CN102940903A - Method for preparing medical dressing of polysaccharide cavernous body - Google Patents
Method for preparing medical dressing of polysaccharide cavernous body Download PDFInfo
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- CN102940903A CN102940903A CN2012104739013A CN201210473901A CN102940903A CN 102940903 A CN102940903 A CN 102940903A CN 2012104739013 A CN2012104739013 A CN 2012104739013A CN 201210473901 A CN201210473901 A CN 201210473901A CN 102940903 A CN102940903 A CN 102940903A
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Abstract
The invention relates to the preparation technique of tissue engineering scaffold materials and provides a crosslinking method for preparing medical dressing of a polysaccharide cavernous body. Chitosan and sodium alga acid serve as the base material, and by means of crosslinking of a couple reaction and the freezing drying technique, water absorption capability of the medical dressing of the polysaccharide cavernous body is improved, and effective protection on skin wound is achieved. When used, the medical dressing of the polysaccharide cavernous body is directly compressed on the wound surface, has excellent adsorption effect, and is particularly suitable for skin diseases of burning, pus, wound drainage, ulcer and the like. The method for preparing medical dressing of the polysaccharide cavernous body is simple in process, low in cost, low in crosslinking temperature, fast in curing, and suitable for large-scale industrial production. By means of the method, water adsorption capability of the dressing is obviously improved, residue of toxic chemical cross-linked agents is avoided simultaneously, chemical stimulation on the skin caused by materials is reduced, and biocompatibility and safety of the dressing are improved.
Description
Technical field
The invention belongs to the crosslinking technological of tissue engineering bracket material, particularly a kind of preparation method of natural polysaccharide spongy body medical dressing.
Background technology
Dressing is a kind of medical material that temporary covering wound uses that is used for, and its topmost function is transudate and the protection wound of control wound, to avoid the pollution of antibacterial and grit, to provide being beneficial to the environment of wound healing.Select suitable dressing to cover on the wound, can assist Bleeding control, protect from infection and absorb secretions, thereby promote wound healing.Dressing this moment plays the protection wound surface, prevents that body fluid and protein run off, prevent the effect that the antibacterial intrusion causes inflammation, and proliferative cell is provided support.
The wound of skin is clinical common disease, and is under situation that large defect or short time be difficult to heal appears in skin, of crucial importance in the dressing of wound surface coverage.For a comparatively long period of time, using the most general surgical wound dressings is medical absorbent cotton and gauze.It can play certain facilitation to the treatment of wound, but has very large deficiency.When for example it uses, the growth and cause adhesion in the dressing of wound surface granulation tissue; During releasing, easily cause secondary insult; Cause easily that owing to the wound surface hydrops antibacterial infects.
Along with the development of the progress in epoch and science and technology, progressively develop into the wound dressing of the high-tech component content of today by traditional gauze, breakthrough variation is occuring in the composition of dressing and kind in the nearly more than ten years.Clinical need to propose requirements at the higher level to the research and development of dressing, also becomes the power that carries out the new pattern compress exploitation.Therefore, develop a kind of new pattern compress, make it can not only flap coverage, can also help wound healing, prevent bacteria attack, reduce superelevation metabolism and the malnutrition of wound area, alleviate wound pain, accelerating wound have become scientific research personnel's main direction.Therefore, extremely important to improve its quality and water absorbing properties to the crosslinking Treatment of dressing.
The matrix material that is generally used for dressing has two classes: natural macromolecular material and synthesized polymer material.Natural macromolecular material mainly contains collagen, gelatin, chitosan, chondroitin sulfate, alginic acid, cellulose etc.Artificial macromolecular material commonly used comprises Polyethylene Glycol (PEG), polyurethane (PU), polyvinylpyrrolidone (PVP) etc.In general, natural polymer has excellent biocompatibility and degradability, and synthetic high polymer has good physical and mechanical properties, processing characteristics and chemical stability.These material controllabilitys are good, and practicality is high, has advantage and disadvantage separately, therefore obtained using widely in organizational project and regenerative medicine field as biomaterial.
