CN106668932A - Bleeding stopping material, preparation method and applications thereof - Google Patents
Bleeding stopping material, preparation method and applications thereof Download PDFInfo
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- CN106668932A CN106668932A CN201610921959.8A CN201610921959A CN106668932A CN 106668932 A CN106668932 A CN 106668932A CN 201610921959 A CN201610921959 A CN 201610921959A CN 106668932 A CN106668932 A CN 106668932A
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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
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
- A61L24/046—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
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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
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/001—Use of materials characterised by their function or physical properties
- A61L24/0015—Medicaments; Biocides
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G81/00—Macromolecular compounds obtained by interreacting polymers in the absence of monomers, e.g. block polymers
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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
- A61L2300/412—Tissue-regenerating or healing or proliferative 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 present invention relates to a bleeding stopping material and a preparation method thereof, wherein an aldehyde modified mixture formed from aldehyde modified sodium alginate and aldehyde modified sodium hyaluronate and an amino modified polyaspartic hydrazide are subjected to a Schiff base reaction to obtain the bleeding stopping material, the bleeding stopping material has characteristics of high coagulation rate and good mechanical property, the mechanical property can be up to 6000 Pa, the wound healing is rapid after the use of the bleeding stopping material, the fastest coagulation rate is 5 s, and the in vivo mouse naked eye wound area observation test results show that the coagulation rate of the bleeding stopping material is 3 days faster than the gauze and is 1 day faster than the commercial sodium alginate dressing. The present invention further provides a bleeding stopping kit, which has characteristics of simple use, high coagulation rate, and rapid wound healing after the use.
Description
Technical field
The invention belongs to technical field of biological material, and in particular to a kind of hemostatic material and preparation method and application, further
Specifically related to a kind of hemostatic material and preparation method thereof and a kind of hemostasis agents box for preparing the hemostatic material.
Background technology
Hemostatic material develops through several sections, by natural Cotton and Linen to artificial macromolecular material again to natural polymer material
Material.Now increasing researcher throws eye on modified to natural polymer, by be modified retain it is original it is nontoxic,
Environmental friendliness, good biocompatibility, it is degradable the advantages of on the basis of, strengthen its ability for wound hemostasis.
Existing hemostatic material blood coagulation speed is low, poor mechanical property, dialysis purification time are long, using rear speed of wound healing
Slowly.
The content of the invention
The technical problem to be solved is to provide a kind of hemostatic material and its system for the deficiencies in the prior art
Preparation Method.The hemostatic material blood coagulation speed is high, mechanical property is good, the dialysis purification time is short, very fast using rear speed of wound healing.
For this purpose, first aspect present invention provides a kind of hemostatic material, it is modified transparent by aldehyde modified sodium alginate and aldehyde
The aldehyde modified mixture that matter acid sodium is formed carries out schiff base reaction and obtains with the modified PAHy of amine.
In the present invention, shown in the aldehyde modified sodium alginate such as formula (I)；The aldehyde modified hyaluronic acid sodium such as formula (II) institute
Show；Shown in the modified PAHy such as formula (III) of the amine：
In some embodiments of the invention, aldehyde modified sodium alginate and aldehyde modified hyaluronic acid in the aldehyde modified mixture
The weight ratio of sodium is 1: 1.
In some embodiments of the invention, the aldehyde modified mixture is 1: 1 with the weight ratio of the modified PAHy of amine.
In the present invention, the percent grafting 30-50% of aldehyde modified sodium alginate.
In the present invention, the percent grafting of aldehyde modified hyaluronic acid sodium is in 30-50%.
In the present invention, the percent grafting of the modified PAHy of amine is 80-92%.
In some embodiments of the invention, aldehyde modified sodium alginate molecular weight is 5100-24700Da.
In some embodiments of the invention, aldehyde modified hyaluronic acid sodium molecule amount is 150000-480000Da.
In some embodiments of the invention, the modified PAHy molecular weight of amine is 20000-100000Da, and preferred amines change
Property PAHy molecular weight be 60000-100000Da, the modified PAHy molecular weight of further preferred amine is 60000Da.
In the present invention, into gel state, gel strength is 1000-6000Pa to the hemostatic material.
Second aspect present invention provide hemostatic material described in a kind of first aspect present invention preparation method, it include by
Aldehyde modified mixture aqueous solution and amine that aldehyde modified sodium alginate aqueous solution and aldehyde modified hyaluronic acid sodium water solution are mixed to form
Carry out after modified PAHy aqueous solution schiff base reaction be obtained gel state hemostatic material the step of.
In some embodiments of the invention, aldehyde modified sodium alginate and the modified hyalomitome of aldehyde in the aldehyde modified mixture
The weight ratio of sour sodium is 1: 1.
In some embodiments of the invention, the aldehyde modified mixture and the weight ratio of the modified PAHy of amine are 1:
1。
In some embodiments of the invention, the concentration of aldehyde modified sodium alginate aqueous solution is 0.05-0.25g/mL, preferably
The concentration of aldehyde modified sodium alginate aqueous solution is 0.10-0.25g/mL.
In some embodiments of the invention, the concentration of aldehyde modified hyaluronic acid sodium water solution is 0.05-0.25g/mL, excellent
The concentration for selecting aldehyde modified hyaluronic acid sodium water solution is 0.10-0.25g/mL.
In some embodiments of the invention, the concentration of the modified PAHy aqueous solution of amine is 0.1-0.5g/mL, preferably
Concentration 0.2-0.5g/mL of the modified PAHy aqueous solution of amine.
In the present invention, the temperature of the schiff base reaction is room temperature.
In some embodiments of the invention, the time of the schiff base reaction be less than 170s, the preferably schiff bases are anti-
The time answered is less than 15s, and the further preferably time of the schiff base reaction is 5-10s.
Third aspect present invention provides a kind of hemostasis agents box, and it includes feed bin A that is independent or being set up in parallel and feed bin
B, wherein, the aldehyde modified mixture that formed containing aldehyde modified sodium alginate and aldehyde modified hyaluronic acid sodium in feed bin A or contain aldehyde
The aldehyde modified mixture aqueous solution of modified sodium alginate and aldehyde modified hyaluronic acid sodium, feed bin B contains the modified PAHy of amine
Or the modified PAHy aqueous solution of amine.
In some embodiments of the invention, aldehyde modified sodium alginate and the modified hyalomitome of aldehyde in the aldehyde modified mixture
The weight ratio of sour sodium is 1: 1.
In some embodiments of the invention, the aldehyde modified mixture and the weight ratio of the modified PAHy of amine are 1:
1。
In some embodiments of the invention, the concentration of aldehyde modified sodium alginate aqueous solution is 0.05-0.25g/mL, preferably
The concentration of aldehyde modified sodium alginate aqueous solution is 0.10-0.25g/mL.
