CN103467771A - Preparation method and application of marine organism active hemostasis dressing - Google Patents

Preparation method and application of marine organism active hemostasis dressing Download PDF

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CN103467771A
CN103467771A CN2013104344244A CN201310434424A CN103467771A CN 103467771 A CN103467771 A CN 103467771A CN 2013104344244 A CN2013104344244 A CN 2013104344244A CN 201310434424 A CN201310434424 A CN 201310434424A CN 103467771 A CN103467771 A CN 103467771A
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preparation
bleeding
wound
chitosan
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CN103467771B (en
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王春青
武容华
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Shandong Beinuo Medical Biology Technology Co ltd
Shandong Mechman Biological Medicine Science And Technology Co ltd
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WEIFANG MEIHEMAN BIO-PHARMACEUTICAL Co Ltd
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Abstract

The invention discloses a preparation method and application of a marine organism active hemostasis dressing. The preparation method comprises the steps of adding equal sodium alga acid solution while stirring a water solution comprising hydroxypropyl trimethyl ammonium chloride chitosan and/or an acetum of chitosan so as to obtain a liquor 1, taking an emulsion comprising paraffin as a liquor 2, mixing the liquor 1 and the liquor 2 according to the proportion of (2-3):5 and stirring uniformly so as to obtain a stable emulsification system, adding a cross-linking agent calcium chloride solution for cross-linking and solidifying the emulsification system, then washing, dewatering and drying so as to obtain the marine organism active hemostasis dressing. The materials of the prepared microballoon product have good biocompatibility and biodegradability as well as special effects of resisting bacterium, stopping bleeding, and promoting healing, when being contacted with a wound, the cross-linking and solidification product can rapidly absorb moisture in blood and concentrate blood platelets and blood coagulation factors into sticky gel, thus effectively sealing the bleeding wound and enhancing the hemostasis performance of the microballoon material, and therefore, the marine organism active hemostasis dressing is stable, efficient and environment-friendly.

