CN106110367A - Based on natural polymer MULTILAYER COMPOSITE medical dressing and preparation method thereof - Google Patents

Based on natural polymer MULTILAYER COMPOSITE medical dressing and preparation method thereof Download PDF

Info

Publication number
CN106110367A
CN106110367A CN201610621172.XA CN201610621172A CN106110367A CN 106110367 A CN106110367 A CN 106110367A CN 201610621172 A CN201610621172 A CN 201610621172A CN 106110367 A CN106110367 A CN 106110367A
Authority
CN
China
Prior art keywords
natural polymer
sponge
layer
preparation
multilayer composite
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CN201610621172.XA
Other languages
Chinese (zh)
Inventor
马贵平
孙文文
陈永惠
聂俊
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Changzhou Institute for Advanced Materials Beijing University of Chemical Technology
Original Assignee
Changzhou Institute for Advanced Materials Beijing University of Chemical Technology
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Changzhou Institute for Advanced Materials Beijing University of Chemical Technology filed Critical Changzhou Institute for Advanced Materials Beijing University of Chemical Technology
Priority to CN201610621172.XA priority Critical patent/CN106110367A/en
Publication of CN106110367A publication Critical patent/CN106110367A/en
Pending legal-status Critical Current

Links

Classifications

    • 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
    • A61L15/00Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/22Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
    • A61L15/225Mixtures of macromolecular compounds
    • 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
    • A61L15/00Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/42Use of materials characterised by their function or physical properties
    • A61L15/425Porous materials, e.g. foams or sponges
    • 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
    • A61L15/00Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/42Use of materials characterised by their function or physical properties
    • A61L15/64Use of materials characterised by their function or physical properties specially adapted to be resorbable inside the body
    • 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
    • A61L2300/23Carbohydrates
    • A61L2300/232Monosaccharides, disaccharides, polysaccharides, lipopolysaccharides
    • 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

Abstract

The present invention is based on natural polymer MULTILAYER COMPOSITE medical dressing and preparation method thereof.It is to be made up of MULTILAYER COMPOSITE natural polymer, by differently configured natural polymer solution, lyophilization is carried out after prefreezing, then by carrying out lyophilization after coating another one or more natural polymer solution, circulation repeatedly, obtains the MULTILAYER COMPOSITE sponge medical dressing of inierpeneirating network structure.This dressing have flexible, biocompatibility is excellent, preferable water absorption, breathability, adhesion and antibacterial action.It can absorb wound exudate, it is ensured that fully drain, can be retained in dressing by liquid permeable portion again, maintains a local moist environment imitating the healing of wound surface physiological, beneficially wound granulation tissue and re-epithelilization, accelerates wound healing.

Description

Based on natural polymer MULTILAYER COMPOSITE medical dressing and preparation method thereof
Technical field
The invention belongs to medical technical field, be specifically related to based on natural polymer MULTILAYER COMPOSITE medical dressing and preparation thereof Methods and applications.
Technical background
Medical dressing has many inconvenience on using at present, and some dressing uses nondegradable polyacrylonitrile material to make For support, causing iatrogenic pollution, meanwhile, dressing absorbs transudate and sticks together with wound surface simultaneously, causes damage when removing new Raw tissue.The most gauzes made with cotton fiber, cotton balls etc., although have certain moisture absorption and protective effect, but more Easy adhesion wound during conjunction, thus cause secondary damage, cause great misery to patient.Along with various countries' medical circle is to hemostasis The raising that material anthemorrhagic performance requires, the bleeding-stopping dressing of exploitation excellent performance becomes a kind of trend.Owing to natural polymer has The characteristic such as nontoxic, good biocompatibility and degradability, thus paid much attention in the research of bleeding-stopping dressing.According to document report Road, Tang N et al. (Tang N, Cai WZ, Deng L, Li SJ, Wang XJ, Li C.Preparation and property of closed dressing intelligent scaffolds.Zhongguo Zuzhi Gongcheng Yanjiu yu Linchuang Kangfu.2010;14 (29): 5325-5328.) pass through with chitosan, gelatin, polyvinyl alcohol After Gong Huning, lyophilizing is prepared for seal wound dressing for wound healing, and result shows significantly to strengthen the water suction of dressing Property, water content and breathability, but for the biological poison of the selection of macromolecular material, the complex method of macromolecular material and material Property be all worth further research and inquire into.
