CN102258802B - A kind of Novel multifunctional hemostatic dressing - Google Patents

A kind of Novel multifunctional hemostatic dressing Download PDF

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CN102258802B
CN102258802B CN201010185470.1A CN201010185470A CN102258802B CN 102258802 B CN102258802 B CN 102258802B CN 201010185470 A CN201010185470 A CN 201010185470A CN 102258802 B CN102258802 B CN 102258802B
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chrysophanol
collagen
chitosan
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novel multifunctional
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CN102258802A (en
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朱楚洪
蒋波
曾文
李立
糜建红
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Army Medical University
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朱楚洪
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Abstract

The feature of the Novel multifunctional hemostatic dressing that the present invention relates to is: adopt following method preparation: 1, the preparation of different desacetylated degree chitosans; 2, the preparation of reconstructed collagen albumen is modified: control the chemical modification degree of collagen protein, molecular entity, molecular weight and concentration; 3, chrysophanol purification; Obtain the active substance stopped blooding in Chinese herb rhubarb, and quantitative study; 4, collagen, chitosan and chrysophanol three are carried out organic composite, guarantee lyophilizing pad composite sponge pliability, adventitia has sealing, adhesiveness and integrity; Described Novel multifunctional hemostatic dressing can quick-acting haemostatic powder, anti-inflammatory and antalgic Promotive union, may be used for army's War injury hemostasis and to repair and as civilian general first-aid hemostatic.

