CN107233617A - A kind of wound dressing of liquid chitosan and its preparation and application - Google Patents

A kind of wound dressing of liquid chitosan and its preparation and application Download PDF

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Publication number
CN107233617A
CN107233617A CN201710412637.5A CN201710412637A CN107233617A CN 107233617 A CN107233617 A CN 107233617A CN 201710412637 A CN201710412637 A CN 201710412637A CN 107233617 A CN107233617 A CN 107233617A
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chitosan
wound dressing
liquid
wound
water
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应国清
易喻
徐云霞
梅建凤
陈建澍
张彦璐
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Zhejiang University of Technology ZJUT
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Zhejiang University of Technology ZJUT
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L26/00Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
    • A61L26/0061Use of materials characterised by their function or physical properties
    • A61L26/0066Medicaments; Biocides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L26/00Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
    • A61L26/0009Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form containing macromolecular materials
    • A61L26/0014Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form containing macromolecular materials obtained by reactions only involving carbon-to-carbon unsaturated bonds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L26/00Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
    • A61L26/0009Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form containing macromolecular materials
    • A61L26/0023Polysaccharides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/10Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing inorganic materials
    • A61L2300/11Peroxy compounds, peroxides, e.g. hydrogen peroxide
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/20Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
    • A61L2300/202Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials with halogen atoms, e.g. triclosan, povidone-iodine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/20Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
    • A61L2300/21Acids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/20Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
    • A61L2300/30Compounds of undetermined constitution extracted from natural sources, e.g. Aloe Vera
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/404Biocides, antimicrobial agents, antiseptic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/412Tissue-regenerating or healing or proliferative agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/45Mixtures of two or more drugs, e.g. synergistic mixtures

Abstract

The invention discloses a kind of liquid chitosan wound dressing and its preparation and application, the liquid chitosan wound dressing is made up of the following raw material:N glycosylations chitosan, aloe extract, the polyvinyl alcohol water solution of mass concentration 10%, polyethylene glycol, glycerine, olive oil, PVP-I, the hydrogen peroxide of mass concentration 30%, lactic acid, menthol, the ethanol water of volumetric concentration 95%, 5mg/mL physiological saline;The fluid wound dressing of the smear type of the present invention is applied to skin abrasion incised wound, chapped skin, slight burn and scald, protection of surgical site infections suture site etc..

Description

A kind of wound dressing of liquid chitosan and its preparation and application
(1) technical field
The present invention relates to a kind of bio-medical dressing and preparation method thereof.
(2) background technology
In actual life, people often can be injured because unexpected, such as scratch, bump injury, knife, which hurt, stab and burnt, scalds Wound etc., this kind of skin injury easily causes bleeding, oozing of blood, and brings constant pain sense.In addition, also cotton-padded mattress within the hospital The wounds such as sore, wound, if these wound processing are incorrect, the lighter's delayed healing time, scar etc.;Severe patient meeting Cause Infective microorganism, it is local red and swollen, suppuration occur, various complication, such as lockjaw, septicemia can be triggered in succession. Therefore, wound is the very important disease of a class, and the wound to skin surface carries out effective treatment and nursing, and actively develops The treatment of wound and repairing research are very necessary.
At present, domestic and international researcher has done numerous studies on wound dressing, but is still used in clinical treatment more Sterile gauze carries out wrapping processing, and this normal gauze dressing mainly plays a part of to protect wound, and to the healing of wound almost There is no facilitation, and such dressing easily sticks together with wound, therefore easily cause secondary damage in more change dressings;And For small area wound, adhesive plaster bandage is still the selection product that people often handle wound, and adhesive plaster bandage is generally by one The adhesive plaster of long shape and a fritter adsorptive pads are constituted, but traditional bandage normally only plays temporarily hemostasis, the work of the protection surface of a wound With use time is unsuitable long.If using for a long time, the adhesive plaster air proof of adhesive bandage outer layer can make wound and wound circumference Skin whitening, softening, cause scabies secondary infection.
According to incompletely statistics, existing more than 2400 kinds wound dressings on the market at present, but without a kind of specific dressing Available for the agglutination of whole wound, the selection of dressing should also be as selecting depending on the situation of wound.Sum it up, being used as reason Think dressing, should possess these advantages:It is waterproof and moisture evaporation can be controlled, the water evaporation rate with similar normal skin;Energy The physiological environment of wound is kept, the surface of a wound is in moistening but the environment without hydrops;Have good compliance, easily remove without Granulation tissue is damaged, pain is not produced;Protect wound to exempt microorganism invasion, play barrier protection, preferably also have certain Wound healing can be promoted and suppress the function of scar hyperplasia;It is safe and nontoxic, without allergy or other adverse reactions.