Common natural polymer mainly has: sodium alginate, chitosan, hyaluronic acid, gelatin and sodium carboxymethyl cellulose Deng.The natural polymer that sodium alginate (Sodium Algenate, SA) is present in Brown algae, is from Brown algae or antibacterial The natural polysaccharide extracted, its good biocompatibility, toxicity are low, have hemostasis, antibacterial, the effect of wound healing.Shell Polysaccharide (Chitosan, CS) is widely present in the Nature, is the deacetylated derivant of natural polysaccharide, glucamine (sloughs Aminoethyl moiety) and ethyl glucuronide amine (part of second) composition, it is a kind of environmentally friendly natural polymer. The advantages such as chitosan not only has nontoxic, good biocompatibility, biodegradability, also have cancer resistance, antibiotic property, Hemostatic and strengthen the plurality of advantages such as human body immunity, it is widely used in organizational project, drug carrier material and wound The aspects such as dressing.Hyaluronic acid (Hyaluronic acid, HA) has another name called hyaluronic acid, is present in extracellular base in biological tissue A kind of acid mucopolysaccharide in matter.By β-D-N-acetylglucosamine and β-D-Glucose sulfonic acid be construction unit with β-1, A kind of chain macromolecule that 4-glycosidic linkage is linked to be.The biocompatibility good due to it and biological degradability and be widely used In fields such as organizational projects.Gelatin (Gelatin, GE) is the mixtures of polypeptides of a kind of solubility, by acid or alkaline extraction, by cattle Or collagenous portion hydrolysis system contained by porcine skin.Different with the triple-helix structure of collagen, gelatin is made up of single chain molecule.Gelatin, Due to its biocompatibility with change with temperature and take the characteristic of gelation, it is widely used in biomedical aspect.Carboxymethyl cellulose Element sodium (CMC) is that cellulose ether apoplexy due to endogenous wind yield is maximum, purposes is the widest, uses product the most easily.Its odorless, tasteless, Nontoxic and hygroscopicity, has excellent water solublity, conjunction shoes, newborn, diffusibility, antienzyme and stability, extensively should For food pharmaceuticals industry.
The present invention, by differently configured natural polymer solution, prepares MULTILAYER COMPOSITE by multistep freeze seasoning natural Macromolecule medical dressing, its have flexible, biocompatibility is excellent, preferable water absorption, breathability, adhesion and antibacterial work With.It can absorb wound exudate, it is ensured that fully drain, can be retained in dressing by liquid permeable portion again, maintains one to imitate wound The local moist environment of rationality of looking unfamiliar healing, beneficially wound granulation tissue and re-epithelilization, accelerates wound healing.
Summary of the invention
It is an object of the invention to, based on natural polymer MULTILAYER COMPOSITE medical dressing and preparation method thereof, use above-mentioned system The dressing that Preparation Method obtains has natural polymer base, compound layer by layer and inierpeneirating network structure and has good biofacies Capacitive, breathability, poisture-penetrability, absorbency and water retainability.
Realize above-mentioned purpose, the following technical scheme that the present invention uses:
(1) preparation of sodium alginate soln: be dissolved in distilled water by sodium alginate, being configured to mass fraction is 1~4% Sodium alginate soln, with motor stirrer stir to being completely dissolved, vacuum defoamation 24h, place stand-by.
(2) preparation of natural polymer solution: natural polymer is dissolved respectively, be configured to mass fraction be 1~ The natural polymer solution of 4%, stirs to being completely dissolved with motor stirrer, vacuum defoamation 24h, places stand-by.
(3) preparation of calcium alginate lyophilizing sponge: the sodium alginate soln configured is injected in mould ,-20~-70 DEG C Low temperature precooling 1~5h, then in-80~-10 DEG C of temperature, in 1~600Pa vacuum, the sodium alginate soln that will freeze Lyophilization 24~48h in freezer dryer, obtain sodium alginate lyophilizing sponge, then soak in cross-linking agent solution 1~5% Bubble 1-5h cross-links, and distilled water cleans, and is then dried to horizontal heavy in 50~80 DEG C of baking ovens, obtains calcium alginate sponge.
(4) preparation based on natural polymer MULTILAYER COMPOSITE medical dressing: by preprepared natural polymer solution It is coated on calcium alginate lyophilizing sponge side ,-20~-70 DEG C of low temperature precoolings 1~5h, then in-80~-10 DEG C of temperature, 1 ~in 600Pa vacuum, it is coated with calcium alginate sponge lyophilization 24 in freezer dryer of natural polymer solution ~48h, obtaining its ground floor of lyophilizing composite sponge is alginic acid calcium layer, and the second layer is single or multiple lift natural polymer, then Sodium alginate soln is coated on natural polymer sublayer side again, and-20~-70 DEG C of low temperature precoolings 1~5h, then-80 ~in-10 DEG C of temperature, in 1~600Pa vacuum, by MULTILAYER COMPOSITE sponge in freezer dryer after lyophilization 24~48h Soaking 1-5h in cross-linking agent solution 1~5% to cross-link, distilled water cleans, and is then dried in 50~80 DEG C of baking ovens to horizontal heavy, Obtaining ground floor is calcium alginate, and the second layer is single or multiple lift natural polymer, and third layer is the MULTILAYER COMPOSITE of calcium alginate Medical dressing.
