CN1351868A - Implanted slow-releasing antiseptic preparation and its preparing method - Google Patents
Implanted slow-releasing antiseptic preparation and its preparing method Download PDFInfo
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- CN1351868A CN1351868A CN 01132215 CN01132215A CN1351868A CN 1351868 A CN1351868 A CN 1351868A CN 01132215 CN01132215 CN 01132215 CN 01132215 A CN01132215 A CN 01132215A CN 1351868 A CN1351868 A CN 1351868A
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Abstract
The present invention relates to the field of medical technology. By using carboxymerhyl chitosan as slow-releasing assistant and antiseptic as carrier and through emulsification and crosslinking process, a kind of degradable slow-releasing microball is prepared capable of being implanted in operation incision to prevnet post-operational local infection. The slow-releasing preparation of the present invention has the features of degradability and small volume, and avoids the shield to biological repair in oganism.
Description
Technical field
The present invention relates to medical technical field, is a kind of degradable implanted slow-releasing about antimicrobial drug and preparation method thereof.
Background technology
Usually all to use the antimicrobial drug of certain hour to prevent the operation etc. of the big operation of infection, the especially wound of patient's operative incision, implants implant surgery, open wound behind the surgical operation.Traditional route of administration of antimicrobial drug is vein, oral, intramuscular injection etc.These systemic administration modes have tangible deficiency: 1. the toxicity, side effect that has whole body; 2. local drug concentration deficiency; 3. use inconvenience etc.Thereby the concern that dosage form is subjected to the clinician is day by day implanted in the part of antimicrobial drug.At present, the implanted slow-releasing of external existing different antimicrobial drugs is applied to clinical, as antimicrobial drug pelletron (Majid SA, etal. Gentamicin PMMA beads in the treatment of chronic osteomeylitis.Acta Orthop Scand 1985), antimicrobial drug gelfoam (Vogel P, et al.Prospective randomised study of gentacoll plus metronidazole versusdalacin in the treatmet of infected pilonidal sinus.Interal Report 1992), antimicrobial drug bone cement (Hoff SF, etal.The dept administration of penicillin G and gentamicin in acrylic bone cement.J Bone Joint Surg1981).Though these dosage forms have solved many shortcomings of whole body application antimicrobial drug, because of slow-release auxiliary material can not be degraded, so the antimicrobial drug pelletron must take out by second operation; It is damaged that gelfoam and bone cement mainly are used to fill osseous tissue, uses limitation, and lamellar or block slow-released carrier retain the reparation of often having blocked between tissue for a long time.Therefore, the implanted slow-releasing of these antimicrobial drugs can not be used for operative incision, particularly the soft tissue otch.
Summary of the invention
The present invention adopts the degradable biomaterial carboxymethyl chitosan as slow-release auxiliary material, makes the antimicrobial drug sustained-release micro-spheres, when operation finishes it is implanted otch and comes the prevention of postoperative infection of incisional wound.Because slow-release auxiliary material can be degraded, so do not need second operation to take out; Again because of the slow release formulation volume is little, so the problem that does not also exist tissue repair to block after implanting.The present invention provides a kind of miniature degradable implantation slow release antimicrobial drug dosage form for clinical treatment.
Preparation method of the present invention is as follows:
1. prepare carboxymethyl chitosan and antimicrobial drug mixing salt solution (abbreviation solution A):
At first, use 1% (W/V) sodium chloride double steaming solution, preparation 2% (W/V) carboxymethyl chitosan sugar juice, the speed with 100 rev/mins in beaker stirred 5 hours, made solution be homogeneous state.Add a certain amount of corresponding antimicrobial drug then and make solution A, 100 rev/mins were stirred 2 hours, and made solution A be homogeneous state.
2. preparation emulsification system:
Tween 80 (Tween80) is joined liquid paraffin in the reaction bulb, is made into Tween80: liquid paraffin=3: 40 (V: liquid paraffin suspension V), with 500 rev/mins speed stir after 5 minutes the suspension of mix homogeneously.Under the stirring of 500 rev/mins of speed, with solution A: (V: ratio V) is poured certain quantity solution A into above-mentioned suspension to liquid paraffin=1: 4, and the speed with 800 rev/mins under 30 ℃ stirred 30 minutes, promptly got the emulsification system of homogeneous state.
3. solidify:
Emulsification system temperature in the reaction bulb is reduced to 5 ℃～8 ℃, content according to carboxymethyl chitosan in the emulsification system, according to glutaraldehyde: carboxymethyl chitosan=1: 1 (W: ratio W), under the stirring of 300 rev/mins of speed, glutaraldehyde solution is added dropwise to emulsification system, and the speed that continues with 300 rev/mins stirred 3 hours.Then this system was left standstill 30 minutes, lurid microsphere precipitation at the bottom of reaction bulb, can occur.This process is curing.