Preparing at present dressing method commonly used is chemical reagent cross-linking method and uv cross-linking method.The chemical reagent cross-linking method is by adding chemical cross-linking agent (such as paraformaldehyde, glutaraldehyde and water-soluble carbodiimide etc.) as condensing agent in matrix, and its effect is through condensation reaction and reach crosslinked purpose with the active group in the substrate molecule (such as amino or carboxyl etc.).Uv cross-linking method is first matrix to be passed through chemical modification, makes it with unsaturated double-bond, then adds initiator, causes the adduction of unsaturated double-bond by ultraviolet light irradiation, thereby it is crosslinked that matrix is occured.Adopt the crosslinked material of these methods more stable on chemical constitution, can satisfy the technological requirement that material is made, but owing to unavoidable produce the residual of poisonous chemical reagent or initiator, so material has in various degree stimulation to human body, and safety can not be protected.In addition, these chemical cross-linking agents are micromolecule usually, and the intermolecular distance of crosslinked rear material is less, causes water absorbing properties lower, directly affect protection effect and the result of use of dressing.Therefore, avoiding using poisonous micromolecule chemical cross-linking agent, is the effective way that reduces dressing toxicity and improve the material swelling behavior.But, do not have the method that adopts nontoxic chemical reagent or initiator crosslinked poly sugar medical dressing in the prior art.
Natural polysaccharide molecule (such as chitosan, alginic acid etc.) is the ideal material of medical dressing, they have good biocompatibility on the one hand, has on the other hand the multiple active function groups that reacts on its strand, can carry out chemical modification by modified methods such as grafting easily, can effectively improve the Performance and quality of material.At present a lot of spongy body dressing if it is crosslinked to avoid using poisonous chemical reagent to carry out, such as adopting bimolecular conjugation reaction cross-linking method, then are expected to obtain the polysaccharide spongy body medical dressing of high swelling ratio and good biocompatibility all based on this class material.
Summary of the invention
The object of the present invention is to provide the preparation method of a kind of conjugation reaction crosslinked poly easy and simple to handle sugar dressing.
The technical solution that realizes the object of the invention is: a kind of preparation method of polysaccharide spongy body medical dressing, adopt Freeze Drying Technique, and take chitosan and sodium alginate as base material, form by the Diels-Alder conjugation reaction is crosslinked, specifically may further comprise the steps:
Under step 1, the room temperature chitosan is dissolved in lactic acid solution, adds succinic anhydrides and react with it, obtain the N-succinyl-chitosan after the dialysis lyophilizing;
Under step 2, the room temperature N-succinyl-chitosan is dissolved in the buffer solution, drips furfuryl amine-2-furylamine and react with it, obtain the furan chitosan after the dialysis lyophilizing;
Under step 3, the room temperature that sodium alginate is soluble in water, under the lucifuge condition, drip Potassium metaperiodate. solution, after reaction a period of time, dialysis and lyophilizing obtain the aldehyde radical sodium alginate;
Step 4, the aldehyde radical sodium alginate is soluble in water adds the reaction of 4-(4-N-maleimide phenyl) butyrate, obtains maleimide amination sodium alginate after the dialysis lyophilizing;
Step 5, prepare certain density furan chitosan and maleimide amination sodium alginate respectively, fully mix in proportion under the room temperature, obtain spongy body dressing after the lyophilization.
The reagent source that the present invention is used: chitosan, sodium alginate, Potassium metaperiodate., furfuryl amine-2-furylamine, water-soluble carbodiimide (EDAC), bovine serum albumin (BSA), 3-(4, the 5-dimethylthiazole)-2,5-diphenyl tetrazole bromine salt (MTT) is purchased from Sigma company; Succinic anhydrides, analytical pure, Chinese Medicine group; Lactic acid, analytical pure, Solution on Chemical Reagents in Shanghai company limited; 4-(4-N-maleimide phenyl) butyrate (MPBH) is purchased from Thermo Fisher company.Sodium chloride, potassium chloride, analytical pure, Shanghai reagent three factories; Sodium hydrogen phosphate, potassium dihydrogen phosphate, analytical pure, Hangzhou chemical reagent company limited; Dimethyl sulfoxide, dodecyl sodium sulfate, analytical pure, Solution on Chemical Reagents in Shanghai factory.Protein determination kit is purchased from green skies biotechnology research institute.The DMEM culture medium, Giboco company; Calf serum, Hangzhou Ilex purpurea Hassk.[I.chinensis Sims biomaterial Graduate School of Engineering; Penicillin, streptomycin, Huabei Pharmaceutic Co., Ltd.
