CN101708159A - Preparation method for heat-sensitive medicament suspension - Google Patents
Preparation method for heat-sensitive medicament suspension Download PDFInfo
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- CN101708159A CN101708159A CN200910241751A CN200910241751A CN101708159A CN 101708159 A CN101708159 A CN 101708159A CN 200910241751 A CN200910241751 A CN 200910241751A CN 200910241751 A CN200910241751 A CN 200910241751A CN 101708159 A CN101708159 A CN 101708159A
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Abstract
The invention discloses a preparation method for a heat-sensitive medicament suspension, which comprises the following steps of: adding a heat-sensitive medicament, a suspending agent and other auxiliary materials into a low-temperature ball mill, and sealing the low-temperature ball mill; and after crushing, mixing and uniformly dispersing the materials in the low-temperature ball mill, filing the mixture and sterilizing the mixture. In the preparation method, parameters, such as work temperature, grinding strength and grinding time can be adjusted according to the thermal stability and the granularity of the heat-sensitive medicament, the temperature of the materials is effectively controlled under the condition of ensuring to reach a target granularity, and the decomposition and the deterioration of the heat-sensitive medicament are prevented. In addition, in the method, a plurality of procedures can be finished at one time by synchronously crushing, mixing and uniformly dispersing, the problem of frequent transferring needed by the plurality of procedures of the traditional preparation process is avoided, and the pollution control links of the product are reduced.
Description
Technical field
The present invention relates to a kind of preparation method of thermal sensitivity pharmaceutical suspension.
Background technology
Suspensoid is meant that the slightly solubility solid drugs is scattered in the liquid preparation heterogeneous that forms in the disperse medium with graininess.Such preparation is generally used for the drug administration mode that accretion rate is fast, the water preparation absorption is too fast, and the action time of prolong drug, is widely used in clinical.The size of granularity has important function to drug effect in suspensoid, and suspensoid Chinese medicine particle mean size is 1～50 μ m.
The preparation of suspensoid is divided into dispersion method and coacervation.Dispersion method is owing to simple to operate, wide accommodation, and therefore, the most drug suspensoid adopts the dispersion method preparation at present.Traditional dispersion method be with coarse grained medicine be ground into meet the granularity that the suspensoid microgranule requires after, redispersion is made the method for suspensoid in disperse medium.
The thermal sensitivity medicine is meant the medicine very responsive to temperature, and such medicine will all or part ofly decompose when surpassing its decomposition temperature, goes bad.Traditional dispersion method prepares the technology of suspensoid owing to can make product temperature raise, and the method for take fragmentation, the substep subset that mixes, is uniformly dispersed carrying out, shift frequent, complex operation, the pollution controlling unit of product is more, so the preparation of thermal sensitivity pharmaceutical suspension is the difficult problem of the vast preparation of puzzlement producer always.
Low temperature ball mill is made up of refrigeration system and grinding system two parts, when low temperature ball mill moves, the cold air that refrigeration system produces is imported in the ball mill that thermal insulation cover is housed continuously, the ball grinder that material, abrading-ball are housed is in certain low temperature environment all the time, thereby guarantees that the thermal sensitivity medicine in the ball grinder can not decompose rotten.
Summary of the invention
The preparation method that the purpose of this invention is to provide a kind of thermal sensitivity pharmaceutical suspension can solve the technological deficiency of above-mentioned thermal sensitivity pharmaceutical suspension preparation, has favorable economic benefit.
For achieving the above object, technical scheme of the present invention provides a kind of preparation method of thermal sensitivity pharmaceutical suspension, thermal sensitivity medicine, suspending agent and other adjuvants is joined in the low temperature ball mill sealing, in low temperature ball mill, carry out fragmentation, mix and be uniformly dispersed, sterilize after the fill then.Wherein the addition sequence of thermal sensitivity medicine, suspending agent and other adjuvants can arbitrarily add, but is best with last adding solvent.The parameter setting of low temperature ball mill is according to the heat stability of thermal sensitivity medicine and product granularity requirement, sets suitable operating temperature, severity of grind, milling time.Adopted ball mill grinding 0.5 hour, common chemicals granularity can reach the following requirement of 10 μ m, as more small grain size requirement of needs, but the proper extension milling time, the medicine particle mean size that this method makes can reach 0.1 μ m.
