CN102772820A - Alkyl modified chitosan/mesoporous silicon dioxide composite quick hemostatic powder and preparation method thereof - Google Patents
Alkyl modified chitosan/mesoporous silicon dioxide composite quick hemostatic powder and preparation method thereof Download PDFInfo
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Abstract
The invention discloses an alkyl modified chitosan/mesoporous silicon dioxide composite quick hemostatic powder and a preparation method thereof. The method comprises the following steps: 1) preparation of alkyl modified chitosan; 2) preparation of mesoporous silicon dioxide particles; and 3) preparation of composite quick hemostatic powder: dissolving the alkyl modified chitosan in an acetic acid water solution, adding polyethyleneglycol 20000 to be dissolved, adding the mesoporous silicon dioxide particles prepared in the step 2), stirring at room temperature, freeze-drying the precipitate, suspending the precipitate in dimethylsulfoxide, regulating the pH value, centrifuging, washing with deionized water, and freeze-drying to obtain the alkyl modified chitosan/mesoporous silicon dioxide composite quick hemostatic powder. The hemostatic powder disclosed by the invention can quickly stop bleeding, and is suitable for pre-hospital emergency treatment of severe bleeding wounded persons. The material has the advantages of high hemostatic speed, excellent hemostatic effect, favorable biocompatibility and histocompatibility, and no side effect.
Description
Technical field
The present invention relates to a kind of hemostatic material and method for preparing, especially relate to compound rapid hemostasis powder of a kind of alkyl-modified chitosan/mesoporous silicon oxide and preparation method thereof.
Background technology
Traumatic hemorrhage is the battlefield and one of the most common traumatic condition of all kinds of scenes of the accident at ordinary times, hemorrhage out of control be the first cause that causes the on-the-spot dead and later stage severe complication of the wounded (like amputation etc.).Therefore, at the scene with institute before to the wounded hemorrhage control effectively significant.Tourniquet be can control over bleeding buoyant apparatus, but a lot of positions of human body such as breast, abdomen, head, neck etc. are located to use tourniquet.Traditional hemostatic material (like cotton yarn, binder) is very undesirable for the haemostatic effect of on-the-spot common wounds such as irregularly shaped, dark, narrow, arteriorrhexis.Therefore, exploitation becomes the important topic in the material science to on-the-spot and pre hospital care with quick, safe and effective novel hemostatic material.
The research of quick-acting haemostatic powder material at present mainly concentrates on high molecular polysaccharide and mineral-type hemostatic material.
Typical case's representative of high molecular polysaccharide hemostatic material is a chitosan.After nineteen eighty-three Malette WG etc. found the hemostatic function of chitosan first, the numerous and confused trial of Chinese scholars developed bleeding-stopping dressing with chitosan.The hemostatic mechanism of chitosan maybe for: 1. with tissue tight adhesion, wound closure; 2. reduce local nitric oxide concentration and cause vasoconstriction, reduce blood flow, reduce intravascular pressure; 3. promote erythrocyte, thrombin, platelet etc. to assemble etc. in that wound is local.The HemCon chitosan dressing obtained FDA Food and Drug Administration (FDA) approval in 2002, played a significant role and well-known in U.S. army Afghanistan and Iraq battlefield subsequently, and HemCon is the thin slice after the chitosan-acetic acid solution lyophilizing.Occurred the CELOX styptic powder in 2007, its functional component is granular chitosan.Also has a kind of starch-polysaccharides hemostatic material TraumaDEX in addition; It is the spheroidal particle of particle diameter 30～100 μ m, porous surface; Can from blood, absorb moisture and low-molecular-weight composition, and then thrombin and platelet are concentrated and reach the purpose that promotes that blood clot forms.Srinivasa R.Raghavan seminar finds in the segmental research of grafting hydrophobic alkyl on the chitosan main chain recently; The hydrophobically modified chitosan has gelling to people's whole blood of heparinization; The hydrophobically modified chitosan of 0.25wt% can make whole blood gelation immediately; Its principle is that the alkyl hydrophobic segment of modification of chitosan can embed platelet, erythrocyte and leukocytic cell membrane, forms the hemocyte network gel.Yet research shows effect and the instability of high molecular polysaccharide hemostatic material for the severe haemorrhage wound surface.In the arterial hemorrhage animal model test of Kheirabadi etc., though chitosan dressing has been realized the hemostasis of 70% animal at first and prolonged the animals survived time, all hemostasis failures after 120 minutes of all animals.And in more serious arterial hemorrhage model test such as Acheson, chitosan dressing reduce hemorrhage with prolong almost not effect on the time-to-live.Alam HB etc. also show in the result of the hemorrhage model of pig thigh arteriovenous crosscut, compare with traditional hemostatic material, and TraumaDEX is reducing blood loss, reduces the mortality rate aspect and does not have clear superiority.