Description

A kind of preparation method and its usage of marine bioactivity bleeding-stopping dressing
Affiliated technical field
The present invention relates to a kind of bleeding-stopping dressing, particularly relate to a kind of preparation method and its usage of marine bioactivity bleeding-stopping dressing.
Background technology
Chitosan is that content is only second to cellulosic second largest natural biological macromolecular material, there are nontoxic, good biocompatibility, anti-inflammatory, anti, antibacterial, wound healing and moisture-absorbing moisture-keeping and easy many excellent properties such as degraded, can be degraded to the available monose of body by N,O-Diacetylmuramidase, show good biodegradability, and play Blood clotting by number of ways.Quaternary Ammonium Salt of Chitosan is a kind of cats product, positively charged in water, can adsorb and the microorganism surface, form micelle, and progressively infiltrate cytoplasmic lipoid layer and protein, thus the permeability of change cytolemma, be that entocyte leaks, cause microbial death; Also can make the structure generation sex change of albumen and enzyme, the metabolism of destroy microorganisms, kill microorganism simultaneously.Lalgine is the natural polyanionic polysaccharide extracted in brown alga, it has similar performance to chitosan, when sodium alginate and calcium chloride crosslinked after, can generate alginate calcium, the alginate calcium generated is with after the purulence blood on wound contacts, can with body fluid in sodium ion generation ion-exchange, be converted into the gel of stickiness when discharging calcium ion.Large quantity research shows, after interacting by certain physics or chemical mode with alginate calcium when chitosan, can form that short more effect is stronger, antibacterial effect better, haemostatic effect is better.The composite marine biomaterial that mechanical property is more excellent.
Wound hemorrhage is one of important illness of harm humans health and lives safety, and no matter War And Peace period, unmanageable profuse bleeding is to cause wounded's main causes of death.The war wound caused owing to losing blood in war is cut personnel larger proportion, and approximately 50% person killed in action is before delivering to dressing station according to statistics, because of severe loss of blood death in several minutes.Injured hemorrhage also very common in peacetime various unexpected incidents.It is exactly the typical case that China's traffic accident and the casualties are continuous ascendant trend.Hemostasis is significant to reducing disability and injures and deaths simply, fast and effectively.Traditional dressing is as the dressing of all kinds of gauze type, and major function is to prevent wound infection, the protection surface of a wound, but little to the effect that promotes wound healing, even also can affect wound healing, and the effect surface of a wound that can not be fully effective.Therefore novel hemostatic material and apparatus are the wound hemostasis urgent problems, are subject to the great attention of countries in the world medical science and military medicine.Along with to the going deep into of researching wound healing, the purpose of using dressing is far from for flap coverage, hemostatic and antibacterial and promote healing to become the certainty of hemostatic material development.Existing hemostatic material is confined to simple hemostasis more, but it is also fewer that anti-infective, promoting healing, promotion tissue repair, prevention are adhered, reduce the research of the aspects such as scar.
Summary of the invention
The technical problem to be solved in the present invention is to provide a kind of preparation method of marine bioactivity bleeding-stopping dressing, and this bleeding-stopping dressing has efficient anthemorrhagic performance to the surface of a wound, and have antibacterial, promote that tissue repair, prevention are adhered, biodegradability.
For solving the problems of the technologies described above, the preparation method of this marine bioactivity bleeding-stopping dressing is:
To contain the acetum of the aqueous solution of HACC and/or chitosan in the situation that stir and add the sodium alginate soln of equivalent as 1 liquid, to contain the emulsion of paraffin as 2 liquid, 1 liquid and 2 liquid are become to stable emulsification system according to the ratio mixing and stirring of 2~3:5, add the linking agent calcium chloride solution to make its crosslinking curing, then be drying to obtain by washing dehydration.
Described HACC and chitosan solution have following general formula:
Figure 720892DEST_PATH_IMAGE001
or
Wherein, polymerization degree n is between 300~2000, and relative molecular mass is 8.4 * 10 4~5.6 * 10 5between;
The general structure of described Lalgine sodium salt is as follows:
