CN104189945B - A kind of two-layer compound biological dressing and without adhesive combination process - Google Patents

A kind of two-layer compound biological dressing and without adhesive combination process Download PDF

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CN104189945B
CN104189945B CN201410508777.9A CN201410508777A CN104189945B CN 104189945 B CN104189945 B CN 104189945B CN 201410508777 A CN201410508777 A CN 201410508777A CN 104189945 B CN104189945 B CN 104189945B
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chitosan
spongy
woven fabrics
dressing
material solution
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CN104189945A (en
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郭养浩
郑允权
石贤爱
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Fuzhou University
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Fuzhou University
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Abstract

The invention provides a kind of two-layer compound biological dressing and without adhesive combination process.Described two-layer compound dressing is made up of chitin fiber nonwoven layer and spongy functional layer, does not need with adhesive gluing between layers.Preparation technology comprises the following steps: (1) is by chitin fiber non-woven fabrics pre-freeze; (2) by macromole chitosan, macromolecular collagen protein, micromolecular collagen and micromolecule chitosan in mass ratio 0.7-1.3:0.1-0.3:0.7-1.3:0.1-0.3 add in slightly acidic water solution, obtained spongy layer material solution; (3) take out through the chitosan non-woven fabrics of pre-freeze, rapidly by spongy layer material solution even application on non-woven fabrics, spray flux 20-60ml/20*20cm 2; (4) the chitosan non-woven fabrics of spraying spongy layer material solution is carried out lyophilization.Obtained two-layer compound dressing is firmly chimeric between layers.Spongy functional layer has and promotes the function of wound healing, can anti; Chitin fiber nonwoven layer has good breathability, comfortableness and antibacterial functions.

Description

A kind of two-layer compound biological dressing and without adhesive combination process
Technical field
The invention belongs to the preparation field of medical wound dressing, be specifically related to a kind of two-layer compound biological dressing and without adhesive combination process.
Background technology
Skin suffers wound or burnt degree. and usually need the wound dressing protection wound surface by a kind of function admirable, an environment being conducive to wound healing is provided.And for the wound of dark more than two degree or burn, providing necessary except needing dressing protects except wound and antibacterial functions, also need the standby function that can promote remaining epithelium regeneration and acceleration wound healing of dressing, until reconstruction permanent skin barrier.
Chitosan has good protecting and creates anthemorrhagic performance and bacteriostasis property, and biocompatibility is strong, and chitin fiber non-woven fabrics can be used as wound dressing.But because chitin fiber is easy and wound sticks together, the granulation that more during change dressings, easy damaged wound is newly-generated, and cause patient suffering, therefore conventional chitin fiber wound dressing surface need adopt chemical adhesive to stick adherence preventing material, as polyester antiblocking layers.The existence of antiblocking layers reduces the probability that wound and fiber stick together, but in wound microenvironment, multiple beneficial effect of chitosan cannot play a role.Moreover for deep burn or degree of depth surgical wound wound, synthetic macromolecule antiblocking layers is inapplicable.
Collagen sponge is the biological dressing with spongy loose structure be made up of collagen protein, usually adopts freeze-drying preparation.Simple collagen sponge is easily dry and cracked, and degradation rate is too fast, mechanical strength is little, is mixed by collagen protein with the natural polysaccharide such as chitosan, hyaluronic acid compound, can improve its performance to a certain extent.Collagen sponge has good hydrophilic and water absorption, and its adhesiveness is good, can the covering for wound surface of long period; Be applicable to deep wounds, there is effect of accelerating wound healing, but it lacks the effect protecting bacteria infection in wound and isolation (or suppression) air, need add a cover multiple ply sterilization gauze during Clinical practice.
The preparation technology of published compound dressing all adopts chemical adhesive to bond.Patent of invention 201310539212.2 discloses a kind of preparation method being urged the compound chitosan dressing that more layer and chitosan hemostatic layer form by chitosan, hemostatic layer is chitosan particle, and the formation of the formation of hemostatic layer and hemostatic layer and short more layer all passes through glue bond.The method that utility model patent 201220613590.1 adopts binding agent to bond has prepared a kind of two-layer compound bio dressing, and described upper strata polyurethane film is the thin film scribbling binding agent, is affixed on lower floor PVA/PVP/ carboxymethyl chitosan/shell iodine material.Adopt adhesive adhesion complex method, introduced by adhesive in dressing, bringing unnecessary composition increases and potential harm.