The research of mineral-type hemostatic material begins from zeolite.The eighties in 20th century, zeolite is had outstanding anastalsis by stumbling on.In May, 2002, QuikClot Zeolite hemostatic powder is used for the first aid of severe haemorrhage wound through the approval of FDA.Its mechanism of action is: the moisture in the absorbing blood concentrates thrombin and platelet and reaches the effect that promotes blood coagulation.The thermocoagulation of organizing that also has the exothermic reaction after research prompting zeolite is used to cause also has certain facilitation to blood coagulation.The WoundStat hemostatic material that is made up of the Montmorillonitum granule appearred in 2007.Discoveries such as Ward are compared with standard gauze, HemCon and QuikClot, and WoundStat can obviously improve survival rate, reduces amount of bleeding, but its haemostatic effect descends under the rainwater environment.Research on 6mm arteriotomy animal model such as Kheirabadi shows, compares with Celox, HemCon etc., and the anthemorrhagic performance of WoundStat is best.The Combat Gauze that put out a new product again in 2007 of the Z-Medica company that releases QuikClot, this is a kind of kaolinic submissive cloth that mixed.Combat Gauze is recommended at present substitutes HemCon as the fatal hemorrhage first-aid product in battlefield.Yet often there is certain defective in the biological safety of mineral-type hemostatic material, and the exothermic reaction meeting the when shortcoming of QuikClot is to use produces and surpasses 100 ℃ of high temperature, causes the wound tissue injury.Wright etc. do the time spent at the research Zeolite hemostatic and find that zeolite is retained in the tissue and inflammatory reaction can occur, have in addition abscess appears.Gerlach etc. to WoundStat long-time safety of using study, the result shows: though WoundStat can effectively stop blooding, up to using the back still to be accompanied by tangible inflammatory reaction 5 weeks and to the injury of neural and blood vessel.The result of study of Kheirabadi seminar shows that also WoundStat graininess hemostatic material is easy in vascular lumen residual, blocks the tip arterial flow and forms thrombosis, even found little blood clot at the part animal lung.Therefore, consider that based on bio-safety U.S. army has announced to ban use of Woundstat.
No matter be based on the QuikClot of zeolitic material; WoundStat based on Montmorillonitum; Also be based on kaolinic Combat Gauze, all utilized characteristics such as natural aluminosilicate silicate material loose structure, high-specific surface area, through moisture content in the absorbing blood; Concentrate the partial hemostatic composition of wound surface, thereby realize quick-acting haemostatic powder.And the mesoporous silicon material of artificial preparation has characteristics such as loose structure, high-specific surface area equally, and has advantages such as composition, particle diameter, controllable aperture than natural aluminosilicate silicate material, and existing in recent years part Study person attempts mesoporous silicon material is applied to hemostasis.TraumaStat is a kind of a kind of novel hemostatic material that has combined mesoporous silicon, chitosan and polythene material.Domestic Zhou Laisheng seminar has developed the inorganic active element bone tissue engineering stent material that multiple inorganic elements such as calcium, phosphorus, silicon is formed, and in animal experiment and clinical practice, finds that this material has good anthemorrhagic performance.Changsheng Liu seminar does in the bone renovating material research at mesoporous silicon material; Find that mesoporous silicon material has outstanding anthemorrhagic performance; And on the mesoporous silicon material basis, introduce antimicrobial component silver and the thrombin calcium ion has prepared a year silver-colored calcic mesoporous silicon material AgCaMSS; Utilize chitosan-mesoporous silica xerogel to be mixed with the CSSX material again, two kinds of materials all have more excellent anthemorrhagic performance.Baker etc. have fixed thrombin on mesoporous silicon material, experiment shows, mesoporous silicon foam material fixedly can remarkable less clotting time behind the thrombin.Yet, the same with the aluminosilicate hemostatic material, the significant too of the biological safety of mesoporous silicon hemostatic material.The mesoporous silicon grain that Hudson etc. have studied different-grain diameter and aperture is at subcutaneous, intraperitoneal and intravenous biological safety; The result shows; Though the reaction of the local organization of mesoporous silicon grain is benign, the mesoporous silicon grain that gets into vascular and histoorgan can cause serious general toxicity.