Specifically, one during described natural polymer is chitosan, hyaluronic acid, gelatin and sodium carboxymethyl cellulose or Several.
Specifically, described second layer natural polymer sublayer is in chitosan, hyaluronic acid, gelatin and sodium carboxymethyl cellulose Single one or more be combined layer by layer.
Specifically, described cryogenic temperature-80~-10 DEG C, vacuum 1~600Pa, cooling time 12~48h.
Specifically, described sodium alginate molecular weight Mw=2 × 103-40×103g·mol-1, chitosan molecule amount Mw=1 ×104-3×104g·mol-1, hyaluronan molecule amount Mw=8 × 105-12×105g·mol-1, gelatine molecular weight Mw=6 × 104-30×104g·mol-1, sodium carboxymethyl cellulose molecular weight Mw=1.8 × 104-2.8×104g·mol-1
Specifically, described cryogenic temperature-80~-10 DEG C, vacuum 1~600Pa, cooling time 12~48h.
Specifically, one or more during described cross-linking agent solution is the ethanol solution of the aqueous solution of calcium chloride, calcium chloride.
Specifically, the medical dressing of described preparation is multilamellar natural polymer composite sponge, and this dressing can be used for biological doctor Medicine technical field.
The invention have the advantages that
1. the preparation method of the MULTILAYER COMPOSITE sponge medical dressing of the present invention uses natural polymer to be raw material, by freezing The technology being dried, with calcium chloride as cross-linking agent, preparing ground floor is calcium alginate, and the second layer is single or multiple lift natural polymer Son, third layer is the medical dressing sponge of calcium alginate.This dressing all uses natural polymer to be base material, has nontoxic, raw Thing degraded, biocompatibility and being readily available property and the method using MULTILAYER COMPOSITE, preparation technology is novel, easy, produce into This is low, it is simple to promoting the use of of medical dressing prepared by natural polymer.
2. the MULTILAYER COMPOSITE dressing sponge that prepared by the method is better than simple natural polymer dressing sponge and the most common Mixed dressing sponge, effectively can substitute traditional wound dressing, is used for treating surgical wound, empyrosis wound surface etc. each The skin trauma of type.
Accompanying drawing explanation
Fig. 1 is the structural representation of MULTILAYER COMPOSITE medical dressing;
In figure: alginic acid calcium layer 1, single or multiple lift natural polymer sublayer 2, alginic acid calcium layer 3.
Fig. 2 is the top view digital photograph of MULTILAYER COMPOSITE medical dressing;
Fig. 3 is the configuration of surface scanning electron microscope (SEM) photograph of MULTILAYER COMPOSITE medical dressing;
Fig. 4 is the front view digital photograph of MULTILAYER COMPOSITE medical dressing;
Fig. 5 is the configuration of surface scanning electron microscope (SEM) photograph of MULTILAYER COMPOSITE medical dressing;
Fig. 6 is the cross-sectional scans Electronic Speculum figure of MULTILAYER COMPOSITE medical dressing.
Specific embodiment
Embodiment one
1g sodium alginate is dissolved in 100g distilled water, is configured to the sodium alginate soln that mass fraction is 1%, electricity consumption Dynamic agitator stirs to being completely dissolved, and vacuum defoamation 24h is standby.1g chitosan is dissolved in 100g 1% (v/v) formic acid solution In, it is configured to the chitosan solution of 1%, is sufficiently stirred for making it uniform, standby.Sodium alginate soln is dispensed in mould, will Mould is placed in pre-freeze in cryogenic refrigerator ,-20 DEG C of pre-freeze 1h, is then placed in freezer dryer by mould, controls in dry run Vacuum is less than below 15Pa, processes 24h in-50 DEG C, and the dried demoulding obtains the sodium alginate sponge being dried, then 1% Crosslinking curing 2h in calcium chloride ethanol solution, is placed on sponge after having solidified in 50 DEG C of vacuum drying ovens and is dried to constant weight, distillation Water is dried to constant weight after cleaning repeatedly in 50 DEG C of vacuum drying ovens, obtains calcium alginate lyophilizing sponge, standby.Chitosan is molten Liquid is coated on this lyophilizing sponge side of alginic acid ,-20 DEG C of low temperature precooling 1h, it is placed in freezer dryer, controls dry run Middle vacuum is less than below 15Pa, processes 24h in-50 DEG C, and obtaining its first top layer of lyophilizing composite sponge is alginic acid calcium layer, the Two layers is chitosan layer.Then sodium alginate soln is coated on chitosan side ,-20 DEG C of low temperature precooling 1h, is placed in freezing dry In dry machine, control vacuum in dry run and, less than below 15Pa, process 24h in-50 DEG C, in 1% calcium chloride ethanol solution Crosslinking curing 2h, is placed on sponge after having solidified in 50 DEG C of vacuum drying ovens and is dried to constant weight, in 50 after distilled water cleaning repeatedly DEG C vacuum drying oven is dried to constant weight, obtain ground floor be calcium alginate, the second layer be chitosan, third layer be calcium alginate MULTILAYER COMPOSITE medical dressing sponge (Fig. 1).Digital camera carries out pictorial diagram shooting top view (Fig. 2).Seen by scanning electron microscope Examine and utilize the medical dressing prepared by case study on implementation 1 to show microscopic appearance (Fig. 3).
