CN108815562A - A kind of preparation method of compound hemostatic material - Google Patents
A kind of preparation method of compound hemostatic material Download PDFInfo
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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
- A61L24/0047—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
- A61L24/0073—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material with a macromolecular matrix
- A61L24/0094—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material with a macromolecular matrix containing macromolecular fillers
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- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/001—Use of materials characterised by their function or physical properties
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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
- A61L24/0042—Materials resorbable by the body
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- D06—TREATMENT OF TEXTILES OR THE LIKE; LAUNDERING; FLEXIBLE MATERIALS NOT OTHERWISE PROVIDED FOR
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- D06M11/00—Treating fibres, threads, yarns, fabrics or fibrous goods made from such materials, with inorganic substances or complexes thereof; Such treatment combined with mechanical treatment, e.g. mercerising
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- D06—TREATMENT OF TEXTILES OR THE LIKE; LAUNDERING; FLEXIBLE MATERIALS NOT OTHERWISE PROVIDED FOR
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- D06M16/00—Biochemical treatment of fibres, threads, yarns, fabrics, or fibrous goods made from such materials, e.g. enzymatic
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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 kind of preparation methods of compound hemostatic material, belong to technical field of composite materials.The present invention is using the silver-colored alginate fibre of load, sodium carboxymethylcellulose, chitosan and starch prepare compound hemostatic material, the material haemostatic effect is good, with anti-microbial property, raw materials used is degradable materials, it will not cause wound inflammation in use, and promote neoblastic growth, chitosan makes erythrocyte surface crosslink with it and make red blood cell adhesion, to form thrombus hemostasis, carboxymethyl cellulose not only has good film forming, and have the function of preventing adhesions, alginate fibre Wound covering material itself has excellent compatibility, it can help wound blood coagulation, absorb the excessive secretion of wound, keep wound that certain humidity is maintained then to promote healing effect, alginate fibre lining material with wound body fluid after contacting, oxygen can be made to pass through, stop bacterium, and then promote neoblastic growth.
Description
Technical field
The present invention relates to a kind of preparation methods of compound hemostatic material, belong to technical field of composite materials.
Background technique
Effectively hemostasis has a very important role for saving patient vitals, to realize effective hemostasis, just be unable to do without only
The application of blood material.Traditional hemostatic material mainly includes gauze, tourniquet or bandage, and wherein tourniquet includes rubber formula and Buddhist nun
Two kinds of imperial button, there are also be exactly triangle bandage and cotton pad etc..Although these tradition hemostasis equipment can in a short time hurt rescue
Member and save life in play the role of it is highly important, but they for big angiorrbagia or large area wound bleeding almost
In vain.Traditional tourniquet hemostasis is to reach the reduction endovascular pressure in bleeding part by blocking wound site upstream blood,
This is to sacrifice the blood supply of remote organization as cost, it is easy to leads to tissue ischemia and metabolic disorder is caused to generate complication,
It even easily causes the aggregation due to toxic metabolite to cause shock or renal failure, can be in peril of one's life, entire body coagulates
Blood mechanism also will receive interference, it may occur that systemic blood coagulation even thrombus generates.To alleviate ischemia injury caused by pressing,
At regular intervals tourniquet loosen and will lead to big bleeding again.In addition, although tourniquet is to can control rescuing for bleeding
Raw equipment, but its big bleeding for the positions such as the torso portion and head of human body, neck, are but difficult with.And traditional hemostatic material
（Such as cotton gauze, triangle bandage, cotton pad etc.）For surface of a wound irregular shape, situations such as blutpunkte is deep, narrow or sound affectionately ruptures
Haemostatic effect be very unsatisfactory.It can be seen that it is novel quickly, the development of effective hemostatic material is urgent need to resolve in the world
It solves the problems, such as.