Chitosan is a kind of natural polymer biomaterial, with good biological functionality and compatibility, blood compatibility Property, security, microbic resolvability etc., while also have broad-spectrum antiseptic, hemostasis and promote wound healing, suppress scar formation etc. Plurality of medical performance, can be used as excellent medical dressing and tissue engineering material.The N- glycosylation chitosan category that the present invention is used In water soluble chitosan, the water-soluble poor shortcoming of chitosan in the prior art is overcome, while deacetylation is in 60%-70% Between, correlative study shows, the chitosan within this deacetylation compares other deacetylations, can more promote red blood cell to coagulate Collection, thus play more preferably anastalsis (Tian F, Yang J, Chen S, Kan Y, Ji FJ Biomed Eng, 2005, 22:999-1003)。
The drawbacks of for existing chitosan class product, preferably supplementary material, each component content is controlled, is prepared a kind of to skin Gentle non-stimulated, film forming is good, antibacterial ability is stronger, safe and efficient novel formulation, to nowadays clinical treatment skin burn, wound Sentiment dye etc. have very important significance, and can further to intractable chronic ulcer of skin (such as Late-stage diabetic skin burst Ecthyma etc. caused by ulcer, varix of lower limb) and common gynecological disease, frequently-occurring disease (such as cervical erosion), create preferably doctor Learn and social benefit.
(3) content of the invention
It is an object of the present invention to provide a kind of fluid wound dressing of smear type (wound dressing of liquid chitosan), institute's film forming is soft Soft sticking nature is good, with good gas permeability and transparency, good antimicrobial effect, while promoting wound healing, suppresses wound tissue Raised scars caused by paraplasm.Another object of the present invention is to the preparation side there is provided this kind of liquid wound dressing Method.
The technical solution adopted by the present invention is:
The present invention provides a kind of liquid chitosan wound dressing, and the liquid chitosan wound dressing is by the following raw material system Into:N- glycosylation chitosan, aloe extract, the polyvinyl alcohol water solution of mass concentration 10%, polyethylene glycol, glycerine, olive oil, PVP-I, the hydrogen peroxide of mass concentration 30%, lactic acid, menthol, the ethanol water of volumetric concentration 95%, 5mg/mL physiology salts Water;The N- glycosylation chitosans and polyethylene glycol and menthol mass ratio are 1:0.01-1:0.01-1.5;The aloe is extracted Thing, the polyvinyl alcohol water solution of mass concentration 10%, glycerine, olive oil, PVP-I, the hydrogen peroxide of mass concentration 30%, lactic acid, body Product concentration 95% ethanol water, 5mg/mL physiological saline volumetric usage are respectively 0.5- in terms of N- glycosylation chitosan masses 20ml/g、1-50ml/g、0.05-5ml/g、0.05-5ml/g、0.1-10ml/g、0.1-10ml/g、0.01-2ml/g、1.5- 50ml/g、1-50ml/g;The aloe extract is the homogenate ultrasound extraction after aloe leaf (need not remove the peel) is smashed to pieces Supernatant afterwards is mixed with deionized water is concentrated into the acquisition of cumulative volume a quarter, or homogenate and the ethanol of volumetric concentration 75% Ultrasound extracts and is concentrated into 1/10th acquisitions of cumulative volume after aqueous solution mixing;The deionized water and supernatant volume ratio For 1.5:1;The ethanol water is 5 with described homogenate volume ratio:1.