Promoting that the collagen sponge of wound healing function protects the chitosan dressing creating bacteria resistance function and carries out compound with having by having, the performance of combine dressing can be brought up to ideal state.A wound dressing for function admirable, if having good biological performance and physical and chemical performance, easy to use, and not containing unnecessary chemical composition, as adhesive etc., then there is application prospect widely.
Summary of the invention
The object of the invention is to the some shortcomings existed for existing dressing, provide a kind of two-layer compound biological dressing and without adhesive combination process.Obtained two-layer compound dressing is firmly chimeric between layers, and spongy functional layer has the function promoting wound healing, can anti; Chitin fiber nonwoven layer breathability and comfortableness good, and there is good antibacterial functions.
For realizing the object of the invention, adopt following technical scheme:
A kind of two-layer compound biological dressing, described dressing is by chitin fiber non-woven fabrics and spongy layer material solution low-temperature freeze drying under the condition not adding adhesive is chimeric forms, and lower floor is chitin fiber nonwoven layer, and upper strata is spongy functional layer; Containing macromole chitosan, micromolecule chitosan, macromolecular collagen protein, micromolecular collagen in described spongy layer material solution.
Chimeric thickness between the upper and lower of combine dressing is 30-120 μm.
Prepare a technique for described two-layer compound biological dressing, comprise the following steps:
(1) after chitin fiber nonwoven surface spray pure water, freeze at-20 ~-40 DEG C;
(2) spongy layer material solution is prepared, after stirring, ultrasonic degas;
(3) take out the chitin fiber non-woven fabrics of prefreezing, rapidly by spongy layer material solution even application on non-woven fabrics;
(4), after the chitin fiber non-woven fabrics that is coated with spongy layer material solution is freezing at-40 ~-50 DEG C, vacuum drying obtains two-layer compound biological dressing.
In described spongy layer material solution in step (2), the quality proportioning of macromole chitosan (molecular weight is greater than 50,000 Da), micromolecule chitosan (mean molecule quantity 2000Da), macromolecular collagen protein (molecular weight is greater than 80,000 Da), micromolecular collagen (mean molecule quantity 1000Da) is: 0.7-1.3:0.1-0.3:0.7-1.3:0.1-0.3, and total concentration is 2.0-3.5wt%;
In described step (3), the spray flux of spongy layer material solution is 20-60ml/20*20cm 2;
Chitin fiber nonwoven be furnished with acupuncture and water thorn, plain edition (hydrophobic) and modified model (easily absorbing water) point, the present invention's first-selection plain edition (hydrophobic) acupuncture chitin fiber non-woven fabrics.
Chitin fiber nonwoven surface has the Inter-fiber voids (0.01-1.0mm) varied in size, and the speed that aqueous solution penetrates into non-woven fabrics gap depends on the hydrophilic of non-woven fabrics and the size of Inter-fiber voids.Excessive spongy layer material solution infiltrates through lower floor's chitosan non-woven fabrics, and not only cause the functional layer inventory being close to wound to decline, and cause final freeze-drying prods quality hardening, comfortableness and permeability significantly decline, and anti-microbial property is corresponding decline also.The present invention, by spraying suitable quantity of water in chitosan nonwoven surface and carrying out the method for pre-freeze, can close the large space between non-woven fabrics fiber, for the infiltration controlling appropriate spongy layer material solution provides condition.
The invention provides a kind of course control method for use controlling combine dressing hybrid layer thickness.Combine dressing hybrid layer thickness can be controlled to the strict control of relevant parameter.Suitable hybrid layer thickness both can ensure that double-deck dressing combined firmly, can ensure that again combine dressing levels is all in the optimum state needed for medical dressing.