At present both at home and abroad research hemostatic material focus in：It, should applied to local hemostasis in human body or animal body
Hemostasis quickly, also want can degradation in vivo, do not have to take out, avoid removal hemostatic material when bleeding again.The material can be used for
Wartime wound hemostasis, accident rescue, surgical hemostasis etc..Therefore, ideal hemostatic material should have these features：
（1）Hemostasis is rapid, it is desirable that can stop the bleeding oozing of blood of main blood vessel and internal internal organs in 2 minutes；
（2）Can voluntarily degrade absorption in vivo, without long-term adverse effect；
（3）It is easy to operate using simplicity with good plasticity and convenience；
（4）Performance is stablized, and is convenient for carrying, and saves；
（5）It has no toxic side effect, without potential pathogenic, does not increase Infection probability；
（6）It is low in cost, price economy；
（7）Do not influence organization healing（Preferably promote organization healing）Deng.
The hemostatic material sold and used currently on the market is broadly divided into 3 classes from mechanism of action：The first kind passes through material
The physically or chemically effect of material absorbs the moisture near wound in blood, the hemostatic composition of wound blood is made to be concentrated, assemble,
To accelerate blood coagulation or material by the electrostatic interaction between surface charge and haemocyte, the viscous of red blood cell or blood platelet is improved
Ability of aggregation is echoed, increases clot viscosity and promotes blood clotting；Second class is directly to be closed using material to the very strong adhesion strength of tissue
The surface of a wound, to realize hemostasis；Third class is the substance for being directly or indirectly provided with styptic activity, and hemostatic material is effective by surface
Chemical component is reacted with blood effective component, starts or improve endogenous and exogenous cruor pathway, and then accelerates to generate
Blood coagulation.
Although having been developed for such as at present：Zeolite, oxycellulose, sponeostan, chitosan tourniquet,
Chitosan styptic powder etc., for their more traditional hemostatic materials, haemostatic effect has large increase, but all lacks there is also larger
Point, and limit its clinical application.Moreover, the preferable product of haemostatic effect that market is sold now is essentially all external product,
Price is 5~10 times of domestic similar product.In addition, the variation of social environment and modern battlefield environment are complicated, to fast short stopping
Diversification and multifunction is presented in the anthemorrhagic performance of blood material and the demand of other biological performance.Therefore, preparing has significantly
Haemostatic effect, excellent biocompatibility and degradable biomedical hemostatic material seem particularly significant and urgent.
Summary of the invention
The technical problems to be solved by the invention：It can cause strong inflammatory reaction in wound for existing hemostatic material
The problem of with bone tissue regeneration is hindered, provide a kind of preparation method of compound hemostatic material.
In order to solve the above technical problems, the technical solution adopted by the present invention is that：
（1）It is to take out in 5% silver nitrate solution after 6~8h that calcium alginate fibre, which is immersed in mass fraction, dry, obtains compound fibre
Dimension；
（2）Sodium carboxymethylcellulose and deionized water are mixed, 10~15min of ultrasonic disperse obtains dispersion liquid；In parts by weight
Meter, weigh respectively 10~20 parts of sodium carboxymethylcelluloses, 30~50 parts of chitosans, 10~16 parts of starch, 8~16 parts of glycerol, 1~
5 parts of glutaraldehydes first mix sodium carboxymethylcellulose and chitosan, quickly stir, obtain mixture, then sequentially add starch,
Glycerol, glutaraldehyde stir, and obtain substrate；
（3）Composite fibre, substrate and deionized water are mixed, aeroge is obtained, pre-freeze processing obtains pre-freeze aeroge, by pre-freeze gas
Gel is put into freeze drier freeze-drying process to get compound hemostatic material.
Step（1）The drying is to be placed in 60~80 DEG C of baking ovens to dry to constant weight.
Step（2）The sodium carboxymethylcellulose and deionized water in mass ratio 1: 3 mixes.
Step（2）The ultrasonic disperse is 10~15min of ultrasonic disperse in the case where power is 100~200W.
Step（2）The quick stirring is that 20~30r/min quickly stirs 5~10min for revolving speed at room temperature.
Step（3）Composite fibre, substrate and the deionized water in mass ratio 1: 2: 20 mixes.
Step（3）The pre-freeze processing is in -10~-20 DEG C of 20~40h of pre-freeze.
Step（3）The freeze-drying process is in the condition that temperature is -40~-20 DEG C, vacuum degree is 10~20Pa
Under, freeze-drying 20~for 24 hours.