Further, preferably described N- glycosylation chitosans and polyethylene glycol and menthol mass ratio are 1:0.01-0.3: 0.03-0.5, more preferably described N- glycosylation chitosans and polyethylene glycol and menthol mass ratio are 1:0.02-0.2:0.04- 0.3。
Further, preferably described aloe extract, the polyvinyl alcohol water solution of mass concentration 10%, glycerine, olive oil, poly- dimension Ketone iodine, the hydrogen peroxide of mass concentration 30%, lactic acid, the ethanol water of volumetric concentration 95%, 5mg/mL physiological saline volumetric usage with N- glycosylation chitosan mass meters are respectively 0.75-7.5ml/g, 2.5-20ml/g, 0.08-2ml/g, 0.08-2ml/g, 0.2- 4ml/g, 0.2-4ml/g, 0.06-0.75ml/g, 2.25-20ml/g, 2-20ml/g, more preferably described aloe extract, quality The polyvinyl alcohol water solution of concentration 10%, glycerine, olive oil, PVP-I, the hydrogen peroxide of mass concentration 30%, lactic acid, volumetric concentration 95% ethanol water, 5mg/mL physiological saline volumetric usage are respectively 1-7ml/g, 4- in terms of N- glycosylation chitosan masses 17ml/g、0.1-1ml/g、0.1-1ml/g、0.2-3ml/g、0.2-3ml/g、0.07-0.5ml/g、3-17ml/g、3-17ml/ g。
Further, the aloe extract is prepared one of as follows:(1) fresh aloe blade, deionized water are chosen Rinsed clean, smashs obtained homogenate to pieces;Homogenate is taken, 5~8min of high temperature sterilization at 95 DEG C is stood after cooling, is surpassed under 450W 20~30min of sound, centrifugation takes supernatant and deionized water by volume 2:3 mixing, in 65~70 DEG C of revolvings to the four of cumulative volume / mono-, that is, obtain aloe water extract;(2) fresh aloe blade is chosen, deionized water rinsed clean smashs obtained homogenate to pieces; Homogenate is taken to add the ethanol water of volumetric concentration 75%, 30~40min of ultrasonic extraction under power 450W, common ultrasonic extraction 2 Secondary, centrifuging and taking supernatant is rotated to 1/10th of cumulative volume at 45~50 DEG C, it is aloe alcohol extract to take concentrate;The second Alcohol solution is 5 with homogenate volume ratio:1.
The present invention also provides a kind of preparation method of the liquid chitosan wound dressing, and methods described is:
(1) formula ratio is pressed, N- is glycosylated into chitosan physiological saline stirring and dissolving, lactic acid is added, N- glycosyls are made Change chitosan solution;
(2) prepared by film liquid:By formula ratio, polyvinyl alcohol is added in deionized water, the heating stirring 2 at 90~100 DEG C ~3h is made the polyvinyl alcohol water solution of mass concentration 10%, produces film liquid to being completely dissolved;
(3) formula ratio is pressed, N- made from step (1) is glycosylated into chitosan solution and aloe extract is mixed, is added Film liquid made from step (2), continuously adds polyethylene glycol, glycerine, olive oil, PVP-I, hydrogen peroxide, menthol, room successively Lower 500~the 700r/min of temperature is uniformly mixed;
(4) formula ratio is pressed, the ethanol water of volumetric concentration 95%, at room temperature 500 are added in the solution prepared to step (3) ~700r/min is uniformly mixed, that is, described liquid chitosan wound dressing is made.
The present invention also provides a kind of application of liquid chitosan wound dressing in wound face healing drug is prepared.
Preparation method of the present invention is simple, and the primary efficacy of each component is:
(1) common chitosan is replaced using N- glycosylation chitosans, N- glycosylation chitosans overcome shell in the prior art The water-soluble poor shortcoming of glycan, and N- glycosylation chitosan of the deacetylation between 60%~70% is chosen, it can more promote Erythrocyte agglutination, so as to play more preferably anastalsis;
(2) physiological saline substituted acetic acid solution is used, on the one hand because physiological saline is generally used for sterilizing wound, the opposing party The pH value of physiological saline is considered close to 7 in face, and modified chitosan is more soluble in neutral solution, accelerates the molten of chitosan Solve speed;
(3) lactic acid is added, the pH value of chitosan biological film-forming glue can be adjusted, and acid condition is conducive to lactic acid bacteria Flourish, and inhibitory action is produced to harmful microorganisms such as Escherichia coli;
(4) polyvinyl alcohol, be have after relatively conventional water miscible macromolecule filming material, film forming certain intensity and Pliability, stimulation will not be produced to skin, also with good hygroscopicity, while also having certain waterproof action.
(5) aloe extract, with bactericidal antiphlogistic, removing toxic substances and the effect for promoting wound healing, while gently calming down scar Trace.