Embodiment two
2g sodium alginate is dissolved in 100g distilled water, is configured to the sodium alginate soln that mass fraction is 2%, electricity consumption Dynamic agitator stirs to being completely dissolved, and vacuum defoamation 24h is standby.2g gelatin is dissolved in 100g distilled water, is configured to 2% Gelatin solution, is sufficiently stirred for making it uniform, standby.Sodium alginate soln is dispensed in mould, mould is placed in cryogenic refrigerator Middle pre-freeze ,-30 DEG C of pre-freeze 2h, then mould is placed in freezer dryer, control in dry run vacuum less than 20Pa with Under, processing 28h in-40 DEG C, the dried demoulding obtains the sodium alginate sponge being dried, and then hands in 2% calcium chloride water Connection solidification 1h, is placed on sponge after having solidified in 50 DEG C of vacuum drying ovens and is dried to constant weight, in 50 DEG C after distilled water cleaning repeatedly Vacuum drying oven is dried to constant weight and obtains calcium alginate sponge.Gelatin solution is coated on calcium alginate lyophilizing sponge side ,- 30 DEG C of low temperature precooling 2h, are placed in freezer dryer, control vacuum in dry run and are less than below 20Pa, at-40 DEG C Reason 28h, obtaining its first top layer of lyophilizing composite sponge is alginic acid calcium layer, and the second layer is gelatin layer.Finally that sodium alginate is molten Liquid is coated on gelatin side ,-30 DEG C of low temperature precooling 2h, is placed in freezer dryer, controls vacuum in dry run and is less than Below 20Pa, processes 28h in-40 DEG C, and in 2% calcium chloride water, crosslinking curing 1h, is placed on 50 by sponge after having solidified Being dried in DEG C vacuum drying oven to constant weight, distilled water is dried to constant weight in 50 DEG C of vacuum drying ovens after cleaning repeatedly, obtains first The MULTILAYER COMPOSITE medical dressing sponge that layer is calcium alginate, the second layer is gelatin, third layer is calcium alginate.Digital camera is carried out Pictorial diagram shooting front view (Fig. 4).The medical dressing prepared by case study on implementation 2 is utilized to show microcosmic shape by scanning electron microscopic observation Looks (Fig. 5).The cross section microscopic appearance (Fig. 6) of medical dressing prepared by case study on implementation is utilized by scanning electron microscopic observation.
Embodiment three
3g sodium alginate is dissolved in 100g distilled water, is configured to the sodium alginate soln that mass fraction is 3%, electricity consumption Dynamic agitator stirs to being completely dissolved, and vacuum defoamation 24h is standby.3g chitosan is dissolved in 100g 1% (v/v) formic acid solution In, it is configured to the chitosan solution of 3%, is sufficiently stirred for making it the most standby.3g sodium carboxymethyl cellulose is dissolved in 100g distillation In water, it is configured to the carboxymethylcellulose sodium solution of 3%, is sufficiently stirred for making it uniform, standby.Sodium alginate soln is dispensed into In mould, mould is placed in pre-freeze in cryogenic refrigerator ,-40 DEG C of pre-freeze 3h, then mould is placed in freezer dryer, control dry During dry, vacuum is less than below 30Pa, processes 30h in-60 DEG C, and the dried demoulding obtains the sodium alginate sponge being dried, so After in 3% calcium chloride water crosslinking curing 3h, sponge is placed in 50 DEG C of vacuum drying ovens after having solidified and is dried to constant weight, Distilled water is dried to constant weight after cleaning repeatedly in 50 DEG C of vacuum drying ovens, obtains calcium alginate lyophilizing sponge.Chitosan is molten Liquid is coated on calcium alginate lyophilizing sponge side ,-40 DEG C of low temperature precooling 3h, is placed in freezer dryer, controls dry run Middle vacuum is less than below 30Pa, processes 30h in-60 DEG C, and obtaining its first top layer of lyophilizing composite sponge is sodium alginate layer, the Two layers is chitosan layer.Then carboxymethylcellulose sodium solution is coated on chitosan side ,-40 DEG C of low temperature precooling 3h, puts In freezer dryer, control vacuum in dry run and, less than below 30Pa, process 30h in-60 DEG C, obtain ground floor for sea Sodium alginate, the second layer are the composite sponge of chitosan-sodium carboxymethyl cellulose.Finally sodium alginate soln is coated on carboxymethyl Sodium cellulosate side ,-40 DEG C of low temperature precooling 3h, it is placed in freezer dryer, controls vacuum in dry run and be less than 30Pa Hereinafter, process 30h, crosslinking curing 3h in 3% calcium chloride water in-60 DEG C, after having solidified, sponge is placed on 50 DEG C very Being dried in empty baking oven to constant weight, distilled water is dried to constant weight after cleaning repeatedly in 50 DEG C of vacuum drying ovens, and obtaining ground floor is Calcium alginate, the second layer be chitosan-carboxymethyl cellulose sodium, third layer be the MULTILAYER COMPOSITE medical dressing sponge of calcium alginate.
