CN110141677A - A kind of topical acute hemostasis absorbable material and preparation method thereof - Google Patents
A kind of topical acute hemostasis absorbable material and preparation method thereof Download PDFInfo
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- CN110141677A CN110141677A CN201910489159.7A CN201910489159A CN110141677A CN 110141677 A CN110141677 A CN 110141677A CN 201910489159 A CN201910489159 A CN 201910489159A CN 110141677 A CN110141677 A CN 110141677A
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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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- 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
- A61L24/043—Mixtures of macromolecular materials
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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 topical acute hemostasis absorbable materials and preparation method thereof, by being that substrate prepares oxidized regenerated cellulose, then obtains with chitosan or the progress Electrostatic Absorption self assembly of chitosan and collagen using bacteria cellulose.The present invention is provided simultaneously with acute hemostasis, broad-spectrum antiseptic, the characteristic for promoting healing and body absorption；Preparation method is environmentally protective, and compound uniform high-efficiency, obtained composite material is highly-safe, has good market application prospect.
Description
Technical field
The invention belongs to bio-medical composition technical field, in particular to a kind of topical acute hemostasis absorbable material
And preparation method thereof.
Background technique
Absorbable hemostatic material is a kind of for wound bleeding position, can quick-acting haemostatic powder, and within a certain period of time can
The bio-medical material being absorbed by the body.Its maximum feature is: sewing up a wound only applied to difficulty local in human body or animal body
Blood, while realizing quick-acting haemostatic powder, can degradation in vivo, without take out, thus avoid hemostasis after the completion of remove dressing two
Secondary injury.Currently used Absorbable hemostatic material has Fibrin Glue class hemostatic material, gelfoam class hemostatic material, oxidation
Cellulose family hemostatic material and chitosan class hemostatic material etc..The each not phase of the hemostatic mechanism and application method of these hemostatic materials
Together, haemostatic effect also has very big difference.
Oxidized regenerated cellulose is successfully prepared for the first time in nineteen sixty, is that cellulose is oxidation-treated as the thin of cellulosic acid
Yarn shape or cotton shape Absorbable hemostatic material, appearance and quality with cotton yarn are soft and belittle, are easy to wrap, apply, filling etc. is grasped
Make.Its hemostatic mechanism is by the platelet aggregation in surgical wound surface blood on mesh gauze, using hemostatic gauze as hemostasis base
Matter quickly forms gel atrament after meeting blood, and condensation clot is to achieve the purpose that hemostasis.It independent of in human body just
Normal clotting mechanism, but blood clotting is promoted rapidly by physical action, effectively control thin vessels bleeding.Currently, only beautiful
State and Britain can produce such product, and the absorabable hemostatic gauze Surgicel (speed i.e. yarn) clinically used is exactly Johnson & Johnson, the U.S.
The product of company, speed are that the main component of yarn is exactly oxidized regenerated cellulose.Oxidized regenerated cellulose is by the C6 primary in cellulose
Hydroxyl high selectivity is oxidized into a kind of derivative of cellulose obtained from carboxyl, has been applied to all trades and professions at present,
And the product of market sale depends on import, the country only has several companies and has produced similar hemostatic gauze.Although oxygen
Change regenerated fiber and be known as many excellent performances, but there is also some drawbacks, if hemostasis efficiency is not high, are not applied for measuring greatly
Blood, anti-microbial property is weak and histocompatbility is low etc..
Currently, having used natural/synthesis high molecular material or inorganic in some disclosures or the patent of invention of authorization
Material is modified oxidized regenerated cellulose to improve its antibacterial and anthemorrhagic performance.As collagen (CN105079886A),
Alginates (CN104013991A) and carbon nanotube (CN105056284A) etc..Although the above compound hemostatic material is to oxidation regeneration
Cellulosic can have certain promotion, but improvement is poor, can only promote its partial properties, and can be to the life of material
Object absorbability can adversely affect.
Summary of the invention
Technical problem to be solved by the invention is to provide a kind of topical acute hemostasis absorbable material and preparation method thereof,
Solve the problems, such as that oxidized regenerated cellulose anti-microbial property is weak, histocompatbility is low, anthemorrhagic speed is slow.