(6) add glycerine, can skin care, prevent cracked skin.In air easily absorb moisture, to wound moisturizing compared with It is good.Modern medicine believes that, in the case where avoiding infecting at wound, maintaining hygrometric state to would be even more beneficial to being cured for wound than dry condition Close.Glycerine can increase the pliability and tensility of film as thickener simultaneously;
(7) olive oil, can increase the pliability and tensility of film, has moisture-keeping function to wound as dispersant, can Prevent wrinkled skin and the itch caused by skin hyposecretion, can mitigate wound pain, promote healing, more after do not leave scar Trace.Olive oil is loaded into pharmacopeia by the western countries such as the U.S., Germany already;
(8) 5% PVP-Is, can inherently be killed as disinfection preservative to various bacteria, brood cell, virus, fungi etc. The effect of going out.Its mechanism of action is that this product is contacted behind the surface of a wound or affected part, and energy depolymerization discharges free-iodine and plays bactericidal action.Feature is It is small to tissue irritation, it is adaptable to skin, mucosa infection.Sterilization available for small area skin, mucous membrane wound;
(9) 30% hydrogen peroxide, are usually used in medical disinfecting sterilization, and its strong oxidizing property can destroy the protein of bacterium, be allowed to Death, on the other hand can make antibacterial film pore breathe freely, add disproportionation anti-as pore-foaming agent, hydrogen peroxide disproportionation release oxygen again Should can heat release, antibacterial film curing rate can be accelerated.Generally medical upper using 3% hydrogen peroxide, the hydrogen peroxide that this experiment is used is micro, And having other reagent dilutions of addition, the hydrogen peroxide concentration finally given will not be caused to stimulate to skin and injured;
(10) menthol, is used frequently as odorant, with refrigerant sense, at the same can anti-inflammatory analgesic it is antipruritic, mitigate edema, add It is added in dressing and is easy to be accepted by patients;
(11) alcohol solvent is used, using the rapid boiling characteristics of ethanol, enables product of the present invention fast rapid-result on the surface of a wound Film, effectively protects the surface of a wound.
Particular combination of the invention by special component, the fluid wound dressing of obtained smear type is medical as external application Had the following technical effect that in dressing:
(1) smear after can quickly be formed with surface of a wound good fit, elastomeric flexible, good air permeability, have fungistatic effect one Layer glued membrane, combines the advantage of adhesive bandage and the professional dressing of new wound;
(2) Moist healing environment is maintained, hygrometric state would be even more beneficial to the healing of wound than dry condition;
(3) have good bactericidal effect, can kill and suppress the pathogen of the surface of a wound, it is ensured that the surface of a wound it is sterile, while energy Suppress inflammatory reaction;
(4) there is good haemostatic effect, promote wound healing effect and suppress projection caused by wound tissue's paraplasm The effect of scars, while fragrant odour, it is small that excitement is spread in painting, very comfortably.
The present invention smear type fluid wound dressing be applied to skin abrasion incised wound, chapped skin, slight burn and scald, outside The protection at section's postoperative adhesions position etc..
(4) embodiment
With reference to specific embodiment, the present invention is described further, but protection scope of the present invention is not limited in This:
Hydrogen peroxide mass concentration used in the embodiment of the present invention is 30%, polyvinyl alcohol (degree of polymerization 1750 ± 50), poly- second two Alcohol (degree of polymerization 6000), PVP-I (molecular weight 365).Room temperature of the present invention is 25-30 DEG C.
Embodiment 1
(1) N- glycosylates the preparation of chitosan:Chitosan 4.0g is weighed, the acetic acid aqueous solution of volumetric concentration 1% is added 0.5h is stirred under 200mL, room temperature (25-30 DEG C), treats that it fully dissolves, the fructose of 4.0 amino of chitosan equivalents is added, 30~ At 35 DEG C after magnetic agitation reaction 7h, sodium borohydride 1.7g reductase 12 4h at room temperature are added, finally with the ethanol of volumetric concentration 95% Aqueous solution terminating reaction, will separate out product and is washed with absolute ethyl alcohol 3~4 times, centrifuging to precipitate, 40 DEG C of vacuum dryings, finally Chitosan is glycosylated to N-, in being saved backup in drier.
(2) aloe water extract preparation method is as follows:Fresh aloe blade is chosen, deionized water rinsed clean smashs obtained to pieces Homogenate.Homogenate 100g is taken, 5~8min of high temperature sterilization at 95 DEG C is stood after cooling, 20~30min of ultrasound under 450W, from The heart takes supernatant, takes 40mL supernatants and 60mL deionized waters to mix, and is heated to 65~70 DEG C of revolving purification 40min, that is, obtains reed Luxuriant growth water extract 25mL, is fitted into brown bottle, and 4 DEG C save backup.
(3) aloe alcohol extract preparation method is as follows:Fresh aloe blade is chosen, deionized water rinsed clean smashs obtained to pieces Homogenate.100g homogenates are taken, the ethanol water 200mL of volumetric concentration 75%, ultrasonic extraction 30~40min (power is added 450W), ultrasonic extraction 2 times altogether, centrifuging and taking supernatant, revolving purification 30min removes alcohol solvent at 45~50 DEG C, finally will concentration Liquid (being aloe alcohol extract, be concentrated into 1/10th times of volumes of cumulative volume) 35mL is fitted into brown reagent bottle, in 4 DEG C of preservations It is standby.