Embodiment four
4g sodium alginate is dissolved in 100g distilled water, is configured to the sodium alginate soln that mass fraction is 4%, electricity consumption Dynamic agitator stirs to being completely dissolved, and vacuum defoamation 24h is standby.4g hyaluronic acid is dissolved in 100g distilled water, is configured to The hyaluronic acid solution of 4%, is sufficiently stirred for making it uniform, standby.4g gelatin is dissolved in 100g distilled water, is configured to 4% Gelatin solution, is sufficiently stirred for making it uniform, standby.Sodium alginate soln is dispensed in mould, mould is placed in cryogenic refrigerator Middle pre-freeze ,-50 DEG C of low temperature precooling 4h, then mould is placed in freezer dryer, controls vacuum in dry run and be less than Below 15Pa, processes 24h in-50 DEG C, and the dried demoulding obtains the sodium alginate sponge being dried, then at 1% calcium chloride ethanol Crosslinking curing 2h in solution, is placed on sponge in 50 DEG C of vacuum drying ovens after having solidified and is dried to constant weight, obtain calcium alginate and freeze Dry sponge.To hyaluronic acid solution being coated on calcium alginate lyophilizing sponge side ,-50 DEG C of low temperature precooling 4h, it is placed in freezing In drying machine, control vacuum in dry run and, less than below 15Pa, process 24h in-50 DEG C, obtain lyophilizing composite sponge its One top layer is sodium alginate layer, and the second layer is hyaluronic acid.Then gelatin solution is coated on hyaluronic acid side ,-50 DEG C Low temperature precooling 4h, is placed in freezer dryer, controls vacuum in dry run and is less than below 15Pa, in-50 DEG C of process 24h, obtain ground floor be sodium alginate, the second layer be the composite sponge of hyaluronic acid-gelatin.Finally sodium alginate soln is coated with It is overlying on gelatin side ,-50 DEG C of low temperature precooling 4h, is placed in freezer dryer, control vacuum in dry run and be less than 15Pa Hereinafter, process 24h, crosslinking curing 2h in 1% calcium chloride ethanol solution in-50 DEG C, after having solidified, sponge is placed on 50 DEG C Vacuum drying oven is dried to constant weight, obtain ground floor be calcium alginate, the second layer be hyaluronic acid-gelatin, third layer be Sargassum The MULTILAYER COMPOSITE medical dressing sponge of acid calcium.
