CN105664224B - A kind of compound alginic acid dressing of low molecular weight carboxymethyl chitosan and preparation method thereof - Google Patents

A kind of compound alginic acid dressing of low molecular weight carboxymethyl chitosan and preparation method thereof Download PDF

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CN105664224B
CN105664224B CN201610103647.6A CN201610103647A CN105664224B CN 105664224 B CN105664224 B CN 105664224B CN 201610103647 A CN201610103647 A CN 201610103647A CN 105664224 B CN105664224 B CN 105664224B
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molecular weight
carboxymethyl chitosan
low molecular
alginic acid
dressing
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CN105664224A (en
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黄姝杰
关静
田丰
李志宏
武继民
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Institute of Medical Equipment Chinese Academy of Military Medical Sciences
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Institute of Medical Equipment Chinese Academy of Military Medical Sciences
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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
    • A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/22—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
    • A61L15/28—Polysaccharides or their derivatives
    • 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
    • A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/42—Use of materials characterised by their function or physical properties
    • 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
    • A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/42—Use of materials characterised by their function or physical properties
    • A61L15/46—Deodorants or malodour counteractants, e.g. to inhibit the formation of ammonia or bacteria
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
    • A61L2300/23—Carbohydrates
    • A61L2300/232—Monosaccharides, disaccharides, polysaccharides, lipopolysaccharides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/404—Biocides, antimicrobial agents, antiseptic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
    • A61L2300/602—Type of release, e.g. controlled, sustained, slow

Abstract

The invention discloses a kind of compound alginic acid dressing of low molecular weight carboxymethyl chitosan, including component and mass ratio are as follows: low molecular weight carboxymethyl chitosan 0.1~8.0%, surplus are alginic acid non-woven fabrics；It the effect of by filtering out existing inhibition bacterium medical grade low-molecular weight chitoglycan carboxy methylation while after not generating cytotoxic concentration, is fixed in alginic acid non-woven fabrics and is formed.In use process, after dressing is by the interstitial fluid contacts with the surface of a wound, it discharges rapidly out carboxymethyl chitosan and plays bacteriostasis efficacy, the fully connected topology of alginic acid prevents carboxymethyl chitosan from discharging completely simultaneously, so that composite material has certain lasting fungistatic effect, dressing of the present invention has good gas permeability, mechanical stretch, hygroscopicity, antibiotic property and biocompatibility.Preparation process is relatively easy, and large-scale production feasibility is strong.Dressing of the present invention is suitable for skin superficial burns, wound and trauma surface infestation and festers, and has effects that control bacterium infection, promotes wound repair.

Description

A kind of compound alginic acid dressing of low molecular weight carboxymethyl chitosan and preparation method thereof
Technical field
The invention belongs to polymeric biomaterial medical dressing technical fields, more particularly to a kind of low molecular weight carboxymethyl The preparation method of the compound alginic acid dressing of chitosan.
Background technique
Chitin is widely present in marine organisms (such as shrimp, crab) shell and the cell wall of fungi, and chitosan is that its is deacetylated Change product, as a kind of glycosaminoglycan, biodegradable in vivo has no toxic side effect.The purposes of chitin increasingly causes numerous The concern and interest of scholar.It due to the water-insoluble of chitin and chitosan, limits its scope of application, therefore, we are to first Shell element synthesizes carboxylate through certain technique with monoxone, and product carboxymethyl chitosan makes have water solubility.Due to carboxymethyl chitosan Sugar has the effects that water-soluble well and has film forming, thickening, moisturizing, gelatinization, and these characteristics can be to the healing of wound Play the role of it is good, it is significantly more efficient to the surface of a wound play hemostasis, antibacterial, promote more, analgesic purpose.Research finds carboxymethyl Significant positive correlation is had no between the bacteriostasis property and degree of substitution by carboxymethyl of chitosan, but the relationship between molecular weight is in negative It closes, with the reduction of molecular weight, fungistatic effect is significantly improved, when molecular weight is greater than 1 × 106When, bacteria resistance function is unobvious, when point Son amount is less than 105When, bacteriostatic activity is remarkably reinforced.Low molecular weight carboxymethyl chitosan be can choose applied to the surface of a wound.