Figure 637143DEST_PATH_IMAGE003
Wherein, polymerization degree n is between 180-930, and relative molecular mass is 3.2 * 10 4~2.5 * 10 5between.
The compound method of described HACC and chitosan-acetic acid solution is: the HACC of equivalent is dissolved in distilled water, be mixed with the aqueous solution that mass percentage concentration is 1.6~2.4%, it is in 1~2:100 acetum that chitosan is joined to volume ratio, stirs and is mixed with the colloidal solution that mass percentage concentration is 1.6~2.4%.
The mass percentage concentration of described sodium alginate soln is 1~2%, during preparation, is sodium alginate is entered in distilled water, is mixed with micro-yellow milky solution.
The compound method of the emulsified soln of described paraffin is: will the class of department 80, tween 80 and stearic acid be mixed into emulsifying agent according to the mass ratio of 9:9:1~3, and by emulsifying agent and whiteruss, the mass ratio according to 12~13:125 mixes, and stirs into O(water under 72~78 ℃)/W(oil) emulsion.
The massfraction of linking agent calcium chloride is 1.6%~3.2%, and it joins in emulsification system liquid according to the volume ratio with emulsification system 1:12~18, and the temperature of reaction is 70~80 ℃, and the reaction times is 50~60min.
Described washing is washings washing, and described washings is Virahol, and except de-emulsifier and paraffin, the translucent microballoon of washing gel carries out gradient with alcohol again and is dehydrated into silt shape solid-state-microspherical, then carries out vacuum-drying and become powder to get final product.
Purposes of the present invention: for the various traumatic surface of a wound, the antibacterial anti hemorrhagic of the surface of a wound such as mucous membrane, the uterine neck surface of a wound, empyrosis wound surface, operative incision, ulcer, bedsore, promotion organization healing, prevent to be adhered and to reduce scar.
The present invention has following advantage:
1. chitosan has the biological activitys such as good biocompatibility and anti-inflammatory, anti, antibacterial, wound healing, can be degraded to the available monose of body by N,O-Diacetylmuramidase, show good biodegradability, and play Blood clotting by number of ways.The chitosan quaternary ammonium salt sterilization effect added is better than chitosan, and biocompatibility is better, has increased the antibacterial ability of particulate.
2. generate the Ah-ACMS complex microsphere after emulsification and cross linked, and alginate calcium has good biocompatibility and biodegradability, and antibacterial, hemostasis, short more, alleviate the specific function such as scar.The Lalgine calcium salt is with after purulence blood on wound contacts, the Lalgine calcium salt can with body fluid in sodium ion generation ion-exchange, be converted into the gel of stickiness when discharging calcium ion, a large amount of assemblies of wound surface calcium ion can be accelerated surface of a wound hemostasis.
3. the microballoon be prepared from after emulsification and cross linked, particle diameter is tiny, there is larger specific surface area, increase the contact area of material and blood, water absorption and swelling becomes the viscogel shape fast, be attached to the surface of a wound, the capillary vessel that the shutoff surface of a wound breaks, strengthened the performance of the promotion erythrocyte aggregation of micro-sphere material itself, keep or the intrinsic anthemorrhagic performance of expansion biomaterial itself, and form water gel at the surface of a wound after hemostasis, the energy wound healing, simultaneously soft, moistening gelinite provides moist repairing environment for wound, accelerate the growth of granulation tissue and the formation of epithelium, thereby make this dressing stronger than the short more effect of other similar dressing, antibacterial effect is better, haemostatic effect is better, mechanical property is more excellent.
4. the preparation technology of the biological bleeding-stopping dressing of the present invention is simple, and material is easy to get, and is applicable to carry out suitability for industrialized production, has a extensive future.
Embodiment
Below in conjunction with specific embodiment, the present invention is described in further detail:
Embodiment 1
Take 18.1g department class 80,18.1g tween 80,2.0g stearic acid and join in the 500ml whiteruss, stir into O(water under 72 ℃)/(oil) W emulsion.Get the 0.8g HACC and be added in the 50ml distilled water, the 0.8g chitosan is dissolved in the acetum that the 50ml volume fraction is 1%, and both mix.The 1.2g sodium alginate is added in the 100ml distilled water, and the salts solution of chitosan is joined to sodium alginate soln fully stirs into stable colloidal solution, then join in the emulsion of paraffin rapid stirring 25 minutes, stirring velocity 800-1000 rev/min.Add again the calcium chloride solution 40ml that massfraction is 1.6%, maintain the temperature at 72 ℃, stirring at low speed 50 minutes, stirring velocity 80-100 rev/min.Mixed solution is fallen to vacuum filtration in core.By 100ml washed with isopropyl alcohol 3 times, then use respectively 30%, 50%, 70%, 100% gradient alcohol dehydration, vacuum-drying becomes powder.