In some embodiments of the invention, the concentration of aldehyde modified hyaluronic acid sodium water solution is 0.05-0.25g/mL, excellent
The concentration for selecting aldehyde modified hyaluronic acid sodium water solution is 0.10-0.25g/mL.
In some embodiments of the invention, the concentration of the modified PAHy aqueous solution of amine is 0.1-0.5g/mL, preferably
Concentration 0.2-0.5g/mL of the modified PAHy aqueous solution of amine.
In some embodiments of the invention, the test kit also includes being connected modified mixed for exporting aldehyde with feed bin A
The injection head A ' of compound aqueous solution and it is connected with feed bin B for the injection head B ' for exporting the modified PAHy aqueous solution of amine.
In other embodiments of the present invention, the test kit also include being connected with feed bin A and feed bin B simultaneously for
The injection head M of output aldehyde modified mixture aqueous solution and the modified PAHy aqueous solution of amine.
The invention has the beneficial effects as follows：
(1) hemostatic material provided by the present invention is changed by the aldehyde that aldehyde modified sodium alginate and aldehyde modified hyaluronic acid sodium are formed
Property the modified PAHy of mixture and amine carry out schiff base reaction and be obtained, its blood coagulation speed is high, mechanical property is good, can reach
Short to 6000Pa, dialysis purification time, most fast 5s blood coagulation very fast using rear speed of wound healing, mice experiment made on the living naked eyes are hindered
Open area is observed 1 day faster than commercially available sodium alginate dressing 3 days faster than gauze.
(2) hemostasis agents box provided by the present invention, operation and easy to use, blood coagulation speed is high, using rear wound healing
Speed.
Description of the drawings
The present invention is illustrated below in conjunction with accompanying drawing.
Fig. 1 is aldehyde modified sodium alginate preparation principle figure.
Fig. 2 is aldehyde modified hyaluronic acid sodium preparation principle figure.
Fig. 3 changes the PAHy preparation principle figure of surname for amido.
Fig. 4 is aldehyde radical and the modified PAHy of amine in aldehyde modified sodium alginate of the present invention and aldehyde modified hyaluronic acid sodium
In hydrazides group reaction principle figure.
Fig. 5 is the schematic diagram of the hemostasis agents box containing two injection heads：
Fig. 6 is the schematic diagram of the hemostasis agents box containing an injection head；
The implication of the reference in Fig. 5 and Fig. 6 is：A feed bin A；B feed bin B；The injection head A ' that A ' is connected with feed bin A；
The injection head B ' that B ' is connected with feed bin B；The injection head M that M is connected with feed bin A and feed bin B simultaneously.
Fig. 7 shows commercially available and experimental group wound initial stage comparing result.
Fig. 8 shows commercially available and experimental group wound phase comparing result.
Specific embodiment
To make the present invention easy to understand, below in conjunction with accompanying drawing the present invention is described in detail.
As it was previously stated, existing hemostatic material blood coagulation speed is low, poor mechanical property, dialysis purification time are long, using rear wound
Mouth healing rate is slow.In consideration of it, the present inventor has carried out lot of experiments for hemostatic material, the present inventor's research finds,
Schiff base reaction will be carried out with the modified PAHy of amine after aldehyde modified sodium alginate and the mixing of aldehyde modified hyaluronic acid sodium, can be with
Plastic is condensed within the extremely short time, thus solidifies blood, produce quick-acting haemostatic powder effect, and resulting gel is solidifying
Glue intensity is high, and mechanical property is good, and wound healing promoting is excellent.The present invention is based on what above-mentioned discovery was made.
It will be understood by a person skilled in the art that hemostatic material provided by the present invention can pass through aldehyde at the position for needing hemostasis
Schiff bases fast reaction is carried out after modified sodium alginate and the mixing of aldehyde modified hyaluronic acid sodium with the modified PAHy of amine to obtain,
So as to play a part of quick-acting haemostatic powder.
Shown in the structural formula such as formula (I) of heretofore described aldehyde modified sodium alginate (ALG-CHO), it is by sodium alginate
(ALG) aqueous solution and sodium metaperiodate aqueous solution carry out lucifuge stirring reaction, and with ethylene glycol terminating reaction, then Jing ultrafiltration and lyophilizing
Obtain.The principle of above-mentioned reaction is as shown in Figure 1.
In some embodiments of the invention, for example, at 30 DEG C, add in the sodium alginate aqueous solution of mass concentration 5%
Equimolar sodium metaperiodate aqueous solution, lucifuge stirring reaction adds ethylene glycol terminating reaction after 3 hours, surpassed with ultrafiltration cup
Filter, lyophilization obtains aldehyde modified sodium alginate.
Heretofore described aldehyde modified hyaluronic acid sodium (HA-CHO+,Or HAALD) structural formula such as formula (II) shown in, its by
Hyaluronic acid (HA) aqueous solution carries out lucifuge stirring reaction with sodium metaperiodate aqueous solution, and super with ethylene glycol terminating reaction, then Jing
Filter and lyophilizing are obtained.The principle of above-mentioned reaction is as shown in Figure 2.
In some embodiments of the invention, for example, at 30 DEG C, add in the hyaluronic acid aqueous solution of mass concentration 5%
Equimolar sodium metaperiodate aqueous solution, lucifuge stirring reaction adds ethylene glycol terminating reaction after 3 hours, surpassed with ultrafiltration cup
Filter, lyophilization obtains aldehyde modified hyaluronic acid sodium.
Shown in the structural formula such as formula (III) of heretofore described amine modified polyaspartic acid (PAHy), it is by by poly- amber
The DMF solution of amber acid imide (PSI) and hydrazine hydrate (NH2-NH2·H2O haptoreaction) is carried out, reactant is taken out
Again Jing ultrafiltration is obtained with being dried after worry.The principle of above-mentioned reaction is as shown in Figure 3.
Aldehyde radical in the present invention in aldehyde modified sodium alginate and aldehyde modified hyaluronic acid sodium is modified in PAHy with amine
Hydrazides group schiff base reaction principle it is as shown in Figure 4.Due to the response speed of hydrazides group and aldehyde radical it is fast, product chemistry
Matter is stablized, and the protein of body surface can also participate in the schiff base reaction of unreacted group around hydrogel, and this can be more
Contribute to material and act on difficult for drop-off with epidermis.
In some embodiments of the invention, for example, 4g polysuccinimides are dissolved in into 20mLN, dinethylformamide
(DMF) 4mL hydrazine hydrates, are added, 40 DEG C are reacted 4 hours, and sucking filtration retains solid dissolving ultrafiltration in water, and lyophilization obtains amine
Modified polyaspartic acid.