Embodiment 2
1) wound dressing of liquid chitosan is formulated:Aloe water extract prepared by N- glycosylation chitosans 2.17g, embodiment 1 10mL, the polyvinyl alcohol of mass concentration 10% (degree of polymerization 1750 ± 50) 30mL, polyethylene glycol (degree of polymerization 6000) 0.43g, glycerine 1.52mL, olive oil 1.52mL, PVP-I (molecular weight 365) 3.91mL, the hydrogen peroxide 3.91mL of mass concentration 30%, lactic acid 0.65mL, menthol 0.43g, ethanol water 32.6mL, 5mg/mL physiological saline 21.74mL of volumetric concentration 95%.
2) preparation process of liquid chitosan wound dressing is as follows:
(1) formula ratio is pressed, N- glycosylation chitosan 2.17g is weighed, adds 5mg/mL physiological saline 21.74mL, at room temperature Stirring and dissolving, adds 0.65mL lactic acid, and N- glycosylation chitosan solutions are made;
(2) prepared by film liquid:By formula ratio, polyvinyl alcohol 0.30g is weighed, is added in deionized water, is added at 90-100 DEG C 2~3h of thermal agitation is made the polyvinyl alcohol water solution 30mL of mass concentration 10%, produces film liquid to being completely dissolved;
(3) N- made from step (1) is glycosylated into chitosan solution and 10mL aloes water extract is mixed, add (2) system The film liquid obtained, continuously adds formula ratio polyethylene glycol 0.43g, glycerine 1.52mL, olive oil 1.52mL, PVP-I successively 3.91mL, hydrogen peroxide 3.91mL, menthol 0.43g, mixing speed are 500~700r/min, are well mixed at room temperature;
(4) to above-mentioned steps (3) prepare solution in add the ethanol waters of 32.6mL 95%, mixing speed be 500~ 700r/min, is well mixed at room temperature, that is, the liquid chitosan wound dressing of the present invention is made.
Embodiment 3
1) wound dressing of liquid chitosan is formulated:Aloe alcohol extract prepared by N- glycosylation chitosans 2.27g, embodiment 1 10.45mL, the polyvinyl alcohol 31.8mL of mass concentration 10%, polyethylene glycol 0.45g, glycerine 1.59mL, olive oil 1.59mL, poly- dimension Ketone iodine 4.09mL, the hydrogen peroxide 3.18mL of mass concentration 30%, lactic acid 0.68mL, menthol 0.45g, the ethanol water of volumetric concentration 95% Solution 30.9mL, 5mg/mL physiological saline 22.7mL.
2) preparation process of liquid chitosan wound dressing is as follows:
(1) formula ratio is pressed, N- glycosylation chitosan 2.27g is weighed, adds 5mg/mL physiological saline 22.7mL, stir at room temperature Dissolving is mixed, 0.68mL lactic acid is added, N- glycosylation chitosan solutions are made;
(2) prepared by film liquid:By formula ratio, polyvinyl alcohol 3.18g is weighed, is added in deionized water, is added at 90-100 DEG C 2~3h of thermal agitation is made the polyvinyl alcohol water solution 31.8mL of mass concentration 10%, produces film liquid to being completely dissolved;
(3) solution made from (1) and 10.45mL aloes alcohol extract are mixed, add film liquid made from (2), successively after It is continuous to add formula ratio polyethylene glycol 0.45g, glycerine 1.59mL, olive oil 1.59mL, PVP-I 4.09mL, hydrogen peroxide 3.18mL, menthol 0.45g, mixing speed are 500~700r/min, are well mixed at room temperature;
(4) to above-mentioned steps (3) prepare solution in add the ethanol waters of 30.9mL 95%, mixing speed be 500~ 700r/min, is well mixed at room temperature, that is, the liquid chitosan wound dressing of the present invention is made.
Embodiment 4
1) wound dressing of liquid chitosan is formulated:Aloe water extract prepared by N- glycosylation chitosans 6.67g, embodiment 1 8.33mL, the polyvinyl alcohol 33.3mL of mass concentration 10%, polyethylene glycol 0.17g, glycerine 0.83mL, olive oil 0.83mL, poly- dimension Ketone iodine 1.67mL, the hydrogen peroxide 1.67mL of mass concentration 30%, lactic acid 0.5mL, menthol 0.33g, the ethanol water of volumetric concentration 95% Solution 23.3mL, 5mg/mL physiological saline 33.3mL.