The present inventor thinks that the alkyl-modified chitosan acetic acid solution of Srinivasa R.Raghavan seminar can make whole blood gelation immediately, but lower gel strength and the water residue problem after the gelation and be unfavorable for the hemostasis control in the practical application; But moisture content in the mesoporous silicon material absorbing blood concentrates local hemostatic composition, thereby realizes quick-acting haemostatic powder, can not be ignored but particulate matter is prone to the residual biological safety hidden danger of bringing.
Summary of the invention
The objective of the invention is to be to overcome the deficiency of prior art; Provide a kind of when quick-acting haemostatic powder can be ensured; Have both good biology and histocompatibility, and solve the compound rapid hemostasis powder of alkyl-modified chitosan/mesoporous silicon oxide that particulate matter is prone to the residual biological safety hidden danger of bringing.
Second purpose of the present invention provides the method for preparing of the compound rapid hemostasis powder of a kind of alkyl-modified chitosan/mesoporous silicon oxide.
Technical scheme of the present invention is summarized as follows:
The method for preparing of the compound rapid hemostasis powder of a kind of alkyl-modified chitosan/mesoporous silicon oxide may further comprise the steps:
1) alkyl-modified Preparation of Chitosan: in proportion, be that 150-300K, deacetylation are that the chitosan of 75%-85% joins in the acetic acid aqueous solution that the 200ml volumetric concentration is 0.5-3% with the 4g mean molecule quantity, fully after the dissolving; Add the blend of 150ml ethanol, use sodium hydrate aqueous solution to regulate pH value and be 4-6, adding 10ml concentration be 15-25mg/ml to octadecyl benzaldehyde alcoholic solution; Add 2-5mg hydroboration cyanogen sodium again; At room temperature stirred 24 hours, and, added the 200ml ethanol precipitation with sodium hydrate aqueous solution adjust pH to 7; Centrifugal; It is 70%, 85% ethanol water and washing with alcohol that precipitate uses volumetric concentration successively, and lyophilization obtains alkyl-modified chitosan; (percent grafting of alkyl-modified chitosan is 1%～8%.）
2) mesoporous silicon silica dioxide granule preparation: with 200ml ethyl orthosilicate, 100ml ethanol, 20-25ml mean molecule quantity is that 5800 PPG P123,10ml2M hydrochloric acid are 45 ℃ of mixed stirrings 4-6 hour; At 500-650 ℃ of calcining 5-8h; Ball milling 2-4h obtains mesoporous silicon silica dioxide granule after 150 orders sieve;
3) compound rapid hemostasis powder preparation: the alkyl-modified chitosan of 4g is dissolved in the acetic acid aqueous solution that the 200ml volumetric concentration is 0.5-2%; Add 6-9g Macrogol 2000 0; Dissolving back adding 15-30g step 2) the mesoporous silicon silica dioxide granule of preparation; Stirring at room 24h is with being suspended in after the precipitate lyophilization in the 300ml dimethyl sulfoxide, with sodium hydrate aqueous solution adjust pH=7; Centrifugal, with 3-5 postlyophilization of deionized water wash, obtain the compound rapid hemostasis powder of alkyl-modified chitosan/mesoporous silicon oxide.
The compound rapid hemostasis powder of alkyl-modified chitosan/mesoporous silicon oxide of method for preparing.
The compound rapid hemostasis powder of alkyl-modified chitosan/mesoporous silicon oxide of the present invention can quick-acting haemostatic powder, is specially adapted to emergency aid and treatment before the severe haemorrhage wounded's the institute.This material hemostasis speed is exceedingly fast (to the external clotting time of rabbit whole blood and heparinemia all less than 10s), and haemostatic effect is superior at present chitosan and molecular sieve product on the market, and biology and histocompatibility are good, without any side effects.
Description of drawings
Fig. 1 is the uv-visible absorption spectroscopy figure of alkyl-modified chitosan among the present invention.