Advantageous Effects of the present invention is:
1 the invention provides one without adhesive two-layer compound biological dressing, has the active layers of two different composition 26S Proteasome Structure and Functions, double-deck knot
Close firmly; Lower floor is that chitin fiber protects wound antibiotic layer, keeps the original breathability of chitosan non-woven fabrics, comfortableness and good anti-microbial property; Upper strata is the spongy functional layer of collagen protein and chitosan, flexible, and absorption speed is fast, has the function promoting wound healing, can anti;
2. the present invention provides a kind of double-deck dressing combination process without adhesive bonding.Spongy functional layer is fitted together to into chitin fiber nonwoven layer, and hybrid layer thickness is about 30-120 μm, can ensure that combine dressing levels is all in the optimum state needed for medical dressing;
3. the invention provides a kind of course control method for use controlling combine dressing hybrid layer thickness, the infiltration capacity of spongy layer material solution to chitin fiber depends on: the performance of chitin fiber non-woven fabrics and the behavior of spongy layer material solution after spray to the non-woven fabrics of pre-freeze, non-woven fabric freezing water quantity and prefreezing temperature, spray is to the spongy layer material solution temperature on non-woven fabrics, volume and concentration, the time difference of pre-freeze non-woven fabrics taking-up operation and again refrigeration operation, aforesaid operations parameter will directly affect spongy layer solution to the time of penetration of lower floor's chitin fiber and length of penetration.Combine dressing hybrid layer thickness can be controlled to the strict control of above-mentioned parameter, thus guarantee the superperformance of double-deck dressing;
4. sponge functional layer of the present invention contains macromole chitosan, micromolecule chitosan, macromolecular collagen protein, micromolecular collagen, and its quality proportioning is: (0.7-1.3)/(0.1-0.3)/(0.7-1.3)/(0.1-0.3).Wherein macromolecular collagen protein and macromole chitosan form the skeleton of spongy layer jointly, and micromolecular collagen and micromolecule chitosan are dissolved in macromolecular skeleton structure; The relative stability of spongy layer framing structure is conducive to keeping high water absorbing properties under a large amount of wound exudate condition and covers the function of wound; Micromolecular collagen and micromolecule chitosan are extracted into wound surface, play effect that is antibacterial and promotion wound healing;
5. two-layer compound biological dressing of the present invention can be used for burn or the surgical wound of dark more than two degree, has following feature: (1) good biocompatibility, is closely affixed with wound, has good to protect wound function; (2) bacteria growing inhibiting, prevent wound infection; (3) wound skin flbroblast growth is promoted, accelerating wound; (4) use safety, no cytotoxicity, without chemical adhesive potential hazard; (5) water absorption, breathability, comfortableness are good; (6) application is convenient, is not adhered and causes secondary injury.
Accompanying drawing explanation
Fig. 1 is the electron-microscope scanning figure in combine dressing cross section.
Detailed description of the invention
The present invention's the following example further illustrates the present invention, but protection scope of the present invention is not limited to the following example.
Embodiment 1
By 20*20cm 2100g/m 2chitin fiber needle punched non-woven fabrics be laid in rustless steel refrigerator tray, at nonwoven surface spray 30mlRO pure water, be placed in ultra cold storage freezer ,-40 DEG C of precooling 30min; Preparation spongy layer material solution, total concentration 3.5wt%, take macromole chitosan 1.1g, micromolecule chitosan 0.3g, macromolecular collagen protein 1.1g, micromolecular collagen 0.3g, be dissolved in the aqueous acetic acid of 80ml0.5wt%, at room temperature refiner is stirred to uniform state, ultrasonic degas, 20 DEG C of preservations; Take out through the chitosan non-woven fabrics refrigerator tray of pre-freeze, rapidly by spongy layer material solution even application on non-woven fabrics, spray flux 40ml/20*20cm 2, the operating time is less than 5min; Put into ultra cold storage freezer again ,-50 DEG C of freezing 60min, proceed in freezer dryer fast, vacuum drying 10h, namely obtained without adhesive two-layer compound biological dressing;
Prepared casting product bilayer combines firmly, and hybrid layer thickness is 30-80 μm, and the spongy functional layer thickness in upper strata is about 450-550 μm, and quality is slightly partially hard, and flexible, absorption speed is fast; Dressing overall air permeability, water absorption and comfortableness are better, and anti-microbial property is strong;
Control experiment, above-mentioned spongy layer material solution is sprayed in not pretreated nonwoven surface, under follow-up same operation condition, prepared dressing has no obvious hybrid layer, upper strata sponge-like layer thickness is less than 50 μm, a large amount of spongy layer material solution infiltrates lower nonwoven cloth, and cause lower nonwoven cloth quality hardening, dressing overall air permeability and comfortableness are not suitable as medical dressing.