Embodiment 2
Take 18.7g department class 80,18.7g tween 80,4.2g stearic acid and join in the 500ml whiteruss, stir into O(water under 75 ℃)/(oil) W emulsion.Get the 1.0g HACC and be added in the 50ml distilled water, the 1.0g chitosan is dissolved in the acetum that the 50ml volume fraction is 1%, and both mix.The 1.5g sodium alginate is added in the 100ml distilled water, and the salts solution of chitosan is joined to sodium alginate soln fully stirs into stable colloidal solution, then join in the emulsion of paraffin rapid stirring 30 minutes, stirring velocity 800-1000 rev/min.Add again the calcium chloride solution 40ml that massfraction is 2.0%, maintain the temperature at 75 ℃, stirring at low speed 55 minutes, stirring velocity 80-100 rev/min.Mixed solution is fallen to vacuum filtration in core.By 100ml washed with isopropyl alcohol 3 times, then use respectively 30%, 50%, 70%, 100% gradient alcohol dehydration, vacuum-drying becomes powder.
Embodiment 3
Take 18.4g department class 80,18.4g tween 80,6.1g stearic acid and join in the 500ml whiteruss, stir into O(water under 78 ℃)/(oil) W emulsion.Get the 1.2g HACC and be added in the 50ml distilled water, the 1.2g chitosan is dissolved in the acetum that the 50ml volume fraction is 1%, and both mix.The 1.8g sodium alginate is added in the 100ml distilled water, and the salts solution of chitosan is joined to sodium alginate soln fully stirs into stable colloidal solution, then join in the emulsion of paraffin rapid stirring 45 minutes, stirring velocity 800-1000 rev/min.Add again the calcium chloride solution 40ml that massfraction is 2.4%, maintain the temperature at 80 ℃, stirring at low speed 1h, stirring velocity 80-100 rev/min.Mixed solution is fallen to vacuum filtration in core.By 100ml washed with isopropyl alcohol 3 times, then use respectively 30%, 50%, 70%, 100% gradient alcohol dehydration, vacuum-drying becomes powder.
Embodiment 4
Take 18.7g department class 80,18.7g tween 80,4.2g stearic acid and join in the 500ml whiteruss, stir into O(water under 75 ℃)/(oil) W emulsion.Getting the 2.0g HACC is dissolved in the 100ml distilled water and mixes, the 1.5g sodium alginate is added in the 100ml distilled water, and the salts solution of chitosan is joined to sodium alginate soln fully stir into stable colloidal solution, join again in the emulsion of paraffin, rapid stirring 30 minutes, stirring velocity 800-1000 rev/min.Adding massfraction is 2.0% calcium chloride solution 40ml again, maintains the temperature at 75 ℃, stirring at low speed 55 minutes, stirring velocity 80-100 rev/min.Mixed solution is fallen to vacuum filtration in core.By 100ml washed with isopropyl alcohol 3 times, then use respectively 30%, 50%, 70%, 100% gradient alcohol dehydration, vacuum-drying becomes powder.
Embodiment 5
Take 18.7g department class 80,18.7g tween 80,4.2g stearic acid and join in the 500ml whiteruss, stir into O(water under 75 ℃)/(oil) W emulsion.Getting the 2.0g chitosan is added in the acetum that the 100ml volume fraction is 1%.The 1.5g sodium alginate is added in the 100ml distilled water, and the salts solution of chitosan is joined to sodium alginate soln fully stirs into stable colloidal solution, then join in the emulsion of paraffin rapid stirring 30 minutes, stirring velocity 800-1000 rev/min.Adding massfraction is 2.0% calcium chloride solution 40ml again, maintains the temperature at 75 ℃, stirring at low speed 55 minutes, stirring velocity 80-100 rev/min.Mixed solution is fallen to vacuum filtration in core.By 100ml washed with isopropyl alcohol 3 times, then use respectively 30%, 50%, 70%, 100% gradient alcohol dehydration, vacuum-drying becomes powder.
HACC of the present invention and chitosan solution have following general formula:
or
Wherein, polymerization degree n is between 300~2000, and relative molecular mass is 8.4 * 10 4~5.6 * 10 5between.
The general structure of Lalgine sodium salt of the present invention is as follows:
Wherein, polymerization degree n is between 180-930, and relative molecular mass is 3.2 * 10 4~2.5 * 10 5between.
Purposes of the present invention: for the various traumatic surface of a wound, the antibacterial anti hemorrhagic of the surface of a wound such as mucous membrane, the uterine neck surface of a wound, empyrosis wound surface, operative incision, ulcer, bedsore, promotion organization healing, prevent to be adhered and to reduce scar.