Each reactant of participation schiff base reaction is carried out reaction in the way of aqueous solution and obtains hemostatic material in this law, specifically
It is water-soluble including the aldehyde modified mixture for being mixed to form aldehyde modified sodium alginate aqueous solution and aldehyde modified hyaluronic acid sodium water solution
The step of schiff base reaction being carried out after the modified PAHy aqueous solution of liquid and amine gel state hemostatic material is obtained.
In some embodiments of the invention, aldehyde modified sodium alginate and the modified hyalomitome of aldehyde in the aldehyde modified mixture
The weight ratio of sour sodium is 1: 1, and the aldehyde modified mixture is 1: 1 with the weight ratio of the modified PAHy of amine.
In some embodiments of the invention, the concentration of aldehyde modified sodium alginate aqueous solution is 0.05-0.25g/mL, preferably
The concentration of aldehyde modified sodium alginate aqueous solution be 0.10-0.25g/mL, further preferred aldehyde modified sodium alginate aqueous solution it is dense
Spend for 0.25g/mL.
In some embodiments of the invention, the concentration of aldehyde modified hyaluronic acid sodium water solution is 0.05-0.25g/mL, excellent
The concentration for selecting aldehyde modified hyaluronic acid sodium water solution is 0.10-0.25g/mL, and further preferred aldehyde modified hyaluronic acid sodium is water-soluble
The concentration of liquid is 0.25g/mL.
In some embodiments of the invention, the concentration of the modified PAHy aqueous solution of amine is 0.1-0.5g/mL, preferably
The concentration of the modified PAHy aqueous solution of amine is 0.2-0.5g/mL, the modified PAHy aqueous solution of further preferred amine
Concentration is 0.5g/mL.
The temperature of schiff base reaction is had no particular limits in the present invention, generally the temperature of the schiff base reaction is room
Temperature.
Those skilled in the art should be recognized that the temperature of above-mentioned schiff base reaction can be 20-25 DEG C.
During the present inventor's research finds, quickly, aldehyde modified sodium alginate aqueous solution and aldehyde change above-mentioned schiff base reaction speed
Property the aldehyde modified mixture aqueous solution that is mixed to form of aqueous solution of sodium hyaluronate and the modified PAHy aqueous solution of amine after
Schiff base reaction can be just completed within the time less than 170s obtain gel state hemostatic material.In some preferred embodiments
In, aldehyde modified mixture aqueous solution that aldehyde modified sodium alginate aqueous solution and aldehyde modified hyaluronic acid sodium water solution are mixed to form with
After the modified PAHy aqueous solution of amine within 10s, or even schiff base reaction can be just completed within 5s obtain gel
State hemostatic material.
Because the mechanism of hemostatic material of the present invention hemostasis is aldehyde modified sodium alginate aqueous solution and aldehyde modified hyaluronic acid sodium
The aldehyde modified mixture aqueous solution that aqueous solution is formed carries out schiff bases fast reaction with the modified PAHy aqueous solution of amine,
Plastic can be condensed within the extremely short time, thus solidifies blood.Therefore, it is readily appreciated that, aldehyde modified sodium alginate water
The aldehyde modified mixture aqueous solution that solution and aldehyde modified hyaluronic acid sodium water solution are mixed to form and the modified PAHy water of amine
Solution carry out the time of schiff bases fast reaction plastic be exactly blood coagulation, hemostasis time.
It is in some specific embodiments of the present invention, 0.5mL concentration is water-soluble for the aldehyde modified sodium alginate of 0.25g/mL
Liquid adds the amine of 1mL concentration 0.5g/mL to be modified after mixing with the aldehyde modified hyaluronic acid sodium water solution of 0.5mL concentration 0.25g/mL
Mix in poly-aspartate aqueous solution, plastic can be reacted within 10s, produce blood coagulation, anastalsis.
People in the art should also be understood that hemostasis agents box provided by the present invention is for convenience of the present invention is applied
Hemostatic material and design, contained reagent in pending wound surface or wound can to carry out original in its two feed bin for being provided
Two kinds of materials of position schiff base reaction and plastic, what is filled in one of feed bin is modified containing aldehyde modified sodium alginate and aldehyde
The aldehyde modified mixture that hyaluronate sodium is formed or the aldehyde containing aldehyde modified sodium alginate and aldehyde modified hyaluronic acid sodium are modified mixed
Compound aqueous solution, what is filled in another feed bin is the modified PAHy of amine or the modified PAHy aqueous solution of amine.Therefore, originally
The there is provided hemostasis agents box of invention is it can be appreciated that a kind of device for administration of drugs that can be used for gel in-situ hemostasis.
It is easy to understand, it is that the aldehyde formed containing aldehyde modified sodium alginate and aldehyde modified hyaluronic acid sodium changes when what is filled in feed bin
Property mixture or during the modified PAHy of amine, the distilled water preparation as medical acceptable carriers can be added when in use
Form corresponding aldehyde modified mixture aqueous solution or amine containing aldehyde modified sodium alginate and aldehyde modified hyaluronic acid sodium modified poly-
Radix Asparagi hydrazides aqueous solution.
It is to be understood that the modified sea of aldehyde modified sodium alginate and aldehyde modified hyaluronic acid sodium or aldehyde in mentioned reagent box
Alginic acid sodium water solution and aldehyde modified hyaluronic acid sodium water solution can before administration be configured to the modified mixing of aldehyde with individualism
Thing or aldehyde modified mixture aqueous solution, used in being fitted in test kit feed bin.
In some specific embodiments of the present invention, hemostasis agents box provided by the present invention, including it is independent or set side by side
The feed bin A for putting and feed bin B, wherein, the aldehyde formed containing aldehyde modified sodium alginate and aldehyde modified hyaluronic acid sodium in feed bin A is modified
Mixture or the aldehyde modified mixture aqueous solution containing aldehyde modified sodium alginate and aldehyde modified hyaluronic acid sodium, feed bin B contains amine
Modified PAHy or the modified PAHy aqueous solution of amine.The test kit also includes being connected for exporting with feed bin A
The injection head A ' of aldehyde modified mixture aqueous solution and it is connected with feed bin B for the note for exporting the modified PAHy aqueous solution of amine
Penetrate a B '.
In some further specific embodiments of the present invention, the using method of test kit provided by the present invention is,
Using two injection head A ' and B ' aldehyde containing aldehyde modified sodium alginate and aldehyde modified hyaluronic acid sodium is modified at the same time or separately
The modified PAHy aqueous solution of mixture aqueous solution amine is expelled in pending wound surface or wound site, quick anti-by the two
Answer plastic and solidify blood, so as to produce anastalsis.
