The compressibility gas, as: dimethyl ether, carbon dioxide, nitrogen, carbon dioxide etc.
Foam preparation technology provided by the present invention comprises following steps:
This method comprises following steps:
(1) with the metronidazole of recipe quantity, clotrimazole, chlorhexidine acetate stirring and dissolving in solvent;
(2) foaming agent, foam substrate, foam stabiliser, spice, antioxidant, antiseptic, the stirring of the ease of solubility of adding recipe quantity make its mix homogeneously;
(3) add pH value regulator, the pH value of regulator solution;
(4) check each drug content of preparating liquid,, qualified medicinal liquid is poured in the pressure vessel, add cap valve and sealing, charge into the propellant of recipe quantity by designed prescription; Or directly assembling produces foamy mechanical pump.
The patient uses for convenience simultaneously, and preparation of the present invention can also be made the foam of suspension type except that above-mentioned solution-type foam aerosol dosage form, and its concrete processing method is as follows:
(1) solution A: take by weighing foaming agent, foam stabiliser, antiseptic, antioxidant, the foam substrate that recipe quantity is insoluble in water and put together, water-bath or slow fire are heated to 50-70 ℃ dissolves it, stirs, and mixes even matter;
(2) solution B: in the solvent of 80% recipe quantity, slowly be heated to the temperature of solution A; And solution A slowly added in the solution B while hot, stirring while adding, even matter is mixed, and makes into emulsion;
When (3) emulsion temperature is reduced to below 40 ℃, add micronized metronidazole, clotrimazole, chlorhexidine acetate, add essence, pH value regulator and solvent simultaneously to full dose, even matter is mixed;
(4) check three kinds of component contents in the preparating liquid,, qualified medicinal liquid is poured in the pressure vessel, add cap valve and sealing, charge into the propellant of recipe quantity by designed prescription; Or directly assembling produces foamy mechanical pump.
When the foamy mechanical pump of generation is directly assembled in employing, can cancel propellant, directly take mechanical system to produce foam, thereby break away from dependence for propellant, alleviate the existence of propellant simultaneously for problems such as environmental pollutions.
The research of foam of the present invention comprises research work such as the design of the design of the investigation of crude drug and adjuvant, supplementary material recipe design, dosage, prescription and optimizations.Prescription research is closely related with quality research, stability and even safety and the effectiveness of foam.Prescription research is the basis of quality of the pharmaceutical preparations research.We have finished following invention work in the prescription research of this foam:
1. the proportioning of crude drug
No matter be agent of solution foam or suspension type foam, the physicochemical property of principal agent exerts an influence to the quality of the pharmaceutical preparations and preparation production.We have carried out deep analysis research to the physicochemical property of crude drug in the prescription research of foam, and the environment special according to intravaginal, through test of many times, have found the crude drug suitable proportioning to make the synergism of each medicine reach best.
2. the proportioning of adjuvant
The kind of adjuvant and consumption also influence the quality of medicine.Increase as adding the viscosity that excessive Tween80 or Span85 may make whole system in the prescription, may the ejection drug content be inhomogeneous because viscosity change makes, the granularity of ejection medicine becomes greatly in the chemical spray process, the residual quantity increase of medicine in container etc.; The composition of foaming agent, foam stabiliser, foam substrate and consumption are bigger etc. to foamy property effect, and dosage inaccurate that these will directly cause medicine influences the curative effect of medicine, and we have found proper supplementary material and proportioning thereof through test of many times.
3, the design of dosage
Because may there be following phenomenon in aerosol under use and condition of storage: 1) a part of medicinal liquid is owing to the pressure reduction of propellant remains in the container; 2) medicine is adsorbed on chamber wall and valve system, causes a part of medicine to spray with propellant, particularly more easily produces for this phenomenon of suspension aerosol; 3) medicinal liquid that ejects does not enter in patient's body fully attached to nozzle.4), make the part drug residue in container and can't use because the poor sealing of valve system causes the leakage of propellant under condition of storage.For issuable above-mentioned situation, we should fully take into account the dispensing dosage of prescription when prescription screening and research, solved problem as above.