The present invention provides a kind of topical acute hemostasis absorbable materials, are aoxidized by being prepared using bacteria cellulose as substrate
Regenerated cellulose (OBC), then carry out Electrostatic Absorption self assembly with chitosan or chitosan and collagen and obtain.
The bacteria cellulose is by using acetobacter xylinum as strain, through fluid nutrient medium constant temperature stationary culture 7-20 days
Afterwards, it is placed in sodium hydroxide solution, takes out after handling 2-4h at 70-90 DEG C, obtained after being rinsed with deionized water to neutrality.
The present invention also provides a kind of preparation methods of topical acute hemostasis absorbable material, comprising:
(1) using bacteria cellulose as substrate, oxidized regenerated cellulose suspension is prepared；
(2) chitosan/dilute acid soln is added dropwise in oxidized regenerated cellulose suspension and carries out Electrostatic Absorption from group
Reaction cartridge then takes out, and rinses, freeze-drying, and obtaining topical acute hemostasis absorbable material, (oxidized regenerated cellulose/chitosan can
Absorb antibacterial anti hemorrhagic material OC)；
Alternatively, by collagen aqueous solution be added in oxidized regenerated cellulose suspension impregnate adsorb, then by chitosan/
Dilute acid soln is added dropwise to progress Electrostatic Absorption self-assembling reaction in oxidized regenerated cellulose suspension, then takes out, and rinses,
Freeze-drying, obtaining topical acute hemostasis absorbable material, (oxidized regenerated cellulose/collagen/chitosan can absorb antibacterial anti hemorrhagic material
OCC)。
The preparation step of oxidized regenerated cellulose suspension in the step (1) is as follows: bacteria cellulose film broken up,
It aoxidizes through TEMPO/NaBr/NaClO mixed oxidization system, is obtained after eccentric cleaning and dialysis at room temperature.
Chitosan/dilute acid soln in the step (2) is shape in the dilute acid soln for dissolve the chitosan in 0.1-5%
At chitosan/dilute acid soln of final concentration of 1-5%.
Collagen in the step (2) is fish source collagen；The concentration of collagen aqueous solution is 0.1-10mg/mL.
The mass ratio of collagen and oxidized regenerated cellulose in the step (2) is 1:1-10:1.
Dipping adsorption time in the step (2) is 0.5-5 hours.
The Electrostatic Absorption self-assembling reaction time in the step (2) is 1-60 minutes.
Oxidized regenerated cellulose (OBC) is prepared by substrate of Nano bacteria cellulose, utilizes its high-purity and Large ratio surface
Product characteristic, accelerates coagulation process.Simultaneously using opposite charge of OBC and chitosan, carry out Electrostatic Absorption self-assembling reaction into
Row is compound, can also introduce collagen wherein, is prepared while having acute hemostasis, antibacterial and promote to be cured inhaling for function
Recover condensation material.
Beneficial effect
(1) topical acute of the invention hemostasis absorbable material prepares oxidation regeneration fiber by substrate of bacteria cellulose
Element, carboxyl-content is higher, and specific surface area is bigger, and the degree of polymerization is lower, and haemostatic effect is more preferable, and biodegradable properties are more preferable, more
It is easy to be absorbed by the body.
(2) the present invention charge carry out Electrostatic Absorption self assembly system opposite with chitosan using oxidized regenerated cellulose
It is standby, without using additional crosslinking agent；Meanwhile the addition of chitosan improves material and promotees blood coagulation and antibacterial characteristics.
(3) present invention is by using the big specific surface area of oxidized regenerated cellulose, sufficiently absorption collagen molecules it
Afterwards again with chitosan carry out Electrostatic Absorption self-assembling reaction, finally obtained material be provided simultaneously with acute hemostasis, antibacterial, promote more and
Absorbable characteristic.
(4) raw material of the present invention is green environment protective biological material, can be according to reality without the chemical substance being harmful to the human body
Situation and feature are prepared into various shape, and safety and environmental protection can degrade rapidly in the environment after discarding, can be used as a kind of functional
And environmentally protective functional material.
(5) preparation method is simple by the present invention, and compound uniform high-efficiency does not use crosslinking agent, will not be to synthetic
Original structure damages, environmentally protective, can industrialized production, have good market application prospect.
