CN108465123A - A kind of compound hemostatic material and preparation method thereof - Google Patents
A kind of compound hemostatic material and preparation method thereof Download PDFInfo
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- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/22—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
- A61L15/28—Polysaccharides or their derivatives
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- A—HUMAN NECESSITIES
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- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/18—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing inorganic materials
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/22—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
- A61L15/32—Proteins, polypeptides; Degradation products or derivatives thereof, e.g. albumin, collagen, fibrin, gelatin
- A61L15/325—Collagen
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/42—Use of materials characterised by their function or physical properties
- A61L15/44—Medicaments
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/42—Use of materials characterised by their function or physical properties
- A61L15/46—Deodorants or malodour counteractants, e.g. to inhibit the formation of ammonia or bacteria
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/10—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing inorganic materials
- A61L2300/102—Metals or metal compounds, e.g. salts such as bicarbonates, carbonates, oxides, zeolites, silicates
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
- A61L2300/23—Carbohydrates
- A61L2300/232—Monosaccharides, disaccharides, polysaccharides, lipopolysaccharides
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/404—Biocides, antimicrobial agents, antiseptic agents
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- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/418—Agents promoting blood coagulation, blood-clotting agents, embolising agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2400/00—Materials characterised by their function or physical properties
- A61L2400/04—Materials for stopping bleeding
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Abstract
The invention discloses a kind of compound hemostatic materials and preparation method thereof, and preparation method includes the following steps：Chitosan is scattered in acetic acid solution, stirring forms homogeneous solution；Hydrogen peroxide is added in the homogeneous solution, obtains chitooligosaccharide- solution；The chitooligosaccharide- solution is mixed evenly with collagen solution, standing obtains mixed gel；Calcium chloride solution and sodium alginate soln is added dropwise successively in the mixed gel, is sufficiently stirred at 50 DEG C, obtains cross-linked gel；The cross-linked gel is placed at 50 DEG C and is pre-chilled overnight, then after vacuum freeze drying 12h, obtains compound hemostatic material.The compound hemostatic material has both the double dominant of chitosan class and collagen class hemostatic material, further increase haemostatic effect, the chitooligosaccharide- obtained simultaneously by degradation of chitosan is outside the performance for possessing chitosan class hemostatic material, the anti-microbial property for improving material itself, wound infection when preventing from using.
Description
Technical field
The present invention relates to field of material technology more particularly to a kind of compound hemostatic material and preparation method thereof.
Background technology
All the time, excessive blood loss is all the first cause of personnel death in all kinds of burst accidents.In war, traffic accident
And in natural calamity, even if the wounded can be rescued in time, being sent to before hospital to bleed excessively can still cause higher death
Rate and serious complication (such as amputation).Therefore, the bleeding situation for effectively controlling the wounded has to reducing dead and disability rate
Very great meaning.
Traditional tourniquet is all difficult to effectively use for the bleeding of trunk position bleeding such as chest, abdomen etc., and tradition is stopped
Blood material is such as：Degreasing cotton, gauze, tourniquet etc. is for the common wound in the scene such as irregular shape, deep, narrow, arteriorrhexis
Haemostatic effect is very undesirable.Although having developed some novel hemostatic materials, such as zeolite, oxycellulose, can inhale
Collagen protein sponge etc. is received, for their more traditional hemostatic materials, haemostatic effect has large increase, but is all lacked there is also larger
Point, and limit its clinical application.For example, meeting heat release during Zeolite hemostatic, even will produce the height more than 100 DEG C sometimes
Temperature causes the secondary injury of the surface of a wound.The shortcomings that collagen class hemostasia products is that its mechanical performance is poor, after encountering blood,
Easily damaged, for haemocyte, the drawing ability of blood platelet is very weak, therefore is difficult to stop for big wound bleeding.
Oxidized regenerated cellulose class hemostatic material contains a large amount of acidic-group, and after water is fully saturated, pH can reach 1.7, in acid
Under property environment, although there is certain bacteriostasis, but it is also possible to which remaining material can be enable to cause strong inflammation in wound
Disease reacts and the regeneration of obstruction bone tissue, or even granuloma, abscess can be formed etc..
Invention content
The present invention provides a kind of compound hemostatic material and preparation method thereof, to prepare with notable haemostatic effect, excellent
Good biocompatibility and degradable biomedical hemostatic material.