4. eluting:
The microsphere precipitation is placed core filter vacuum filtering liquid.Use an amount of petroleum ether then 3 times, an amount of dehydrated alcohol of reuse dewaters three times, gets lurid microsphere.Be placed in the vacuum desiccator dry 12 hours, and promptly got antimicrobial drug sustained-release micro-spheres of the present invention.
Clinical use:
Before closing operative incision, an amount of antimicrobial drug microsphere is sprinkled into operative incision, especially around the implants, in the residual cavity, potentially contaminated is than large part, for example around intestinal, the vermiform appendix otch etc., and it is evenly distributed, and closes operative incision then.Make that like this microsphere discharges antimicrobial drug in local slow, keep high local concentrations, heal until operative incision.Through the safety, effective that confirms on probation.
The invention has the advantages that:
With antimicrobial drug microsphere implant surgery otch, make partial drug level maintain minimum inhibitory concentration (MIC
90) above 5～7 days, obviously reduced the toxic and side effects that the antimicrobial drug general is used.As slow-release auxiliary material, make patient avoid the misery of second operation with absorbable biological compatible polymer material carboxymethyl chitosan.Because it is little that microsphere has a volume, lowered implant blocking the body biological restoration greatly.This dosage form is disposable topical application antibacterials, has both reduced misery to patient, also brings convenience to clinical medical and nursing, and reduces the use amount of operation back antimicrobial drug greatly.
The specific embodiment
Embodiment one: preparation ciprofloxacin sustained-release micro-spheres
1. 1 gram sodium chloride is dissolved in 100 milliliters of distilled waters, adds 2 gram carboxymethyl chitosans, the speed with 100 rev/mins in beaker stirred 5 hours.Add 2 gram ciprofloxacins again, stirred 2 hours, promptly get solution A with 100 rev/mins speed
2. 30 milliliters of Tween80 are joined 400 milliliters of liquid paraffin in the reaction bulb, stirred 5 minutes, promptly get suspension with 500 rev/mins speed.Under 500 rev/mins of stirrings, slowly pour 100 ml soln A into above-mentioned suspension, the speed with 800 rev/mins under 30 ℃ stirred 30 minutes.Promptly get emulsification system.
3. the emulsification system temperature in the reaction bulb is reduced to 5 ℃～8 ℃, the solution that will contain 2 gram glutaraldehydes under 300 rev/mins speed stir splashes into emulsification system, and the speed that continues with 300 rev/mins stirred 3 hours.Then, left standstill 30 minutes, lurid microsphere precipitation at the bottom of reaction bulb, can occur.
4. the upper strata liquid in the reaction bulb is poured out, the microsphere precipitation is taken out be placed on vacuum filtering liquid in the core filter.Use 50 milliliters of petroleum ether 3 times then respectively, with 100 milliliters of dehydrated alcohol dehydrations 3 times, get light yellow microsphere respectively.Be placed in the vacuum desiccator dry 12 hours, and promptly got spacetabs type ciprofloxacin microsphere.
Embodiment two: preparation gentamycin sustained-release micro-spheres
1. 2 gram sodium chloride are dissolved in 200 milliliters of distilled waters, add 4 gram carboxymethyl chitosans, the speed with 100 rev/mins in beaker stirred 5 hours.Add 10 gram gentamycins again, stirred 2 hours, promptly get solution A with 100 rev/mins speed
2. 60 milliliters of Tween80 are joined 800 milliliters of liquid paraffin in the reaction bulb, stirred 5 minutes, promptly get suspension with 500 rev/mins speed.Under 500 rev/mins of stirrings, slowly pour 200 ml soln A into above-mentioned suspension, the speed with 800 rev/mins under 30 ℃ stirred 30 minutes.Promptly get emulsification system.
3. the emulsification system temperature in the reaction bulb is reduced to 5 ℃～8 ℃, the solution that will contain 4 gram dialdehyde under 300 rev/mins speed stir splashes into emulsification system, and the speed that continues with 300 rev/mins stirred 3 hours.Then, left standstill 30 minutes, lurid microsphere precipitation at the bottom of reaction bulb, can occur.
4. the upper strata liquid in the reaction bulb is poured out, the microsphere precipitation is taken out be placed on vacuum filtering liquid in the core filter.Use 100 milliliters of petroleum ether 3 times then respectively,, get light yellow microsphere with 200 milliliters of dehydrated alcohol dehydrations 3 times.Be placed in the vacuum desiccator dry 12 hours, and promptly got spacetabs type gentamycin microsphere.
Embodiment three: preparation ofloxacin slow-release microsphere
1. 10 gram sodium chloride are dissolved in 1000 milliliters of distilled waters, add 20 gram carboxymethyl chitosans, the speed with 100 rev/mins in beaker stirred 5 hours.Add 20 gram ofloxacins again, stirred 2 hours, promptly get solution A with 100 rev/mins speed
2. 300 milliliters of Tween80 are joined in 4000 milliliters of the liquid paraffin in the reaction bulb, stirred 5 minutes, promptly get suspension with 500 rev/mins speed.Under 500 rev/mins of stirrings, slowly pour 1000 ml soln A into above-mentioned suspension, the speed with 800 rev/mins under 30 ℃ stirred 30 minutes.Promptly get emulsification system.
