CN103610648A - Preparation method of enrofloxacin composite sustained-release microspheres - Google Patents
Preparation method of enrofloxacin composite sustained-release microspheres Download PDFInfo
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- CN103610648A CN103610648A CN201310646546.XA CN201310646546A CN103610648A CN 103610648 A CN103610648 A CN 103610648A CN 201310646546 A CN201310646546 A CN 201310646546A CN 103610648 A CN103610648 A CN 103610648A
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Abstract
The invention discloses a preparation method of enrofloxacin composite sustained-release microspheres, and belongs to the technical field of pharmacy. The method comprises the following steps: adding a calcium chloride water solution after mixing Span80, sodium alga acid, gelatin, enrofloxacin and deionized water; continuing to agitate at constant temperature, and then carrying out centrifugal separation; taking a solid phase to dry, so as to obtain the enrofloxacin composite sustained-release microspheres. The enrofloxacin achieves the maximal release peak by soaking the product prepared by the method disclosed by the invention into the deionized water for 2-3 hours. By adopting the product, distribution of the drug inside a human body and dynamic characteristics of the drug can be changed, the sustained-release effect is significant, the targets of stabilizing blood concentration, reducing clinical administration frequency and improving the palatability of the drug are achieved, the defects and disadvantages that the traditional enrofloxacin preparation is wide in distribution inside the body and quick in diffusion are avoided and compensated. The enrofloxacin composite sustained-release microspheres also have certain target properties; drug exposure of normal tissues is reduced; the toxic and side effects are reduced; the therapeutic effect of the drug is improved.
Description
Technical field
The invention belongs to pharmaceutical technology field.
Background technology
Microball preparation is the novel form that development in recent years is got up, and refers to that drug molecule is adsorbed or is dispersed in the microparticulate system forming in high molecular polymer carrier, and medicine is made the stability that can improve medicine after microsphere, medicine is had to slow release long-acting and targeting.Microball preparation not only can reduce administration number of times, simplification therapeutic scheme, improve the compliance of body, the efficiency that can also reduce the fluctuation of blood drug level peak valley, reduce or avoid untoward reaction, raising Drug therapy, the exploitation of microball preparation has important clinical meaning.
Enrofloxacin (enrofloxacin, ENR) is the animal specific fluoroquinolones of being succeeded in developing by German Bayer AG for 1987, becomes first for the clinical fluoroquinolones of animal simultaneously.Enrofloxacin is since coming out, and clinical veterinary both domestic and external pays special attention to it, and it is mainly used in treating digestive system, respiratory system and the urinary system infection of birds, house pet, pig and cattle, also very effective to mycoplasma and staphylococcus.Yet enrofloxacin palatability is poor, oral administration, limits its administering mode because the feed intakes such as pig reduce.Meanwhile, the elimination half-life of enrofloxacin in pig body is relatively short, needs continuous several times administration can reach the effect for the treatment of, and still frequent medication causes very burden to clinical use, easily causes the stress of animal.Therefore, develop veterinary drug preparation novel form and just seem extremely important.
Sodium alginate (sodium alginate, SA) claim again Algin sodium, is the by-product extracting from the Thallus Laminariae (Thallus Eckloniae) of Brown algae or Alga Sgrgassi Enerves after iodine and mannitol.Alginic acid molecule is a kind of nontoxic natural polymer, by
β-D-MANNOSE aldehydic acid (
β-D-mannuronic, M) and
α-L-guluronic acid (
α-L-guluronic, G) press the linear polymer that (1 → 4) key is formed by connecting, its sodium salt be alginic acid with in alkali and after product, there is the required stability of pharmaceutical preparation adjuvant, dissolubility, viscosity and safety, it is the good natural polymeric material of preparing microsphere, the microsphere of preparing with it has nontoxic, can microbial degradation, the advantage such as function Ji Tezheng, bioadhesive, targeting, in fields such as medical science, chemistry, be widely used.The hydrophilic of sodium alginate is stronger, higher to the load factor of hydrophilic medicament, the pharmaceutical preparation made from sodium alginate micro ball can effectively improve medicine stability, control drug release, target administration, cover the bad smell of medicine etc.Therefore,, in the exploitation of drug system, the release vehicle of sodium alginate Chang Zuowei medicine is used.