Claims (8)

1. the preparation method of a marine bioactivity bleeding-stopping dressing, it is characterized in that containing the acetum of the aqueous solution of HACC and/or chitosan in the situation that stir and add the sodium alginate soln of equivalent as 1 liquid, to contain the emulsion of paraffin as 2 liquid, 1 liquid and 2 liquid are become to stable emulsification system according to the ratio mixing and stirring of 2~3:5, add the linking agent calcium chloride solution to make its crosslinking curing, then be drying to obtain by washing dehydration.
2. the preparation method of marine bioactivity bleeding-stopping dressing as claimed in claim 1 is characterized in that described HACC and chitosan solution have following general formula:
Figure 359635DEST_PATH_IMAGE002
or
Figure 945337DEST_PATH_IMAGE003
Wherein, polymerization degree n is between 300~2000, and relative molecular mass is 8.4 * 10 4~5.6 * 10 5between;
The general structure of described Lalgine sodium salt is as follows:
Wherein, polymerization degree n is between 180-930, and relative molecular mass is 3.2 * 10 4~2.5 * 10 5between.
3. the preparation method of marine bioactivity bleeding-stopping dressing as claimed in claim 1, the compound method that it is characterized in that described HACC and chitosan-acetic acid solution is: the HACC of equivalent is dissolved in distilled water, be mixed with the aqueous solution that mass percentage concentration is 1.6~2.4%, it is in 1~2:100 acetum that chitosan is joined to volume ratio, stirs and is mixed with the colloidal solution that mass percentage concentration is 1.6~2.4%.
4. the preparation method of marine bioactivity bleeding-stopping dressing as claimed in claim 1, is characterized in that the mass percentage concentration of described sodium alginate soln is 1~2%, during preparation, is that sodium alginate is entered in distilled water, is mixed with micro-yellow milky solution.
5. the preparation method of marine bioactivity bleeding-stopping dressing as claimed in claim 1, the compound method that it is characterized in that the emulsified soln of described paraffin is: will the class of department 80, tween 80 and stearic acid be mixed into emulsifying agent according to the mass ratio of 9:9:1~3, and by emulsifying agent and whiteruss, the mass ratio according to 12~13:125 mixes, and stirs into O(water under 72~78 ℃)/W(oil) emulsion.
6. the preparation method of marine bioactivity bleeding-stopping dressing as claimed in claim 1, the massfraction that it is characterized in that linking agent calcium chloride is 1.6%~3.2%, it joins in emulsification system liquid according to the volume ratio with emulsification system 1:12~18, the temperature of reaction is 70~80 ℃, and the reaction times is 50~60min.
7. the preparation method of marine bioactivity bleeding-stopping dressing as claimed in claim 1, it is characterized in that described washing is the washings washing, described washings is Virahol, except de-emulsifier and paraffin, washing gel translucent microballoon carries out gradient with alcohol again and is dehydrated into silt shape solid-state-microspherical, then carries out vacuum-drying and become powder to get final product.
8. the purposes of a marine bioactivity bleeding-stopping dressing, is characterized in that for the various traumatic surface of a wound, and the antibacterial anti hemorrhagic of the surface of a wound such as mucous membrane, the uterine neck surface of a wound, empyrosis wound surface, operative incision, ulcer, bedsore, promotion organization healing, prevent to be adhered and to reduce scar.
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Cited By (10)

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Publication number Priority date Publication date Assignee Title
CN104998293A (en) * 2015-08-17 2015-10-28 青岛卫辽医用生物材料有限公司 Styptic powder
CN105031708A (en) * 2015-08-25 2015-11-11 东莞市达庆医疗器械有限公司 Rapid hemostatic powder for injury and preparation method of rapid hemostatic powder
CN105169460A (en) * 2015-10-26 2015-12-23 广东泰宝医疗科技股份有限公司 Magnetically therapeutic antibacterial haemostatic wound dressing and preparation method thereof
CN107335091A (en) * 2017-08-31 2017-11-10 河南汇博医疗股份有限公司 A kind of long acting antibiotic hydrogel and preparation method thereof
CN108126236A (en) * 2017-12-20 2018-06-08 浙江科技学院 A kind of medicine coating material and preparation method thereof
CN108744022A (en) * 2018-07-06 2018-11-06 中国热带农业科学院农产品加工研究所 A kind of functionality absorbable hemostatic powder and preparation method thereof
CN109364288A (en) * 2018-11-26 2019-02-22 温州生物材料与工程研究所 Hole-hole composite micro-nano structure polysaccharide microsphere is in the purposes for preparing bleeding-stopping dressing
CN110180018A (en) * 2019-05-24 2019-08-30 武汉理工大学 A kind of preparation method of calcic alginate/chitosan hemostatic microsphere
CN111632188A (en) * 2020-06-09 2020-09-08 湖北精耕生物工程有限公司 Seaweed polysaccharide composite biological matrix dressing and preparation method thereof
CN112755239A (en) * 2020-12-08 2021-05-07 上海市肿瘤研究所 Composite porous microsphere and preparation method and application thereof

