CN104998293A - Styptic powder - Google Patents
Styptic powder Download PDFInfo
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- CN104998293A CN104998293A CN201510501974.2A CN201510501974A CN104998293A CN 104998293 A CN104998293 A CN 104998293A CN 201510501974 A CN201510501974 A CN 201510501974A CN 104998293 A CN104998293 A CN 104998293A
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- polyglutamic acid
- acid calcium
- crosslinked
- microsphere
- oil
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Abstract
The invention aims to provide a crosslinking poly glutamic acid calcium microsphere. The adopted base material poly glutamic acid is a polyamino acid material obtained through microorganism fermentation synthesis, controllable in structure, biodegradable, excellent in biocompatibility, simple in product forming technology and easy to control in quality; in addition, the hemostasis process of the crosslinking poly glutamic acid calcium microsphere is not affected by normal clotting mechanism and can still play the stypticity for patients using an anticoagulant and with low blood platelets and complete blood cells; release of Ca <2+> in the material can accelerate activation of intrinsic coagulation factors to realize the auxiliary stypticity; moreover, poly glutamic acid has better biological adhesiveness, facilitates control of continuous errhysis of tissues, and is higher in hemostasis capacity.
Description
Technical field
The invention belongs to biology medical material technical field, be specifically related to a kind of styptic powder.
Background technology
In a lot of situation, injured or postoperative uncontrollable hemorrhage be murderous main cause.And Absorbable hemostatic material is in various surgical operation, directly can reduces body and lose blood thus effectively maintain blood volume, avoid whole body blood-clotting agent to use the untoward reaction brought, reduce blood transfusion and operating time; Reduce and postoperatively to ooze out, reduce complication, be therefore subject to the great attention of various countries' medical circle and industrial circle.Common hemostatic material has multiple dosage form, and comprise sponge, thin film, micropowder, gel etc., the suitable application area of different dosage form hemostatic material is also not quite similar.
Absorbable hemostatic powder is the novel hemostatic material of one that development in recent years is got up, and is usually processed obtained by plant amylum modification, in microporous molecular sieve structure.Be applied to bleeding part, absorbable hemostatic powder can play molecular sieve effect, moisture in rapid absorbing blood, platelet, erythrocyte are condensed, thus reach hemostasis object, be suitable for all section office of hospital, be especially useful in the operation that cerebral surgery operation, neurosurgery etc. cannot adopt ligation, electric coagulation hemostasis.Although these absorbable hemostatic powder obtain from plant extract natural polysaccharide modification processing, avoid animal sources, safety has had good guarantee, owing to being crude polysaccharide preparation, production still exists the problems such as lot stability difference, Quality Control are difficult; In addition, its anthemorrhagic performance need further raising.Therefore, exploitation has good biological safety and quick-acting haemostatic powder performance, and be easy to process, the absorbable hemostatic powder of sterilizing and quality control has significant application value.
Summary of the invention
Primary and foremost purpose of the present invention is that the shortcoming overcoming prior art is with not enough, provides a kind of emulsification and cross linked preparation method of absorbable hemostatic powder.
First the present invention provides a kind of crosslinked polyglutamic acid calcium microsphere, and its preparation method comprises the steps:
(1) polyglutamic acid calcium and cross-linking agent be dissolved in aqueous phase obtain aqueous phase solution,
(2) emulsifying agent is added mix homogeneously in oil-phase medium and obtains oil-phase solution,
(3) aqueous phase solution and oil-phase solution are mixed to get emulsification system;
(4) react adding activator in emulsification system, the product obtained completes preparation after break milk separation, washing, drying, sterilizing.
Described polyglutamic acid calcium and the mass ratio of water are preferably 0.002 ~ 0.1;
The preferred adipic dihydrazide of described cross-linking agent;
Described polyglutamic acid calcium and the mass ratio of cross-linking agent are preferably 0.1 ~ 10;
One or more of described emulsifying agent preferred Span, Tween are composite; Consumption is preferably 0.2% ~ 2% of the volume of oil phase;
Described oil phase preferred liquid paraffin, toluene, normal heptane, cyclohexane extraction;
The volume ratio of described aqueous phase/oil phase is preferably 1:2 ~ 1:5;
Described activator preferred N, N cyclohexylcarbodiimide hydrochlorate (EDAC);
Described sterilization method optimization ethylene oxide or irradiation sterilization.
Above-mentioned crosslinked polyglutamic acid calcium microsphere is for the preparation of agent for stanching;
Described agent for stanching, is preferably powder.