Embodiment 2
By 20*20cm 2100g/m 2chitin fiber needle punched non-woven fabrics be laid in rustless steel refrigerator tray, at nonwoven surface spray 40mlRO pure water, be placed in ultra cold storage freezer ,-40 DEG C of precooling 30min; Preparation spongy layer material solution, total concentration 2.5wt%, take macromole chitosan 0.8, micromolecule chitosan 0.2g, macromolecular collagen protein 0.8g, micromolecular collagen 0.2g, be dissolved in the aqueous acetic acid of 80ml0.5wt%, at room temperature refiner is stirred to uniform state, ultrasonic degas, 20 DEG C of preservations; Take out through the chitosan non-woven fabrics refrigerator tray of pre-freeze, rapidly by spongy layer material solution even application on non-woven fabrics, spray flux 60ml/20*20cm 2, the operating time is less than 5min; Put into ultra cold storage freezer again ,-40 DEG C of freezing 60min, proceed in freezer dryer fast, vacuum drying 12h, namely obtained without glue composite sponge dressing;
Prepared casting product bilayer combines firmly, hybrid layer thickness 60-120 μm, and the spongy functional layer thickness in upper strata is about 700-800 μm, and quality is soft, and flexible, absorption speed is fast; Dressing overall air permeability, water absorption and comfortableness are good, and anti-microbial property is strong;
Control experiment, above-mentioned spongy layer material solution is sprayed in not pretreated nonwoven surface, under follow-up same operation condition, prepared dressing has no obvious hybrid layer, upper strata sponge-like layer thickness is less than 50 μm, a large amount of functional layer material solution infiltrates lower nonwoven cloth, and cause lower nonwoven cloth quality hardening, dressing overall air permeability and comfortableness are not suitable as medical dressing.
Embodiment 3
By 20*20cm 2100g/m 2chitin fiber needle punched non-woven fabrics be laid in rustless steel refrigerator tray, at nonwoven surface spray 30mlRO pure water, be placed in ultra cold storage freezer ,-30 DEG C of precooling 30min; Preparation spongy layer material solution, total concentration 2.0wt%, take macromole chitosan 0.8g, micromolecule chitosan 0.2g, macromolecular collagen protein 0.8g, micromolecular collagen 0.2g, be dissolved in the aqueous acetic acid of 0.5% of 100ml, at room temperature refiner is stirred to uniform state, ultrasonic degas, 20 DEG C of preservations; Take out through the chitosan non-woven fabrics refrigerator tray of pre-freeze, rapidly by spongy layer material solution even application on non-woven fabrics, spray flux 50ml/20*20cm 2, the operating time is less than 5min; Put into cryogenic refrigerator again ,-40 DEG C of freezing 60min, proceed in freezer dryer fast, vacuum drying 11h, namely obtained without glue composite sponge dressing;
Prepared casting product bilayer combines firmly, hybrid layer thickness 60-110 μm, and the spongy functional layer thickness in upper strata is about 550-600 μm, and quality is soft, and flexible, absorption speed is fast.Dressing overall air permeability, water absorption and comfortableness are good, and anti-microbial property is strong.