The present invention is compared with other methods, and advantageous effects are：
（1）The present invention is prepared for carrying silver-colored alginate fibre using chemical reaction method, and alginate fibre has very high moisture pick-up properties, in sea
The silver ion with anti-microbial property is added in algae fiber, make alginate fibre that there is very high moisture pick-up properties while there is antibiotic property
Energy；
（2）The present invention prepares compound hemostatic material using silver-colored alginate fibre, sodium carboxymethylcellulose, chitosan and starch is carried, should
Material haemostatic effect is good, has anti-microbial property, raw materials used is degradable materials, wound will not be caused to send out in use
Inflammation, and promote neoblastic growth, chitosan makes erythrocyte surface crosslink with it and make red blood cell adhesion, in blood
Certain polymerization reaction occurs, forms space network, captures red blood cell and makes its polymerization, to form thrombus hemostasis, carboxylic first
Base sodium cellulosate has good cementability, emulsibility, biocompatibility and biodegradability, and filming performance is good, carboxylic first
Base cellulose is a kind of anionic linear polymeric polysaccharose substance, belongs to one kind of cellulose ether, usually with cellulose carboxylic
Acid salts exist, and not only have good film forming, and have the function of preventing adhesions, preventing adhesions mechanism master
If mechanical isolation acts on and weaken fibroblastic activity or proliferation, alginate fibre Wound covering material itself has excellent
Different compatibility, the secretion that wound blood coagulation, absorption wound can be helped excessive, the certain humidity of holding wound maintenance, which are then promoted, to be cured
Effect is closed, after contacting with wound body fluid, the calcium ion in material can be handed over alginate fibre lining material with the sodium ion in body fluid
It changes, so that alginate fibre material becomes water-setting glue by threadiness, since gel has hydrophily, oxygen can be made to pass through, stopped carefully
Bacterium, and then promote neoblastic growth.
Specific embodiment
It is to take out in 5% silver nitrate solution after 6~8h, be placed in 60~80 that calcium alginate fibre, which is immersed in mass fraction,
It dries in DEG C baking oven to constant weight, obtains composite fibre；In mass ratio 1: 3 mixes sodium carboxymethylcellulose and deionized water, in function
Rate is 10~15min of ultrasonic disperse under 100~200W, obtains dispersion liquid；According to parts by weight, 10~20 parts of carboxymethyls are weighed respectively
Sodium cellulosate, 30~50 parts of chitosans, 10~16 parts of starch, 8~16 parts of glycerol, 1~5 part of glutaraldehyde, first by carboxymethyl cellulose
Plain sodium and chitosan mixing, revolving speed is that 20~30r/min quickly stirs 5~10min at room temperature, obtains mixture, then successively
Starch, glycerol, glutaraldehyde is added to stir, obtains substrate；In mass ratio 1: 2: 20 by composite fibre, substrate and deionization
Water mixing, obtains aeroge, in -10~-20 DEG C of 20~40h of pre-freeze, obtains pre-freeze aeroge, pre-freeze aeroge is put into freeze-drying
In machine, under conditions of temperature is -40~-20 DEG C, vacuum degree is 10~20Pa, freeze-drying 20~for 24 hours to get compound hemostatic
Material.
It is to take out in 5% silver nitrate solution after 6h, be placed in 60 DEG C of baking ovens that calcium alginate fibre, which is immersed in mass fraction,
Middle drying obtains composite fibre to constant weight；In mass ratio 1: 3 mixes sodium carboxymethylcellulose and deionized water, is in power
Ultrasonic disperse 10min under 100W, obtains dispersion liquid；According to parts by weight, it is poly- that 10 parts of sodium carboxymethylcelluloses, 30 parts of shells are weighed respectively
Sugar, 10 parts of starch, 8 parts of glycerol, 1 part of glutaraldehyde first mix sodium carboxymethylcellulose and chitosan, and revolving speed is at room temperature
20r/min quickly stirs 5min, obtains mixture, then sequentially adds starch, glycerol, glutaraldehyde and stirs, obtains substrate；
In mass ratio 1: 2: 20 mixes composite fibre, substrate and deionized water, obtains aeroge, in -10 DEG C of pre-freeze 20h, obtains pre-freeze gas
Pre-freeze aeroge is put into freeze drier by gel, under conditions of temperature is -20 DEG C, vacuum degree is 10Pa, freeze-drying
20h is to get compound hemostatic material.