Fig. 2 is the stereoscan photograph of mesoporous silica particles among the present invention.
Fig. 3 cultivates L929 cell, cell growth state behind the 24h for the lixiviating solution of the compound rapid hemostasis powder of alkyl-modified chitosan/mesoporous silicon oxide among the present invention.Measure cytotoxicity multiple correlation standard with reference to GB/T 16886.5-2003 " medical apparatus and instruments biological assessment the 5th part: vitro cytotoxicity test ".
The specific embodiment
In order to make those skilled in the art person understand technical scheme of the present invention better, the present invention is done further detailed description below in conjunction with accompanying drawing and embodiment.
Embodiment 1
The method for preparing of the compound rapid hemostasis powder of a kind of alkyl-modified chitosan/mesoporous silicon oxide may further comprise the steps:
(1) alkyl-modified Preparation of Chitosan: in proportion, be that 300K, deacetylation are that to join the 200ml volumetric concentration be in 1% the acetic acid aqueous solution, fully after the dissolving for 85% chitosan with the 4g mean molecule quantity; Add the blend of 150ml ethanol, using the 1M sodium hydrate aqueous solution to regulate pH value is 5, add 10ml concentration and be 25mg/ml to octadecyl benzaldehyde alcoholic solution; Add 5mg hydroboration cyanogen sodium again, at room temperature stirred 24 hours, with 1M sodium hydrate aqueous solution adjust pH to 7; Add the 200ml ethanol precipitation, centrifugal, it is 70%, 85% ethanol water and washing with alcohol that precipitate uses volumetric concentration successively; Lyophilization obtains alkyl-modified chitosan;
Fig. 1 is the uv-visible absorption spectroscopy figure of alkyl-modified chitosan, can see with the chitosan raw material and comparing, and there is tangible phenyl ring absworption peak at modification of chitosan 270nm place.
2) mesoporous silicon silica dioxide granule preparation: with 200ml ethyl orthosilicate, 100ml ethanol, 25ml mean molecule quantity is that 5800 PPG P123,10ml 2M hydrochloric acid are 45 ℃ of mixed stirrings 5 hours; At 600 ℃ of calcining 8h; Ball milling 3h obtains mesoporous silicon silica dioxide granule after 150 orders sieve;
Fig. 2 is the scanning electron microscope picture of mesoporous silicon silica dioxide granule.
3) compound rapid hemostasis powder preparation: it is in 0.5% the acetic acid aqueous solution that the alkyl-modified chitosan of 4g is dissolved in the 200ml volumetric concentration; Add 8g Macrogol 2000 0; Dissolving back adding 20g step 2) the mesoporous silicon silica dioxide granule of preparation; Stirring at room 24h is with being suspended in after the precipitate lyophilization in the 300ml dimethyl sulfoxide, with 1M sodium hydrate aqueous solution adjust pH=7; Centrifugal, with 4 postlyophilizations of deionized water wash, obtain the compound rapid hemostasis powder of alkyl-modified chitosan/mesoporous silicon oxide.
Fig. 3 is the growth conditions that the compound rapid hemostasis powder lixiviating solution of alkyl-modified chitosan/mesoporous silicon oxide is cultivated L929 cell cell after 24 hours; Cell overwhelming majority well-grown shows that the compound rapid hemostasis powder of alkyl-modified chitosan/mesoporous silicon oxide has excellent biological compatibility.