The instrument that the present invention is used: scanning electron microscope (JSM-6330F, JEOL), microplate reader (Biorad, Model 550).
The present invention compared with prior art is characterized in that: 1) based on the conjugation reaction principle of crosslinking, the present invention avoids having used poisonous chemical cross-linking agent, so does not have the residual of toxic reagent in the dressing, has guaranteed the safety of dressing; 2) owing to related conjugation reaction among the present invention results between macromole-macromole, protect space structure and distance between the macromole, therefore improved the water absorbing properties of dressing, realized the effective protection to wound; 3) in the present invention, matrix used material is natural polysaccharide material, demonstrates admirably biocompatibility, and the body sense is good; 4) the crosslinked spongy body dressing water absorption of the present invention is strong, and is high with the bond strength of wound surface, avoided coming off in the materials'use, and had good permeability; 5) the technology of the present invention has the advantages such as crosslinking temperature is low, curing rate fast, the crosslinking Treatment cycle is short; 6) simple, the easy row of technology and equipment of the present invention, handling safety without toxic reagent, does not produce pollution to environment, and the cost of raw material of use is cheap, is applicable to large-scale industrial production.
Further specify the present invention below by embodiment.
Description of drawings
Fig. 1 is for adopting the sketch map of the crosslinked preparation chitin-sodium alginate of Diels-Alder conjugation reaction spongy body medical dressing.
Fig. 2 is the stereoscan photograph of chitin-sodium alginate spongy body medical dressing internal structure.
The water absorption rate of the chitin-sodium alginate spongy body medical dressing of Fig. 3 different proportion (chitosan/sodium alginate soln volume ratio is respectively 1/2,1/1 and 2/1).
The moisture evaporation rate of the chitin-sodium alginate spongy body medical dressing of Fig. 4 different proportion (chitosan/sodium alginate soln volume ratio is respectively 1/2,1/1 and 2/1).
The albumen adhesiveness of the chitin-sodium alginate spongy body medical dressing of Fig. 5 different proportion.
The cell adhesion of the chitin-sodium alginate spongy body medical dressing of Fig. 6 different proportion.
The specific embodiment
Lyophilization is a kind of common technology of preparation polymer tissue engineering scaffold material, and the preparation method of a kind of polysaccharide spongy body medical dressing of the present invention is take chitosan and sodium alginate as base material, forms by Diels-Alder conjugation reaction crosslinking curing.Chitosan and sodium alginate are carried out respectively modification, make them respectively carry the active group that can react, can automatically cross-linked molding under temperate condition after making it to mix, need not to add poisonous chemical cross-linking agent, guaranteed the safety of material.Specifically may further comprise the steps:
In the lactic acid aqueous solution of 5% (v/v), add the gram chitosan under step 1, the room temperature, stirred 3 hours, form homogeneous solution, add subsequently succinic anhydrides, stirred under the room temperature 12 ~ 24 hours, then with reaction solution dialysis 3 ~ 5 days, last lyophilizing obtains the N-succinyl-chitosan, wherein the lactic acid aqueous solution quality is 4 times of chitosan, and the succinic anhydrides quality is 1 ~ 4 times of chitosan;
Under step 2, the room temperature N-succinyl-chitosan is dissolved in the phosphate buffered solution, then drip the furfuryl amine of 100 ~ 500 microlitres-2-furylamine, stirred 12 ~ 24 hours under the room temperature behind the adding water-soluble carbodiimide, dialysing, lyophilizing obtains the furan chitosan after 3 ~ 5 days, wherein the quality of N-succinyl-chitosan is 1 ~ 5 times of furfuryl amine-2-furylamine, the quality of phosphate buffer is 80 times of N-succinyl-chitosan, and the water-soluble carbodiimide quality is 0.5 times of N-succinyl-chitosan;