Preparation method of the present invention, being specially adapted to described thermal sensitivity medicine is the preparation that temperature is higher than the suspensoid of 50 ℃ of medicines that promptly decompose, go bad.During preparation, select adjuvant and The suitable solvent according to the character of thermal sensitivity medicine.
Preparation method of the present invention, described adjuvant are one or more in antioxidant, emulsifying agent, the antibacterial.Described suspending agent is that sodium carboxymethyl cellulose, Cera Flava, bran wax, polyethylene pyrrole iron one or more in alkane ketone, stearic acid, gelatin, hydrogenated vegetable oil, aluminum monostearate and the methylcellulose.Described antioxidant is one or more in butylated hydroxyarisol, propyl gallate, alpha-tocopherol and the ascorbyl palmitate.Described emulsifying agent is one or more in pluronic F-68, tween 80, Arlacel-80, lecithin and the fabaceous lecithin.Described antibacterial is one or more in phenol, cresol, chlorobutanol, phenyl methylcarbamate and the parabens.
Preparation method of the present invention, wherein low temperature ball mill preferably adopts with liquid nitrogen as low-temperature receiver.
Preparation method of the present invention is 0.1～20 μ m by its suspensoid product granularity that makes.
Technique scheme has following advantage: this preparation method is disposable in milling apparatus synchronous finishes fragmentation, the multiple tracks process of mixing, be uniformly dispersed, and does not need to carry out the transfer between the equipment, has reduced and has transferred the pollution, and operates also more simple; In addition, this method is controlled factors such as operating temperature, severities of grind by using low temperature ball mill, has controlled the decomposition, rotten of thermal sensitivity medicine effectively, has guaranteed the drug effect and the safety of medicine.This method is guaranteeing can to realize that granularity reaches 0.1～20 μ m under the Undec prerequisite of thermal sensitivity medicine, and this also is that existing at present method institute can not reach.In a word, this method is simple to operate, has reduced pollution probability, and product granularity is little, and the preparation effect of thermal sensitivity pharmaceutical suspension is very remarkable.
The specific embodiment
Below in conjunction with embodiment, the specific embodiment of the present invention is described in further detail.Following examples are used to illustrate the present invention, but are not used for limiting the scope of the invention.
Embodiment 1
The preparation of cefquinome sulfate injection
With Cefquinome sulfate 5.5g, stearic acid 0.04g, chlorobutanol 0.01g, propyl gallate 0.01g, soybean oil 200mL joins in the QM-DY type liquid nitrogen cryogenics ball mill successively, after airtight, it is 5～10 ℃ that operating temperature is set, and milling time is 0.5 hour, severity of grind is a middle rank, after grinding end, fill is sealed, radiation sterilization promptly, product quality meets the requirements.
Embodiment 2
The preparation of compound ceftiofur suspension type injection
With ceftiofur 5.5g, sulbactam 2.75g, aluminum monostearate 0.07g, chlorobutanol 0.02g, soybean oil 40mL joins in the QM-DY type liquid nitrogen cryogenics ball mill successively, after airtight, it is 5～10 ℃ that operating temperature is set, and milling time is 0.5 hour, severity of grind is a middle rank, after grinding end, fill is sealed, radiation sterilization promptly, product quality meets the requirements.
The thermal sensitivity medicine easily decomposes under the high situation of temperature, goes bad, and therefore, in the process of preparation thermal sensitivity pharmaceutical suspension, how controlling the decomposition of thermal sensitivity medicine, going bad is its preparation technology's difficult point.Preparation method of the present invention can be regulated parameters such as operating temperature, severity of grind, milling time according to the heat stability and the drug particle size size target of thermal sensitivity medicine, reach under the situation of targeted particle size in assurance, effective control material temperature has prevented the decomposition, rotten of thermal sensitivity medicine.In addition, this method can be implemented in and disposablely finish fragmentation synchronously, the multiprogramming that mixes, is uniformly dispersed, and has avoided the multiprogramming of traditional preparation process technology to need the problem that repeatedly shifts, and has reduced the pollution controlling unit of product.
The above only is a preferred implementation of the present invention, should be pointed out that for those skilled in the art, under the prerequisite that does not break away from the technology of the present invention principle, can also make some improvement, and these improvement also should be considered as protection scope of the present invention.
Claims (9)
1. the preparation method of a thermal sensitivity pharmaceutical suspension is characterized in that, thermal sensitivity medicine, suspending agent and other adjuvants are joined in the low temperature ball mill, and sealing is carried out fragmentation, mixes and is uniformly dispersed in low temperature ball mill, sterilize after the fill then.