4, the micronization of medicine
Should carry out rational micronization processes to medicine for the suspension type foam, the micromeritis characteristics such as form of the particle size distribution of the powder behind the micronization, flowability, bulk density, surface charge, powder surface are bigger to the quality influence of aerosol.We the time have found suitable micronization granularity and mass range in research, make the particle size distribution, flowability, bulk density etc. of the powder behind the micronization all reach best.
5, the flocculation of medicine
There is density contrast for suspension type foam medicine and dispersion solvent, will inevitably produces sedimentation within a certain period of time.If this sedimentation phenomenon can not be uniformly dispersed jolting under the condition, and certainly will have a strong impact on the use of medicine.So how to prevent the flocculation of medicine at the suspension type foam, this is the problem that need pay close attention in the prescription screening process.In order effectively to reduce the flocculation of medicine, we find that by a large amount of experiments following method can address the above problem: reduce drug particle size, make micronized drug particles fully be suspended in the solvent; Add surfactant, make wetting of particulates, reduce the surface tension of particle surface and solvent; Increase the viscosity of solvent, add an amount of adjuvant, can effectively reduce accumulation and sedimentation between the granule to increase the viscosity of solvent; Add deflocculant, can effectively prevent the post-depositional caking of drug particles, make settled granule be easy to disperse.
6, propellant proportioning
For the foam that adds propellant, requirement for the clinical dispersion that adapts to aerosol, single propellant often can not meet the demands, at this moment should mix according to the difference of different propellant vapour pressures and use, when prescription screening, we have found suitable propellant component level consumption proportion by test of many times.
This medicine that adopts foam dosage form and preparation technology to make, its drug quality is stable, and is controlled, evident in efficacy and this preparation technology is simple, is fit to that industry is big produces.
The present inventor has finished invention as above; advantages such as that the metronidazole that obtains, clotrimazole, chlorhexidine acetate foam have is soft, fine and smooth, non-stimulated, good adsorption and dilatancy; can go deep into the general unapproachable positions of medicine such as mucosa fold; fully contact with focus, comprehensively killing does not stay the dead angle; and formation protecting film; prevention infection, and patient's medication feel comfortable, do not have the sense of discomfort of dosage forms such as picture suppository etc.
The specific embodiment
Embodiment 1
A kind of foam that is used for vagina administration, this foam is made up of following composition, and its proportioning of every bottle is:
Metronidazole 3.00g, clotrimazole 2.00g, chlorhexidine acetate 0.10g, tween 80 0.50g, sodium lauryl sulphate 1.00g, water 13.10g, ethanol 6.00, glycerol 1.5g, tetrafluoroethane 2.80g makes the solution-type foam, and its preparation method is as follows:
(1) with the metronidazole of recipe quantity, clotrimazole, chlorhexidine acetate stirring and dissolving in ethanol, glycerol, water mixed solvent;
(2) sodium lauryl sulphate of adding recipe quantity, tween 80 stir and make its mixed dissolution;
(3) check the content of preparating liquid, qualified medicinal liquid is poured in the pressure vessel;
(4) add cap valve and sealing, charge into the propellant of recipe quantity.
Also can not use propellant, directly assembling produces foamy mechanical pump.
Component among the embodiment 2-7 is as shown in the table, the preparation method of its preparation method such as embodiment 1.