In a first aspect, the preparation method of compound hemostatic material provided by the invention, includes the following steps：
(1) chitosan is scattered in acetic acid solution, stirring forms homogeneous solution；
(2) hydrogen peroxide is added in the homogeneous solution, obtains chitooligosaccharide- solution；
(3) the chitooligosaccharide- solution is mixed evenly with collagen solution, standing obtains mixed gel；
(4) calcium chloride solution and sodium alginate soln is added dropwise successively in the mixed gel, is sufficiently stirred, obtains at 50 DEG C
To cross-linked gel；
(5) cross-linked gel is placed at -50 DEG C and is pre-chilled overnight, then after vacuum freeze drying 12h, obtain compound hemostatic
Material.
Optionally, in step (2), under the action of microwave and/or ultraviolet lamp, peroxidating is added in the homogeneous solution
Hydrogen obtains chitooligosaccharide- solution.
Optionally, the mass ratio of chitooligosaccharide-, collagen, calcium chloride and sodium alginate is 1：(0.1-0.5)：
(0.001-0.003)：(0.01-0.02).
Optionally, the mass ratio of the chitosan and acetic acid solution is 1：40, wherein the acetic acid solution it is a concentration of
1%.
Optionally, a concentration of 8-10% of the chitooligosaccharide- solution, a concentration of 1-5% of the collagen solution,
A concentration of 0.1-0.3% of the calcium chloride solution, a concentration of 1-2% of the sodium alginate soln.
Preferably, preparation method includes the following steps：
(1) 1g chitosans are scattered in 1% acetic acid solution of 40g concentration, stirring forms homogeneous solution；
(2) under the action of microwave and ultraviolet lamp, 2mL hydrogen peroxide is added in the homogeneous solution, it is oligomeric to obtain shell
Sugar juice；
(3) it takes the collagen solution 100g of 10% chitooligosaccharide- solution 100g and 3% to be mixed evenly, stands
Obtain mixed gel；
(4) 0.15% calcium chloride solution 10g and 1.5% sodium alginate soln is added dropwise successively in the mixed gel
10g is sufficiently stirred at 50 DEG C, obtains cross-linked gel；
(5) cross-linked gel is placed at -50 DEG C and is pre-chilled overnight, then after vacuum freeze drying 12h, obtain compound hemostatic
Material.
Second aspect, compound hemostatic material provided by the invention are prepared by method made above.
The invention has the advantages that：
(1) present invention is using chitooligosaccharide- and collagen as basic system, using calcium chloride as coagulation factor, with seaweed
Sour sodium makes chitooligosaccharide- system and collagen System forming composite network structure, wound surface can be made fast as crosslinking agent
Speed forms clot, reaches hemostasis purpose, while having both the double dominant of chitosan class and collagen class hemostatic material, further
Improve haemostatic effect.
(2) chitooligosaccharide- obtained by degradation of chitosan improves material outside the performance for possessing chitosan class hemostatic material
The anti-microbial property of material itself, wound infection when preventing from using.
It should be understood that above general description and following detailed description is only exemplary and explanatory, not
It can the limitation present invention.
Specific implementation mode
The present invention provides a kind of compound hemostatic material and preparation method thereof, to prepare with notable haemostatic effect, excellent
Good biocompatibility and degradable biomedical hemostatic material.Below in conjunction with the embodiment of the present invention, technical solution is carried out
It clearly and completely describes, it is clear that described embodiments are only a part of the embodiments of the present invention, rather than whole implementation
Example.Based on the embodiments of the present invention, obtained by those of ordinary skill in the art without making creative efforts
Every other embodiment, shall fall within the protection scope of the present invention.
Embodiment 1
A kind of compound hemostatic material provided in this embodiment, preparation method are as follows：
(1) 1g chitosans are scattered in 1% acetic acid solution of 40g concentration, stirring forms homogeneous solution.
(2) under the action of microwave and ultraviolet lamp, 2mL hydrogen peroxide is added in the homogeneous solution, it is oligomeric to obtain shell
Sugar juice.
(3) it takes the collagen solution 100g of 10% chitooligosaccharide- solution 100g and 3% to be mixed evenly, stands
Obtain mixed gel.
(4) 0.15% calcium chloride solution 10g and 1.5% sodium alginate soln is added dropwise successively in the mixed gel
10g is sufficiently stirred at 50 DEG C, obtains cross-linked gel.
(5) cross-linked gel is placed at -50 DEG C and is pre-chilled overnight, then after vacuum freeze drying 12h, obtain compound hemostatic
Materials A.