Alginic acid is a kind of natural polysaccharide, is mainly derived from sea-plant Phaeophyceae.The chemical composition of alginic acid is by G unit With M unit by Isosorbide-5-Nitrae-glucosides key connection, single MMM or GGG or MGGGMM alternate combinations are formd during connection.Perhaps Mostly the study found that alginate can promote many immunologic functions of macrophage and people's thick liquid cell, having enhances its cell Dissolution activity and the biology performances such as a large amount of interleukins L of stimulation these cells secretion and interleukin-6.It is defended in medicine Raw field, for alginate as a kind of functional biomedical material, the Ministry of Public Health, China has promulgated a alginate dressing Ministry standard (WS1-128-89).As Devoting Major Efforts To Developing utilizes marine resources, alginates are more and more, and to act on the mankind strong Health field.
The skin of human body is badly damaged by extraneous its defense function of damage, in turn result in body's immunity it is serious under Drop is easy to cause trauma surface infestation.In the trauma surface infestation of fire victim, staphylococcus aureus, pseudomonas aeruginosa, large intestine angstrom Uncommon bacterium is the most common pathogen.Research shows that low molecular weight carboxymethyl chitosan all has significant inhibition to above-mentioned pathogen Effect, and human body is not likely to produce drug resistance.
Therefore, one kind is developed using low molecular weight carboxymethyl chitosan as main functional component, and utilizes alginic acid fibre material Material itself has effects that the advanced composite material (ACM) of antibacterial heal-promoting function is played in collaboration, is modern medicine function of emergency treatment material neck The trend of domain development, it is contemplated that such functionality combine dressing has good market prospects.
Summary of the invention
For above-mentioned existing Wound dressing technology, the present invention provides a kind of low molecular weight carboxymethyl chitosan and compounding seas Alginic acid dressing and preparation method thereof is by carrying out chemistry to low molecular weight medical grade chitosan and repairing using monoxone as modifying agent Decorations, the low molecular weight carboxymethyl chitosan of preparation by dipping wipe to sop up liquid the techniques such as pressure formed with alginic acid fibre Material cladding it is novel multiple Close dressing.Dressing of the present invention is suitable for skin superficial burns, wound and trauma surface infestation and festers, and has control bacterium infection, promotees The effect of into wound repair.
In order to solve the above-mentioned technical problem, a kind of compound alginic acid of low molecular weight carboxymethyl chitosan proposed by the present invention applies The preparation method of material, comprising the following steps:
Step 1: the preparation sterile low molecular weight carboxymethyl chitosan of medical grade, spare；
Step 2: medical grade alginic acid non-woven fabrics is prepared by needling process by alginate fiber, it is spare；
Step 3: the sterile low molecular weight carboxymethyl chitosan of medical grade that step 1 obtains is fixed on step 2 acquisition In medical alginic acid non-woven fabrics, to obtain the compound alginic acid dressing of low molecular weight carboxymethyl chitosan, wherein low molecular weight carboxylic The mass percent of methyl chitosan is 0.1%~8.0%, is preferably 1.2%；Surplus is medical alginic acid non-woven fabrics.
Further, detailed process is as follows for step 1；
Step 1-1, in 105 DEG C of dry low-molecular weight chitoglycan powder 4h, it is according to chitosan and isopropanol quality volume The ratio of 0.1g/ml is put into flask, and 4h is stirred at room temperature；
Step 1-2, the sodium hydroxide solution of 35wt%, the sodium hydroxide solution and above-mentioned body are added in Xiang Shangshu system The volume ratio of system is 2:1, is stirred at room temperature uniformly, and alkalization expansion 10h is carried out at -20 DEG C；According to 1ml/3min's in 60 DEG C of water-baths The pure chloroacetic aqueous isopropanol of analysis that mass-volume concentration is 2g/ml is added dropwise in speed, and it is molten to analyze pure chloroacetic isopropanol The volume ratio 1:1 of liquid and sodium hydroxide solution reacts 6h in 60 DEG C of water-baths, carries out carboxy methylation, obtains product A；
Step 1-3, it is 100:1 proportion according to the volume ratio of distilled water and product A, product A is sufficiently dissolved, with 50% vinegar Aqueous acid carries out being neutralized to 3pH=7.0, and Buchner funnel filters separation, and filtrate is used in common after sufficiently being precipitated with dehydrated alcohol Fast filter paper filtering, is packed into the bag filter for the molecular weight 14000 that shuts off after filtered solid product is washed 5 times with acetone repeatedly In；
Step 1-4, bag filter is immersed in distilled water and is dialysed for 24 hours, 95% ethanol water is put into after bag filter is taken out Bag filter is taken out again after middle dialysis for 24 hours；Repeat process 3~4 times of step 1-4；
Step 1-5, the carboxymethyl chitosan sugar aqueous solution in bag filter is precipitated with dehydrated alcohol, solid is taken out after suction filtration and is produced Object is placed in 60 DEG C of vacuum drying, vacuum degree -0.1MPa, time 5h, after sealed packaging, temperature is 115 DEG C, pressure is Sterilize 30min under 0.15MPa, can obtain the sterile low molecular weight carboxymethyl chitosan of medical grade.