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CN1850111A (en) * 2006-02-28 2006-10-25 中国人民解放军第二军医大学 Biodegradeable hemostasis powder
CN101613420A (en) * 2009-08-06 2009-12-30 浙江澳兴生物科技有限公司 A kind of preparation method of 2-HACC
CN101735339A (en) * 2010-01-12 2010-06-16 浙江理工大学 Reactive chitosan derivative and preparation method thereof

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CN1850111A (en) * 2006-02-28 2006-10-25 中国人民解放军第二军医大学 Biodegradeable hemostasis powder
CN101613420A (en) * 2009-08-06 2009-12-30 浙江澳兴生物科技有限公司 A kind of preparation method of 2-HACC
CN101735339A (en) * 2010-01-12 2010-06-16 浙江理工大学 Reactive chitosan derivative and preparation method thereof

Cited By (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104998293A (en) * 2015-08-17 2015-10-28 青岛卫辽医用生物材料有限公司 Styptic powder
CN105031708A (en) * 2015-08-25 2015-11-11 东莞市达庆医疗器械有限公司 Rapid hemostatic powder for injury and preparation method of rapid hemostatic powder
CN105031708B (en) * 2015-08-25 2018-03-23 东莞市达庆医疗器械有限公司 A kind of wound rapid hemostasis powder and preparation method thereof
CN105169460B (en) * 2015-10-26 2018-09-25 广东泰宝医疗科技股份有限公司 A kind of magnetic therapy antibacterial anti hemorrhagic dressing and preparation method thereof
CN105169460A (en) * 2015-10-26 2015-12-23 广东泰宝医疗科技股份有限公司 Magnetically therapeutic antibacterial haemostatic wound dressing and preparation method thereof
CN107335091A (en) * 2017-08-31 2017-11-10 河南汇博医疗股份有限公司 A kind of long acting antibiotic hydrogel and preparation method thereof
CN108126236A (en) * 2017-12-20 2018-06-08 浙江科技学院 A kind of medicine coating material and preparation method thereof
CN108744022A (en) * 2018-07-06 2018-11-06 中国热带农业科学院农产品加工研究所 A kind of functionality absorbable hemostatic powder and preparation method thereof
CN109364288A (en) * 2018-11-26 2019-02-22 温州生物材料与工程研究所 Hole-hole composite micro-nano structure polysaccharide microsphere is in the purposes for preparing bleeding-stopping dressing
CN109364288B (en) * 2018-11-26 2021-04-02 温州生物材料与工程研究所 Application of hole-hole composite micro-nano structure polysaccharide microspheres in preparation of hemostatic dressing
CN110180018A (en) * 2019-05-24 2019-08-30 武汉理工大学 A kind of preparation method of calcic alginate/chitosan hemostatic microsphere
CN111632188A (en) * 2020-06-09 2020-09-08 湖北精耕生物工程有限公司 Seaweed polysaccharide composite biological matrix dressing and preparation method thereof
CN112755239A (en) * 2020-12-08 2021-05-07 上海市肿瘤研究所 Composite porous microsphere and preparation method and application thereof

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