Embodiment 2
Another kind compound hemostatic material provided in this embodiment, preparation method are as follows：
(1) 1g chitosans are scattered in 1% acetic acid solution of 40g concentration, stirring forms homogeneous solution.
(2) under the action of microwave and ultraviolet lamp, 2mL hydrogen peroxide is added in the homogeneous solution, it is oligomeric to obtain shell
Sugar juice.
(3) it takes the collagen solution 100g of 10% chitooligosaccharide- solution 100g and 1% to be mixed evenly, stands
Obtain mixed gel.
(4) it is added dropwise 1% calcium chloride solution 10g and 1% sodium alginate soln 10g successively in the mixed gel, 50
It is sufficiently stirred at DEG C, obtains cross-linked gel.
(5) cross-linked gel is placed at -50 DEG C and is pre-chilled overnight, then after vacuum freeze drying 12h, obtain compound hemostatic
Material B.
Embodiment 3
Another compound hemostatic material provided in this embodiment, preparation method are as follows：
(1) 1g chitosans are scattered in 1% acetic acid solution of 40g concentration, stirring forms homogeneous solution.
(2) under the action of microwave and ultraviolet lamp, 2mL hydrogen peroxide is added in the homogeneous solution, it is oligomeric to obtain shell
Sugar juice.
(3) it takes the collagen solution 100g of 10% chitooligosaccharide- solution 100g and 5% to be mixed evenly, stands
Obtain mixed gel.
(4) 0.3% calcium chloride solution 10g and 2% sodium alginate soln 10g is added dropwise successively in the mixed gel,
It is sufficiently stirred at 50 DEG C, obtains cross-linked gel.
(5) cross-linked gel is placed at -50 DEG C and is pre-chilled overnight, then after vacuum freeze drying 12h, obtain compound hemostatic
Material C.
Comparative example 1
A kind of compound hemostatic material that this comparative example provides, preparation method are as follows：
(1) it takes the collagen solution 100g of 10% chitosan solution 100g and 3% to be mixed evenly, stands
To mixed gel.
(2) 0.15% calcium chloride solution 10g and 1.5% sodium alginate soln is added dropwise successively in the mixed gel
10g is sufficiently stirred at 50 DEG C, obtains cross-linked gel
(3) cross-linked gel is placed at -50 DEG C and is pre-chilled overnight, then after vacuum freeze drying 12h, obtain compound hemostatic
Material D.
Comparative example 2
A kind of chitooligosaccharide- hemostatic material that this comparative example provides, preparation method are as follows：
(1) 1g chitosans are scattered in 1% acetic acid solution of 40g concentration, stirring forms homogeneous solution.
(2) under the action of microwave and ultraviolet lamp, 2mL hydrogen peroxide is added in the homogeneous solution, it is oligomeric to obtain shell
Sugar juice.
(3) cross-linked gel is placed at -50 DEG C and is pre-chilled overnight, then after vacuum freeze drying 12h, obtain chitooligosaccharide-
Hemostatic material.
Comparative example 3
A kind of collagen hemostatic material that this comparative example provides, preparation method are as follows：
(1) 3% collagen solution 100g, standing is taken to obtain gel.
(2) cross-linked gel is placed at -50 DEG C and is pre-chilled overnight, then after vacuum freeze drying 12h, obtain collagen
Hemostatic material.
External coagulant property test
The present invention carries out the external coagulant property test of hemostatic material using BCI (Blood Clotting Index).It takes out
It takes the new blood of rabbit and the Abs values of anti-coagulants detection detected materials is added.
Clotting index BCI=ASample/ADeionized water×100。
The BCI of 1 each detected materials of table is compared
The value of clotting index BCI is smaller, and the coagulating effectiveness for representing its respective material is better, on the contrary then opposite.It can by upper table
Know that the coagulating effectiveness of chitooligosaccharide- (chitosan)/collagen compound hemostatic material is above chitooligosaccharide- hemostatic material or collagen
Albumen hemostatic material.
Bacteriostasis property is tested
Bacteriostatic test uses U.S. textile dyeing chemistry association AATCC 100-2004 bacteriostatic experiment standards.Testing strain is
Gram-negative bacteria ATCC No.8739 Escherichia coli and gram-positive bacteria ATCC No.6538 staphylococcus aureuses, will survey
Examination strain cultivates 18h under the conditions of 37 DEG C in 4mL culture solutions, is at growth logarithmic phase.Then by bacteria culture fluid with general
Logical culture medium is diluted to 10,102,104,108 times successively.All detected materials are cut into the disk of a diameter of 4cm, and divide
It is not put in different ground conical flasks, while above-mentioned bacterial solution is added, calculate bacteriostasis rate.