Embodiment five
1g sodium alginate is dissolved in 100g distilled water, is configured to the sodium alginate soln that mass fraction is 1%, electricity consumption Dynamic agitator stirs to being completely dissolved, and vacuum defoamation 24h is standby.1g sodium carboxymethyl cellulose is dissolved in 100g distilled water, joins It is set to the carboxymethylcellulose sodium solution of 1%, is sufficiently stirred for making it uniform, standby.1g gelatin is dissolved in 100g distilled water, joins It is set to the gelatin solution of 1%, is sufficiently stirred for making it uniform, standby.Sodium alginate soln is dispensed in mould, mould is placed in Pre-freeze in cryogenic refrigerator ,-60 DEG C of low temperature precooling 5h, then mould is placed in freezer dryer, controls in dry run true Reciprocal of duty cycle is less than below 15Pa, processes 24h in-50 DEG C, and the dried demoulding obtains the sodium alginate sponge being dried, then at 1% chlorine Change crosslinking curing 2h in calcium ethanol solution, sponge is placed in 50 DEG C of vacuum drying ovens after having solidified and is dried to constant weight, distilled water It is dried to constant weight in 50 DEG C of vacuum drying ovens after cleaning repeatedly, obtains calcium alginate lyophilizing sponge.By sodium carboxymethyl cellulose Solution is coated on this lyophilizing sponge side of alginic acid ,-60 DEG C of low temperature precooling 5h, is placed in freezer dryer, controls dried In journey, vacuum is less than below 15Pa, processes 24h in-50 DEG C, and obtaining its first top layer of lyophilizing composite sponge is sodium alginate layer, The second layer is sodium carboxymethyl cellulose layer.Then gelatin solution is coated on sodium carboxymethyl cellulose side ,-60 DEG C of low temperature pre-coolings Freeze 5h, be placed in freezer dryer, control vacuum in dry run and, less than below 15Pa, process 24h in-50 DEG C, obtain the One layer is composite sponge that sodium alginate, the second layer are sodium carboxymethyl cellulose-gelatin.Finally sodium alginate soln is coated on Gelatin side ,-60 DEG C of low temperature precooling 5h, it is placed in freezer dryer, controls vacuum in dry run and be less than below 15Pa, Process 24h, crosslinking curing 2h in 1% calcium chloride ethanol solution in-50 DEG C, after having solidified, sponge is placed on 50 DEG C of vacuum and dries Being dried in case to constant weight, distilled water is dried to constant weight after cleaning repeatedly in 50 DEG C of vacuum drying ovens, and obtaining ground floor is Sargassum Acid calcium, the second layer be sodium carboxymethyl cellulose-gelatin, third layer be the MULTILAYER COMPOSITE medical dressing sponge of calcium alginate.
Embodiment six
1g sodium alginate is dissolved in 100g distilled water, is configured to the sodium alginate soln that mass fraction is 1%, electricity consumption Dynamic agitator stirs to being completely dissolved, and vacuum defoamation 24h is standby.1g chitosan is dissolved in 100g 1% (v/v) formic acid solution In, it is configured to the chitosan solution of 1%, is sufficiently stirred for making it uniform, standby.1g sodium carboxymethyl cellulose is dissolved in 100g distillation In water, it is configured to the carboxymethylcellulose sodium solution of 1%, is sufficiently stirred for making it uniform, standby.1g gelatin is dissolved in 100g distillation In water, it is configured to the gelatin solution of 1%, is sufficiently stirred for making it uniform, standby.Sodium alginate soln is dispensed in mould, will Mould is placed in pre-freeze in cryogenic refrigerator ,-70 DEG C of pre-freeze 1h, is then placed in freezer dryer by mould, controls in dry run Vacuum is less than below 15Pa, processes 24h in-50 DEG C, and the dried demoulding obtains the sodium alginate sponge being dried, then 1% Crosslinking curing 2h in calcium chloride ethanol solution, is placed on sponge after having solidified in 50 DEG C of vacuum drying ovens and is dried to constant weight, distillation Water is dried to constant weight after cleaning repeatedly in 50 DEG C of vacuum drying ovens, obtains calcium alginate lyophilizing sponge, standby.Chitosan is molten Liquid is coated on this lyophilizing sponge side of alginic acid ,-70 DEG C of low temperature precooling 1h, is placed in freezer dryer, controls dry run Middle vacuum is less than below 15Pa, processes 24h in-50 DEG C, and obtaining its first top layer of lyophilizing composite sponge is alginic acid calcium layer, the Two layers is chitosan layer.Then carboxymethylcellulose sodium solution is coated on chitosan side ,-70 DEG C of low temperature precooling 1h, is placed in In freezer dryer, controlling vacuum in dry run and, less than below 15Pa, process 24h in-50 DEG C, obtaining ground floor is Sargassum Acid calcium, the MULTILAYER COMPOSITE sponge of the second layer-sodium carboxymethyl cellulose.Gelatin solution is coated on sodium carboxymethyl cellulose side ,- 70 DEG C of low temperature precooling 1h, are placed in freezer dryer, control vacuum in dry run and are less than below 15Pa, at-50 DEG C Reason 24h, obtaining ground floor is calcium alginate, the MULTILAYER COMPOSITE sponge of the second layer-sodium carboxymethyl cellulose-gelatin.Finally by sea Solution of sodium alginate is coated on gelatin side ,-70 DEG C of low temperature precooling 1h, is placed in freezer dryer, controls in dry run true Reciprocal of duty cycle is less than below 15Pa, processes 24h, crosslinking curing 2h in 1% calcium chloride ethanol solution in-50 DEG C, will after having solidified Sponge is placed in 50 DEG C of vacuum drying ovens and is dried to constant weight, and distilled water is dried to perseverance after cleaning repeatedly in 50 DEG C of vacuum drying ovens Weight, obtain ground floor be calcium alginate, the second layer be chitosan-sodium carboxymethyl cellulose-gelatin, third layer be calcium alginate MULTILAYER COMPOSITE medical dressing sponge.