2) preparation process of liquid chitosan wound dressing is as follows:
(1) formula ratio is pressed, N- glycosylation chitosan 6.67g is weighed, adds 5mg/mL physiological saline 33.3mL, stir at room temperature Dissolving is mixed, 0.5mL lactic acid is added, N- glycosylation chitosan solutions are made;
(2) prepared by film liquid:By formula ratio, polyvinyl alcohol 3.33g is weighed, is added in deionized water, is added at 90-100 DEG C 2~3h of thermal agitation is made the polyvinyl alcohol water solution 33.3mL of mass concentration 10%, produces film liquid to being completely dissolved;
(3) solution made from (1) and 8.33mL aloes water extract are mixed, adds film liquid 33.3mL made from (2), according to It is secondary to continuously add formula ratio polyethylene glycol 0.17g, glycerine 0.83mL, olive oil 0.83mL, PVP-I 1.67mL, hydrogen peroxide 1.67mL, menthol 0.33g, mixing speed are 500~700r/min, are well mixed at room temperature;
(4) to above-mentioned steps (3) prepare solution in add 23.3mL95% ethanol waters, mixing speed be 500~ 700r/min, is well mixed at room temperature, that is, the liquid chitosan wound dressing of the present invention is made.
Embodiment 5
1) wound dressing of liquid chitosan is formulated:Aloe alcohol extract prepared by N- glycosylation chitosans 6.9g, embodiment 1 8.62mL, the polyvinyl alcohol 34.5mL of mass concentration 10%, polyethylene glycol 0.17g, glycerine 0.86mL, olive oil 0.86mL, poly- dimension Ketone iodine 1.72mL, the hydrogen peroxide 1.72mL of mass concentration 30%, lactic acid 0.52mL, menthol 0.34g, the ethanol water of volumetric concentration 95% Solution 20.69mL, 5mg/mL physiological saline 34.48mL.
2) preparation process of liquid chitosan wound dressing is as follows:
(1) formula ratio is pressed, N- glycosylation chitosan 6.9g is weighed, adds 5mg/mL physiological saline 34.48mL, stir at room temperature Dissolving is mixed, 0.52mL lactic acid is added, N- glycosylation chitosan solutions are made;
(2) prepared by film liquid:By formula ratio, polyvinyl alcohol 3.45g is weighed, is added in deionized water, is added at 90-100 DEG C 2~3h of thermal agitation is made the polyvinyl alcohol water solution 34.5mL of mass concentration 10%, produces the film liquid to being completely dissolved;
(3) N- made from (1) is glycosylated into chitosan solution and 8.62mL aloes alcohol extract is mixed, added (2) and be made Film liquid 34.5mL, formula ratio polyethylene glycol 0.17g, glycerine 0.86mL, olive oil 0.86mL, PVP-I are continuously added successively 1.72mL, hydrogen peroxide 1.72mL, menthol 0.34g, mixing speed are 500~700r/min, are well mixed at room temperature;
(4) 20.69mL95% ethanol is added in the solution prepared to above-mentioned steps (3), mixing speed is 500~700r/ Min, is well mixed at room temperature, that is, the liquid chitosan wound dressing of the present invention is made.
Embodiment 6
Carry out performance and pharmacology test respectively to the liquid chitosan wound dressing that embodiment 2- embodiments 5 are obtained, it is real Test result as follows:
Test 1:Particular product performance parameters are detected
Embodiment 2-5 product, which is accorded with, to be detected to liquid chitosan wound dressing performance parameter prepared by the present invention Close claimed below:
1. character:It is homogeneous for slightly yellow, transparency liquid.
2.pH:Example 2-5 sample is each a little, and pH is measured with pH meter all between 4.0~6.0.
Test 2:Liquid chitosan wound dressing sample fungistatic effect
Press《Medicine microbiological Test handbook》(Science Press, version in 2001) the 18th chapter Section 1 cylinder-plate method is tried Test, measurement result is referring to table 1:
The antibacterial circle diameter (mm) of each test group of table 1
It has been shown that, product of the invention has obvious inhibition zone, illustrate to Escherichia coli, golden grape ball from the result of table 1 Bacterium, Candida albicans, the growth of pseudomonas aeruginosa have obvious inhibitory action.
Test 3:Liquid chitosan wound dressing sample skin irritation index (PII) is determined
Rabbit 6 (being purchased from Zhejiang University of Traditional Chinese Medicine's animal experimental center) is taken, it is in back backbone both sides that hair remover is uniform Coat, 5 pilot regions (No. 1-No. 5) are set, and each region area is about 1cm × 1cm, clean hair remover, return cage to observe 24h.After 24 hours, applied in No. 1-No. 4 liquid chitosan wounds for smearing 2-5 of embodiment of the present invention productions respectively of hair removal section Material, smears 0.1mL, and No. 5 hair removal sections are not dealt with, and are used as own control.Medicine is removed after continuing 24h, visually observes and uses coating Skin locally whether there is erythema and oedema, pigmentation, blutpunkte, pachylosis or epidermatic atrophy etc., cleaned after terminating with warm water to Medicine position.Skin Irritation Test reaction scoring and stimulus intensity evaluation are shown in Table 2, table 3.