In some embodiments of the invention, hemostasis agents box provided by the present invention include the feed bin A that is set up in parallel and
Feed bin B, wherein, the aldehyde modified mixture that formed containing aldehyde modified sodium alginate and aldehyde modified hyaluronic acid sodium in feed bin A or contain
There is an aldehyde modified mixture aqueous solution of aldehyde modified sodium alginate and aldehyde modified hyaluronic acid sodium, feed bin B contains amine and is modified poly- Radix Asparagi
Hydrazides or the modified PAHy aqueous solution of amine.The test kit also includes being connected for exporting with feed bin A and feed bin B simultaneously
The injection head M of aldehyde modified mixture aqueous solution and the modified PAHy aqueous solution of amine.
In some further specific embodiments of the present invention, the using method of test kit provided by the present invention is,
Using an injection head M simultaneously by the aldehyde modified mixture aqueous solution containing aldehyde modified sodium alginate and aldehyde modified hyaluronic acid sodium
It is expelled in pending wound surface or wound site with the modified PAHy aqueous solution of amine, is made by the two fast reaction plastic
Blood solidifies, so as to produce anastalsis.
In the present invention, aldehyde modified mixture aqueous solution and amine containing aldehyde modified sodium alginate and aldehyde modified hyaluronic acid sodium
It is liquid after modified PAHy aqueous solution, reaction plastic is completed in a flash.Therefore, term of the present invention
" gelation time " refers to the time for starting to be mixed into this moment of plastic.
Using the molecular weight of each material of gel chromatography in the present invention：Using gel permeation chrommatograph (E2695, water generation
Company), chromatographic column selects watersGPC gel chromatographic columnses, and standard substance are dextran standard.Examine under 25 DEG C of room temperature conditions
Survey.
The present invention is determined under 25 DEG C of room temperature environments and stopped using rotary rheometer (AR2000ex, TA instrument companies of the U.S.)
The gel strength of blood material product.
The present invention is determined under 25 DEG C of room temperature environments and stopped using rotary rheometer (AR2000ex, TA instrument companies of the U.S.)
The gelation time of blood material product.
Embodiment
To make the present invention easier to understand, the present invention is further described below in conjunction with drawings and Examples,
These embodiments only play illustrative effect, it is not limited to the range of application of the present invention.Raw material or group used in the present invention
If divide can be obtained by commercial sources or conventional method without specified otherwise.
Embodiment 1：One is prepared using aldehyde modified hyaluronic acid sodium and aldehyde modified sodium alginate with the modified PAHy of amine
Plant hemostatic material.
At (1) 30 DEG C, 6.5g sodium metaperiodates, lucifuge stirring reaction 3 are added in the sodium alginate aqueous solution of mass concentration 5%
Ethylene glycol terminating reaction is added after hour, ultrafiltration is carried out with ultrafiltration cup, lyophilization obtains the modified sea of aldehyde that percent grafting is 30%
Sodium alginate, molecular weight is 24700Da；
At (2) 30 DEG C, 7.5g sodium metaperiodates, lucifuge stirring reaction 3 are added in the hyaluronic acid aqueous solution of mass concentration 5%
Ethylene glycol terminating reaction is added after hour, ultrafiltration is carried out with ultrafiltration cup, it is modified saturating that lyophilization obtains the aldehyde that percent grafting is 30%
Bright matter acid sodium, molecular weight is 480000Da；
(3) 4g polysuccinimides are dissolved in into 20mLN, dinethylformamide adds 4mL hydrazine hydrates, and 40 DEG C of reactions 4 are little
When, sucking filtration retains solid dissolving ultrafiltration in water, and lyophilization obtains the modified PAHy of amine that percent grafting is 80-92%,
Molecular weight is 60000Da；
(4) the aldehyde modified sodium alginate aqueous solution by 1mL concentration for 0.05g/mL is modified with the aldehyde of 1mL concentration 0.05g/mL
Aqueous solution of sodium hyaluronate is added after mixing and mixed in the modified PAHy aqueous solution of the amine of 1mL concentration 0.1g/mL.React into
The glue time is 170s.
Embodiment 2：Using aldehyde modified hyaluronic acid sodium and the modified PAHy of aldehyde modified sodium alginate and amine prepare
A kind of hemostatic material.
At (1) 30 DEG C, 7.5g sodium metaperiodates, lucifuge stirring reaction 3 are added in the sodium alginate aqueous solution of mass concentration 5%
Ethylene glycol terminating reaction is added after hour, ultrafiltration is carried out with ultrafiltration cup, lyophilization obtains the modified sea of aldehyde that percent grafting is 36%
Sodium alginate, molecular weight is 18200Da；
At (2) 30 DEG C, 8.5g sodium metaperiodates, lucifuge stirring reaction 3 are added in the hyaluronic acid aqueous solution of mass concentration 5%
Ethylene glycol terminating reaction is added after hour, ultrafiltration is carried out with ultrafiltration cup, it is modified saturating that lyophilization obtains the aldehyde that percent grafting is 36%
Bright matter acid sodium, molecular weight is 320000Da；
(3) 4g polysuccinimides are dissolved in into 20mLN, dinethylformamide adds 4mL hydrazine hydrates, and 40 DEG C of reactions 4 are little
When, sucking filtration retains solid dissolving ultrafiltration in water, and lyophilization obtains the modified PAHy of amine that percent grafting is 80-92%,
Molecular weight is 60000Da；
(4) the aldehyde modified sodium alginate aqueous solution by 1mL concentration for 0.05g/mL is modified with the aldehyde of 1mL concentration 0.05g/mL
Aqueous solution of sodium hyaluronate is added after mixing and mixed in the modified PAHy aqueous solution of the amine of 1mL concentration 0.1g/mL.React into
The glue time is 145s.
Embodiment 3：One is prepared using aldehyde modified hyaluronic acid sodium and aldehyde modified sodium alginate with the modified PAHy of amine
Plant hemostatic material.