For the sterile low molecular weight carboxymethyl chitosan molecular weight of the medical grade being prepared between 1W-2W, appearance is in class White or pale yellow powder, can flow freely, free from extraneous odour, diameter is between 100um-200um, pH=7.5, viscosity 60mpa.s, carboxylic Methyl substitution 90.2%.
The detailed process of step 3 is: the sterile low molecular weight carboxymethyl chitosan of medical grade for taking step 1 to obtain, configuration Mass fraction is the low molecular weight carboxymethyl chitosan sugar aqueous solution of 0.32~3.2wt%, at room temperature with the revolving speed magnetic of 120r/min Power stirs 1h；The medical grade alginic acid non-woven fabrics that step 2 obtains is cut to be impregnated in after the sheet material of required specification above-mentioned In low molecular weight carboxymethyl chitosan sugar aqueous solution, 60 DEG C of water-bath 40-50r/min shake 1h, are laid on glass after taking-up, with stone roller After son flattens, 60 DEG C of vacuum drying are placed on, vacuum degree -0.1MPa, time 6h are packaged in medicinal low density polyethylene after taking-up Alkene bag, sealed after being vacuumized,60Co irradiation dose 25kGy sterilizes for 24 hours, and the compound seaweed of low molecular weight carboxymethyl chitosan is made Sour dressing.
By the compound alginic acid dressing for the low molecular weight carboxymethyl chitosan that preparation method of the present invention obtains,
With following performance: moisture-vapor transmission is 3027.75g/ (m2·24h)±54.63；Hygroscopicity is 6.33g/g ±0.03；Mechanical stretch performance, in which: ultimate strength is longitudinally 55.17N ± 0.02, is laterally 74.68N ± 0.27；Fracture is stretched Long rate is longitudinally 81.15% ± 2.66, is laterally 72.61% ± 1.37.
The physical and chemical index having is as follows: ash content is 0.26% ± 0.05；Content of beary metal is 2.23ug/g ± 0.10；Fluorescence Substance is feminine gender；Infusion pH value is 7.63 ± 0.22；Surface reactive material is feminine gender；In water soluble matter be 5.71% ± 1.24；Soluble matter is 0.23% ± 0.02 in ether；
The anti-microbial property having is as follows: antibacterial bandwidth 2.6mm ± 0.06, remove covering surface after contact zone bacterium without Breed situation；
The biocompatibility having: sample leaching liquor cell with respect to appreciation rate RGR up to 92.5%, cell-cytotoxic reaction I Grade；The cellular morphology of 72h leaching liquor is in normal fusiform, and Density Distribution is uniform.
Compared with prior art, the beneficial effects of the present invention are:
Since the alginic acid in composite material has stronger imbibition ability, the low molecular weight carboxylic first of material surface can be made Base enclosure glycan rapidly releases, so can quickly and effectively inhibit bacterial reproduction.Meanwhile the fully connected topology of alginic acid Carboxymethyl chitosan is prevented to discharge completely, so that composite material has certain lasting fungistatic effect, effective time be can achieve 48h。
Wherein, the lasting fungistatic effect of composite material the results are shown in Table 1；
1 different multiples minimum bactericidal concentration of table (minimum bactericidal concentration, MBC) compounding sea The anti-microbial property (n=6) of alginic acid dressing；
Detailed description of the invention
Fig. 1 is the SEM figure of low molecular weight carboxymethyl chitosan contained in dressing of the present invention；
Fig. 2 (a) is the SEM figure of the compound alginic acid dressing surface of low molecular weight carboxymethyl chitosan of the present invention；
Fig. 2 (b) is the SEM figure of the compound alginic acid dressing of low molecular weight carboxymethyl chitosan of the present invention cross section；
Fig. 3 (a) is the compound alginic acid dressing of low molecular weight carboxymethyl chitosan of the present invention antibacterial band biocidal property for 24 hours in vitro Energy；
Fig. 3 (b) is the bacterial reproduction in the compound alginic acid dressing vitro exposure area of low molecular weight carboxymethyl chitosan of the present invention Situation；
Fig. 4 is the compound alginic acid dressing vitro cytotoxicity test NCTC of low molecular weight carboxymethyl chitosan of the present invention Clone929 cell (l cell) × 40 light microscope photo.