Embodiment 4
By 20*20cm 2100g/m 2chitin fiber needle punched non-woven fabrics be laid in rustless steel refrigerator tray, at nonwoven surface spray 30mlRO pure water, be placed in ultra cold storage freezer ,-20 DEG C of precooling 30min; Preparation spongy layer material solution, total concentration 3.0wt%, take macromole chitosan 0.7g, micromolecule chitosan 0.2g, macromolecular collagen protein 1.3g, micromolecular collagen 0.2g, be dissolved in the aqueous acetic acid of 80ml0.5wt%, at room temperature refiner is stirred to uniform state, ultrasonic degas, 20 DEG C of preservations; Take out through the chitosan non-woven fabrics refrigerator tray of pre-freeze, rapidly by spongy layer material solution even application on non-woven fabrics, spray flux 40ml/20*20cm 2, the operating time is less than 5min; Put into cryogenic refrigerator again ,-40 DEG C of freezing 60min, proceed in freezer dryer fast, vacuum drying 10h, namely obtained without glue composite sponge dressing;
Prepared casting product bilayer combines firmly, and hybrid layer thickness is about 50-100 μm, and the spongy functional layer thickness in upper strata is about 450-500 μm, and quality is comparatively soft, and absorption speed is fast, but after inhaling a small amount of water, spongy layer skeleton is yielding.Dressing overall air permeability, water absorption and comfortableness are better, and anti-microbial property is strong.
Embodiment 5
By 20*20cm 2100g/m 2chitin fiber needle punched non-woven fabrics be laid in rustless steel refrigerator tray, at nonwoven surface spray 30mlRO pure water, be placed in ultra cold storage freezer ,-30 DEG C of precooling 30min; Preparation spongy layer material solution, total concentration 3.0wt%, take macromole chitosan 1.3g, micromolecule chitosan 0.2g, macromolecular collagen protein 0.7g, micromolecular collagen 0.2g, be dissolved in the aqueous acetic acid of 80ml0.6wt%, at room temperature refiner is stirred to uniform state, ultrasonic degas, 20 DEG C of preservations; Take out through the chitosan non-woven fabrics refrigerator tray of pre-freeze, rapidly by spongy layer material solution even application on non-woven fabrics, spray flux 30ml/20*20cm 2, the operating time is less than 5min; Put into cryogenic refrigerator again ,-40 DEG C of freezing 60min, proceed in freezer dryer fast, vacuum drying 10h, namely obtained without glue composite sponge dressing;
Prepared casting product bilayer combines firmly, see accompanying drawing, hybrid layer thickness 60-100 μm, the spongy functional layer thickness in upper strata is about 250-300 μm, and quality is comparatively soft, flexible, absorption speed is fast, after inhaling a small amount of water, spongy layer skeleton is not out of shape, and dressing overall air permeability, water absorption and comfortableness are good, and anti-microbial property is strong.
Embodiment 6
By 20*20cm 2100g/m 2chitin fiber needle punched non-woven fabrics be laid in rustless steel refrigerator tray, at nonwoven surface spray 40mlRO pure water, be placed in ultra cold storage freezer ,-40 DEG C of precooling 30min; Preparation spongy layer material solution, total concentration 2.5wt%, take macromole chitosan 1.3g, micromolecule chitosan 0.2g, macromolecular collagen protein 0.8g, micromolecular collagen 0.2g, be dissolved in the aqueous acetic acid of 100ml0.6wt%, at room temperature refiner is stirred to uniform state, ultrasonic degas, 20 DEG C of preservations; Take out through the chitosan non-woven fabrics refrigerator tray of pre-freeze, rapidly by spongy layer material solution even application on non-woven fabrics, spray flux 40ml/20*20cm 2, the operating time is less than 5min; Put into cryogenic refrigerator again ,-40 DEG C of freezing 60min, proceed in freezer dryer fast, vacuum drying 10-12h, namely obtained without glue composite sponge dressing;
Prepared casting product bilayer combines firmly, hybrid layer thickness 60-100 μm, and the spongy functional layer thickness in upper strata is about 400-450 μm, and quality is soft, and flexible, absorption speed is fast; Dressing overall air permeability, water absorption and comfortableness are good, and anti-microbial property is strong.