At (1) 30 DEG C, 8.5g sodium metaperiodates, lucifuge stirring reaction 3 are added in the sodium alginate aqueous solution of mass concentration 5%
Ethylene glycol terminating reaction is added after hour, ultrafiltration is carried out with ultrafiltration cup, lyophilization obtains aldehyde modified sodium alginate, and molecular weight is
9800Da；
At (2) 30 DEG C, 9.5g sodium metaperiodates, lucifuge stirring reaction 3 are added in the hyaluronic acid aqueous solution of mass concentration 5%
Ethylene glycol terminating reaction is added after hour, ultrafiltration is carried out with ultrafiltration cup, it is modified saturating that lyophilization obtains the aldehyde that percent grafting is 42%
Bright matter acid sodium, molecular weight is 230000Da；
(3) 4g polysuccinimides are dissolved in into 20mLN, dinethylformamide adds 4mL hydrazine hydrates, and 40 DEG C of reactions 4 are little
When, sucking filtration retains solid dissolving ultrafiltration in water, and lyophilization obtains the modified PAHy of amine that percent grafting is 42%, point
Son amount is 60000Da；
(4) the aldehyde modified sodium alginate aqueous solution by 1mL concentration for 0.05g/mL is modified with the aldehyde of 1mL concentration 0.05g/mL
Aqueous solution of sodium hyaluronate is added after mixing and mixed in the modified PAHy aqueous solution of the amine of 1mL concentration 0.1g/mL.React into
The glue time is 125s.
Embodiment 4：One is prepared using aldehyde modified hyaluronic acid sodium and aldehyde modified sodium alginate with the modified PAHy of amine
Plant hemostatic material.
At (1) 30 DEG C, 9.5g sodium metaperiodates, lucifuge stirring reaction 3 are added in the sodium alginate aqueous solution of mass concentration 5%
Ethylene glycol terminating reaction is added after hour, ultrafiltration is carried out with ultrafiltration cup, lyophilization obtains the modified sea of aldehyde that percent grafting is 50%
Sodium alginate, molecular weight is 5100Da；
At (2) 30 DEG C, 10.5g sodium metaperiodates, lucifuge stirring reaction are added in the hyaluronic acid aqueous solution of mass concentration 5%
Ethylene glycol terminating reaction is added after 3 hours, ultrafiltration is carried out with ultrafiltration cup, it is modified saturating that lyophilization obtains the aldehyde that percent grafting is 50%
Bright matter acid sodium, molecular weight is 150000Da；
(3) 4g polysuccinimides are dissolved in into 20mLN, dinethylformamide adds 4mL hydrazine hydrates, and 40 DEG C of reactions 4 are little
When, sucking filtration retains solid dissolving ultrafiltration in water, and lyophilization obtains the modified PAHy of amine that percent grafting is 36%, point
Son amount is 60000Da；
(4) the aldehyde modified sodium alginate aqueous solution by 1mL concentration for 0.05g/mL is modified with the aldehyde of 1mL concentration 0.05g/mL
Aqueous solution of sodium hyaluronate is added after mixing and mixed in the modified PAHy aqueous solution of the amine of 1mL concentration 0.1g/mL.React into
The glue time is 110s.
Embodiment 5：One is prepared using aldehyde modified hyaluronic acid sodium and aldehyde modified sodium alginate with the modified PAHy of amine
Plant hemostatic material.
At (1) 30 DEG C, 6.5g sodium metaperiodates, lucifuge stirring reaction 3 are added in the sodium alginate aqueous solution of mass concentration 5%
Ethylene glycol terminating reaction is added after hour, ultrafiltration is carried out with ultrafiltration cup, lyophilization obtains the modified sea of aldehyde that percent grafting is 30%
Sodium alginate, molecular weight is 24700Da；
At (2) 30 DEG C, 7.5g sodium metaperiodates, lucifuge stirring reaction 3 are added in the hyaluronic acid aqueous solution of mass concentration 5%
Ethylene glycol terminating reaction is added after hour, ultrafiltration is carried out with ultrafiltration cup, it is modified saturating that lyophilization obtains the aldehyde that percent grafting is 30%
Bright matter acid sodium, molecular weight is 480000Da；
(3) 4g polysuccinimides are dissolved in into 20mLN, dinethylformamide adds 4mL hydrazine hydrates, and 40 DEG C of reactions 4 are little
When, sucking filtration retains solid dissolving ultrafiltration in water, and lyophilization obtains the modified PAHy of amine that percent grafting is 80-92%,
Molecular weight is 60000Da；
(4) it is that the aldehyde modified sodium alginate aqueous solution of 0.1g/mL and the aldehyde of 1mL concentration 0.1g/mL are modified saturating by 1mL concentration
Bright matter acid sodium aqueous solution is added after mixing and mixed in the modified PAHy aqueous solution of the amine of 1mL concentration 0.2g/mL.Reaction plastic
Time is 54s.
Embodiment 6：One is prepared using aldehyde modified hyaluronic acid sodium and aldehyde modified sodium alginate with the modified PAHy of amine
Plant hemostatic material.
At (1) 30 DEG C, 7.5g sodium metaperiodates, lucifuge stirring reaction 3 are added in the sodium alginate aqueous solution of mass concentration 5%
Ethylene glycol terminating reaction is added after hour, ultrafiltration is carried out with ultrafiltration cup, lyophilization obtains the modified sea of aldehyde that percent grafting is 36%
Sodium alginate molecular weight is 18200Da；
At (2) 30 DEG C, 8.5g sodium metaperiodates, lucifuge stirring reaction 3 are added in the hyaluronic acid aqueous solution of mass concentration 5%
Ethylene glycol terminating reaction is added after hour, ultrafiltration is carried out with ultrafiltration cup, it is modified saturating that lyophilization obtains the aldehyde that percent grafting is 36%
Bright matter acid sodium, molecular weight is 320000Da；
(3) 4g polysuccinimides are dissolved in into 20mLN, dinethylformamide adds 4mL hydrazine hydrates, and 40 DEG C of reactions 4 are little
When, sucking filtration retains solid dissolving ultrafiltration in water, and lyophilization obtains the modified PAHy of amine that percent grafting is 80-92%,
Molecular weight is 60000Da；
(4) it is that the aldehyde modified sodium alginate aqueous solution of 0.1g/mL and the aldehyde of 1mL concentration 0.1g/mL are modified saturating by 1mL concentration
Bright matter acid sodium aqueous solution is added after mixing and mixed in the modified PAHy aqueous solution of the amine of 1mL concentration 0.2g/mL.Reaction plastic
Time is 40s.
Embodiment 7：One is prepared using aldehyde modified hyaluronic acid sodium and aldehyde modified sodium alginate with the modified PAHy of amine
Plant hemostatic material.