Gelatin (Gelatin) be a kind of can biodegradable natural synthesized polymer material, be that the collagen protein partial hydrolysis in animal skins, bone, tendon and ligament tissue obtains, by 18 seed amino acids, formed, be the mixture of protein fragments.Gelatin, with its cheap, good biocompatibility and good physicochemical property, becomes rare microsphere and prepares material.
At present, the research about enrofloxacin microball preparation mainly contains: the slow-release micro-pill of being prepared by medicine and adjuvant, microcapsule formulation (patent No.: CN102648896A, CN101273980, CN102949365A, CN102302472A, CN1723902, CN101732315A); With medicine and A type gelatin, the gelatine microsphere (patent No.: CN101099739) that adopts emulsifying condensation method to prepare; Compound recipe micropill (the patent No.: CN102526054A) etc. of preparing with medicine and amoxicillin and adjuvant.
Summary of the invention
The object of the invention is to propose a kind of easy and simple to handle, condition is easily controlled, be easy to the preparation method of the enrofloxacin composite slow release microsphere of industrialized high drug load.
Technical solution of the present invention is: Span 80, sodium alginate, gelatin, enrofloxacin and deionized water are mixed, under 40 ℃ of temperature environments, stir after 1h, add calcium chloride water, continue constant temperature, stir 30min, then centrifugalize, get solid phase dry, obtain enrofloxacin composite slow release microsphere.
It is base material that gelatin-sodium alginate complex is take in the present invention, take calcium chloride as cross-linking agent, and broad spectrum antibiotic enrofloxacin is wrapped up, and is prepared into microcapsule medicine preparation.Meanwhile, regulate and control the particle size of complex microsphere by changing gelatin-sodium alginate system, make the particle diameter of microcapsule reach 800～1500nm, drug loading is greater than 35%.The product of making by the inventive method is soaked 2～3 hours in deionized water, and enrofloxacin reaches the maximum peak value that discharges.This product can change the distribution of medicine in human body and the dynamics of medicine, slow releasing function successful, the object that reach stabilised blood concentration, reduces clinical administration number of times and improve the palatability of medicine, avoids and makes up traditional enrofloxacin preparation and distribute in vivo extensively, spread fast shortcoming with not enough.Meanwhile, because the composite slow release microspherulite diameter of making is little, therefore also have certain targeting concurrently, reduced the drug exposure of normal structure, reduce toxic and side effects, improve curative effect of medication.
Described sodium alginate, gelatin, enrofloxacin, dehydrated alcohol, Span 80, calcium chloride and deionized water account for respectively the total amount that feeds intake 0.5～5.0%, 0.5～1.1%, 35.1～47.6%, 12.1～13.3%, 1.6～1.7%,, 8.2～10.0%, 29.5～33.8%.When the addition of above-mentioned each raw material is in the above scope limiting, the encapsulation ratio of prepared enrofloxacin composite slow release microsphere can be higher than 45%, and cost is lower, and technological requirement is simple.
Accompanying drawing explanation
The infrared spectrum evaluation figure that Fig. 1 is the enrofloxacin composite slow release microgranule that adopts the present invention and make.
Fig. 2 and 3 is for adopting the transmission electron microscope picture of the enrofloxacin composite slow release microgranule that the present invention makes.
The specific embodiment
One, prepare enrofloxacin composite slow release microsphere:
The logical method of preparation: get appropriate Span 80, sodium alginate, gelatin, enrofloxacin and deionized water and mix, stir after 1h under 40 ℃ of ambient temperatures, slowly add calcium chloride water, continue constant temperature, stir 30min.Then centrifugalize, gets solid phase and is dried, and obtains enrofloxacin composite slow release microgranule.
In kind, adopt following five kinds of different mix proportion schemes to go out to prepare respectively five parts of enrofloxacin composite slow release microgranules (adding up to 100%):
Scheme 1: sodium alginate 1.0%, gelatin 1.0%, enrofloxacin 41.5%, dehydrated alcohol 13.0%, class of department 80 1.6%, calcium chloride 9.0%, all the other are deionized water.
Scheme 2: sodium alginate 2.0%, gelatin 1.0%, enrofloxacin 42.0%, dehydrated alcohol 12.0%, class of department 80 1.6%, calcium chloride 9.5%, all the other are deionized water.