The base material polyglutamic acid that the present invention adopts is a kind of polyamino acid material obtained by fermentable synthesis, and structure-controllable, biodegradable, biocompatibility are good, and product forming technique is simple, and quality is easy to control; Secondly, the hemostasis of product can not affect by normal coagulation mechanism, to using the low patient of the patient of anticoagulant, platelet and complete blood cell still can play anastalsis, and Ca in material
2+the release of ion also can accelerate the activation of the intrinsic coagulation factor, reaches auxiliary anastalsis; And polyglutamic acid has good bioadhesive, be conducive to the persistence oozing of blood controlling tissue, hemostatic capability is stronger.
Accompanying drawing explanation
Fig. 1 is scanning electron microscope (SEM) photo that adipic dihydrazide is cross-linked polyglutamic acid calcium styptic powder.
Detailed description of the invention
Styptic powder prepared by the present invention has strongly hydrophilic micro-sphere structure, therefore after contacting with hemorrhage wound surface, absorbing fluid is swelling fast for energy, form high viscosity hydrocolloid, rapid and wound surface closely attaches, form effective physics shutoff, mechanicalness sealing blood vessels cut and organize wound surface, reach the object of quick-acting haemostatic powder; Meanwhile, visible component (as platelet, erythrocyte, thrombin and the fibrin etc.) enrichment of wound surface blood, and Ca in material
2+the release of ion all can accelerate the activation of the intrinsic coagulation factor, reaches auxiliary anastalsis; Material self degradation in vivo becomes aminoacid to be absorbed by the body.
The molecular chemical formula of the polyglutamic acid calcium that the present invention uses is (C
10h
12o
6n
2ca)
m(C
5h
7o
3n)
n, wherein n:m=0 ~ 18; As n:m=0, the mol ratio 0.5 of Ca2+ and carboxyl; During n:m=18, the mol ratio 0.05 of Ca2+ and carboxyl.
Below in conjunction with embodiment and accompanying drawing, the present invention is described in further detail.
Embodiment 1
Preparation is aqueous phase containing the aqueous solution 100mL of 0.2g polyglutamic acid calcium and 0.2g adipic dihydrazide; Take normal heptane as oil-phase medium, after adding emulsifying agent Tween80 mix homogeneously by emulsifying agent/oil phase=1/100 (w/w), then press water/oil ratio=1:4 (v/v) by even for the emulsifying of water oil two-phase mixtures.Add the hydrochloric acid 1mL of aqueous solution 4mL and 0.1mol/L containing 0.24gEDAC successively, stirring reaction 6h, add 400mL water, centrifugalize, isopropyl alcohol fully washs, vacuum drying, obtain adipic dihydrazide and be cross-linked polyglutamic acid calcium styptic powder, its stereoscan photograph as shown in Figure 1.
Embodiment 2
Preparation is aqueous phase containing the aqueous solution 100mL of 0.4g polyglutamic acid calcium and 0.2g adipic dihydrazide; Take cyclohexane extraction as oil-phase medium, after adding emulsifying agent Tween80 mix homogeneously by emulsifying agent/oil phase=1/100 (w/w), then press water/oil ratio=1:4 (v/v) by even for the emulsifying of water oil two-phase mixtures.Add the hydrochloric acid 0.1mL of aqueous solution 4mL and 0.1mol/L containing 0.24gEDAC successively, stirring reaction 24h, add 200mL isopropyl alcohol, centrifugalize, isopropyl alcohol fully washs, vacuum drying, obtains adipic dihydrazide and is cross-linked polyglutamic acid calcium styptic powder.
Embodiment 3
The anthemorrhagic performance evaluation test of crosslinked polyglutamic acid calcio styptic powder.Set up rat femoral Hemorrhage Model, evaluation comparison is cross-linked the haemostatic effect of polyglutamic acid calcio styptic powder 1 (prepared by embodiment 1), crosslinked polyglutamic acid calcio styptic powder 2 (prepared by embodiment 2) and YUNNAN BAIYAO (matched group) respectively.Select SD rat (body weight is 200 scholar 20g) 48, male female half and half, be divided into 4 groups at random, often organize 12, male and female half and half.4 groups are respectively: crosslinked polyglutamic acid calcio styptic powder 1 (prepared by embodiment 1), crosslinked polyglutamic acid calcio styptic powder 2 (prepared by embodiment 2), YUNNAN BAIYAO (matched group) and gauze (blank group).It is 0.1g that experimental group and matched group styptic powder once add dosage.All animals all adopts 3% pentobarbital sodium intraperitoneal injection of anesthesia, and dosage is 30mg/Kg.