Under step 3, the room temperature sodium alginate is dissolved in the water, then drip the sodium periodate solution that concentration is 0.5M, stirred under the lucifuge condition 1 ~ 4 hour, dialysing, lyophilizing obtains the aldehyde radical sodium alginate after 3 ~ 5 days, wherein the mass ratio of sodium alginate and water is 1:100, and the quality of sodium alginate is 200 ~ 500 times of sodium metaperiodate;
Under step 4, the room temperature aldehyde radical sodium alginate is dissolved in the water, then add concentration and be 0.5% 4-(4-N-maleimide phenyl) butyrate solution, reacted under the room temperature 0.5 ~ 3 hour, dialysing, lyophilizing obtains maleimide amination sodium alginate after 3 ~ 5 days, wherein the mass ratio of aldehyde radical sodium alginate and water is 1:100, and the quality of 4-(4-N-maleimide phenyl) butyrate is 0.015 ~ 0.06 times of aldehyde radical sodium alginate;
Step 5, compound concentration is furan chitosan and the maleimide amination sodium alginate aqueous solution of 0.5% ~ 2.0% (w/v) respectively, under the room temperature by volume ratio 1:2/1:1/2:1 fully mix 37
oC transfers and sets to 0 .5 ~ 2 hour, then is placed on-20
oUnder the C freezing 2 hours, at last-50
oLyophilization obtained spongy body dressing in 24 hours under the C.
Wherein, the preparation of phosphate buffered solution (PBS): take by weighing analytical pure sodium chloride 8 grams, potassium chloride 0.2 gram, sodium hydrogen phosphate 2.9 grams, potassium dihydrogen phosphate 0.2 gram, be dissolved in 1000 ml distilled waters, regulating pH is 7.4.
The constructed observation of dressing: through-50
oC lyophilization (FD1A50, Beijing rich doctor health) with dressing metal spraying (Cressington 108 Auto), was then observed internal microstructure in scanning electron microscope (JSM-6330F, JEOL) after 24 hours.
The water absorption of dressing detects: (W weighs dressing first
d), 25
oIn phosphate buffered solution, soak 6 hours under the C to guarantee abundant swelling.During test, take out dressing from solution, suck the water on dressing surface with filter paper, (W at once weighs
w), each sample parallel testing 5 times.Calculate dressing water absorbing properties P
aFormula be P
a=(W
w– W
d)/W
d
The rate of perviousness of dressing detects: rate of perviousness represents is the quality (unit: mgcm of the aqueous vapor passed through on the unit interval area
-2H
-1).Measure fixedly dressing thoroughly wet bottle (capacity is 5 milliliters, includes 4 milliliters of distilled water, and aperture area is 1.18cm
2) quality (W
0), the bottle that then will thoroughly wet places the exsiccator of constant temperature and humidity.With reference to general thoroughly wet method of testing ASTM method E96-90 standard, in exsiccator, place a large amount of silica gel, keep humidity about 40RH.Quality (Wt) with the saturating wet bottle of testing time mensuration obtains over time curve of quality.Calculate the rate of perviousness of dressing according to slope of a curve, computing formula is rate of perviousness=L/S
0Wherein L is wet slope of a curve, and the representation unit time is by the quality (unit: mgh of aqueous vapor
-1); S
0Be the effective area of penetrating aqueous vapor, the bottle aperture area that namely thoroughly wets is 1.18cm
2).
The protein adsorption detection of dressing: the protein solution of preparation 0.2wt%, 25
oUnder the C dressing is dipped in this solution, takes out dressing after 24 hours, use a large amount of distilled water flushings, again dressing is placed the sodium dodecyl sulfate solution of 0.1wt%, 37
oShaking table is 24 hours under the C, will be adsorbed in the albumen stripping of dressing.The protein adsorption quantity measuring method is carried out according to the protein determination kit Standard Operating Procedure.