Detailed description of the invention
Fig. 1 is the flow diagram of preparation method of the present invention；
Fig. 2 is the product figure of topical acute hemostasis absorbable material；Wherein, 1 is oxidized regenerated cellulose (OBC), and 2 be oxygen
Change regenerated cellulose/chitosan (OC), 3 be oxidized regenerated cellulose/collagen/chitosan (OCC)；
Fig. 3 be embodiment 1-3 under identical extension rate to the fungistatic effect figure of Escherichia coli and staphylococcus aureus,
Sterile gauze is control group；
Fig. 4 is the ex vivo whole blood setting time test result of embodiment 1-3.
Specific embodiment
Present invention will be further explained below with reference to specific examples.It should be understood that these embodiments are merely to illustrate the present invention
Rather than it limits the scope of the invention.In addition, it should also be understood that, after reading the content taught by the present invention, those skilled in the art
Member can make various changes or modifications the present invention, and such equivalent forms equally fall within the application the appended claims and limited
Range.
Embodiment 1
(1) it using acetobacter xylinum as strain, after fluid nutrient medium constant temperature stationary culture 10 days, takes out bacteria cellulose film and sets
In sodium hydroxide solution, is taken out after handling 2h at 80 DEG C, obtain bacteria cellulose film after being rinsed with deionized water to neutrality；
It is soaked in 6h in hyaluronic acid solution, obtains the bacteria cellulose film after hyaluronic acid impregnates；
(2) bacteria cellulose film of 4g after purification is weighed, is broken up in high-speed homogenization machine after being shredded, bacterium fibre is become
Tie up plain suspension.
(3) by bacterial cellulose suspension (solid content 1-10g/L) obtained in step (2) through TEMPO/NaBr/
NaClO mixed oxidization system is aoxidized at room temperature, and TEMPO dosage is 0.1mmol/g, NaBr 1mmol/g.It is added certain
The 10%NaClO solution of amount starts to react, and maintains pH=10 ± 0.5 of reaction system by the way that 0.5M NaOH solution is added dropwise, until
When NaOH solution is no longer consumed, ethyl alcohol is added and terminates reaction.Obtained oxidation product is placed on through centrifugation, rinsing and high pressure sterilization
It is saved under 4 DEG C of environment.It is 23% by the carboxyl-content that conductometry measures TEMPO oxidized regenerated cellulose suspension.
(4) the oxidized regenerated cellulose suspension that step (3) obtains is freeze-dried, finally obtains oxidation regeneration fibre
Tie up plain hemostatic material.
Embodiment 2
(1) it using acetobacter xylinum as strain, after fluid nutrient medium constant temperature stationary culture 10 days, takes out bacteria cellulose film and sets
In sodium hydroxide solution, is taken out after handling 2h at 80 DEG C, obtain bacteria cellulose film after being rinsed with deionized water to neutrality；
It is soaked in 6h in hyaluronic acid solution, obtains the bacteria cellulose film after hyaluronic acid impregnates；
(2) bacteria cellulose film of 4g after purification is weighed, is broken up in high-speed homogenization machine after being shredded, bacterium fibre is become
Tie up plain suspension.
(3) by bacterial cellulose suspension (solid content 1-10g/L) obtained in step (2) through TEMPO/NaBr/
NaClO mixed oxidization system is aoxidized at room temperature, and TEMPO dosage is 0.1mmol/g, NaBr 1mmol/g.It is added certain
The 10%NaClO solution of amount starts to react, and maintains pH=10 ± 0.5 of reaction system by the way that 0.5M NaOH solution is added dropwise, until
When NaOH solution is no longer consumed, ethyl alcohol is added and terminates reaction.Obtained oxidation product is placed on through centrifugation, rinsing and high pressure sterilization
It is saved under 4 DEG C of environment.It is 23% by the carboxyl-content that conductometry measures TEMPO oxidized regenerated cellulose suspension.
(4) it weighs 2g chitosan to be completely dissolved in the acetum of 100mL 3%, the shell for forming final concentration of 2% gathers
Malt sugar acid solution.