Embodiment 7
By 20*20cm 2100g/m 2chitin fiber needle punched non-woven fabrics be laid in rustless steel refrigerator tray, at nonwoven surface spray 40mlRO pure water, be placed in ultra cold storage freezer ,-30 DEG C of precooling 30min; Preparation spongy layer material solution, total concentration 2.5wt%, take macromole chitosan 0.8g, micromolecule chitosan 0.2g, macromolecular collagen protein 0.8g, micromolecular collagen 0.2g, be dissolved in the aqueous acetic acid of 80ml0.5wt%, at room temperature refiner is stirred to uniform state, ultrasonic degas, 20 DEG C of preservations; Take out through the chitosan non-woven fabrics refrigerator tray of pre-freeze, rapidly by spongy layer material solution even application on non-woven fabrics, spray flux 20ml/20*20cm 2, the operating time is less than 5min; Put into cryogenic refrigerator again ,-50 DEG C of freezing 60min, proceed in freezer dryer fast, vacuum drying 11h, namely obtained without glue composite sponge dressing;
Prepared casting product bilayer combines firmly, hybrid layer thickness 60-100 μm; The spongy functional layer thickness in upper strata is about 100-150 μm, and quality is comparatively soft, flexible, and absorption speed is fast; Dressing overall air permeability, water absorption and comfortableness are good.
Application Example 1
Double-deck dressing prepared by embodiment 6 is used for the deep second degree burn experiment of pig back, control sample is silver sulfadiazine/gauze and chitin fiber adhesive-bonded fabric dressing.Experimental result shows, for deep second degree burn, use the wound healing rate of the experimental group of the double-deck dressing prepared by the present invention all higher than silver sulfadiazine/gauze matched group and chitin fiber adhesive-bonded fabric dressing matched group, the healing rate of double-deck dressing group reaches 92.5%, and matched group is all lower than 85.0%; When changing dressings, double-deck dressing and wound adhesion, and chitin fiber adhesive-bonded fabric dressing is changed dressings ninety-nine times out of a hundred and is all sticked together.This shows, double-deck dressing of the present invention is conducive to the healing of deep second degree burn wound, is suitable for wound dressing purposes.
The foregoing is only preferred embodiment of the present invention, all equalizations done according to the present patent application the scope of the claims change and modify, and all should belong to covering scope of the present invention.

Claims (5)

1. a two-layer compound biological dressing, it is characterized in that: described dressing forms by chitin fiber non-woven fabrics and spongy layer material solution low-temperature freeze drying under the condition not adding adhesive is chimeric, lower floor is chitin fiber nonwoven layer, and upper strata is spongy functional layer; Containing macromole chitosan, micromolecule chitosan, macromolecular collagen protein, micromolecular collagen in described spongy layer material solution; The quality proportioning of macromole chitosan, micromolecule chitosan, macromolecular collagen protein, micromolecular collagen is: 0.7-1.3:0.1-0.3:0.7-1.3:0.1-0.3, and total concentration is 2.0-3.5wt%.
2. two-layer compound biological dressing according to claim 1, it is characterized in that: described macromole chitosan molecule amount is greater than 50,000 Da, micromolecule chitosan mean molecule quantity 2000Da, macromolecular collagen protein molecular weight is greater than 80,000 Da, micromolecular collagen mean molecule quantity 1000Da.
3. two-layer compound biological dressing according to claim 1, is characterized in that: the chimeric thickness between the upper and lower is 30 ~ 120 μm.
4. a preparation technology for two-layer compound biological dressing as claimed in claim 1, is characterized in that: comprise the following steps:
(1) after chitin fiber nonwoven surface spray pure water, freeze at-20 ~-40 DEG C;
(2) spongy layer material solution is prepared, after stirring, ultrasonic degas;
(3) take out the chitin fiber non-woven fabrics of prefreezing, rapidly by spongy layer material solution even application on non-woven fabrics;
(4), after the chitin fiber non-woven fabrics that is coated with spongy layer material solution is freezing at-40 ~-50 DEG C, vacuum drying obtains two-layer compound biological dressing.
5. the preparation technology of two-layer compound biological dressing according to claim 4, is characterized in that: in step (3), the spray flux of spongy layer material solution is 20-60ml/20*20cm 2.
CN201410508777.9A 2014-09-29 2014-09-29 A kind of two-layer compound biological dressing and without adhesive combination process Expired - Fee Related CN104189945B (en)

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