The cell adhesion of dressing detects: dressing scissors are circular, and size and 24 well culture plate (Nunc
TM, Denmark) aperture is consistent, with dressing confluent cultures plate bottom.Before the use first with dressing with 75% soak with ethanol 2 hours sterilization, then with phosphate buffered solution repeatedly rinsing remove ethanol.Be 4 * 10 in dressing surface seeding quantity
4The human body fibroblast, and add 2 milliliters of culture fluid (DMEM culture medium+10% calf serum+100 unit/ml penicillin/streptomycin), it is put in 37
oHatch under the C after 4 hours and take out, repeatedly wash to remove the cell that does not adhere to phosphate buffered solution, then add the phosphate buffered solution of 20 microlitre 0.5wt%MTT, place 37
oHatch under the C and add 200 microlitre dimethyl sulfoxide after 4 hours, the even rear absorbance that adopts microplate reader (Biorad, Model 550) to measure the purple material in 570 nanometers of vibration.
The present invention adopts the ANOVA method of analysis of variance, the significant difference value
pBe made as≤0.05.
The prepared dressing of the present invention is the sponge loose structure, and average pore size is about 200 microns and mutually runs through, and is conducive to the absorption of ventilative and moisture.
Below in conjunction with embodiment the present invention is done further detailed description:
Embodiment 1:
Concrete operation step is:
(1) in the lactic acid solution of 40 milliliter 5% (v/v), adds 0.5 gram chitosan, stirred 3 hours under the room temperature, form homogeneous solution, add subsequently 2.0 gram succinic anhydrides, stirred 24 hours under the room temperature, then with reaction solution dialysis 3 days, last lyophilizing obtains the N-succinyl-chitosan;
(2) under the room temperature 0.5 gram N-succinyl-chitosan is dissolved in 40 milliliters of buffer solution, then drip the furfuryl amine of 100 microlitres-2-furylamine, stirred 18 hours under the room temperature behind the adding 0.2 gram water-soluble carbodiimide, dialysing, lyophilizing obtains the furan chitosan after 3 days;
(3) under the room temperature 1.0 gram sodium alginates are dissolved in 100 ml waters, then drip the sodium periodate solution that 5 ml concns are 0.5M, stirred 2 hours under the lucifuge condition, dialysing, lyophilizing obtains the aldehyde radical sodium alginate after 3 days;
(4) under the room temperature 1.0 gram aldehyde radical sodium alginates are dissolved in 100 ml waters, then add 6 ml concns and be 0.5% 4-(4-N-maleimide phenyl) butyrate solution, reaction is 0.5 hour under the room temperature, and dialysing, lyophilizing obtains maleimide amination sodium alginate after 3 days;
(5) compound concentration is furan chitosan and the maleimide amination sodium alginate aqueous solution of 0.5% (w/v) respectively, under the room temperature by volume ratio 1:1 fully mix 37
oPlaced 1 hour under the C, then be placed on-20
oUnder the C freezing 2 hours, at last-50
oLyophilization obtained spongy body dressing in 24 hours under the C.
Embodiment 2:
Concrete operation step is:
(1) in the lactic acid solution of 40 milliliter 5% (v/v), adds 0.5 gram chitosan, stirred 3 hours under the room temperature, form homogeneous solution, add subsequently 1.8 gram succinic anhydrides, stirred 20 hours under the room temperature, then with reaction solution dialysis 3 days, last lyophilizing obtains the N-succinyl-chitosan;
(2) under the room temperature 0.5 gram N-succinyl-chitosan is dissolved in 40 milliliters of buffer solution, then drip the furfuryl amine of 200 microlitres-2-furylamine, stirred 16 hours under the room temperature behind the adding 0.2 gram water-soluble carbodiimide, dialysing, lyophilizing obtains the furan chitosan after 3 days;
(3) under the room temperature 1.0 gram sodium alginates are dissolved in 100 ml waters, then drip the sodium periodate solution that 4 ml concns are 0.5M, stirred 4 hours under the lucifuge condition, dialysing, lyophilizing obtains the aldehyde radical sodium alginate after 3 days;
(4) under the room temperature 1.0 gram aldehyde radical sodium alginates are dissolved in 100 ml waters, then add 8 ml concns and be 0.5% 4-(4-N-maleimide phenyl) butyrate solution, reaction is 1 hour under the room temperature, and dialysing, lyophilizing obtains maleimide amination sodium alginate after 3 days;
(5) compound concentration is furan chitosan and the maleimide amination sodium alginate aqueous solution of 0.5% (w/v) respectively, under the room temperature by volume ratio 1:1 fully mix 37
oPlaced 1.5 hours under the C, then be placed on-20
oUnder the C freezing 2 hours, at last-50
oLyophilization obtained spongy body dressing in 24 hours under the C.