2. preparation method as claimed in claim 1 is characterized in that, described thermal sensitivity medicine is that temperature is higher than 50 ℃ of medicines that promptly decompose, go bad.
3. preparation method as claimed in claim 1 or 2 is characterized in that, described adjuvant is one or more in antioxidant, emulsifying agent, the antibacterial.
4. preparation method as claimed in claim 3 is characterized in that, described suspending agent is that sodium carboxymethyl cellulose, Cera Flava, bran wax, polyethylene pyrrole iron one or more in alkane ketone, stearic acid, gelatin, hydrogenated vegetable oil, aluminum monostearate and the methylcellulose.
5. preparation method as claimed in claim 3 is characterized in that, described antioxidant is one or more in butylated hydroxyarisol, propyl gallate, alpha-tocopherol and the ascorbyl palmitate.
6. preparation method as claimed in claim 3 is characterized in that, described emulsifying agent is one or more in pluronic F-68, tween 80, Arlacel-80, lecithin and the fabaceous lecithin.
7. preparation method as claimed in claim 3 is characterized in that, described antibacterial is one or more in phenol, cresol, chlorobutanol, phenyl methylcarbamate and the parabens.
8. as each described preparation method of claim 1-7, it is characterized in that, described low temperature ball mill with liquid nitrogen or refrigerated air as low-temperature receiver.
9. as each described preparation method of claim 1-8, it is characterized in that, is 0.1～20 μ m by its suspensoid product granularity that makes.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2009102417511A CN101708159B (en) | 2009-12-04 | 2009-12-04 | Preparation method for heat-sensitive medicament suspension |
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| Application Number | Priority Date | Filing Date | Title |
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| CN2009102417511A CN101708159B (en) | 2009-12-04 | 2009-12-04 | Preparation method for heat-sensitive medicament suspension |
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| CN101708159A true CN101708159A (en) | 2010-05-19 |
| CN101708159B CN101708159B (en) | 2011-06-15 |
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| CN2009102417511A Expired - Fee Related CN101708159B (en) | 2009-12-04 | 2009-12-04 | Preparation method for heat-sensitive medicament suspension |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104394865A (en) * | 2012-04-17 | 2015-03-04 | 韩国联合制药株式会社 | Composite composition having improved stability and containing amlodipine and rozaltan |
| CN105726461A (en) * | 2014-12-10 | 2016-07-06 | 瑞普（天津）生物药业有限公司 | Ceftiofur hydrochloride breast injectant during dry period |
| CN111419795A (en) * | 2020-05-09 | 2020-07-17 | 上药东英（江苏）药业有限公司 | Danqulin sodium suspension for injection and preparation method thereof |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1431072A (en) * | 2003-01-23 | 2003-07-23 | 上海交通大学 | Vertical type agitation ball grinding mill of low temp |
| CN2621811Y (en) * | 2003-03-26 | 2004-06-30 | 南京大学仪器厂 | Low temp planetary ball mill |
| CN1289199C (en) * | 2003-07-10 | 2006-12-13 | 中山大学 | Low-temperature ultramicro disintegrating method of Chinese traditional medicinal materials |
| CN1709583A (en) * | 2005-04-07 | 2005-12-21 | 王永清 | Superlow temperature disintegrating machine |
-
2009
- 2009-12-04 CN CN2009102417511A patent/CN101708159B/en not_active Expired - Fee Related
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104394865A (en) * | 2012-04-17 | 2015-03-04 | 韩国联合制药株式会社 | Composite composition having improved stability and containing amlodipine and rozaltan |
| CN104394865B (en) * | 2012-04-17 | 2016-11-09 | 韩国联合制药株式会社 | The stability-enhanced compositions comprising amlodipine and losartan |
| CN105726461A (en) * | 2014-12-10 | 2016-07-06 | 瑞普（天津）生物药业有限公司 | Ceftiofur hydrochloride breast injectant during dry period |
| CN111419795A (en) * | 2020-05-09 | 2020-07-17 | 上药东英（江苏）药业有限公司 | Danqulin sodium suspension for injection and preparation method thereof |
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| Publication number | Publication date |
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| CN101708159B (en) | 2011-06-15 |
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Granted publication date: 20110615 Termination date: 20191204 |