At (1) 30 DEG C, 8.5g sodium metaperiodates, lucifuge stirring reaction 3 are added in the sodium alginate aqueous solution of mass concentration 5%
Ethylene glycol terminating reaction is added after hour, ultrafiltration is carried out with ultrafiltration cup, lyophilization obtains the modified sea of aldehyde that percent grafting is 42%
Sodium alginate, molecular weight is 9800Da；
At (2) 30 DEG C, 9.5g sodium metaperiodates, lucifuge stirring reaction 3 are added in the hyaluronic acid aqueous solution of mass concentration 5%
Ethylene glycol terminating reaction is added after hour, ultrafiltration is carried out with ultrafiltration cup, it is modified saturating that lyophilization obtains the aldehyde that percent grafting is 42%
Bright matter acid sodium, molecular weight is 230000Da；
(3) 4g polysuccinimides are dissolved in into 20mLN, dinethylformamide adds 4mL hydrazine hydrates, and 40 DEG C of reactions 4 are little
When, sucking filtration retains solid dissolving ultrafiltration in water, and lyophilization obtains the modified PAHy of amine that percent grafting is 80-92%,
Molecular weight is 60000Da；
(4) it is that the aldehyde modified sodium alginate aqueous solution of 0.1g/mL and the aldehyde of 1mL concentration 0.1g/mL are modified saturating by 1mL concentration
Bright matter acid sodium aqueous solution is added after mixing and mixed in the modified PAHy aqueous solution of the amine of 1mL concentration 0.2g/mL.Reaction plastic
Time is 35s.
Embodiment 8：One is prepared using aldehyde modified hyaluronic acid sodium and aldehyde modified sodium alginate with the modified PAHy of amine
Plant hemostatic material.
At (1) 30 DEG C, 9.5g sodium metaperiodates, lucifuge stirring reaction 3 are added in the sodium alginate aqueous solution of mass concentration 5%
Ethylene glycol terminating reaction is added after hour, ultrafiltration is carried out with ultrafiltration cup, lyophilization obtains the modified sea of aldehyde that percent grafting is 50%
Sodium alginate, molecular weight is 5100Da；
At (2) 30 DEG C, 10.5g sodium metaperiodates, lucifuge stirring reaction are added in the hyaluronic acid aqueous solution of mass concentration 5%
Ethylene glycol terminating reaction is added after 3 hours, ultrafiltration is carried out with ultrafiltration cup, it is modified saturating that lyophilization obtains the aldehyde that percent grafting is 50%
Bright matter acid sodium, molecular weight is 150000Da；
(3) 4g polysuccinimides are dissolved in into 20mLN, dinethylformamide adds 4mL hydrazine hydrates, and 40 DEG C of reactions 4 are little
When, sucking filtration retains solid dissolving ultrafiltration in water, and lyophilization obtains the modified PAHy of amine that percent grafting is 80-92%,
Molecular weight is 60000Da；
(4) it is that the aldehyde modified sodium alginate aqueous solution of 0.1g/mL and the aldehyde of 1mL concentration 0.1g/mL are modified saturating by 1mL concentration
Bright matter acid sodium aqueous solution is added after mixing and mixed in the modified PAHy aqueous solution of the amine of 1mL concentration 0.2g/mL.Reaction plastic
Time is 30s.
Embodiment 9：One is prepared using aldehyde modified hyaluronic acid sodium and aldehyde modified sodium alginate with the modified PAHy of amine
Plant hemostatic material.
At (1) 30 DEG C, 6.5g sodium metaperiodates, lucifuge stirring reaction 3 are added in the sodium alginate aqueous solution of mass concentration 5%
Ethylene glycol terminating reaction is added after hour, ultrafiltration is carried out with ultrafiltration cup, lyophilization obtains the modified sea of aldehyde that percent grafting is 30%
Sodium alginate, molecular weight is 24700Da；
At (2) 30 DEG C, 7.5g sodium metaperiodates, lucifuge stirring reaction 3 are added in the hyaluronic acid aqueous solution of mass concentration 5%
Ethylene glycol terminating reaction is added after hour, ultrafiltration is carried out with ultrafiltration cup, it is modified saturating that lyophilization obtains the aldehyde that percent grafting is 30%
Bright matter acid sodium, molecular weight is 480000Da；
(3) 4g polysuccinimides are dissolved in into 20mLN, dinethylformamide adds 4mL hydrazine hydrates, and 40 DEG C of reactions 4 are little
When, sucking filtration retains solid dissolving ultrafiltration in water, and lyophilization obtains the modified PAHy of amine that percent grafting is 80-92%,
Molecular weight is 60000Da；
(4) it is that the aldehyde modified sodium alginate aqueous solution of 0.2g/mL and the aldehyde of 1mL concentration 0.2g/mL are modified saturating by 1mL concentration
Bright matter acid sodium aqueous solution is added after mixing and mixed in the modified PAHy aqueous solution of the amine of 1mL concentration 0.4g/mL.Reaction plastic
Time is 20s.
Embodiment 10：One is prepared using aldehyde modified hyaluronic acid sodium and aldehyde modified sodium alginate with the modified PAHy of amine
Plant hemostatic material.
At (1) 30 DEG C, 7.5g sodium metaperiodates, lucifuge stirring reaction 3 are added in the sodium alginate aqueous solution of mass concentration 5%
Ethylene glycol terminating reaction is added after hour, ultrafiltration is carried out with ultrafiltration cup, lyophilization obtains the modified sea of aldehyde that percent grafting is 36%
Sodium alginate molecular weight is 18200Da；
At (2) 30 DEG C, 8.5g sodium metaperiodates, lucifuge stirring reaction 3 are added in the hyaluronic acid aqueous solution of mass concentration 5%
Ethylene glycol terminating reaction is added after hour, ultrafiltration is carried out with ultrafiltration cup, it is modified saturating that lyophilization obtains the aldehyde that percent grafting is 36%
Bright matter acid sodium, molecular weight is 320000Da；
(3) 4g polysuccinimides are dissolved in into 20mLN, dinethylformamide adds 4mL hydrazine hydrates, and 40 DEG C of reactions 4 are little
When, sucking filtration retains solid dissolving ultrafiltration in water, and lyophilization obtains the modified PAHy of amine that percent grafting is 80-92%,
Molecular weight is 60000Da；
(4) it is that the aldehyde modified sodium alginate aqueous solution of 0.2g/mL and the aldehyde of 1mL concentration 0.2g/mL are modified saturating by 1mL concentration
Bright matter acid sodium aqueous solution is added after mixing and mixed in the modified PAHy aqueous solution of the amine of 1mL concentration 0.4g/mL.Reaction plastic
Time is 18s.
Embodiment 11：One is prepared using aldehyde modified hyaluronic acid sodium and aldehyde modified sodium alginate with the modified PAHy of amine
Plant hemostatic material.