(5) oxidation regeneration of 50mL step (3) preparation is added dropwise in the chitosan dilute acid soln for taking 5mL step (4) to prepare
In cellulose suspension, product is centrifuged repeatedly rinsing after sixty minutes by reaction, is finally freeze-dried, and obtains oxidation regeneration fibre
Tie up element/chitosan compound hemostatic material.
Embodiment 3
(1) it using acetobacter xylinum as strain, after fluid nutrient medium constant temperature stationary culture 10 days, takes out bacteria cellulose film and sets
In sodium hydroxide solution, is taken out after handling 2h at 80 DEG C, obtain bacteria cellulose film after being rinsed with deionized water to neutrality；
It is soaked in 6h in hyaluronic acid solution, obtains the bacteria cellulose film after hyaluronic acid impregnates；
(2) bacteria cellulose film of 4g after purification is weighed, is broken up in high-speed homogenization machine after being shredded, bacterium fibre is become
Tie up plain suspension.
(3) by bacterial cellulose suspension (solid content 1-10g/L) obtained in step (2) through TEMPO/NaBr/
NaClO mixed oxidization system is aoxidized at room temperature, and TEMPO dosage is 0.1mmol/g, NaBr 1mmol/g.It is added certain
The 10%NaClO solution of amount starts to react, and maintains pH=10 ± 0.5 of reaction system by the way that 0.5M NaOH solution is added dropwise, until
When NaOH solution is no longer consumed, ethyl alcohol is added and terminates reaction.Obtained oxidation product is placed on through centrifugation, rinsing and high pressure sterilization
It is saved under 4 DEG C of environment.It is 23% by the carboxyl-content that conductometry measures TEMPO oxidized regenerated cellulose suspension.
(4) the fish source collagen albumen for weighing 30mg is completely dissolved in 10mL sterile water, forms final concentration of 3mg/mL's
Protein solution.
(5) oxidized regenerated cellulose that 40mL step (3) preparation is added in the protein solution for taking 10mL step (4) to prepare is suspended
In liquid, absorption 1 hour is sufficiently stirred, obtains the oxidized regenerated cellulose suspension for being adsorbed with collagen.
(6) it weighs 2g chitosan to be completely dissolved in the acetum of 100mL 3%, the shell for forming final concentration of 2% gathers
Malt sugar acid solution.
(7) take 5mL step (6) prepare chitosan dilute acid soln be added dropwise 50mL step (5) preparation be adsorbed with glue
In the oxidized regenerated cellulose suspension of former albumen, product is centrifuged repeatedly rinsing after sixty minutes by reaction, and it is dry finally to carry out freezing
It is dry, obtain oxidized regenerated cellulose/collagen/chitosan compound hemostatic material.
From the figure 3, it may be seen that oxidized regenerated cellulose has certain bacteriostasis compared with gauze, this is mainly due to
The low ph conditions that a large amount of carboxyls are formed in oxidized regenerated cellulose inhibit the proliferation and breeding of bacterium.But its fungistatic effect is
It is very limited, still there is the bacteria living of a great deal of.On the contrary, be compounded with the anti-microbial property of chitosan experimental group (OC, OCC) compared with
Be significantly improved for oxidized regenerated cellulose, and to Escherichia coli and staphylococcus aureus have identical it is antibacterial become
Gesture.Excellent broad spectrum antibacterial shows that OCC has applied to clinical potentiality.
As shown in Figure 4, the whole blood clotting time of OBC, OC, OCC are respectively 248s, 220s and 180s, and it is excellent to show that OCC has
Different anthemorrhagic performance.Its mechanism may be the synergistic effect due to oxidized regenerated cellulose, chitosan and collagen three.
The rush coagulant property of these three materials has all been confirmed in many documents, and the present invention is not in the case where destroying original structure
These three materials are dexterously combined together, the new composite material of one kind is formed and obtain excellent anthemorrhagic performance, there is application
In the clinical potentiality as acute hemostasis material.
Claims (9)
- The absorbable material 1. a kind of topical acute stops blooding, it is characterised in that: by being aoxidized again by substrate preparation of bacteria cellulose Raw cellulose, then carry out Electrostatic Absorption self assembly with chitosan or chitosan and collagen and obtain.