It is to take out in 5% silver nitrate solution after 7h, be placed in 70 DEG C of baking ovens that calcium alginate fibre, which is immersed in mass fraction,
Middle drying obtains composite fibre to constant weight；In mass ratio 1: 3 mixes sodium carboxymethylcellulose and deionized water, is in power
Ultrasonic disperse 12min under 150W, obtains dispersion liquid；According to parts by weight, it is poly- that 15 parts of sodium carboxymethylcelluloses, 40 parts of shells are weighed respectively
Sugar, 13 parts of starch, 12 parts of glycerol, 3 parts of glutaraldehydes first mix sodium carboxymethylcellulose and chitosan, and revolving speed is at room temperature
25r/min quickly stirs 8min, obtains mixture, then sequentially adds starch, glycerol, glutaraldehyde and stirs, obtains substrate；
In mass ratio 1: 2: 20 mixes composite fibre, substrate and deionized water, obtains aeroge, in -15 DEG C of pre-freeze 30h, obtains pre-freeze gas
Pre-freeze aeroge is put into freeze drier by gel, under conditions of temperature is -30 DEG C, vacuum degree is 15Pa, freeze-drying
22h is to get compound hemostatic material.
It is to take out in 5% silver nitrate solution after 8h, be placed in 80 DEG C of baking ovens that calcium alginate fibre, which is immersed in mass fraction,
Middle drying obtains composite fibre to constant weight；In mass ratio 1: 3 mixes sodium carboxymethylcellulose and deionized water, is in power
Ultrasonic disperse 15min under 200W, obtains dispersion liquid；According to parts by weight, it is poly- that 20 parts of sodium carboxymethylcelluloses, 50 parts of shells are weighed respectively
Sugar, 16 parts of starch, 16 parts of glycerol, 5 parts of glutaraldehydes first mix sodium carboxymethylcellulose and chitosan, and revolving speed is at room temperature
30r/min quickly stirs 10min, obtains mixture, then sequentially adds starch, glycerol, glutaraldehyde and stirs, obtains base
Material；In mass ratio 1: 2: 20 mixes composite fibre, substrate and deionized water, obtains aeroge, in -20 DEG C of pre-freeze 40h, obtains pre-freeze
Pre-freeze aeroge is put into freeze drier by aeroge, and under conditions of temperature is -40 DEG C, vacuum degree is 20Pa, freezing is dry
It is dry for 24 hours to get compound hemostatic material.
Reference examples：The compound hemostatic material of Suzhou company production.
The compound hemostatic material of example and reference examples is detected, specific detection is as follows：
The external clotting index of BCI：The external coagulant property of evaluation and test hemostatic material is carried out using clotting index BCI.
Mechanics Performance Testing：Hemostatic material is cut into the strip of 10 × 10 × 5mm, tests on universal testing machine.
Inhibition zone test method：Test strain is inoculated into 37 DEG C of culture 18h in fluid nutrient medium, 1mL bacterial liquid culture solution is taken, with nothing
Bacterium PBS is diluted to 5 × 105-5×106CFU/mL obtains bacterial suspension.Take 200 μ L bacterial suspension drops in plating medium
On, it is uniformly smeared one week, is covered around plate with sterile cotton swab, after 5min, then will be cut into diameter is the circular hemostatic material of 1cm
（Sterilization treatment through ultraviolet light 30min）, gently be attached to planar surface, cover surface plate, trained in 37 DEG C of incubator
After supporting for 24 hours, result is observed.
External degradation：Hemostatic material is cut into 2 × 1 × 0.5cm3Size, weigh and number respectively, then each sample
After ultraviolet light irradiation 30min disinfection, sufficiently washed 3 times with sterile water, then with corresponding degradation solution rinse 2 times, by what is prewetted
Sample is sequentially placed into 10mL centrifuge tube and is added corresponding degradation solution 8mL, is placed in oscillation incubation at 37 DEG C, frequency of oscillation 60
Beat/min；It was changed the liquid once in experiment every 3.5 days, above centrifuge tube 3/4 degradation solution is only replaced when changing liquid.The PBS displaced is stayed
Sample does the measurement of pH value（PH meter, Sartorius AG）, it is observed continuously 8 weeks.0, l, 2,3,4,5,6,7 after experiment, 8 weeks
It draws materials respectively, deionized water is sufficiently rinsed, and in air drying 24 hours, after 48 hours dry in vacuum oven, is used as matter
Amount loss and the observation of configuration of surface.