At (1) 30 DEG C, 8.5g sodium metaperiodates, lucifuge stirring reaction 3 are added in the sodium alginate aqueous solution of mass concentration 5%
Ethylene glycol terminating reaction is added after hour, ultrafiltration is carried out with ultrafiltration cup, lyophilization obtains the modified sea of aldehyde that percent grafting is 42%
Sodium alginate, molecular weight is 9800Da；
At (2) 30 DEG C, 9.5g sodium metaperiodates, lucifuge stirring reaction 3 are added in the hyaluronic acid aqueous solution of mass concentration 5%
Ethylene glycol terminating reaction is added after hour, ultrafiltration is carried out with ultrafiltration cup, it is modified saturating that lyophilization obtains the aldehyde that percent grafting is 42%
Bright matter acid sodium, molecular weight is 230000Da；
(3) 4g polysuccinimides are dissolved in into 20mLN, dinethylformamide adds 4mL hydrazine hydrates, and 40 DEG C of reactions 4 are little
When, sucking filtration retains solid dissolving ultrafiltration in water, and lyophilization obtains the modified PAHy of amine that percent grafting is 80-92%,
Molecular weight is 60000Da；
(4) it is that the aldehyde modified sodium alginate aqueous solution of 0.2g/mL and the aldehyde of 1mL concentration 0.2g/mL are modified saturating by 1mL concentration
Bright matter acid sodium aqueous solution is added after mixing and mixed in the modified PAHy aqueous solution of the amine of 1mL concentration 0.4g/mL.Reaction plastic
Time is 15s.
Embodiment 12：One is prepared using aldehyde modified hyaluronic acid sodium and aldehyde modified sodium alginate with the modified PAHy of amine
Plant hemostatic material.
At (1) 30 DEG C, 9.5g sodium metaperiodates, lucifuge stirring reaction 3 are added in the sodium alginate aqueous solution of mass concentration 5%
Ethylene glycol terminating reaction is added after hour, ultrafiltration is carried out with ultrafiltration cup, lyophilization obtains the modified sea of aldehyde that percent grafting is 50%
Sodium alginate, molecular weight is 5100Da；
At (2) 30 DEG C, 10.5g sodium metaperiodates, lucifuge stirring reaction are added in the hyaluronic acid aqueous solution of mass concentration 5%
Ethylene glycol terminating reaction is added after 3 hours, ultrafiltration is carried out with ultrafiltration cup, it is modified saturating that lyophilization obtains the aldehyde that percent grafting is 50%
Bright matter acid sodium, molecular weight is 150000Da；
(3) 4g polysuccinimides are dissolved in into 20mLN, dinethylformamide adds 4mL hydrazine hydrates, and 40 DEG C of reactions 4 are little
When, sucking filtration retains solid dissolving ultrafiltration in water, and lyophilization obtains the modified PAHy of amine that percent grafting is 80-92%,
Molecular weight is 60000Da；
(4) it is that the aldehyde modified sodium alginate aqueous solution of 0.2g/mL and the aldehyde of 1mL concentration 0.2g/mL are modified saturating by 1mL concentration
Bright matter acid sodium aqueous solution is added after mixing and mixed in the modified PAHy aqueous solution of the amine of 1mL concentration 0.4g/mL.Reaction plastic
Time is 10s.
Embodiment 13：One is prepared using aldehyde modified hyaluronic acid sodium and aldehyde modified sodium alginate with the modified PAHy of amine
Plant hemostatic material.
At (1) 30 DEG C, 9.5g sodium metaperiodates, lucifuge stirring reaction 3 are added in the sodium alginate aqueous solution of mass concentration 5%
Ethylene glycol terminating reaction is added after hour, ultrafiltration is carried out with ultrafiltration cup, lyophilization obtains the modified sea of aldehyde that percent grafting is 50%
Sodium alginate, molecular weight is 5100Da；
At (2) 30 DEG C, 10.5g sodium metaperiodates, lucifuge stirring reaction are added in the hyaluronic acid aqueous solution of mass concentration 5%
Ethylene glycol terminating reaction is added after 3 hours, ultrafiltration is carried out with ultrafiltration cup, it is modified saturating that lyophilization obtains the aldehyde that percent grafting is 50%
Bright matter acid sodium, molecular weight is 150000Da；
(3) 4g polysuccinimides are dissolved in into 20mLN, dinethylformamide adds 4mL hydrazine hydrates, and 40 DEG C of reactions 4 are little
When, sucking filtration retains solid dissolving ultrafiltration in water, and lyophilization obtains the modified PAHy of amine that percent grafting is 80-92%,
Molecular weight is 60000Da；
(4) the aldehyde modified sodium alginate aqueous solution by 1mL concentration for 0.25g/mL is modified with the aldehyde of 1mL concentration 0.25g/mL
Aqueous solution of sodium hyaluronate is added after mixing and mixed in the modified PAHy aqueous solution of the amine of 1mL concentration 0.5g/mL.React into
The glue time is 5s.
Embodiment 14：
It is placed in after rat anesthesia on sterile working's plate, in the circular wound that behind both sides cutting diameter is 8mm, (depth is about
Reach the degree for switching to fascia).Rat is divided into 2 groups of AB, per group of 4 rat different number of days.A groups are that matched group adopts commercially available hemostasis
Material, B groups are experimental group, PAHy and ALG-CHO powder need to be configured to be applied to wound rapidly after the mixing of 0.2g/mL solution
On use.
Without the need for more conversion materials in experimentation, can suitably take gauze wrapping to prevent material to be destroyed, need during film recording
Remove gauze to observe.Wound healing rate is calculated using below equation
Computing formula：Wound healing rate=[(- the n-th day wound surface area of the 0th day wound surface area)/the 0th day wound surface area] *
100% (n=0,3,7,14)
Experiment made on the living process and result：
Because wound surface exposes in the environment in wound healing, dehydration is dried, generally interim extracellular environment is difficult to set up,
Therefore it is many to promote the somatomedin of healing to be difficult to play due promoting healing function in the case where slightly environment is disliked, therefore produce in wound
The interim extracellular environment of life, the healing that basic physical protection is conducive to wound is played to wound.
After after mouse anesthesia by the removing of back relevant position epidermal hair, fascia layer all of the above epidermal tissue is cut off, most
End form has two controls into the circular hole wound of a diameter of 8mm in a mouse back, and one material of general attack carries out 4 controls,
8 parallel wounds altogether.
Commercially available and experimental group wound initial stage comparing result is as shown in fig. 7, the commercially available Sargassum commonly used for hospital of Fig. 7 middle and upper parts
The experimental conditions of sour sodium gel class dressing, bottom be this laboratory prepare raw material carry out on wound it is in-situ cross-linked after feelings
Condition.It can be seen that commercially available material can not play good anastalsis, wound can continue oozing of blood, and hemostasis gel then can
Anastalsis is played in the quick crosslinking on wound.And there is gel in experimental group wound outside as protection when the 3rd day, no to send out
The pernicious necrosis of life, and commercially available material then there occurs the situation of blackening.Simultaneously material does not need other dressings to process, and mice can be free
Activity.