Scheme 3: sodium alginate 4.0%, gelatin 0.5%, enrofloxacin 40.0%, dehydrated alcohol 13.2%, class of department 80 1.7%, calcium chloride 10.0%, all the other are deionized water.
Scheme 4: sodium alginate 4.0%, gelatin 1.1%, enrofloxacin 40%, dehydrated alcohol 12.2%, class of department 80 1.6%, calcium chloride 8.5%, all the other are deionized water.
Scheme 5: sodium alginate 5.0%, gelatin 1.1%, enrofloxacin 38.0%, dehydrated alcohol 12.5%, class of department 80 1.7%, calcium chloride 8.5%, all the other are deionized water.
Scheme 6: sodium alginate 0.5%, gelatin 0.5%, enrofloxacin 47.6%, dehydrated alcohol 12.1%, class of department 80 1.6%, calcium chloride 8.2%, all the other are deionized water.
Scheme 7: sodium alginate 5.0%, gelatin 1.1%, enrofloxacin 35.1%, dehydrated alcohol 13.3%, class of department 80 1.7%, calcium chloride 10.0%, all the other are deionized water.
Two, product is identified with infrared spectrum:
Infrared spectrum is recorded by Fourier infrared spectrograph (NEXUS-670F-IR).As shown in Figure 1, wherein curve 1 is the infrared spectrogram of enrofloxacin composite slow release microgranule (scheme 5), the infrared spectrogram that curve 2 is enrofloxacin, the infrared spectrogram that curve 3 is sodium alginate.
As seen from Figure 1: enrofloxacin is at 1628cm
-1, 1496 cm
-1the characteristic absorption peak at place also embodies in the infared spectrum of composite slow release microsphere, prove that enrofloxacin is wrapped to have entered complex microsphere inside, contains enrofloxacin composition in sustained-release micro-spheres.
By Fig. 2,3 findings: prepared enrofloxacin composite slow release diameter of particle mainly concentrates on 800～1500nm left and right.
Working concentration is that 10% hydrochloric acid solution is invaded the prepared enrofloxacin composite slow release microgranule of bubble, then by the method for infiltration, shell material (sodium alginate-gelatin) is separated with core (enrofloxacin), after washing, dry step, ponderable quantity obtains the effective content of enrofloxacin in whole microsphere and reaches 45% left and right.
Claims (2)
1. the preparation method of an enrofloxacin composite slow release microsphere, it is characterized in that Span 80, sodium alginate, gelatin, enrofloxacin and deionized water to mix, under 40 ℃ of temperature environments, stir after 1h, add calcium chloride water, continue constant temperature, stir 30min, then centrifugalize, gets solid phase and is dried, and obtains enrofloxacin composite slow release microsphere.
2. preparation method according to claim 1, is characterized in that: described sodium alginate, gelatin, enrofloxacin, dehydrated alcohol, Span 80, calcium chloride and deionized water account for respectively the total amount that feeds intake 0.5～5.0%, 0.5～1.1%, 35.1～47.6%, 12.1～13.3%, 1.6～1.7%,, 8.2～10.0%, 29.5～33.8%.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113368036A (en) * | 2021-05-29 | 2021-09-10 | 塔里木大学 | Enrofloxacin composite nano gel for livestock and preparation method thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101099739A (en) * | 2006-07-03 | 2008-01-09 | 肖希龙 | Enrofloxacin gelatine microball and its preparation method |
| CN101732315A (en) * | 2009-12-30 | 2010-06-16 | 洛阳普莱柯生物工程有限公司 | Method for preparing enrofloxacin microcapsules |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101099739A (en) * | 2006-07-03 | 2008-01-09 | 肖希龙 | Enrofloxacin gelatine microball and its preparation method |
| CN101732315A (en) * | 2009-12-30 | 2010-06-16 | 洛阳普莱柯生物工程有限公司 | Method for preparing enrofloxacin microcapsules |
Non-Patent Citations (1)
| Title |
|---|
| 于莲等: "恩诺沙星微囊的制备", 《黑龙江医药科学》, vol. 31, no. 6, 31 December 2009 (2009-12-31), pages 30 - 31 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113368036A (en) * | 2021-05-29 | 2021-09-10 | 塔里木大学 | Enrofloxacin composite nano gel for livestock and preparation method thereof |
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