Specific testing result such as table 1.
1 performance characterization contrast table of table
| Detection project | Example 1 | Example 2 | Example 3 | Reference examples |
| BCI index | 11.2 | 10.9 | 11.0 | 45.6 |
| Young's modulus/MPa | 2.51 | 2.88 | 2.93 | 0.26 |
| Tensile strength/MPa | 1.81 | 1.79 | 1.86 | 0.12 |
| Inhibition zone/cm | 1 | 1.2 | 1.5 | 0.1 |
| Degradation rate/% | 99.8 | 99.7 | 99.5 | 45.6 |
As shown in Table 1, compound hemostatic material prepared by the present invention has good anthemorrhagic performance, bacteriostasis property and degradation property.
Claims (8)
1. a kind of preparation method of compound hemostatic material, it is characterised in that specifically preparation step is：
（1）It is to take out in 5% silver nitrate solution after 6~8h that calcium alginate fibre, which is immersed in mass fraction, dry, obtains compound fibre
Dimension；
（2）Sodium carboxymethylcellulose and deionized water are mixed, 10~15min of ultrasonic disperse obtains dispersion liquid；In parts by weight
Meter, weigh respectively 10~20 parts of sodium carboxymethylcelluloses, 30~50 parts of chitosans, 10~16 parts of starch, 8~16 parts of glycerol, 1~
5 parts of glutaraldehydes first mix sodium carboxymethylcellulose and chitosan, quickly stir, obtain mixture, then sequentially add starch,
Glycerol, glutaraldehyde stir, and obtain substrate；
（3）Composite fibre, substrate and deionized water are mixed, aeroge is obtained, pre-freeze processing obtains pre-freeze aeroge, by pre-freeze gas
Gel is put into freeze drier freeze-drying process to get compound hemostatic material.
2. a kind of preparation method of compound hemostatic material according to claim 1, it is characterised in that：Step（1）Described
It is dry to dry to be placed in 60~80 DEG C of baking ovens to constant weight.
3. a kind of preparation method of compound hemostatic material according to claim 1, it is characterised in that：Step（2）Described
Sodium carboxymethylcellulose and deionized water in mass ratio 1: 3 mix.
4. a kind of preparation method of compound hemostatic material according to claim 1, it is characterised in that：Step（2）Described
Ultrasonic disperse is 10~15min of ultrasonic disperse in the case where power is 100~200W.
5. a kind of preparation method of compound hemostatic material according to claim 1, it is characterised in that：Step（2）Described
Quickly stirring is that 20~30r/min quickly stirs 5~10min for revolving speed at room temperature.
6. a kind of preparation method of compound hemostatic material according to claim 1, it is characterised in that：Step（3）Described
Composite fibre, substrate and deionized water in mass ratio 1: 2: 20 mixes.
7. a kind of preparation method of compound hemostatic material according to claim 1, it is characterised in that：Step（3）Described
Pre-freeze processing is in -10~-20 DEG C of 20~40h of pre-freeze.
8. a kind of preparation method of compound hemostatic material according to claim 1, it is characterised in that：Step（3）Described
Freeze-drying process be under conditions of temperature be -40~-20 DEG C, vacuum degree is 10~20Pa, be freeze-dried 20~for 24 hours.
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| CN111905139B (en) * | 2020-08-14 | 2022-04-19 | 广州润虹医药科技股份有限公司 | Composite dressing capable of rapidly stopping bleeding and preparation method thereof |
| CN113521380A (en) * | 2021-06-30 | 2021-10-22 | 东南大学 | Rapid polymerization hydrogel material and preparation method and application thereof |
| CN114057898A (en) * | 2021-11-19 | 2022-02-18 | 沭阳富宴生物科技有限公司 | Modified cellulose and preparation method and application thereof |
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