The skin wound repair standards of grading of table 2
The skin irritatin intensity evaluation standard of table 3
Skin Irritation Test reaction average value=(erythema formation total score+oedema formation total score)/total experiment number
The skin irritation test of table 4
Show from the result of table 4, liquid chitosan wound dressing prepared by the present invention reacts without sensitization of skin.
Test 4:The contrast test of wound healing
Test sample:Liquid chitosan wound dressing prepared by embodiment 2- embodiments 5
Reference substance:Yunnan Baiyao styptic powder
Experimental animal uses common rabbit (being purchased from Zhejiang University of Traditional Chinese Medicine's animal experimental center), 10% chloral hydrate anesthesia Lost hair or feathers afterwards with 4% vulcanized sodium, take prone position.After routine disinfection skin, in every rabbit away from cutting length at the 1.0cm of backbone both sides 1.5cm, wide 1.0cm wound 4, depth is from skin to muscle layer, and the thickness of wound is 0.3cm.4 wounds are respectively labeled as A, B, C, No. D, use normal saline flushing wound, it is standby.A wounds are added medicine to 0.9% physiological saline, each 0.1mL, are negative Control;B wounds are using Yunnan Baiyao styptic powder as positive control, and get it filled 0.1g every time, be uniformly applied to and wound is completely covered, often 12h is changed once;C and D wounds (rabbit sets 2 parallel tests, i.e. what C and D were smeared is identical dressing) are respectively Using embodiments of the invention 2-5 liquid chitosan wound dressings, each 0.1mL is uniformly applied to and wound is completely covered, often 12h is changed once, continuous use 15 days (" my god " represented with " d ").Every group of experimental animal 8, male and female half and half, the scale of construction is about 2.0 ~2.5kg.Wound healing situation is observed, wound healing time is recorded, record time point is respectively 3d, 6d, 9d, 12d, 15d, together When calculate Wound healing rate.
The method for calculating Wound healing rate is as follows:First the surface of a wound is marked on hyaline membrane, then it is as template that quality is equal Even hard paper be cut into it is onesize, then weigh in the balance weight, surface of a wound size is indirectly indicative with cardboard sheet weight.Press examination meter Calculate Wound healing rate:
Do not heal Wound healing rate (%)=(original surface of a wound area-surface of a wound area)/original surface of a wound area.
Each group wound healing rate of table 5 compares
As known to table 5, after liquid wound dressing use of the invention, the average healing rate of each surface of a wound is above negative control group And positive controls, and the average healing rate of wound is more than 99% at 15 days, higher than negative control group more than 30%, higher than the positive Control group more than 14%, illustrates that the smear type fluid wound dressing of the present invention promotes wound healing effect very good.Meanwhile, implement Example 4 and embodiment 5 just reached the recovery from illness of wound at the 14th day, and crust all comes off naturally, the scar protrusion skin of formation Skin face is not obvious, touches and finds without scleroma block, the calmness also without black purple pigment, and wound is in fair and tender shape, close to rabbit The former colour of skin, the paraplasm of wound tissue's scar can be suppressed by illustrating the fluid wound dressing of the smear type of the present invention.
Above-described embodiment is the present invention preferably implementation, and in addition, the present invention can be realized with other manner, Any obvious replacement on the premise of present inventive concept is not departed from, within protection scope of the present invention.

Claims (8)

1. a kind of liquid chitosan wound dressing, it is characterised in that the liquid chitosan wound dressing is made up of the following raw material: It is N- glycosylations chitosan, aloe extract, the polyvinyl alcohol water solution of mass concentration 10%, polyethylene glycol, glycerine, olive oil, poly- Tie up ketone iodine, the hydrogen peroxide of mass concentration 30%, lactic acid, menthol, the ethanol water of volumetric concentration 95%, 5mg/mL physiological saline; The N- glycosylation chitosans and polyethylene glycol and menthol mass ratio are 1:0.01-1:0.01-1.5;The aloe extract, The polyvinyl alcohol water solution of mass concentration 10%, glycerine, olive oil, PVP-I, the hydrogen peroxide of mass concentration 30%, lactic acid, volume The ethanol water of concentration 95%, 5mg/mL physiological saline volumetric usage are respectively 0.5- in terms of N- glycosylation chitosan masses 20ml/g、1-50ml/g、0.05-5ml/g、0.05-5ml/g、0.1-10ml/g、0.1-10ml/g、0.01-2ml/g、1.5- 50ml/g、1-50ml/g;The aloe extract be after aloe leaf is smashed to pieces homogenate ultrasound extraction after supernatant with After deionized water mixing is concentrated into what cumulative volume a quarter was obtained, or homogenate is mixed with the ethanol water of volumetric concentration 75% Ultrasound extracts and is concentrated into 1/10th acquisitions of cumulative volume;The deionized water is 1.5 with supernatant volume ratio:1;It is described Ethanol water is 5 with described homogenate volume ratio:1.