Embodiment seven
2g sodium alginate is dissolved in 100g distilled water, is configured to the sodium alginate soln that mass fraction is 2%, electricity consumption Dynamic agitator stirs to being completely dissolved, and vacuum defoamation 24h is standby.2g gelatin is dissolved in 100g distilled water, is configured to 2% Gelatin solution, is sufficiently stirred for making it uniform, standby.2g hyaluronic acid is dissolved in 100g distilled water, is configured to the hyalomitome of 2% Acid solution, is sufficiently stirred for making it uniform, standby.2g sodium carboxymethyl cellulose is dissolved in 100g distilled water, is configured to the carboxylic of 2% Methylcellulose sodium solution, is sufficiently stirred for making it uniform, standby.Sodium alginate soln is dispensed in mould, mould is placed in Pre-freeze in cryogenic refrigerator ,-30 DEG C of pre-freeze 2h, then mould is placed in freezer dryer, controls vacuum in dry run low In below 20Pa, processing 28h in-40 DEG C, the dried demoulding obtains the sodium alginate sponge being dried, then at 2% calcium chloride water Crosslinking curing 1h in solution, is placed on sponge after having solidified in 50 DEG C of vacuum drying ovens and is dried to constant weight, and distilled water cleans repeatedly After be dried in 50 DEG C of vacuum drying ovens to constant weight and obtain calcium alginate sponge.Gelatin solution is coated on calcium alginate lyophilizing sea Continuous side ,-30 DEG C of pre-freeze 2h, it is placed in freezer dryer, controls vacuum in dry run and be less than below 20Pa, in-40 DEG C Processing 28h, obtaining its first top layer of lyophilizing composite sponge is alginic acid calcium layer, and the second layer is gelatin layer.Then hyaluronic acid is molten Liquid is coated on gelatin side, is placed in freezer dryer, controls vacuum in dry run and is less than below 15Pa, at-50 DEG C Reason 24h, obtain ground floor be calcium alginate, the second layer be the MULTILAYER COMPOSITE sponge of gelatin-hyaluronic acid.By carboxymethyl cellulose Sodium solution is coated on sodium carboxymethyl cellulose side ,-30 DEG C of pre-freeze 2h, is placed in freezer dryer, controls in dry run true Reciprocal of duty cycle is less than below 15Pa, processes 24h in-50 DEG C, obtain ground floor be calcium alginate, the second layer be gelatin-hyaluronic acid-carboxylic The MULTILAYER COMPOSITE sponge of sodium carboxymethylcellulose pyce.Finally sodium alginate soln is coated on gelatin side ,-30 DEG C of pre-freeze 2h, is placed in In freezer dryer, control vacuum in dry run and, less than below 20Pa, process 28h in-40 DEG C, water-soluble at 2% calcium chloride Crosslinking curing 1h in liquid, is placed on sponge after having solidified in 50 DEG C of vacuum drying ovens and is dried to constant weight, after distilled water cleans repeatedly Be dried to constant weight in 50 DEG C of vacuum drying ovens, obtain ground floor be calcium alginate, the second layer be gelatin-hyaluronic acid-carboxylic first Base sodium cellulosate, third layer are the MULTILAYER COMPOSITE medical dressing sponge of calcium alginate.
Embodiment eight
4g sodium alginate is dissolved in 100g distilled water, is configured to the sodium alginate soln that mass fraction is 4%, electricity consumption Dynamic agitator stirs to being completely dissolved, and vacuum defoamation 24h is standby.4g chitosan is dissolved in 100g 1% (v/v) formic acid solution In, it is configured to the chitosan solution of 4%, is sufficiently stirred for making it uniform, standby.4g hyaluronic acid is dissolved in 100g distilled water, It is configured to the hyaluronic acid solution of 4%, is sufficiently stirred for making it uniform, standby.4g gelatin is dissolved in 100g distilled water, is configured to The gelatin solution of 4%, is sufficiently stirred for making it uniform, standby.4g sodium carboxymethyl cellulose is dissolved in 100g distilled water, is configured to The carboxymethylcellulose sodium solution of 4%, is sufficiently stirred for making it uniform, standby.Sodium alginate soln is dispensed in mould, by mould Have and be placed in pre-freeze in cryogenic refrigerator ,-50 DEG C of low temperature precooling 4h, then mould is placed in freezer dryer, controls dried In journey, vacuum is less than below 15Pa, processes 24h in-50 DEG C, and the dried demoulding obtains the sodium alginate sponge being dried, then exists Crosslinking curing 2h in 1% calcium chloride ethanol solution, is placed on sponge in 50 DEG C of vacuum drying ovens after having solidified and is dried to constant weight, Calcium alginate lyophilizing sponge.Chitosan solution is coated on calcium alginate lyophilizing sponge side ,-50 DEG C of low temperature precooling 4h, puts In