Bacteriostasis rate Reduction in CFU=(C-A)/C × 100%.
The bacteriostasis rate of 2 each detected materials of table compares
Bacteriostasis rate is bigger, and the antibacterial effect for representing its respective material is better, on the contrary then opposite.Shell is oligomeric as seen from the above table
The antibacterial effect of sugar/collagen compound hemostatic material is above other three kinds.In particular, comparative example 1 and comparative example 1,
By the chitooligosaccharide- obtained after degradation of chitosan to prepare compound hemostatic material, antibacterial effect is apparently higher than directly with shell
Compound hemostatic material prepared by glycan.
Invention described above embodiment is not intended to limit the scope of the present invention..
Those skilled in the art will readily occur to its of the present invention after considering specification and putting into practice the disclosure invented here
Its embodiment.The present invention is directed to cover the present invention any variations, uses, or adaptations, these modifications, purposes or
Person's adaptive change follows the general principle of the present invention and includes undocumented common knowledge in the art of the invention
Or conventional techniques.The description and examples are only to be considered as illustrative, and true scope and spirit of the invention are by following
Claim is pointed out.
Claims (7)
1. a kind of preparation method of compound hemostatic material, which is characterized in that include the following steps：
(1) chitosan is scattered in acetic acid solution, stirring forms homogeneous solution；
(2) hydrogen peroxide is added in the homogeneous solution, obtains chitooligosaccharide- solution；
(3) the chitooligosaccharide- solution is mixed evenly with collagen solution, standing obtains mixed gel；
(4) calcium chloride solution and sodium alginate soln is added dropwise successively in the mixed gel, is sufficiently stirred, is handed at 50 DEG C
Join gel；
(5) cross-linked gel is placed at -50 DEG C and is pre-chilled overnight, then after vacuum freeze drying 12h, obtain compound hemostatic material
Material.
2. preparation method according to claim 1, which is characterized in that in step (2), in microwave and/or the work of ultraviolet lamp
Under, hydrogen peroxide is added in the homogeneous solution, obtains chitooligosaccharide- solution.
3. preparation method according to claim 1, which is characterized in that chitooligosaccharide-, collagen, calcium chloride and alginic acid
The mass ratio of sodium is 1：(0.1-0.5)：(0.001-0.003)：(0.01-0.02).
4. preparation method according to claim 1, which is characterized in that the mass ratio of the chitosan and acetic acid solution is 1：
40, wherein a concentration of the 1% of the acetic acid solution.
5. preparation method according to claim 3, which is characterized in that a concentration of 8-10% of the chitooligosaccharide- solution,
A concentration of 1-5% of the collagen solution, a concentration of 0.1-0.3% of the calcium chloride solution, the sodium alginate are molten
A concentration of 1-2% of liquid.
6. preparation method according to claim 1, which is characterized in that include the following steps：
(1) 1g chitosans are scattered in 1% acetic acid solution of 40g concentration, stirring forms homogeneous solution；
(2) under the action of microwave and ultraviolet lamp, 2mL hydrogen peroxide is added in the homogeneous solution, it is molten to obtain chitooligosaccharide-
Liquid；
(3) the collagen solution 100g of 10% chitooligosaccharide- solution 100g and 3% is taken to be mixed evenly, standing obtains
Mixed gel；
(4) it is added dropwise 0.15% calcium chloride solution 10g and 1.5% sodium alginate soln 10g successively in the mixed gel, 50
It is sufficiently stirred at DEG C, obtains cross-linked gel；
(5) cross-linked gel is placed at -50 DEG C and is pre-chilled overnight, then after vacuum freeze drying 12h, obtain compound hemostatic material
Material.
7. the compound hemostatic material that a kind of preparation method as described in claim 1-6 is prepared.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11806430B1 (en) | 2023-02-24 | 2023-11-07 | King Faisal University | Rectal gel with date palm phenolics and vanillic acid |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11806430B1 (en) | 2023-02-24 | 2023-11-07 | King Faisal University | Rectal gel with date palm phenolics and vanillic acid |
| US11833246B1 (en) | 2023-02-24 | 2023-12-05 | King Faisal University | Rectal gel with date palm phenolics and vanillic acid |
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