Embodiment 2
The method for preparing of the compound rapid hemostasis powder of a kind of alkyl-modified chitosan/mesoporous silicon oxide may further comprise the steps:
Alkyl-modified Preparation of Chitosan: in proportion, be that 200K, deacetylation are that to join the 200ml volumetric concentration be in 1% the acetic acid aqueous solution, fully after the dissolving for 75% chitosan with the 4g mean molecule quantity; Add the blend of 150ml ethanol, using the 1M sodium hydrate aqueous solution to regulate pH value is 5, add 10ml concentration and be 25mg/ml to octadecyl benzaldehyde alcoholic solution; Add 5mg hydroboration cyanogen sodium again, at room temperature stirred 24 hours, with sodium hydrate aqueous solution adjust pH to 7; Add the 200ml ethanol precipitation, centrifugal, it is 70%, 85% ethanol water and washing with alcohol that precipitate uses volumetric concentration successively; Lyophilization obtains alkyl-modified chitosan;
2) mesoporous silicon silica dioxide granule preparation: with 200ml ethyl orthosilicate, 100ml ethanol, 25ml mean molecule quantity is that 5800 PPG P123,10ml 2M hydrochloric acid are 45 ℃ of mixed stirrings 5 hours; At 600 ℃ of calcining 8h; Ball milling 2h obtains mesoporous silicon silica dioxide granule after 150 orders sieve;
3) compound rapid hemostasis powder preparation: the alkyl-modified chitosan of 4g is dissolved in the acetic acid aqueous solution that the 200ml volumetric concentration is 0.5-2%; Add 9g Macrogol 2000 0; Dissolving back adding 20g step 2) the mesoporous silicon silica dioxide granule of preparation; Stirring at room 24h is with being suspended in after the precipitate lyophilization in the 300ml dimethyl sulfoxide, with sodium hydrate aqueous solution adjust pH=7; Centrifugal, with 3-5 postlyophilization of deionized water wash, obtain the compound rapid hemostasis powder of alkyl-modified chitosan/mesoporous silicon oxide.
Embodiment 3
The method for preparing of the compound rapid hemostasis powder of a kind of alkyl-modified chitosan/mesoporous silicon oxide may further comprise the steps:
(1) alkyl-modified Preparation of Chitosan: in proportion, be that 150K, deacetylation are that to join the 200ml volumetric concentration be in 1% the acetic acid aqueous solution, fully after the dissolving for 85% chitosan with the 4g mean molecule quantity; Add the blend of 150ml ethanol, using the 1M sodium hydrate aqueous solution to regulate pH value is 5, add 10ml concentration and be 25mg/ml to octadecyl benzaldehyde alcoholic solution; Add 5mg hydroboration cyanogen sodium again, at room temperature stirred 24 hours, with 1M sodium hydrate aqueous solution adjust pH to 7; Add the 200ml ethanol precipitation, centrifugal, it is 70%, 85% ethanol water and washing with alcohol that precipitate uses volumetric concentration successively; Lyophilization obtains alkyl-modified chitosan;
2) mesoporous silicon silica dioxide granule preparation: with 200ml ethyl orthosilicate, 100ml ethanol, 25ml mean molecule quantity is that 5800 PPG P123,10ml 2M hydrochloric acid are 45 ℃ of mixed stirrings 5 hours; At 600 ℃ of calcining 8h; Ball milling 4h obtains mesoporous silicon silica dioxide granule after 150 orders sieve;
3) compound rapid hemostasis powder preparation: it is in 0.5% the acetic acid aqueous solution that the alkyl-modified chitosan of 4g is dissolved in the 200ml volumetric concentration; Add 6g Macrogol 2000 0; Dissolving back adding 20g step 2) the mesoporous silicon silica dioxide granule of preparation; Stirring at room 24h is with being suspended in after the precipitate lyophilization in the 300ml dimethyl sulfoxide, with sodium hydrate aqueous solution adjust pH=7; Centrifugal, with 5 postlyophilizations of deionized water wash, obtain the compound rapid hemostasis powder of alkyl-modified chitosan/mesoporous silicon oxide.
Embodiment 4
The method for preparing of the compound rapid hemostasis powder of a kind of alkyl-modified chitosan/mesoporous silicon oxide may further comprise the steps:
(1) alkyl-modified Preparation of Chitosan: in proportion, be that 300K, deacetylation are that to join the 200ml volumetric concentration be in 0.5% the acetic acid aqueous solution, fully after the dissolving for 85% chitosan with the 4g mean molecule quantity; Add the blend of 150ml ethanol, using the 1M sodium hydrate aqueous solution to regulate pH value is 4, add 10ml concentration and be 15mg/ml to octadecyl benzaldehyde alcoholic solution; Add 2mg hydroboration cyanogen sodium again, at room temperature stirred 24 hours, with 1M sodium hydrate aqueous solution adjust pH to 7; Add the 200ml ethanol precipitation, centrifugal, it is 70%, 85% ethanol water and washing with alcohol that precipitate uses volumetric concentration successively; Lyophilization obtains alkyl-modified chitosan;
2) mesoporous silicon silica dioxide granule preparation: with 200ml ethyl orthosilicate, 100ml ethanol, 25ml mean molecule quantity is that 5800 PPG P123,10ml 2M hydrochloric acid are 45 ℃ of mixed stirrings 4 hours; At 500 ℃ of calcining 8h; Ball milling 3h obtains mesoporous silicon silica dioxide granule after 150 orders sieve;
3) compound rapid hemostasis powder preparation: it is in 2% the acetic acid aqueous solution that the alkyl-modified chitosan of 4g is dissolved in the 200ml volumetric concentration; Add 9g Macrogol 2000 0; Dissolving back adding 15g step 2) the mesoporous silicon silica dioxide granule of preparation; Stirring at room 24h is with being suspended in after the precipitate lyophilization in the 300ml dimethyl sulfoxide, with 1M sodium hydrate aqueous solution adjust pH=7; Centrifugal, with 4 postlyophilizations of deionized water wash, obtain the compound rapid hemostasis powder of alkyl-modified chitosan/mesoporous silicon oxide.