Commercially available and experimental group wound mid-term comparing result is as shown in figure 8, the commercially available Sargassum commonly used for hospital of Fig. 8 middle and upper parts
The experimental conditions of sour sodium gel class dressing, lower cloth be this laboratory prepare raw material carry out on wound it is in-situ cross-linked after feelings
Condition.It can be seen that commercially available material later stage healing state is similar to experimental group, experimental group is slightly faster than commercially available group, can play normal
Promoting healing effect.
The gel for determining hemostatic material prepared in above-described embodiment using 25 DEG C of room temperature environments of rotary rheometer is strong
Degree, the gel strength for as a result showing hemostatic material prepared in above-described embodiment is 1000-6000Pa；And mice experiment made on the living
As a result show, process wound surface or wound using hemostatic material prepared in above-described embodiment, naked eyes wound area of the present invention is seen
Examine faster 3 days than using gauze process, it is faster 1 day than using commercially available sodium alginate dressing process.
It should be noted that embodiment described above is only used for explaining the present invention, do not constitute to any of the present invention
Limit.By referring to exemplary embodiments, invention has been described, it should be appreciated that word wherein used is descriptive
With explanatory vocabulary, rather than limited vocabulary.By regulation the present invention can be made within the scope of the claims
Modification, and the present invention is revised in without departing substantially from scope and spirit of the present invention.Although the present invention described in it is related to
And specific method, material and embodiment, it is not intended that the present invention is limited to wherein disclosed particular case, conversely, this
It is bright to can be extended to other all methods and applications with identical function.
Claims (10)
1. a kind of hemostatic material, its aldehyde modified mixture formed by aldehyde modified sodium alginate and aldehyde modified hyaluronic acid sodium and amine
Modified PAHy carries out schiff base reaction and obtains.
2. hemostatic material according to claim 1, it is characterised in that shown in the aldehyde modified sodium alginate such as formula (I)；Institute
State shown in aldehyde modified hyaluronic acid sodium such as formula (II)；Shown in the modified PAHy such as formula (III) of the amine：
3. hemostatic material according to claim 1 and 2, it is characterised in that the modified Sargassum of aldehyde in the aldehyde modified mixture
Sour sodium is 1: 1 with the weight ratio of aldehyde modified hyaluronic acid sodium；And/or the aldehyde modified mixture and the modified PAHy of amine
Weight ratio is 1: 1；And/or the percent grafting 30-50% of aldehyde modified sodium alginate；And/or the percent grafting of aldehyde modified hyaluronic acid sodium
In 30-50%；And/or the percent grafting of the modified PAHy of amine is 80-92%；And/or aldehyde modified sodium alginate molecular weight is
5100-24700Da；And/or aldehyde modified hyaluronic acid sodium molecule amount is 150000-480000Da；And/or amine is modified poly- Radix Asparagi acyl
Hydrazine molecular weight is 20000-100000Da, and the modified PAHy molecular weight of preferred amines is 60000-100000Da；And/or it is described
Into gel state, gel strength is 1000-6000Pa to hemostatic material.
4. in a kind of claim 1-3 hemostatic material described in any one preparation method, it is included aldehyde modified sodium alginate
The aldehyde modified mixture aqueous solution that aqueous solution and aldehyde modified hyaluronic acid sodium water solution are mixed to form and the modified PAHy of amine
Carry out after aqueous solution schiff base reaction be obtained gel state hemostatic material the step of.
5. method according to claim 4, it is characterised in that aldehyde modified sodium alginate and aldehyde in the aldehyde modified mixture
The weight ratio of modified hyaluronic acid sodium is 1: 1；And/or the aldehyde modified mixture is with the weight ratio of the modified PAHy of amine
1∶1；And/or the concentration of aldehyde modified sodium alginate aqueous solution is 0.05-0.25g/mL, preferred aldehydes modified sodium alginate aqueous solution
Concentration is 0.10-0.25g/mL；And/or the concentration of aldehyde modified hyaluronic acid sodium water solution is 0.05-0.25g/mL, preferred aldehydes change
Property aqueous solution of sodium hyaluronate concentration be 0.10-0.25g/mL；The concentration of the modified PAHy aqueous solution of amine is 0.1-
0.5g/mL, concentration 0.2-0.5g/mL of the modified PAHy aqueous solution of preferred amines.
6. the method according to claim 4 or 5, it is characterised in that the temperature of the schiff base reaction is room temperature；And/or
The time of the schiff base reaction is less than 170s, and the preferably time of the schiff base reaction is less than 15s, further preferably described uncommon
The time of husband's alkali reaction is 5-10s.
7. a kind of hemostasis agents box, it includes individually or the feed bin A that is set up in parallel and feed bin B, wherein, change containing aldehyde in feed bin A
Property the aldehyde modified mixture or modified saturating containing aldehyde modified sodium alginate and aldehyde that formed of sodium alginate and aldehyde modified hyaluronic acid sodium
The aldehyde modified mixture aqueous solution of bright matter acid sodium, feed bin B contains the modified PAHy of amine or the modified PAHy of amine is water-soluble
Liquid.
8. test kit according to claim 7, it is characterised in that in the aldehyde modified mixture aldehyde modified sodium alginate with
The weight ratio of aldehyde modified hyaluronic acid sodium is 1: 1；And/or the weight ratio of the aldehyde modified mixture and the modified PAHy of amine
For 1: 1；And/or the concentration of aldehyde modified sodium alginate aqueous solution be 0.05-0.25g/mL, preferred aldehydes modified sodium alginate aqueous solution
Concentration be 0.10-0.25g/mL；And/or the concentration of aldehyde modified hyaluronic acid sodium water solution is 0.05-0.25g/mL, aldehyde is modified
The concentration of aqueous solution of sodium hyaluronate is 0.10-0.25g/mL；The concentration of the modified PAHy aqueous solution of amine is 0.1-0.5g/
ML, concentration 0.2-0.5g/mL of the modified PAHy aqueous solution of preferred amines.
9. the test kit according to claim 7 or 8, it is characterised in that the test kit also includes the use that is connected with feed bin A
It is connected water-soluble for exporting the modified PAHy of amine in the injection head A ' of output aldehyde modified mixture aqueous solution and with feed bin B
The injection head B ' of liquid.
10. the test kit according to claim 7 or 8, it is characterised in that the test kit also include simultaneously with feed bin A and
Feed bin B is connected for the injection head M for exporting aldehyde modified mixture aqueous solution and the modified PAHy aqueous solution of amine.
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| CN110251721A (en) * | 2019-08-02 | 2019-09-20 | 山东百多安医疗器械有限公司 | A kind of formed in situ selfreparing anti-bacterial hydrogel and preparation method thereof |
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