Specific embodiment
It is provided in the present invention it is a kind of prepare the sterile low molecular weight carboxymethyl chitosan of medical grade, key step includes: system The standby sterile low molecular weight carboxymethyl chitosan of medical grade；Medical grade seaweed is prepared by needling process by alginate fiber Sour non-woven fabrics；By the sterile low molecular weight carboxymethyl chitosan glycopexis of the medical grade of above-mentioned acquisition (as using dipping boulton process) In above-mentioned medical alginic acid non-woven fabrics (it is unrestricted that the alginic acid diverts from one use to another the preparation process in non-woven fabrics), to obtain low The compound alginic acid dressing of molecular weight carboxymethyl chitosan, wherein the mass percent of low molecular weight carboxymethyl chitosan is 0.1% ~8.0%, surplus is medical alginic acid non-woven fabrics.
Wherein, the process for preparing the sterile low molecular weight carboxymethyl chitosan of medical grade is as follows；
In 105 DEG C of dry low-molecular weight chitoglycan powder, the ratio for being 0.1g/ml according to chitosan and isopropanol quality volume Example is put into flask, and 4h is stirred at room temperature, is swollen it sufficiently；The sodium hydroxide of the 35wt% of 2 times of above-mentioned system volumes is added Solution is stirred at room temperature uniformly, and alkalization expansion 10h is carried out at -20 DEG C；According to the speed of 1ml/3min in 60 DEG C of water-baths, matter is added dropwise The pure chloroacetic aqueous isopropanol of analysis that volumetric concentration is 2g/ml is measured, pure chloroacetic aqueous isopropanol and hydroxide are analyzed The volume ratio 1:1 of sodium solution, 6h is reacted in 60 DEG C of water-baths, is carried out carboxymethylation reaction, is obtained product A；After reaction, The distilled water of 100 times of product A is added, product A is sufficiently dissolved, is carried out being neutralized to pH=7.0, cloth with 50% aqueous acetic acid Family name's funnel filters separation, and filtrate is sufficiently precipitated with dehydrated alcohol, filtered with ordinary filter paper, by head product low molecular weight carboxymethyl shell Glycan is fitted into the bag filter for the molecular weight 14000 that shuts off after washing 5 times repeatedly, is immersed in distilled water and is dialysed for 24 hours, taking-up is put into It dialyses in 95% ethanol water for 24 hours, takes out be put into distilled water again, 7d is purified repeatedly；Finally in bag filter Carboxymethyl chitosan sugar aqueous solution is precipitated with dehydrated alcohol, and sediment is filtered, and 60 DEG C of vacuum drying, vacuum degree-are put into after taking-up 0.1MPa, time 5h, after sealed packaging, sterilize 30min in the case where temperature is 115 DEG C, pressure is 0.15MPa, can obtain medical grade Sterile low molecular weight carboxymethyl chitosan.
The concentration of the sterile low molecular weight carboxymethyl chitosan of above-mentioned medical grade of compound alginic acid dressing load is sieved Choosing, referring to the evaluation third portion of GB/T20944.3-2008 antibacterial textile performance: succusion, 37 DEG C are cultivated for 24 hours and after 48h, A series of low molecular weight carboxymethyl chitosan of different quality concentration is measured in wavelength 475nm absorbance, it is determined that above-mentioned medical The sterile low molecular weight carboxymethyl chitosan three kinds of mixing bacterium colony common to wound of grade (including staphylococcus aureus ATCC 6538, Large intestine Erichsen bacterium 8099 and pseudomonas aeruginosa CMCC (B) 10010, and the concentration of three kinds of mixing bacterium colonies is 1*108) minimum suppression Bacteria concentration (MIC) and minimum bactericidal concentration (MBC), outcome quality concentration are 0.156% and 0.3125%.
For the sterile low molecular weight carboxymethyl chitosan molecular weight of medical grade of the present invention between 1W-2W, appearance is in off-white color or light Yellow powder can flow freely, free from extraneous odour, and diameter takes between 100um-200um, Ph value 7.5, viscosity 60mpa.s, carboxymethyl For degree 90.2%.