Embodiment 5
The method for preparing of the compound rapid hemostasis powder of a kind of alkyl-modified chitosan/mesoporous silicon oxide may further comprise the steps:
(1) alkyl-modified Preparation of Chitosan: in proportion, be that 300K, deacetylation are that to join the 200ml volumetric concentration be in 3% the acetic acid aqueous solution, fully after the dissolving for 85% chitosan with the 4g mean molecule quantity; Add the blend of 150ml ethanol, using the 1M sodium hydrate aqueous solution to regulate pH value is 6, add 10ml concentration and be 25mg/ml to octadecyl benzaldehyde alcoholic solution; Add 5mg hydroboration cyanogen sodium again, at room temperature stirred 24 hours, with 1M sodium hydrate aqueous solution adjust pH to 7; Add the 200ml ethanol precipitation, centrifugal, it is 70%, 85% ethanol water and washing with alcohol that precipitate uses volumetric concentration successively; Lyophilization obtains alkyl-modified chitosan;
2) mesoporous silicon silica dioxide granule preparation: with 200ml ethyl orthosilicate, 100ml ethanol, 20ml mean molecule quantity is that 5800 PPG P123,10ml 2M hydrochloric acid are 45 ℃ of mixed stirrings 6 hours; At 650 ℃ of calcining 5h; Ball milling 3h obtains mesoporous silicon silica dioxide granule after 150 orders sieve;
3) compound rapid hemostasis powder preparation: it is in 0.5% the acetic acid aqueous solution that the alkyl-modified chitosan of 4g is dissolved in the 200ml volumetric concentration; Add 6g Macrogol 2000 0; Dissolving back adding 30g step 2) the mesoporous silicon silica dioxide granule of preparation; Stirring at room 24h is with being suspended in after the precipitate lyophilization in the 300ml dimethyl sulfoxide, with 1M sodium hydrate aqueous solution adjust pH=7; Centrifugal, with 4 postlyophilizations of deionized water wash, obtain the compound rapid hemostasis powder of alkyl-modified chitosan/mesoporous silicon oxide.
Embodiment 6
The method for preparing of the compound rapid hemostasis powder of a kind of alkyl-modified chitosan/mesoporous silicon oxide may further comprise the steps:
(1) alkyl-modified Preparation of Chitosan: in proportion, be that 300K, deacetylation are that to join the 200ml volumetric concentration be in 1% the acetic acid aqueous solution, fully after the dissolving for 85% chitosan with the 4g mean molecule quantity; Add the blend of 150ml ethanol, using the 1M sodium hydrate aqueous solution to regulate pH value is 5, add 10ml concentration and be 25mg/ml to octadecyl benzaldehyde alcoholic solution; Add 5mg hydroboration cyanogen sodium again, at room temperature stirred 24 hours, with 1M sodium hydrate aqueous solution adjust pH to 7; Add the 200ml ethanol precipitation, centrifugal, it is 70%, 85% ethanol water and washing with alcohol that precipitate uses volumetric concentration successively; Lyophilization obtains alkyl-modified chitosan;
2) mesoporous silicon silica dioxide granule preparation: with 200ml ethyl orthosilicate, 100ml ethanol, 20ml mean molecule quantity is that 5800 PPG P123,10ml 2M hydrochloric acid are 45 ℃ of mixed stirrings 5 hours; At 650 ℃ of calcining 8h; Ball milling 4h obtains mesoporous silicon silica dioxide granule after 150 orders sieve;
3) compound rapid hemostasis powder preparation: it is in 0.5% the acetic acid aqueous solution that the alkyl-modified chitosan of 4g is dissolved in the 200ml volumetric concentration; Add 8g Macrogol 2000 0; Dissolving back adding 20g step 2) the mesoporous silicon silica dioxide granule of preparation; Stirring at room 24h is with being suspended in after the precipitate lyophilization in the 300ml dimethyl sulfoxide, with 1M sodium hydrate aqueous solution adjust pH=7; Centrifugal, with 4 postlyophilizations of deionized water wash, obtain the compound rapid hemostasis powder of alkyl-modified chitosan/mesoporous silicon oxide.