Embodiment 3:
Concrete operation step is:
(1) in the lactic acid solution of 40 milliliter 5% (v/v), adds 0.5 gram chitosan, stirred 3 hours under the room temperature, form homogeneous solution, add subsequently 1.5 gram succinic anhydrides, stirred 18 hours under the room temperature, then with reaction solution dialysis 4 days, last lyophilizing obtains the N-succinyl-chitosan;
(2) under the room temperature 0.5 gram N-succinyl-chitosan is dissolved in 40 milliliters of buffer solution, then drip the furfuryl amine of 250 microlitres-2-furylamine, stirred 24 hours under the room temperature behind the adding 0.2 gram water-soluble carbodiimide, dialysing, lyophilizing obtains the furan chitosan after 4 days;
(3) under the room temperature 1.0 gram sodium alginates are dissolved in 100 ml waters, then drip the sodium periodate solution that 5 ml concns are 0.5M, stirred 3 hours under the lucifuge condition, dialysing, lyophilizing obtains the aldehyde radical sodium alginate after 4 days;
(4) under the room temperature 1.0 gram aldehyde radical sodium alginates are dissolved in 100 ml waters, then add 10 ml concns and be 0.5% 4-(4-N-maleimide phenyl) butyrate solution, reaction is 1.5 hours under the room temperature, and dialysing, lyophilizing obtains maleimide amination sodium alginate after 4 days;
(5) compound concentration is 1.0% furan chitosan and maleimide amination sodium alginate aqueous solution respectively, under the room temperature by volume ratio 1:2 fully mix 37
oPlaced 2 hours under the C, then be placed on-20
oUnder the C freezing 2 hours, at last-50
oLyophilization obtained spongy body dressing in 24 hours under the C.
Embodiment 4:
Concrete operation step is:
(1) in the lactic acid solution of 40 milliliter 5% (v/v), adds 0.5 gram chitosan, stirred 3 hours under the room temperature, form homogeneous solution, add subsequently 1.2 gram succinic anhydrides, stirred 16 hours under the room temperature, then with reaction solution dialysis 4 days, last lyophilizing obtains the N-succinyl-chitosan;
(2) under the room temperature 0.5 gram N-succinyl-chitosan is dissolved in 40 milliliters of buffer solution, then drip the furfuryl amine of 300 microlitres-2-furylamine, stirred 20 hours under the room temperature behind the adding 0.2 gram water-soluble carbodiimide, dialysing, lyophilizing obtains the furan chitosan after 4 days;
(3) under the room temperature 1.0 gram sodium alginates are dissolved in 100 ml waters, then drip the sodium periodate solution that 3 ml concns are 0.5M, stirred 2.5 hours under the lucifuge condition, dialysing, lyophilizing obtains the aldehyde radical sodium alginate after 4 days;
(4) under the room temperature 1.0 gram aldehyde radical sodium alginates are dissolved in 100 ml waters, then add 3 ml concns and be 0.5% 4-(4-N-maleimide phenyl) butyrate solution, reaction is 2 hours under the room temperature, and dialysing, lyophilizing obtains maleimide amination sodium alginate after 4 days;
(5) compound concentration is furan chitosan and the maleimide amination sodium alginate aqueous solution of 1.0% (w/v) respectively, under the room temperature by volume ratio 1:2 fully mix 37
oC transfers and sets to 0 .5 hour, then is placed on-20
oUnder the C freezing 2 hours, at last-50
oLyophilization obtained spongy body dressing in 24 hours under the C.