Description

A kind of Novel multifunctional hemostatic dressing
Technical field
The present invention relates to the multifunctional hemostatic dressing of a kind of energy quick-acting haemostatic powder, anti-inflammatory and antalgic, Promotive union.
Technical background
Wound hemorrhage is one of important disease of harm humans health and lives safety, no matter War And Peace period, and unmanageable massive hemorrhage causes wounded's main causes of death.The war wound caused owing to losing blood in war is cut personnel larger proportion, and the person killed in action of about 50% is before delivering to first aid station according to statistics, dead in several minutes because of severe loss of blood.Injured hemorrhage also very common in peacetime various unexpected incidents.China's vehicle accident and the number of casualties are continuous ascendant trend is exactly typical case.Wound severe loss of blood makes wounded's pain, stupor, shock even dead, and hemostasis becomes the important step of war wound and sudden accident first aid.
The object of quick-acting haemostatic powder is to win the therapeutic time to wounded body and acquisition good prognosis.Traditional wrapping hemostasis can cause necrosis and the dysfunction of wrapping up the following limbs in position, advocates and does not abuse tourniquet.And wrapping hemostasis cannot press the massive hemorrhage pricking position to seem helpless to those.Therefore seek novel hemostatic material and apparatus is wound hemostasis urgent problem, be subject to the great attention of countries in the world medical science and military medicine.Along with going deep into researching wound healing, use the object of dressing to stop blooding far from order to flap coverage, analgesia and Promotive union have become the certainty of hemostatic material development.Existing hemostatic material is confined to simple hemostasis more, and the research and development for aspects such as analgesia, infection, Promotive union are also fewer.
Chitosan, collagen protein and Chinese herb rhubarb have different structure feature, hemorrhage of good performance, and research finds that they have complementation and cooperative effect, has blood coagulation enhancing effect to heparinized blood.Novel multifunctional hemostatic dressing is exactly recombination chitosan, collagen and Chinese herb rhubarb phenol are integrated, can quick-acting haemostatic powder, anti-inflammatory and antalgic the novel hemostatic material of Promotive union.
Novel multifunctional hemostatic dressing has started the innovative thinking developing into the synthtic price index solutions such as quick-acting haemostatic powder, antalgic and inflammation relieving, Promotive union from simple wound hemostasis.Solve clinically by synthtic price index such as hemostasis, infection, alleviating pains in the insurmountable sudden accident emergency treatment of traditional method, make war or peacetime wound hemorrhage not only obtain rapidly effectively controlling but also play to infect analgesic effect, improve the quality of life of the wounded.
The advantages such as this multifunctional hemostatic dressing also has easy to carry, easy preservation, not only for first-aid personnel provides effective means, and wounded body only just can self rescue otherwise lose consciousness.Its scope of application is very wide, and the personnel of the soldier on battlefield, dangerous work post, even common laboratory, hospital, medical station, family emergency all can be equipped with this pad binder.Solve the emergency treatment hemostasis problem of the insurmountable sudden accident of traditional method, be adapted to the treatment strategy of the War injury self rescue under peacetime and New military transform.
Summary of the invention
The object of the present invention is to provide a kind of on the basis of hemostatic material simple at present, collagen, chitosan, chrysophanol are complex as a whole, can quick-acting haemostatic powder, antalgic and inflammation relieving and the Novel multifunctional hemostatic dressing of Promotive union.Meet wartime and first-aid hemostatic needs at ordinary times, improve the quality of life of the wounded, for the wounded win therapeutic time, improve prognosis.
The technical scheme adopted for realizing above-mentioned purpose of the present invention is such, i.e. a kind of Novel multifunctional hemostatic dressing, can quick-acting haemostatic powder, antalgic and inflammation relieving and Promotive union, it is characterized in that: adopt following method preparation:
1, the preparation of different desacetylated degree chitosans;
2, the preparation of reconstructed collagen albumen is modified: control the chemical modification degree of collagen protein, molecular entity, molecular weight and concentration;
3, chrysophanol purification; Obtain the active substance stopped blooding in Chinese herb rhubarb, and quantitative study;
4, collagen, chitosan and chrysophanol three are carried out organic composite, guarantee lyophilizing pad composite sponge pliability, adventitia has sealing, adhesiveness and integrity.
In above-mentioned preparation method, chitosan described in step 1 adopts the method for de-acetyl to make; Collagen protein modifies reconstructed collagen albumen by controlling its chemical modification degree, molecular entity, molecular weight and concentration in step 2; Chrysophanol in step 3 extracts in the middle of Chinese herb rhubarb; Step 4 is that collagen and chitosan are coordinated formation molecular link by a certain percentage, adding that chrysophanol carries out being cross-linked, lyophilizing, control slow release.
The subject matter that the present invention solves is wartime and the Novel multifunctional hemostatic dressing at ordinary times needed for first aid, can quick-acting haemostatic powder, antalgic and inflammation relieving Promotive union, compared with prior art tool has the following advantages:
1. material characteristics complement and collaborative characteristic.Chitosan, collagen protein and Chinese herb rhubarb have different structure feature, and they have complementation and cooperative effect, have blood coagulation enhancing effect to heparinized blood.Chitosan is degradable polysaccharide polymer prepared by the shell of a kind of Shrimp waste animal, there is Bleeding control, antibacterial/antibiotic property, biocompatibility, promotion wound healing and be easy to be formed the character of gel, impart the superperformance that it is used as bleeding-stopping dressing or hemorrhage.Chemical modification collagenous source, in extra-cellular matrix structure albumen, when spongiform chemical modification collagen and contacting blood, can utilize the capillarity of its sponge structure, rapid adsorption blood, cause platelet aggregation, platelet destruction, activation and release thrombin, thus promote coagulation process.The Chinese medicine of Radix Et Rhizoma Rhei " being gas medicine, is again blood medicine, stops blooding and does not stay the stasis of blood, particularly panacea ", along with deepening continuously to Radix Et Rhizoma Rhei hemostasis pharmacological research, Chinese herb rhubarb has promotion hemagglutinative function and obtains remarkable break-throughs in clinical research and application.
2. the multi-functional characteristic of product.Multi-functional quick-acting haemostatic powder first aid pad by different deacetylation chitosan, modify reconstructed collagen and chrysophanol compound and prepare.Hemostasis in abundant research emergency care of trauma, infection, Theory of Pain Mechanism, integrate the effects such as quick-acting haemostatic powder, infection control and alleviating pain, and exploitation possesses the multifunctional product of these features.