In the compound alginic acid dressing of low molecular weight carboxymethyl chitosan of the present invention, low molecular weight carboxymethyl chitosan accounts for compound Alginic acid dressing mass percent is 0.1%~8.0%.And it is prepared according to the following steps: takes in right amount according to above-mentioned preparation method The sterile low molecular weight carboxymethyl chitosan of medical grade obtained configures the medical grade low molecular weight carboxymethyl of 0.32~3.2wt% Chitosan aqueous solution, magnetic agitation 120r/min about 1h is until clear is presented in solution at room temperature；By above-mentioned acquisition Alginic acid non-woven fabrics is impregnated in above-mentioned low molecular weight carboxymethyl chitosan after cutting out the alginic acid nonwoven fabric sheets of various effective specifications In sugar aqueous solution, 60 DEG C of water-bath 40-50r/min shake 1h, come into full contact with alginic acid non-woven fabrics with carboxymethyl chitosan solution, It is laid on glass after taking-up, after being flattened with roller, is placed in 60 DEG C of vacuum oven vacuum drying, vacuum degree -0.1MPa, about 5h；Medicinal low density polyethylene (LDPE) bag is packaged in after taking-up, sealed after being vacuumized uses60The sterilizing of Co- gamma-ray irradiation, dosage 25kGy, sterilization time for 24 hours, finally prepare the compound alginic acid dressing of low molecular weight carboxymethyl chitosan.
The compound alginic acid dressing of low molecular weight carboxymethyl chitosan of the present invention has good moisture-vapor transmission, moisture absorption Property, mechanical stretch performance, in which:
Moisture-vapor transmission: data measured is 3027.75g/ (m224h) ± 54.63；
Hygroscopicity: data measured is 6.33g/g ± 0.03；
Mechanical stretch performance: data measured is ultimate strength longitudinal direction 55.17N ± 0.02, lateral 74.68N ± 0.27；Fracture Elongation longitudinal 81.15% ± 2.66, lateral 72.61% ± 1.37；
Every physical and chemical index of the compound Wound dressing of the present invention meets industry internal standard, in which:
Ash content: data measured is 0.26% ± 0.05；
Content of beary metal: data measured is 2.23ug/g ± 0.10；
Fluorescent material: data measured is feminine gender；
Infusion pH value: data measured is 7.63 ± 0.22；
Surface reactive material: data measured is feminine gender；
Soluble matter in water: data measured is 5.71% ± 1.24；
Soluble matter in ether: data measured is 0.23% ± 0.02；
The compound Wound dressing of the present invention has good anti-microbial property and biocompatibility, in which:
Anti-microbial property: antibacterial bandwidth 2.6mm ± 0.06, the bacterium of the contact zone after removing covering surface is without breeding situation
Biocompatibility: sample leaching liquor cell can achieve 92.5% with respect to appreciation rate RGR, cell-cytotoxic reaction I Grade.The cellular morphology of its 72h leaching liquor is in normal fusiform, and Density Distribution is uniform,
To sum up, low molecular weight carboxymethyl of the present invention is shown by the optimization of technique preparation process and wound dressing analysis detection The compound alginic acid dressing of chitosan has good absorbent, is capable of the tissue fluid of the efficient absorption surface of a wound, meanwhile, have certain Moisture-vapor transmission, balance the physiological humidity of the surface of a wound, accelerate to promote wound healing.Natural biologic material therein passes through excellent Change the techniques such as compound, has effects that significantly to inhibit to surface of a wound common bacteria, while passing through the topological structure of alginic acid non-woven fabrics It can make combine dressing of the invention that there is the bacteriostasis of 48h.It appropriate can slow down the replacement frequency of dressing, to mitigate The financial burden of patient.
The compound alginic acid dressing raw material sources of low molecular weight carboxymethyl chitosan of the present invention are extensive, and preparation process is simply easy It realizes, product resultant effect is significant, and some shortcomings of the dressing of the existing surface of a wound of solution in production application has Certain economy and society value.The compound alginic acid dressing of low molecular weight carboxymethyl chitosan of the present invention combines two kinds natural high The biological sexual clorminance of molecular polysaccharide has good gas permeability, mechanical stretch, hygroscopicity, antibiotic property and biocompatibility, energy The wettability physiological environment of enough feasible simulation surface of a wound, effectively facilitates wound healing.Preparation process is relatively easy, and scale production can Row is strong.
Technical solution of the present invention is described in further detail in the following with reference to the drawings and specific embodiments, it is described specific Embodiment is only explained the present invention, is not intended to limit the invention.