Embodiment 5:
Concrete operation step is:
(1) in the lactic acid solution of 40 milliliter 5% (v/v), adds 0.5 gram chitosan, stirred 3 hours under the room temperature, form homogeneous solution, add subsequently 1.0 gram succinic anhydrides, stirred 24 hours under the room temperature, then with reaction solution dialysis 5 days, last lyophilizing obtains the N-succinyl-chitosan;
(2) under the room temperature 0.5 gram N-succinyl-chitosan is dissolved in 40 milliliters of buffer solution, then drip the furfuryl amine of 400 microlitres-2-furylamine, stirred 12 hours under the room temperature behind the adding 0.2 gram water-soluble carbodiimide, dialysing, lyophilizing obtains the furan chitosan after 5 days;
(3) under the room temperature 1.0 gram sodium alginates are dissolved in 100 ml waters, then drip the sodium periodate solution that 4 ml concns are 0.5M, stirred 2 hours under the lucifuge condition, dialysing, lyophilizing obtains the aldehyde radical sodium alginate after 5 days;
(4) under the room temperature 1.0 gram aldehyde radical sodium alginates are dissolved in 100 ml waters, then add 8 ml concns and be 0.5% 4-(4-N-maleimide phenyl) butyrate solution, reaction is 2.5 hours under the room temperature, and dialysing, lyophilizing obtains maleimide amination sodium alginate after 5 days;
(5) compound concentration is furan chitosan and the maleimide amination sodium alginate aqueous solution of 0.8% (w/v) respectively, under the room temperature by volume ratio 2:1 fully mix 37
oPlaced 2 hours under the C, then be placed on-20
oUnder the C freezing 2 hours, at last-50
oLyophilization obtained spongy body dressing in 24 hours under the C.
Embodiment 6:
Concrete operation step is:
(1) in the lactic acid solution of 40 milliliter 5% (v/v), adds 0.5 gram chitosan, stirred 3 hours under the room temperature, form homogeneous solution, add subsequently 0.5 gram succinic anhydrides, stirred 12 hours under the room temperature, then with reaction solution dialysis 3 days, last lyophilizing obtains the N-succinyl-chitosan;
(2) under the room temperature 0.5 gram N-succinyl-chitosan is dissolved in 40 milliliters of buffer solution, then drip the furfuryl amine of 500 microlitres-2-furylamine, stirred 24 hours under the room temperature behind the adding 0.2 gram water-soluble carbodiimide, dialysing, lyophilizing obtains the furan chitosan after 5 days;
(3) under the room temperature 1.0 gram sodium alginates are dissolved in 100 ml waters, then drip the sodium periodate solution that 2 ml concns are 0.5M, stirred 1 hour under the lucifuge condition, dialysing, lyophilizing obtains the aldehyde radical sodium alginate after 5 days;
(4) under the room temperature 1.0 gram aldehyde radical sodium alginates are dissolved in 100 ml waters, then add 12 ml concns and be 0.5% 4-(4-N-maleimide phenyl) butyrate solution, reaction is 3 hours under the room temperature, and dialysing, lyophilizing obtains maleimide amination sodium alginate after 5 days;
(5) compound concentration is furan chitosan and the maleimide amination sodium alginate aqueous solution of 0.8% (w/v) respectively, under the room temperature by volume ratio 2:1 fully mix 37
oPlaced 1.5 hours under the C, then be placed on-20
oUnder the C freezing 2 hours, at last-50
oLyophilization obtained spongy body dressing in 24 hours under the C.
The dressing of the present invention's preparation is the sponge loose structure, and average pore size is about 200 microns and mutually runs through, and is conducive to the absorption (Fig. 1) of ventilative and moisture.The water absorbing capacity of this dressing is extremely strong, can absorb the liquid (Fig. 2) that is equivalent to 52 ~ 57 times of own wts.The water evaporation speed of this dressing is at 2100g/m
2About (Fig. 3), it is generally acknowledged that control moisture evaporation rate is at 2000 ~ 2500g/m every day
2Can satisfy preferably wound surface to the requirement of wound, so this dressing satisfies the requirement to water vapor transmittance fully.The protein adsorption ability of this dressing significantly is lower than conventional hospital gauze (Fig. 4), illustrates that this dressing hydrophilic is strong, thereby is not easy to cause the adhesion of cell.Cell adhesion is the very important problem that the dressing design needs consideration.The dressing that causes owing to material is incorrect adheres to granulation tissue, thereby causes the secondary damage that brings when dressing removes, and comprises the adhesion to granulation, to the epithelial cell of migration, fibroblastic infringement of hypertrophy, even than not using dressing more serious.This dressing superficial cell adhesion value is very low, significantly be lower than tissue culturing plate and hospital gauze (Fig. 5), this protein adsorption result with dressing is consistent, illustrates that the hydrophilic of dressing is high, water absorbing capacity is strong, thereby be unfavorable for the adhesion of cell, such dressing is unlikely to cause the tissue adhesion.