Embodiment 8
A kind of foam that is used for vagina administration, this foam is made up of following composition, and its proportioning of every bottle is: metronidazole 2.00g, clotrimazole 2.00g, chlorhexidine acetate 0.20g, Arlacel-85 0.20g, sodium lauryl sulphate 0.80g, hexadecanol 1.20g, stearic acid 0.60g, essence 0.01g, water 19.99g, tetrafluoroethane 3.00g makes the suspension type foam, and its preparation method is as follows:
(1) take by weighing recipe quantity hexadecanol, hard ester acid, Arlacel-85 heating in water bath and it is dissolved to 50-70 ℃, for A liquid, standby;
(2) get recipe quantity 80% water, slowly be heated to 60-70 ℃, add the sodium lauryl sulphate of recipe quantity, stir and make dissolving, be B liquid; Solution A is slowly added in the solution B while hot, and the limit edged stirs, and emulsion is made in even matter emulsifying;
When (3) the emulsion room temperature is reduced to below 40 ℃, add micronized metronidazole, clotrimazole, chlorhexidine acetate, add essence, water simultaneously, even matter emulsifying to full dose;
(4) check preparating liquid content,, qualified medicinal liquid is poured in the pressure vessel by designed prescription;
(5) add cap valve and sealing, charge into the propellant of recipe quantity; Or do not add propellant, directly assembling produces foamy mechanical pump.
The proportioning of embodiment 9,10 is as above shown described, makes the foam of suspendible shape, and its preparation method is as described in the embodiment 8.
Embodiment 1-10 all can make solution or suspension ability foam.
(two appendix XIX of Chinese Pharmacopoeia version in 2005) have carried out influence factor's test, accelerated test, long term test to continuous 3 batch samples of this foam preparation that adopt proportioning of the present invention and processing method to make according to " medicine stability test guideline ".High spot reviews the character of sample, related substance and content, and accelerated test 6 months and long term test December sample carried out limit test of microbe, wherein high effective liquid chromatography for measuring is adopted in metronidazole, clotrimazole, chlorhexidine acetate related substance and content inspection.The result is as follows: (videing infra)
Table 1 metronidazole, clotrimazole and chlorhexidine acetate compound recipe foam influence factor result of the test
Table 2 metronidazole, clotrimazole and chlorhexidine acetate compound recipe foam accelerated test result
Table 3 metronidazole, clotrimazole and chlorhexidine acetate compound recipe foam long-term test results
Conclusion
1. influence factor's test: metronidazole of the present invention, clotrimazole and chlorhexidine acetate compound recipe foam were placed under high temperature, illumination 5,10 days, and every index has no significant change; This product was transferred 5,10 days in super-humid conditions, had the increase except that related substance is little, other every index has no significant change, so this product should be airtight, dry, preserves in the cool.
2. accelerated test: metronidazole of the present invention, clotrimazole and chlorhexidine acetate compound recipe foam 40 ℃ ± 2 ℃,, accelerated test 6 months under relative humidity 75% ± 5% condition, relevant every index is not seen significant change.6 months sample limit test of microbe of accelerated test is all up to specification.
3. long term test: metronidazole of the present invention, clotrimazole and chlorhexidine acetate compound recipe foam long term test 12 months under 25 ℃ ± 2 ℃, relative humidity 60% ± 10% condition, relevant every index is not seen significant change, and 12 months sample limit test of microbe of long term test is all up to specification.
Medicine of the present invention shows through Mount Taishan hospital clinical observed result: metronidazole, clotrimazole and chlorhexidine acetate compound recipe foam are treated cervicitis, vaginitis is better than other dosage form effects.Concrete clinical test results is as follows:
1, material and method
1.1 case is selected and grouping
According to the principle of clinical design, adopt the method for contrast at random to study, respectively case is divided into corresponding treatment group and matched group with table of random number.Each 20 example of cervicitis patient wherein, age 25-45 year; Each 20 example of trichomonal vaginitis, age 23-48 year, each 20 example of colpitis mycotica, age 25-47 year, each 20 example of bacterial vaginitis, age 22-50 year.
1.2 Therapeutic Method:
(1) treatment group: the metronidazole, clotrimazole and the chlorhexidine acetate compound recipe foam that adopt proportioning of the present invention and preparation method to make
(2) matched group 1: adopt the agent of listing product metronidazole,clotrimazole and chlorhexidine acetate suppositories, the same metronidazole of medication number of times, clotrimazole and chlorhexidine acetate compound recipe foam group.
(3) matched group 2: adopt listing product metronidazole effervescence patch, the same metronidazole of medication number of times, clotrimazole and chlorhexidine acetate compound recipe foam group.