Embodiment one: the preparation and particle diameter distribution of low molecular weight carboxymethyl chitosan
The dry medical grade low-molecular weight chitoglycan powder of 1g is taken to be put into flask, 10ml isopropanol, which is added, and is stirred at room temperature makes it Sufficiently swelling, about 4h；20ml 35wt% sodium hydroxide solution is added to be stirred at room temperature uniformly, -20 DEG C carry out alkalization expansion, about 10h.1h drips off the pure chloroacetic aqueous isopropanol of analysis that 20ml mass-volume concentration is 2g/ml in 60 DEG C of water-baths, at 60 DEG C 6h is reacted in water-bath, carries out carboxy methylation；50mL distilled water is added after reaction, product is sufficiently dissolved, with 50% acetic acid It being neutralized, pH value is made to reach 7.0, Buchner funnel filters separation, and filtrate is sufficiently precipitated with dehydrated alcohol, ordinary filter paper filtering, It washs 5 times, is fitted into bag filter (shut off molecular weight 14000) repeatedly, be immersed in distilled water and dialyse for 24 hours, taking-up is put into 95% second It dialyses in alcohol for 24 hours, takes out be put into distilled water again, 7d is purified repeatedly, finally the carboxymethyl chitosan in bag filter Aqueous solution is precipitated with dehydrated alcohol, 60 DEG C, vacuum degree -0.1MPa, time 5h of vacuum drying after taking out after pumping rate, after sealed packaging 115 DEG C of high temperature and pressure, 30min sterilizing can obtain the sterile low molecular weight carboxymethyl chitosan of medical grade.
Above-mentioned carboxymethyl chitosan is ground in powdered with ball mill or mortar, takes to be evenly distributed in right amount and is stained with conduction It on the silicon wafer of glue, is fixed on sample copper platform, vacuum metal spraying 10min, the form of scanning electron microscopic observation sample, size and table Face, the result is shown in Figure 1 show sample in the form of sheets, and diameter is between 100um-200um, and surface is with the presence of certain concave-convex fold.
Embodiment two: the preparation of the compound alginic acid dressing of low molecular weight carboxymethyl chitosan
The sterile low molecular weight carboxymethyl chitosan configuration quality concentration of the medical grade being prepared using embodiment 1 is 3.0% low molecular weight carboxymethyl chitosan sugar aqueous solution, 25 DEG C of room temperature magnetic agitation 120r/min about 1h are clear until solution presentation It is clear it is bright until；The alginic acid non-woven fabrics for cutting out 2.5cm*2.5cm is impregnated in above-mentioned solution, 60 DEG C of water-bath 40-50r/min shakes 1h is swung, alginic acid non-woven fabrics is come into full contact with carboxymethyl chitosan, is laid on glass after taking-up, after being flattened with roller, is put 60 DEG C of vacuum oven are placed in, vacuum degree -0.1MPa, about 5h；It takes out afterwards and is packaged in medicinal low density polyethylene (LDPE) bag, after vacuumizing Sealing uses60The sterilizing of Co- gamma-ray irradiation, dosage 25kGy, time for 24 hours, finally prepare low molecular weight carboxymethyl chitosan Compound alginic acid dressing.
The compound alginic acid dressing for the low molecular weight carboxymethyl chitosan that the present invention prepares must be kept in dark place.
The SEM stereoscan photograph surface of the compound alginic acid dressing of low molecular weight carboxymethyl chitosan made from embodiment two It is shown with cross section such as Fig. 2 (a) and Fig. 2 (b).
The physicochemical property for the compound alginic acid dressing that embodiment two obtains is examined referring to national standard and professional standard It surveys, specific as follows:
Moisture-vapor transmission is referring to " YY/T0471.2-2004 contact Wound dressing test method part 2: ventilative to apply Expect moisture-vapor transmission ", data measured 3027.75g/m2·24h±54.63。
Hygroscopicity reference " YY/T0471.2-2004 contact Wound dressing test method part 1: liquid-absorbent ", Data measured is 6.33g/g ± 0.03.
Mechanical stretch performance is surveyed referring to " measurement of FZ/T 60005-90 non-woven cloth ultimate strength and elongation at break " Obtaining data is ultimate strength longitudinal direction 55.17N ± 0.02, lateral 74.68N ± 0.27；Elongation at break longitudinal 81.15% ± 2.66, lateral 72.61% ± 1.37.
For ash content referring to " 05 edition CP, mono- Ⅸ K of annex ", data measured is 0.26% ± 0.05.
Referring to " GB/T11593-1998 textile detection of heavy metal ion method ", data measured is content of beary metal 2.23ug/g±0.10。
For fluorescent material referring to " YY/T0471.2-2004 contact Wound dressing test method ", data measured is feminine gender.
Referring to " YY/T0471.2-2004 contact Wound dressing test method ", data measured is infusion pH value 7.63±0.22。
For surface reactive material referring to " YY/T0471.2-2004 contact Wound dressing test method ", data measured is yin Property.
Referring to " YY/T0471.2-2004 contact Wound dressing test method ", data measured is soluble matter in water 5.71% ± 1.24.