2. liquid chitosan wound dressing as claimed in claim 1, it is characterised in that the N- glycosylation chitosans and poly- second two Alcohol and menthol mass ratio are 1:0.01-0.3:0.03-0.5.
3. liquid chitosan wound dressing as claimed in claim 2, it is characterised in that the N- glycosylation chitosans and poly- second two Alcohol and menthol mass ratio are 1:0.02-0.2:0.04-0.3.
4. liquid chitosan wound dressing as claimed in claim 1, it is characterised in that the aloe extract, mass concentration 10% Polyvinyl alcohol water solution, glycerine, olive oil, PVP-I, the hydrogen peroxide of mass concentration 30%, lactic acid, the ethanol of volumetric concentration 95% The aqueous solution, 5mg/mL physiological saline volumetric usage are respectively 0.75-7.5ml/g, 2.5- in terms of N- glycosylation chitosan masses 20ml/g、0.08-2ml/g、0.08-2ml/g、0.2-4ml/g、0.2-4ml/g、0.06-0.75ml/g、2.25-20ml/g、2- 20ml/g。
5. liquid chitosan wound dressing as claimed in claim 4, it is characterised in that the aloe extract, mass concentration 10% Polyvinyl alcohol water solution, glycerine, olive oil, PVP-I, the hydrogen peroxide of mass concentration 30%, lactic acid, the ethanol of volumetric concentration 95% The aqueous solution, 5mg/mL physiological saline volumetric usage by N- glycosylation chitosan mass in terms of be respectively 1-7ml/g, 4-17ml/g, 0.1-1ml/g、0.1-1ml/g、0.2-3ml/g、0.2-3ml/g、0.07-0.5ml/g、3-17ml/g、3-17ml/g。
6. liquid chitosan wound dressing as claimed in claim 1, it is characterised in that the aloe extract as follows it One prepares:(1) fresh aloe blade is chosen, deionized water rinsed clean smashs obtained homogenate to pieces;Homogenate is taken, at 95 DEG C 5~8min of high temperature sterilization, stands after cooling, 20~30min of ultrasound under 450W, and centrifugation takes supernatant and deionized water by volume Than 2:3 mixing, in 65~70 DEG C of revolvings to a quarter of cumulative volume, that is, obtain aloe water extract;(2) fresh aloe leaf is chosen Piece, deionized water rinsed clean smashs obtained homogenate to pieces;Homogenate is taken to add the ethanol water of volumetric concentration 75%, in power 30~40min of ultrasonic extraction under 450W, is total to ultrasonic extraction 2 times, centrifuging and taking supernatant, is rotated at 45~50 DEG C to cumulative volume very One of, it is aloe alcohol extract to take concentrate;The ethanol water is 5 with homogenate volume ratio:1.
7. the preparation method of liquid chitosan wound dressing described in a kind of claim 1, it is characterised in that methods described is:
(1) formula ratio is pressed, N- is glycosylated into chitosan physiological saline stirring and dissolving, lactic acid is added, N- glycosylation shells are made Glycan solution;
(2) prepared by film liquid:By formula ratio, polyvinyl alcohol is added in deionized water, 2~3h of heating stirring at 90~100 DEG C To being completely dissolved, the polyvinyl alcohol water solution of mass concentration 10% is made, film liquid is produced;
(3) formula ratio is pressed, N- made from step (1) is glycosylated into chitosan solution and aloe extract is mixed, step is added (2) film liquid made from, continuously adds polyethylene glycol, glycerine, olive oil, PVP-I, hydrogen peroxide, menthol, at room temperature successively 500~700r/min is uniformly mixed;
(4) formula ratio is pressed, the ethanol water of volumetric concentration 95% is added in the solution prepared to step (3), at room temperature 500~ 700r/min is uniformly mixed, that is, described liquid chitosan wound dressing is made.
8. application of the liquid chitosan wound dressing in wound face healing drug is prepared described in a kind of claim 1.
CN201710412637.5A 2017-06-05 2017-06-05 A kind of wound dressing of liquid chitosan and its preparation and application Pending CN107233617A (en)

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Application publication date: 20171010