Above embodiment has been contained the most representative experimental data.
Claims (7)
1. a method for preparing polysaccharide spongy body medical dressing is characterized in that, may further comprise the steps:
Step 1, chitosan is dissolved in lactic acid aqueous solution, stirs and form homogeneous solution, add succinic anhydrides, stirring reaction under the room temperature obtains the N-succinyl-chitosan after the dialysis lyophilizing;
Step 2, the N-succinyl-chitosan is dissolved in the phosphate buffered solution, drips furfuryl amine-2-furylamine, add behind the water-soluble carbodiimide stirring reaction under the room temperature, obtain the furan chitosan after the dialysis lyophilizing;
Step 3, sodium alginate is soluble in water drips Potassium metaperiodate. solution, stirring reaction under the lucifuge condition, and the dialysis lyophilizing obtains the aldehyde radical sodium alginate;
Step 4, the aldehyde radical sodium alginate is soluble in water adds 4-(4-N-maleimide phenyl) butyrate and reacts under room temperature, obtains maleimide amination sodium alginate after the dialysis lyophilizing;
Step 5, furan chitosan and maleimide amination sodium alginate aqueous solution are at room temperature fully mixed, freezing placement after room temperature is placed obtains spongy body dressing after the lyophilization.
2. the method for preparing polysaccharide spongy body medical dressing according to claim 1, it is characterized in that, lactic acid aqueous solution concentration is percent by volume 5% in the step 1, described lactic acid aqueous solution quality is 4 times of chitosan, the succinic anhydrides quality is 1 ~ 4 times of chitosan, chitosan is dissolved in behind the lactic acid aqueous solution stirred 3 hours, stirred 12 ~ 24 hours after adding succinic anhydrides.
3. the method for preparing polysaccharide spongy body medical dressing according to claim 1, it is characterized in that, drip in the step 2 furfuryl amine-the 2-furylamine is 100 ~ 500 microlitres, the quality of described N-succinyl-chitosan is 1 ~ 5 times of furfuryl amine-2-furylamine, the quality of buffer is 80 times of N-succinyl-chitosan, the water-soluble carbodiimide quality is 0.5 times of N-succinyl-chitosan, stirs 12 ~ 24 hours.
4. the method for preparing polysaccharide spongy body medical dressing according to claim 1, it is characterized in that, the sodium periodate solution that drips in the step 3 is 2 ~ 5 milliliters, concentration is 0.5M, stirred 1 ~ 4 hour, the mass ratio of described sodium alginate and water is 1:100, and the quality of sodium alginate is 200 ~ 500 times of sodium metaperiodate.
5. the method for preparing polysaccharide spongy body medical dressing according to claim 1, it is characterized in that, 4-(4-N-maleimide phenyl) the butyrate solution that adds in the step 4 is 3 ~ 12 milliliters, concentration is quality percent by volume 0.5%, reacted 0.5 ~ 3 hour, the mass ratio of described aldehyde radical sodium alginate and water is 1:100, and the quality of 4-(4-N-maleimide phenyl) butyrate is 0.015 ~ 0.06 times of aldehyde radical sodium alginate.
6. the method for preparing polysaccharide spongy body medical dressing according to claim 1 is characterized in that, the reaction volume of furan chitosan and maleimide amination sodium alginate is than being 1:2,1:1 or 2:1 in the step 5; Wherein participating in the furan chitosan of reaction and the concentration of maleimide amination sodium alginate is quality percent by volume 0.5% ~ 2.0%; Room temperature was placed 0.5 ~ 2 hour, freezing being placed as-20
oUnder the C freezing 2 hours.
7. the method for preparing polysaccharide spongy body medical dressing according to claim 1 is characterized in that, the time of described dialysis is 3 ~ 5 days.
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| CN107432951B (en) * | 2017-07-14 | 2020-05-01 | 四川省中医药科学院 | Sodium alginate-chitosan dressing loaded with tetrahydrocurcumin nanoparticles and preparation method thereof |
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