The uv-visible absorption spectroscopy figure that the alkyl-modified chitosan of embodiment 2-6 preparation has similar embodiment 1.
The scanning electron microscope picture that the mesoporous silicon silica dioxide granule of embodiment 2-6 preparation has similar embodiment 1.
The compound rapid hemostasis powder lixiviating solution of alkyl-modified chitosan/mesoporous silicon oxide of experiment proof embodiment 2-6 preparation is cultivated the growth conditions of L929 cell cell after 24 hours; Cell overwhelming majority well-grown shows that the compound rapid hemostasis powder of alkyl-modified chitosan/mesoporous silicon oxide has excellent biological compatibility.
Table 1 is the results of elemental analyses of the alkyl-modified chitosan of chitosan raw material among the present invention and embodiment 1 step (1) acquisition.
The results of elemental analyses of table 1 modification of chitosan
| Sample | N（％） | C（％） | H（％） | C/N?ratio | C/H?ratio |
| Chitosan | 7.31 | 39.70 | 6.73 | 5.43 | 5.90 |
| Modification of chitosan | 7.08 | 41.60 | 7.11 | 5.87 | 5.85 |
Can find out that by table 1 behind the octadecyl benzyl grafted chitosan, the C content of modification of chitosan obviously rises, because before and after the modification, the amount of N elemental substance is less than changing, so the variation of C/N ratio has proved the generation of alkyl-modified chitosan.
Claims (2)
1. the method for preparing of the compound rapid hemostasis powder of alkyl-modified chitosan/mesoporous silicon oxide is characterized in that may further comprise the steps:
1) alkyl-modified Preparation of Chitosan: in proportion, be that 150-300K, deacetylation are that the chitosan of 75%-85% joins in the acetic acid aqueous solution that the 200ml volumetric concentration is 0.5-3% with the 4g mean molecule quantity, fully after the dissolving; Add the blend of 150ml ethanol, use sodium hydrate aqueous solution to regulate pH value and be 4-6, adding 10ml concentration be 15-25mg/ml to octadecyl benzaldehyde alcoholic solution; Add 2-5mg hydroboration cyanogen sodium again; At room temperature stirred 24 hours, and, added the 200ml ethanol precipitation with sodium hydrate aqueous solution adjust pH to 7; Centrifugal; It is 70%, 85% ethanol water and washing with alcohol that precipitate uses volumetric concentration successively, and lyophilization obtains alkyl-modified chitosan;
2) mesoporous silicon silica dioxide granule preparation: with 200ml ethyl orthosilicate, 100ml ethanol, 20-25ml mean molecule quantity is that 5800 PPG P123,10ml 2M hydrochloric acid are 45 ℃ of mixed stirrings 4-6 hour; At 500-650 ℃ of calcining 5-8h; Ball milling 2-4h obtains mesoporous silicon silica dioxide granule after 150 orders sieve;
3) compound rapid hemostasis powder preparation: the alkyl-modified chitosan of 4g is dissolved in the acetic acid aqueous solution that the 200ml volumetric concentration is 0.5-2%; Add 6-9g Macrogol 2000 0; Dissolving back adding 15-30g step 2) the mesoporous silicon silica dioxide granule of preparation; Stirring at room 24h is with being suspended in after the precipitate lyophilization in the 300ml dimethyl sulfoxide, with sodium hydrate aqueous solution adjust pH=7; Centrifugal, with 3-5 postlyophilization of deionized water wash, obtain the compound rapid hemostasis powder of alkyl-modified chitosan/mesoporous silicon oxide.
2. the compound rapid hemostasis powder of alkyl-modified chitosan/mesoporous silicon oxide of the method for claim 1 preparation.
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