(4) matched group 3: adopt the safe ointment of the two azoles of listing product, the same metronidazole of medication number of times, clotrimazole and chlorhexidine acetate compound recipe foam group.
2, result
The cure rate of metronidazole, clotrimazole and chlorhexidine acetate compound recipe foam group is than matched group height, and difference has statistical significance (P＜0.01).
Conclusion: metronidazole, clotrimazole and chlorhexidine acetate compound recipe foam are treated various vaginitis curative effect cure rates and are significantly higher than with the metronidazole,clotrimazole and chlorhexidine acetate suppositories of listing, the safe ointment of two azoles, metronidazole effervescence patch, may can fully contact with tract mucosa and wrinkle wall in tract with foam, the medicinal liquid holdup time is long relevant.Product of the present invention be a kind of collect imitate excellent, effect is fast, toxic and side effects is little, easy to use, steady quality, controlled novel gynecological external use medicine.
Claims (5)
1. pharmaceutical composition that is used for the treatment of colpitis, it is characterized in that: this pharmaceutical composition is made up of following composition:
Metronidazole 2.00g, clotrimazole 2.00g, chlorhexidine acetate 0.20g, Arlacel-85 0.20g, sodium lauryl sulphate 0.80g, hexadecanol 1.20g, stearic acid 0.60g, essence 0.01g, water 19.99g, tetrafluoroethane 3.00g.
2. pharmaceutical composition that is used for the treatment of colpitis, it is characterized in that: this pharmaceutical composition is made up of following composition:
Metronidazole 2.70g, clotrimazole 2.40g, chlorhexidine acetate 0.12g, Arlacel-85 0.20g, sodium lauryl sulphate 0.80g, glycerol 2.00g,, essence 0.01g, water 18.23g, tetrafluoroethane 3.00g.
3. pharmaceutical composition that is used for the treatment of colpitis, it is characterized in that: this pharmaceutical composition is made up of following composition:
Metronidazole 3.00g, clotrimazole 2.00g, chlorhexidine acetate 0.10g, tween 80 0.50g, sodium lauryl sulphate 1.00g, water 13.10g, ethanol 6.00, glycerol 1.5g, tetrafluoroethane 2.80g.
4. pharmaceutical composition that is used for the treatment of colpitis, it is characterized in that: this pharmaceutical composition is made up of following composition:
Metronidazole 3.00g, clotrimazole 2.50g, chlorhexidine acetate 0.10g, tween 80 0.30g, sodium lauryl sulphate 1.00g, octadecanol 1.5g, water 18.80g, heptafluoro-propane 2.80g.
5. pharmaceutical composition that is used for the treatment of colpitis, it is characterized in that: this pharmaceutical composition is made up of following composition:
Metronidazole 3.20g, clotrimazole 2.80g, chlorhexidine acetate 0.06g, sorbester p17 0.30g, lanoline 2.00g, water 16.60g, glycerol 2.00g, triethanolamine 0.04g, monochlorodifluoromethane 3.00g.
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1857243A (en) * | 2006-03-10 | 2006-11-08 | 贵州宏宇药业有限公司 | Vaginal foam preparation of chlorhexidine acetate and its preparing process |
| CN101152176A (en) * | 2007-09-03 | 2008-04-02 | 山东龙山制药有限公司 | Metronidazole effervescence patch and technique of preparing the same |
| CN101199588A (en) * | 2007-12-14 | 2008-06-18 | 郑起平 | Fudekang foam dose and preparing method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1857243A (en) * | 2006-03-10 | 2006-11-08 | 贵州宏宇药业有限公司 | Vaginal foam preparation of chlorhexidine acetate and its preparing process |
| CN101152176A (en) * | 2007-09-03 | 2008-04-02 | 山东龙山制药有限公司 | Metronidazole effervescence patch and technique of preparing the same |
| CN101199588A (en) * | 2007-12-14 | 2008-06-18 | 郑起平 | Fudekang foam dose and preparing method thereof |
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