3. carry, preserve and use all very convenient.This multi-functional quick-acting haemostatic powder first aid pad product is not only for first-aid personnel provides effective means, and wounded body only just can self rescue otherwise lose consciousness.Be adapted to accident and first aid of battle field especially.
4. have independent intellectual property right.Quick-acting haemostatic powder, antibacterial, the multi-functional quick-acting haemostatic powder first aid in analgesic pad product have independent intellectual property right, will indicate that China finishes not have for many years a kind of like this situation of emergency aid articles, and the advanced product that possesses skills will match in excellence or beauty with same kind of products at abroad.
5. propose the concept of all-direction multi-functional first aid pad first and give its content.Emergency equipment concentrates on the hemorrhage aspect of minimizing mostly both at home and abroad at present, and rescues scene in accident, not only exists hemorrhage but also there will be infection, again processing all very difficult so that deliver to hospital.And the information summary at scene is considered and analyzed by we, propose the new concept of all-direction multi-functional process.
6. take the lead at home developing this product and putting on market.There is no this series products both at home and abroad at present, so the launch products researched and developed of employing new technology under new theory instructs, not only have novelty but also have powerful vitality.
Detailed description of the invention:
Below in conjunction with embodiment, content of the present invention is described further.
1, the preparation of different de-acetyl shell degree polysaccharide; Chitin is after high alkali liquid process, and in molecule, acetamido can remove in partial hydrolysis, just becomes chitosan when acetyl group more than half in molecule removes.Because on chitin monomer C2 position, acetamido instead of hydroxyl, it is insoluble to diluted acid diluted alkaline and organic solvent, its character like fibrous element. just can dissolve in acid when acetyl group more than half is removed.When chitosan dissolves in an acidic solution, the free amino (-NH2) on monomer molecule is protonated and positively charged (-NH3+) becomes cationic polymer, can adsorb the material that some are electronegative.This experiment just carries out coagulant and antibacterial further research to the chitosan of different deacetylation in the larger chitosan (9.3 × 105 ~ 9.8 × 105) of molecular weight, and the multifunctional hemostatic dressing be composited for building collagen, chitosan and chrysophanol provides theoretical foundation
2, the preparation of reconstructed collagen albumen is modified: control the chemical modification degree of collagen protein, molecular entity, molecular weight and concentration; Collagen types and content: type i collagen, noncollagen protein impurity content < 1%.Melt temperature Tp:50 DEG C-80 DEG C.Total metals: < 10mg/kg.Sugar content: < 1.0g/kg.Fat content: < 0.1%.Ash: < 1.0%.PH value: 7.0 ± 0.4.Pyrogen: the qualification determination requirement that should meet Pharmacopoeia of People's Republic of China 2000 editions two annex pyrogen tests.Haemolysis: hemolysis rate≤5%.Cytotoxicity: cytotoxicity I-O level.
3, chrysophanol purification; Obtain the active substance stopped blooding in Chinese herb rhubarb, and quantitative study; First with dilution heat of sulfuric acid, All Kind of Anthraquinone In Rhubarb glycosides is hydrolyzed into aglycon, reusable heat chloroform extraction aglycon, with alkali liquor by chrysophanic acid, emodin, aloe-emodin removing in chloroform solution, and is separated chrysophanol and emodin with column chromatography, through the repeated multiple times recrystallization of ethanol, obtain highly purified chrysophanol; Adopt the content of high effective liquid chromatography for measuring wherein chrysophanol.Chrysophanol purity is made to reach more than 98%.
4, collagen, chitosan and chrysophanol three are carried out organic composite, guarantee lyophilizing pad composite sponge pliability, adventitia has sealing, adhesiveness and integrity: the impact of proportioning on haemostatic effect studying different collagen and chitosan, and to anti-inflammatory and antalgic, agglutinant effect after passing through animal experiment study compound chrysophanol slow release.
Citing is below described, but application of the present invention is not only this.
The preparation of embodiment 1. Novel multifunctional hemostatic dressing, prepares corresponding chitosan, collagen and chrysophanol by above-mentioned steps (1) (2) (3) method, carries out the compound of different proportionings by step (4).
After the collagen obtained, chitosan, chrysophanol composite are cross-linked lyophilizing, cover the mice position that limb injury is hemorrhage, observe its haemostatic effect, find stopped bleeding after 1 minute.And use merely collagen to cover the mice bleeding part of same damage, stopped bleeding after 5 minutes as hemostatic material.Simple use chitosan covers the mice bleeding part of same damage as hemostatic material, stopped bleeding after 4 minutes.The material of collagen and chitosan compound is utilized to cover the mice bleeding part of same damage, stopped bleeding after 2 minutes.
The preparation of embodiment 2. Novel multifunctional hemostatic dressing, prepares corresponding chitosan, collagen and chrysophanol by above-mentioned steps (1) (2) (3) method, carries out the compound of different proportionings by step (4).
After the collagen obtained, chitosan, chrysophanol composite are cross-linked lyophilizing, same condition of culture is adopted to cultivate staphylococcus and anaerobe.After the composite overnight incubation of observation discovery collagen, chitosan and chrysophanol, the growth of antibacterial is obviously suppressed, and on simple collagen material, bacterial growth is vigorous.On simple chitosan material bacterial growth quantity lower than collagen group higher than the composite group of collagen, chitosan and chrysophanol.To use on the material of collagen and chitosan compound bacterial growth quantity in bacterial growth quantity and simple chitosan material basically identical.
The preparation of embodiment 3. Novel multifunctional hemostatic dressing, prepares corresponding chitosan, collagen and chrysophanol by above-mentioned steps (1) (2) (3) method, carries out the compound of different proportionings by step (4).
After the collagen obtained, chitosan, chrysophanol composite are cross-linked lyophilizing, cover the mice position that limb injury is hemorrhage, observe mice and enliven very soon, it is freely movable to start.And using merely the group of collagen-based materials and chitosan material, mice activity is restricted, and illustrates that the hemostatic material that collagen, chitosan and chrysophanol are composited can not only stop blooding rapidly, can also alleviating pain, recovers the mobility of mice.
The preparation of embodiment 4. Novel multifunctional hemostatic dressing, prepares corresponding chitosan, collagen and chrysophanol by above-mentioned steps (1) (2) (3) method, carries out the compound of different proportionings by step (4).
After the collagen obtained, chitosan, chrysophanol composite are cross-linked lyophilizing, cover the mice position that limb injury is hemorrhage, observe wound after 1 day and substantially heal.And the mice wound using merely collagen, simple use chitosan and use collagen and Chitosan Composites to cover heals after 3 days substantially.Illustrate that the hemostatic material that collagen, chitosan and chrysophanol are composited can not only stop blooding rapidly, the healing of wound can also be promoted.