After rat holonarcosis, be fixed on plank by its backstroke, extremity and head fix.In tested region depilation preserved skin, sterilization, successively cut skin, be separated femoral artery, use No. 12 syringe needles (external diameter 1.2mm) to puncture femoral artery, after blood is gushed out, apply styptic powder in bleeding part immediately, start timing simultaneously, observe haemostatic effect.Increase styptic powder if desired, until stop blooding completely, record bleeding stopping period, the results are shown in table 1.
Table 1: rat femoral anthemorrhagic performance evaluation test result
| Sequence number | Embodiment 1 | Embodiment 2 | Control sample | Blank group |
| Bleeding stopping period (s) | 41±13 | 48±17 | 98±4 | >300 |
Result shows: the bleeding stopping period of crosslinked polyglutamic acid calcio styptic powder is all significantly less than matched group, has better haemostatic effect.
Above-described embodiment is the present invention's preferably embodiment; but embodiments of the present invention are not restricted to the described embodiments; change, the modification done under other any does not deviate from spirit of the present invention and principle, substitute, combine, simplify; all should be the substitute mode of equivalence, be included within protection scope of the present invention.
Claims (10)
1. a crosslinked polyglutamic acid calcium microsphere, its preparation method is as follows:
Polyglutamic acid calcium and cross-linking agent are dissolved in aqueous phase and obtain aqueous phase solution,
Emulsifying agent is added mix homogeneously in oil-phase medium and obtains oil-phase solution,
Aqueous phase solution and oil-phase solution are mixed to get emulsification system;
React adding activator in emulsification system, the product obtained completes preparation after break milk separation, washing, drying, sterilizing.
2. crosslinked polyglutamic acid calcium microsphere as claimed in claim 1, it is characterized in that, described polyglutamic acid calcium and the mass ratio of water are 0.002 ~ 0.1.
3. crosslinked polyglutamic acid calcium microsphere as claimed in claim 1, it is characterized in that, described polyglutamic acid calcium and the quality of cross-linking agent are 0.1 ~ 10.
4. the crosslinked polyglutamic acid calcium microsphere as described in claim 1 or 3, it is characterized in that, described cross-linking agent is adipic dihydrazide.
5. polyglutamic acid calcium microsphere as claimed in claim 1 crosslinked, is characterized in that, described emulsifying agent is one or more of Span, Tween, and consumption is preferably 0.2% ~ 2% of the volume of oil phase.
6. crosslinked polyglutamic acid calcium microsphere as claimed in claim 1, it is characterized in that, the volume ratio of described aqueous phase/oil phase is 1:2 ~ 1:5.
7. the crosslinked polyglutamic acid calcium microsphere as described in claim 1 or 6, it is characterized in that, described oil phase is liquid paraffin, toluene, normal heptane or cyclohexane extraction.
8. crosslinked polyglutamic acid calcium microsphere as claimed in claim 1, it is characterized in that, described activator is N, N cyclohexylcarbodiimide hydrochlorate (EDAC).
9. crosslinked polyglutamic acid calcium microsphere according to claim 1 is for the preparation of agent for stanching.
10. a styptic powder, is characterized in that, described styptic powder includes crosslinked polyglutamic acid calcium microsphere according to claim 1.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510501974.2A CN104998293A (en) | 2015-08-17 | 2015-08-17 | Styptic powder |
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|---|---|---|---|
| CN201510501974.2A CN104998293A (en) | 2015-08-17 | 2015-08-17 | Styptic powder |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107376010A (en) * | 2017-07-14 | 2017-11-24 | 山东省药学科学院 | A kind of injection crosslinking polyglutamic acid gel micro-ball suspension and preparation method thereof |
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2015
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Patent Citations (5)
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| US20090062849A1 (en) * | 2007-09-04 | 2009-03-05 | Matthew Dowling | Advanced functional biocompatible polymeric matrix used as a hemostatic agent and system for damaged tissues and cells |
| CN101485899A (en) * | 2008-01-16 | 2009-07-22 | 广州倍绣生物技术有限公司 | Method for preparing fibrin ferment-chitosan self-assembly nano particle and use thereof |
| CN103007342A (en) * | 2012-12-12 | 2013-04-03 | 广东省微生物研究所 | Biodegradable and medical tricalcium phosphate/gamma-polyglutamic acid composite and preparation method thereof |
| CN103467772A (en) * | 2013-09-12 | 2013-12-25 | 中国人民武装警察部队后勤学院 | Chitosan/gamma-polyglutamic acid polyelectrolyte sponge as well as preparation method and application thereof |
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| CN107376010A (en) * | 2017-07-14 | 2017-11-24 | 山东省药学科学院 | A kind of injection crosslinking polyglutamic acid gel micro-ball suspension and preparation method thereof |
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Application publication date: 20151028 |