CN103610648B - Preparation method of enrofloxacin composite sustained-release microspheres - Google Patents
Preparation method of enrofloxacin composite sustained-release microspheres Download PDFInfo
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- CN103610648B CN103610648B CN201310646546.XA CN201310646546A CN103610648B CN 103610648 B CN103610648 B CN 103610648B CN 201310646546 A CN201310646546 A CN 201310646546A CN 103610648 B CN103610648 B CN 103610648B
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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 sectors.
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 formed in high molecular polymer carrier, can improve the stability of medicine, has slow release long-acting and targeting to medicine after microsphere made by medicine.The compliance that microball preparation not only can reduce administration number of times, simplify therapeutic scheme, improves body, can also reduce the fluctuation of blood drug level peak valley, reduce or avoid untoward reaction, improve the efficiency of Drug therapy, the exploitation of microball preparation has important clinical meaning.
Enrofloxacin (enrofloxacin, ENR) is the animal specific fluoroquinolones succeeded in developing by the Bayer AG of Germany for 1987, becomes first fluoroquinolones for animal clinical simultaneously.Enrofloxacin is since appearance, and clinical veterinarian both domestic and external is paid special attention to it, and it is mainly used in treating birds, house pet, the digestive system of pig and cattle, respiratory system and urinary system infection, to mycoplasma and staphylococcus also very effective.But enrofloxacin palatability is poor, oral administration, limit 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, but frequent medication causes very burden to Clinical practice, easily causes the stress of animal.Therefore, develop veterinary drug preparation novel form and just seem extremely important.
Sodium alginate (sodium alginate, SA), also known as Algin sodium, is the by-product extracted from the Thallus Laminariae (Thallus Eckloniae) or Alga Sgrgassi Enerves of Brown algae 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) linear polymer that (1 → 4) key is formed by connecting is pressed, its sodium salt be in alginic acid alkali and after product, there is the stability needed for pharmaceutical preparation adjuvant, dissolubility, viscosity and safety, it is the good natural polymeric material preparing microsphere, the microsphere prepared with it has nontoxic, can the advantage such as microbial degradation, function Ji Tezheng, bioadhesive, targeting, is widely used in the field such as medical science, chemistry.The hydrophilic of sodium alginate is comparatively strong, higher to the load factor of hydrophilic medicament, and the pharmaceutical preparation made from sodium alginate micro ball effectively can improve the stability of medicine, Drug controlled release, target administration, cover the bad smell etc. of medicine.Therefore, in the exploitation of drug system, the release vehicle of sodium alginate Chang Zuowei medicine uses.
Gelatin (Gelatin) is that one can biodegradable natural synthesized polymer material, and be obtained by the collagen protein partial hydrolysis in animal skins, bone, tendon and ligament tissue, being made up of 18 seed amino acids, is the mixture of protein fragments.The biocompatibility that gelatin is cheap with it, good and excellent physicochemical property, become rare microsphere and prepare material.
At present, about the research of enrofloxacin microball preparation mainly contains: the slow-release micro-pill prepared by medicine and adjuvant, microcapsule formulation (patent No.: CN102648896A, CN101273980, CN102949365A, CN102302472A, CN1723902, CN101732315A); With medicine and A type gelatin, adopt gelatine microsphere (patent No.: CN101099739) prepared by emulsifying condensation method; With compound recipe micropill (patent No.: CN102526054A) etc. prepared by 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 sustained-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, stir 1h under 40 DEG C of temperature environments after, add calcium chloride water, continue constant temperature, stir 30min, then centrifugalize, get solid phase drying, obtain enrofloxacin composite sustained-release microsphere.
The present invention for base material with gelatin-sodium alginate complex, take calcium chloride as cross-linking agent, wraps up broad spectrum antibiotic enrofloxacin, be prepared into microcapsule pharmaceutical 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 made by the inventive method is soaked 2 ~ 3 hours in deionized water, and enrofloxacin reaches maximum release peak value.This product can change the distribution of medicine in human body and the dynamics of medicine, slow releasing function successful, reach stabilised blood concentration, reduce clinical administration number of times and improve the object of palatability of medicine, avoid and make up traditional enrofloxacin preparation and distribute in vivo extensively, spread fast shortcoming and deficiency.Meanwhile, because the composite slow release microspherulite diameter made is little, therefore also have certain targeting concurrently, decrease 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 limited, the encapsulation ratio of prepared enrofloxacin composite sustained-release microsphere can higher than 45%, and cost is lower, and technological requirement is simple.
Accompanying drawing explanation
Fig. 1 is the infrared spectrum qualification figure of the enrofloxacin composite sustained-release microgranule adopting the present invention to make.
Fig. 2 and 3 is the transmission electron microscope picture of the enrofloxacin composite sustained-release microgranule adopting the present invention to make.
Detailed description of the invention
One, enrofloxacin composite sustained-release microsphere is prepared:
The logical method of preparation: get appropriate Span 80, sodium alginate, gelatin, enrofloxacin and deionized water mixing, after 40 DEG C of stirred at ambient temperature 1h, slowly add calcium chloride water, continue constant temperature, stir 30min.Then centrifugalize, gets solid phase and carries out drying, obtain enrofloxacin composite sustained-release microgranule.
In kind, following five kinds of different mix proportion schemes are adopted to go out to prepare respectively five parts of enrofloxacin composite sustained-release microgranules (adding up to 100%):
Scheme 1: sodium alginate 1.0%, gelatin 1.0%, enrofloxacin 41.5%, dehydrated alcohol 13.0%, class 80 1.6% of department, 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 80 1.6% of department, 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 80 1.7% of department, 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 80 1.6% of department, 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 80 1.7% of department, 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 80 1.6% of department, 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 80 1.7% of department, calcium chloride 10.0%, all the other are deionized water.
Two, product infrared spectrum is identified:
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 sustained-release microgranule (scheme 5), and curve 2 is the infrared spectrogram of enrofloxacin, and curve 3 is the infrared spectrogram of 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, proves that enrofloxacin is wrapped and enters complex microsphere inside, containing enrofloxacin composition in sustained-release micro-spheres.
By Fig. 2,3 findings: prepared enrofloxacin composite sustained-release diameter of particle mainly concentrates on about 800 ~ 1500nm.
The hydrochloric acid solution that working concentration is 10% invades the enrofloxacin composite sustained-release microgranule prepared by 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 about 45%.
Claims (1)
1. the preparation method of an enrofloxacin composite sustained-release microsphere, it is characterized in that the raw materials of described enrofloxacin composite sustained-release microsphere consists of sodium alginate, gelatin, enrofloxacin, dehydrated alcohol, Span 80, calcium chloride and deionized water, sodium alginate, gelatin, enrofloxacin, dehydrated alcohol, Span 80, calcium chloride and deionized water account for 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% of the total amount that feeds intake respectively; Preparation method is: Span 80, sodium alginate, gelatin, enrofloxacin and deionized water are mixed, after stirring 1h, add calcium chloride water under 40 DEG C of temperature environments, continue constant temperature, stir 30min, then centrifugalize, gets solid phase drying, obtains enrofloxacin composite sustained-release microsphere.
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| CN101099739B (en) * | 2006-07-03 | 2011-03-30 | 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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Granted publication date: 20150408 Termination date: 20171206 |