Referring to " YY/T0471.2-2004 contact Wound dressing test method ", data measured is soluble matter in ether 0.23% ± 0.02.
Reference standard " the evaluation part 1 of GB/T20944.1-2007 antibacterial textile performance: agar plate diffusion method " Operate the auxiliary material progress in-vitro antibacterial performance evaluation obtained to embodiment two, as the result is shown dressing of the present invention it is common for the surface of a wound by Try the year-on-year of strain staphylococcus aureus ATCC 6538, large intestine Erichsen bacterium 8099 and pseudomonas aeruginosa CMCC (B) 10010 The antibacterial bandwidth for 24 hours of example mixing can achieve 2.6mm ± 0.06, and remove the bacterium of the contact zone after covering surface without numerous Situation is grown, effect is good, referring to Fig. 3 (a) and Fig. 3 (b).
Biocompatibility analysis: reference standard " GB/T16886.5-2003 medical treatment is carried out to the auxiliary material that embodiment two obtains The 5th part of instrument biological assessment: vitro cytotoxicity test " uses mtt assay therein, and sample leaching liquor cell is opposite to rise in value Rate RGR can achieve 92.5%, and cell-cytotoxic reaction is I grade.The cellular morphology of its 72h leaching liquor is in normal fusiform, and density It is evenly distributed, referring to fig. 4.
Although above in conjunction with figure, invention has been described, and the invention is not limited to above-mentioned specific embodiment parties Formula, the above mentioned embodiment is only schematical, rather than restrictive, and those skilled in the art are in this hair Under bright enlightenment, without deviating from the spirit of the invention, many variations can also be made, these belong to guarantor of the invention Within shield.

Claims (3)

1. a kind of preparation method of the compound alginic acid dressing of low molecular weight carboxymethyl chitosan, which is characterized in that by following steps Composition:
Step 1: the preparation sterile low molecular weight carboxymethyl chitosan of medical grade, spare；
Step 1 the following steps are included:
It step 1-1, is 0.1g/ according to chitosan and isopropanol quality volume in 105 DEG C of dry low-molecular weight chitoglycan powder 4h The ratio of ml is put into flask, and 4h is stirred at room temperature；
Step 1-2, the sodium hydroxide solution of 35wt%, the sodium hydroxide solution and above-mentioned system are added in Xiang Shangshu system Volume ratio is 2:1, is stirred at room temperature uniformly, and alkalization expansion 10h is carried out at -20 DEG C；According to the speed of 1ml/3min in 60 DEG C of water-baths The pure chloroacetic aqueous isopropanol of analysis that mass-volume concentration is 2g/ml is added dropwise, analyze pure chloroacetic aqueous isopropanol with The volume ratio 1:1 of sodium hydroxide solution reacts 6h in 60 DEG C of water-baths, carries out carboxy methylation, obtains product A；
Step 1-3, it is 100:1 proportion according to the volume ratio of distilled water and product A, product A is sufficiently dissolved, with 50% acetic acid water Solution be neutralized to pH=7.0, and Buchner funnel filters separation, filtrate sufficiently precipitated with dehydrated alcohol after with common Medium speed filter paper Filtering, is fitted into the bag filter for the molecular weight 14000 that shuts off after filtered solid product is washed 5 times with acetone repeatedly；
Step 1-4, bag filter is immersed in distilled water and is dialysed for 24 hours, is put into after bag filter is taken out in 95% ethanol water thoroughly Bag filter is taken out again after analysis for 24 hours；Repeat process 3~4 times of step 1-4；
Step 1-5, the carboxymethyl chitosan sugar aqueous solution in bag filter is precipitated with dehydrated alcohol, solid product is taken out after suction filtration and is set It is dried in vacuo in 60 DEG C, vacuum degree -0.1MPa, time 5h, after sealed packaging, in the case where temperature is 115 DEG C, pressure is 0.15MPa Sterilize 30min, can obtain the sterile low molecular weight carboxymethyl chitosan of medical grade；
Step 2: medical grade alginic acid non-woven fabrics is prepared by needling process by alginate fiber, it is spare；
Step 3: the sterile low molecular weight carboxymethyl chitosan of medical grade that step 1 obtains is fixed on the medical of step 2 acquisition In alginic acid non-woven fabrics, to obtain the compound alginic acid dressing of low molecular weight carboxymethyl chitosan, wherein low molecular weight carboxymethyl The mass percent of chitosan is 0.1%~8.0%, and surplus is medical alginic acid non-woven fabrics；
Step 3 the following steps are included:
The sterile low molecular weight carboxymethyl chitosan of medical grade for taking step 1 to obtain, configuration quality score are 0.32~3.2wt% Low molecular weight carboxymethyl chitosan sugar aqueous solution, at room temperature with the revolving speed magnetic agitation 1h of 120r/min；
It is cut to the medical grade alginic acid non-woven fabrics that step 2 obtains to be impregnated in above-mentioned low point after the sheet material of required specification In son amount carboxymethyl chitosan sugar aqueous solution, 60 DEG C of water-bath 40-50r/min shake 1h, are laid on glass after taking-up, with roller pressure After smooth, 60 DEG C of vacuum drying are placed on, vacuum degree -0.1MPa, time 6h are packaged in medicinal low density polyethylene (LDPE) after taking-up Bag, sealed after being vacuumized,60Co irradiation dose 25kGy sterilizes for 24 hours, and the compound alginic acid of low molecular weight carboxymethyl chitosan is made Dressing；
For the sterile low molecular weight carboxymethyl chitosan molecular weight of medical grade between 1W-2W, appearance is in off-white color or yellowish toner End can flow freely, free from extraneous odour, and diameter is between 100um-200um, pH=7.5, viscosity 60mpa.s, degree of substitution by carboxymethyl 90.2%.