Claims (1)

1. can quick-acting haemostatic powder, antalgic and inflammation relieving and a Novel multifunctional hemostatic dressing for Promotive union, it is characterized in that: adopt following method preparation:
(1), the preparation of different desacetylated degree chitosans; By chitin after high alkali liquid process, acetamido meeting partial hydrolysis in molecule, just chitosan is become when acetyl group more than half in molecule removes, because on chitin monomer C2 position, acetamido instead of hydroxyl, it is insoluble to diluted acid diluted alkaline and organic solvent, its character like fibrous element, just can dissolve when acetyl group more than half is removed in acid; When chitosan dissolves in an acidic solution, the free amino (-NH on monomer molecule 2) protonated and positively charged (-NH 3+) become cationic polymer, the material that some are electronegative can be adsorbed;
(2), the preparation of reconstructed collagen albumen is modified: control the chemical modification degree of collagen protein, molecular entity, molecular weight and concentration, wherein, collagen types and content: NTx, noncollagen protein impurity content <1 ‰; Melt temperature Tp:50 DEG C-80 DEG C; Total metals: <10mg/kg; Sugar content: <1.0g/kg; Fat content: <0.1 ‰; Ash: <1.0 ‰; PH value: 7.0 ± 0.4; Pyrogen: the qualification determination requirement meeting Pharmacopoeia of People's Republic of China 2000 editions two annex pyrogen tests; Haemolysis: hemolysis rate≤5%; Cytotoxicity: cytotoxicity I-0 grade;
(3), chrysophanol purification; Obtain the active substance stopped blooding in Chinese herb rhubarb; First with dilution heat of sulfuric acid, All Kind of Anthraquinone In Rhubarb glycosides is hydrolyzed into aglycon in this step, reusable heat chloroform extraction aglycon, with alkali liquor by chrysophanic acid, emodin, aloe-emodin removing in chloroform solution, and be separated chrysophanol and emodin with column chromatography, through the repeated multiple times recrystallization of ethanol, obtain highly purified chrysophanol; Adopt the content of high effective liquid chromatography for measuring wherein chrysophanol, make chrysophanol purity reach more than 98%;
(4), by above-mentioned collagen, chitosan and chrysophanol three carry out organic composite, guarantee lyophilizing pad composite sponge pliability, adventitia has sealing, adhesiveness and integrity.
CN201010185470.1A 2010-05-28 2010-05-28 A kind of Novel multifunctional hemostatic dressing Active CN102258802B (en)

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CN103007337B (en) * 2012-12-31 2014-11-19 凌峰 Polymer dressing and dressing patch
CN104043147B (en) * 2014-06-25 2016-06-29 崔超 Anesthesia Department sucks blood by the preparation method of sponge
CN106491568A (en) * 2016-11-09 2017-03-15 山东百玛海洋生物科技有限公司 A kind of marine organisms spray film for treating skin injury and infection and preparation method thereof
CN109303930A (en) * 2018-09-27 2019-02-05 湖南然元医用高科技蛋白线有限公司 A kind of Medical absorbable antiseptic dressing and preparation method thereof
CN111588902A (en) * 2020-05-25 2020-08-28 医工瑞思(福建)工程研究中心有限公司 Large-area wound first-aid dressing and preparation method thereof

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