3. the emulsification system temperature in the reaction bulb is reduced to 5 ℃～8 ℃, the drips of solution that will contain 20 gram glutaraldehydes under 300 rev/mins speed stir adds emulsification system, and the speed that continues with 300 rev/mins stirred 3 hours.Then, left standstill 30 minutes, lurid microsphere precipitation at the bottom of reaction bulb, can occur.
4. the upper strata liquid in the reaction bulb is poured out, the microsphere precipitation is taken out be placed on vacuum filtering liquid in the core filter.Use 500 milliliters of petroleum ether 3 times then respectively,, get light yellow microsphere with 1000 milliliters of dehydrated alcohol dehydrations 3 times.Be placed in the vacuum desiccator dry 12 hours, and promptly got spacetabs type ofloxacin microsphere.
Claims (3)
1. an implanted slow-releasing antiseptic is made up of antimicrobial drug and slow-release auxiliary material, it is characterized in that said slow-release auxiliary material is a carboxymethyl chitosan.
2. by the described implanted slow-releasing antiseptic of claim 1, it is characterized in that said antimicrobial drug is a ciprofloxacin.
3. the preparation method of the described implanted slow-releasing antiseptic of claim 1 comprises the steps:
＜1〉preparation contains the solution A of carboxymethyl chitosan and antimicrobial drug:
The homogeneous solution A that contains 2% (W/V) carboxymethyl chitosan and corresponding content antibacterial with 1% sodium chloride double steaming solution preparation;
＜2〉preparation emulsification system:
Press Tween80: liquid paraffin=3: 40 (V: proportional arrangement liquid paraffin suspension V), again in solution A: liquid paraffin suspension=ratio of 1: 4 prepares the emulsification system of homogenizing;
＜3〉solidify:
Under 5～8 ℃, in glutaraldehyde: carboxymethyl chitosan=1: 1 (W: ratio W) splashes into emulsification system with glutaraldehyde, stirs, leave standstill, lurid microsphere precipitation;
＜4〉eluting:
The microsphere precipitation is placed core filter vacuum filtration, use petroleum ether,, place vacuum desiccator dry with the dehydrated alcohol dehydration.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 01132215 CN1130197C (en) | 2001-11-15 | 2001-11-15 | Implanted slow-releasing antiseptic preparation and its preparing method |
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| Application Number | Priority Date | Filing Date | Title |
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| CN 01132215 CN1130197C (en) | 2001-11-15 | 2001-11-15 | Implanted slow-releasing antiseptic preparation and its preparing method |
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| Publication Number | Publication Date |
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| CN1351868A true CN1351868A (en) | 2002-06-05 |
| CN1130197C CN1130197C (en) | 2003-12-10 |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100393782C (en) * | 2006-03-29 | 2008-06-11 | 武汉大学 | Carboxymethyl chitosan nanoparticles as medicine carrier and method for preparing same |
| CN101543477B (en) * | 2009-05-06 | 2011-01-19 | 河北科技大学 | Sustained-release microsphere of chitosan-coated 3,5-dihydroxy-4-isopropyl toluylene and preparation method thereof |
| CN102210655A (en) * | 2011-04-11 | 2011-10-12 | 山东大学 | Cefpiramide sodium micro-spheres and preparing method thereof |
| CN102274192A (en) * | 2011-08-09 | 2011-12-14 | 山西医科大学第一医院 | Carboxymethyl chitosan medicament-carrying microspheres and preparation method thereof |
-
2001
- 2001-11-15 CN CN 01132215 patent/CN1130197C/en not_active Expired - Fee Related
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100393782C (en) * | 2006-03-29 | 2008-06-11 | 武汉大学 | Carboxymethyl chitosan nanoparticles as medicine carrier and method for preparing same |
| CN101543477B (en) * | 2009-05-06 | 2011-01-19 | 河北科技大学 | Sustained-release microsphere of chitosan-coated 3,5-dihydroxy-4-isopropyl toluylene and preparation method thereof |
| CN102210655A (en) * | 2011-04-11 | 2011-10-12 | 山东大学 | Cefpiramide sodium micro-spheres and preparing method thereof |
| CN102210655B (en) * | 2011-04-11 | 2012-10-03 | 山东大学 | Cefpiramide sodium micro-spheres and preparing method thereof |
| CN102274192A (en) * | 2011-08-09 | 2011-12-14 | 山西医科大学第一医院 | Carboxymethyl chitosan medicament-carrying microspheres and preparation method thereof |
| CN102274192B (en) * | 2011-08-09 | 2013-08-28 | 山西医科大学第一医院 | Carboxymethyl chitosan medicament-carrying microspheres and preparation method thereof |
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| Publication number | Publication date |
|---|---|
| CN1130197C (en) | 2003-12-10 |
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