Low point that 2. the preparation method of the compound alginic acid dressing of low molecular weight carboxymethyl chitosan according to claim 1 obtains The compound alginic acid dressing of son amount carboxymethyl chitosan, has following performance:
Moisture-vapor transmission is 3027.75g/ (m2·24h)±54.63；
Hygroscopicity is 6.33g/g ± 0.03；
Mechanical stretch performance, in which: ultimate strength is longitudinally 55.17N ± 0.02, is laterally 74.68N ± 0.27；Extension at break Rate is longitudinally 81.15% ± 2.66, is laterally 72.61% ± 1.37.
3. the compound alginic acid dressing of low molecular weight carboxymethyl chitosan according to claim 2, which is characterized in that
The physical and chemical index having is as follows: ash content is 0.26% ± 0.05；Content of beary metal is 2.23ug/g ± 0.10；Fluorescent material For feminine gender；Infusion pH value is 7.63 ± 0.22；Surface reactive material is feminine gender；Soluble matter is 5.71% ± 1.24 in water； Soluble matter is 0.23% ± 0.02 in ether；
The anti-microbial property having is as follows: antibacterial bandwidth 2.6mm ± 0.06, and the bacterium of the contact zone after removing covering surface is without breeding Situation；
The biocompatibility having: for sample leaching liquor cell with respect to appreciation rate RGR up to 92.5%, cell-cytotoxic reaction is 1 grade； The cellular morphology of 72h leaching liquor is in normal fusiform, and Density Distribution is uniform.
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Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040101547A1 (en) * 2002-11-26 2004-05-27 Pendharkar Sanyog Manohar Wound dressing containing aldehyde-modified regenerated polysaccharide
EP1481694A1 (en) * 2003-05-30 2004-12-01 Ethicon, Inc. Biodegradable hemostatic wound dressings
CN1686572A (en) * 2005-05-13 2005-10-26 褚省吾 Ultra strong absorption calcium alginate henatischesis dressing and its preparation method
CN101569761A (en) * 2008-12-31 2009-11-04 褚加冕 Preparation method for medical honey dressing
CN102526795A (en) * 2012-02-15 2012-07-04 中国人民解放军广州军区武汉总医院 Chitosan-based styptic sponge and preparation method thereof
CN102579194A (en) * 2012-03-07 2012-07-18 苏州美迪斯医疗运动用品有限公司 Composite self-adhering elastic bandage for functional biological dressing

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040101547A1 (en) * 2002-11-26 2004-05-27 Pendharkar Sanyog Manohar Wound dressing containing aldehyde-modified regenerated polysaccharide
EP1481694A1 (en) * 2003-05-30 2004-12-01 Ethicon, Inc. Biodegradable hemostatic wound dressings
CN1686572A (en) * 2005-05-13 2005-10-26 褚省吾 Ultra strong absorption calcium alginate henatischesis dressing and its preparation method
CN101569761A (en) * 2008-12-31 2009-11-04 褚加冕 Preparation method for medical honey dressing
CN102526795A (en) * 2012-02-15 2012-07-04 中国人民解放军广州军区武汉总医院 Chitosan-based styptic sponge and preparation method thereof
CN102579194A (en) * 2012-03-07 2012-07-18 苏州美迪斯医疗运动用品有限公司 Composite self-adhering elastic bandage for functional biological dressing

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