- The absorbable material 2. a kind of topical acute according to claim 1 stops blooding, it is characterised in that: the bacteria cellulose Be by after fluid nutrient medium constant temperature stationary culture 7-20 days, being placed in sodium hydroxide solution using acetobacter xylinum as strain, It takes out after handling 2-4h at 70-90 DEG C, is obtained after being rinsed with deionized water to neutrality.
- 3. a kind of preparation method of topical acute hemostasis absorbable material, comprising:(1) using bacteria cellulose as substrate, oxidized regenerated cellulose suspension is prepared；(2) by chitosan/dilute acid soln be added dropwise in oxidized regenerated cellulose suspension carry out Electrostatic Absorption self assembly it is anti- It answers, then takes out, rinse, freeze-drying obtains topical acute hemostasis absorbable material；It is adsorbed alternatively, collagen aqueous solution is added to impregnate in oxidized regenerated cellulose suspension, then by chitosan/diluted acid Solution is added dropwise to progress Electrostatic Absorption self-assembling reaction in oxidized regenerated cellulose suspension, then takes out, and rinses, and freezes It is dry, obtain topical acute hemostasis absorbable material.
- 4. preparation method according to claim 3, it is characterised in that: the oxidized regenerated cellulose in the step (1) is outstanding The preparation step of turbid is as follows: bacteria cellulose film being broken up, at room temperature through TEMPO/NaBr/NaClO mixed oxidization system It is obtained after oxidation, eccentric cleaning and dialysis.
- 5. preparation method according to claim 3, it is characterised in that: chitosan/dilute acid soln in the step (2) is It dissolves the chitosan in the dilute acid soln of 0.1-5%, forms chitosan/dilute acid soln of final concentration of 1-5%.
- 6. preparation method according to claim 3, it is characterised in that: the collagen in the step (2) is source of fish glue It is former；The concentration of collagen aqueous solution is 0.1-10mg/mL.
- 7. the preparation method according to claim 3 or 6, it is characterised in that: collagen and oxidation in the step (2) The mass ratio of regenerated cellulose is 1:1-10:1.
- 8. preparation method according to claim 3, it is characterised in that: the dipping adsorption time in the step (2) is 0.5-5 hours.
- 9. preparation method according to claim 3, it is characterised in that: the Electrostatic Absorption self assembly in the step (2) is anti- It is 1-60 minutes between seasonable.
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Cited By (5)
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| CN110507844A (en) * | 2019-09-06 | 2019-11-29 | 东华大学 | A kind of absorbable composite material and preparation method for topical acute hemostasis based on oxidizing bacteria cellulose |
| CN111939314A (en) * | 2020-07-28 | 2020-11-17 | 天津科技大学 | Preparation method of bacterial cellulose ointment for wound surface |
| CN112773941A (en) * | 2020-12-31 | 2021-05-11 | 东华大学 | Chitosan microsphere-bacterial cellulose composite material and preparation and application thereof |
| CN112773929A (en) * | 2020-12-31 | 2021-05-11 | 东华大学 | Absorbable hemostatic composite material based on polyanionic cellulose and preparation method thereof |
| CN114288480A (en) * | 2021-12-06 | 2022-04-08 | 盐城工学院 | Biological modified oxidized regenerated cellulose hemostatic anti-adhesion material and preparation method thereof |
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| CN110507844A (en) * | 2019-09-06 | 2019-11-29 | 东华大学 | A kind of absorbable composite material and preparation method for topical acute hemostasis based on oxidizing bacteria cellulose |
| CN111939314A (en) * | 2020-07-28 | 2020-11-17 | 天津科技大学 | Preparation method of bacterial cellulose ointment for wound surface |
| CN112773941A (en) * | 2020-12-31 | 2021-05-11 | 东华大学 | Chitosan microsphere-bacterial cellulose composite material and preparation and application thereof |
| CN112773929A (en) * | 2020-12-31 | 2021-05-11 | 东华大学 | Absorbable hemostatic composite material based on polyanionic cellulose and preparation method thereof |
| CN114288480A (en) * | 2021-12-06 | 2022-04-08 | 盐城工学院 | Biological modified oxidized regenerated cellulose hemostatic anti-adhesion material and preparation method thereof |
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