freezer dryer, control vacuum in dry run and, less than below 15Pa, process 24h in-50 DEG C, obtain lyophilizing compounding sea Its first top layer continuous is sodium alginate layer, and the second layer is chitosan layer.Then hyaluronic acid solution is coated on chitosan one Side ,-50 DEG C of low temperature precooling 4h, it is placed in freezer dryer, controls vacuum in dry run and be less than below 15Pa, in-50 DEG C process 24h, obtain ground floor be sodium alginate, the second layer be the composite sponge of Chitosan-Hyaluronic Acid.Then gelatin is molten Liquid is coated on hyaluronic acid side ,-50 DEG C of low temperature precooling 4h, is placed in freezer dryer, controls vacuum in dry run Less than below 15Pa, process 24h in-50 DEG C, obtain ground floor be sodium alginate, the second layer be Chitosan-Hyaluronic Acid-gelatin Composite sponge.Then carboxymethylcellulose sodium solution is coated on gelatin side ,-50 DEG C of low temperature precooling 4h, is placed in freezing In drying machine, controlling vacuum in dry run and, less than below 15Pa, process 24h in-50 DEG C, obtaining ground floor is alginic acid Sodium, the second layer are the composite sponge of Chitosan-Hyaluronic Acid-gelatin-sodium carboxymethyl cellulose.Finally sodium alginate soln is coated with It is overlying on sodium carboxymethyl cellulose side ,-50 DEG C of low temperature precooling 4h, is placed in freezer dryer, control vacuum in dry run Degree, less than below 15Pa, processes 24h in-50 DEG C, and crosslinking curing 2h in 1% calcium chloride ethanol solution, by sea after having solidified Silk floss is placed in 50 DEG C of vacuum drying ovens and is dried to constant weight, obtain ground floor be calcium alginate, the second layer be Chitosan-Hyaluronic Acid- Gelatin-sodium carboxymethyl cellulose, third layer are the MULTILAYER COMPOSITE medical dressing sponge of calcium alginate.

Claims (7)

1. based on natural polymer MULTILAYER COMPOSITE medical dressing and preparation method thereof, it is characterized in that: this dressing is by the natural height of multilamellar Molecule is compound to be constituted, wherein ground floor be calcium alginate, the second layer be single or multiple lift natural polymer, third layer be alginic acid Calcium, this preparation method comprises the following steps:
(1) preparation of sodium alginate soln: be dissolved in distilled water by sodium alginate, is configured to the sea that mass fraction is 1~4% Solution of sodium alginate, stirs to being completely dissolved with motor stirrer, vacuum defoamation 24h, places stand-by;
(2) preparation of natural polymer solution: dissolved respectively by natural polymer, being configured to mass fraction is 1~4% Natural polymer solution, stirs to being completely dissolved with motor stirrer, vacuum defoamation 24h, places stand-by;
(3) preparation of calcium alginate lyophilizing sponge: the sodium alginate soln configured is injected in mould ,-20~-70 DEG C of low temperature Precooling 1~5h, then in-80~-10 DEG C of temperature, in 1~600Pa vacuum, by the sodium alginate soln that freezes cold Lyophilization 24~48h in lyophilizer, obtain sodium alginate lyophilizing sponge, then soak 1-1~5% in cross-linking agent solution 5h cross-links, and distilled water cleans, and is then dried to horizontal heavy in 50~80 DEG C of baking ovens, obtains calcium alginate sponge;
(4) preparation based on natural polymer MULTILAYER COMPOSITE medical dressing: preprepared natural polymer solution is coated In calcium alginate lyophilizing sponge side ,-20~-70 DEG C of low temperature precoolings 1~5h, then in-80~-10 DEG C of temperature, 1~ In 600Pa vacuum, be coated with the calcium alginate sponge of natural polymer solution in freezer dryer lyophilization 24~ 48h, obtaining its ground floor of lyophilizing composite sponge is alginic acid calcium layer, and the second layer is single or multiple lift natural polymer, then will Sodium alginate soln is coated on single or multiple lift natural polymer sublayer side again ,-20~-70 DEG C of low temperature precoolings 1~5h, so After in-80~-10 DEG C of temperature, in 1~600Pa vacuum, by MULTILAYER COMPOSITE sponge lyophilization 24 in freezer dryer ~1~5%, cross-linking agent solution soaks 1-5h after 48h and cross-link, distilled water cleans, and is then dried in 50~80 DEG C of baking ovens To horizontal heavy, obtaining ground floor is calcium alginate, and the second layer is single or multiple lift natural polymer, and third layer is that calcium alginate is many Layer based composite dressing for medical use.
The most according to claim 1 based on natural polymer MULTILAYER COMPOSITE medical dressing and preparation method thereof, its feature exists One or more in described natural polymer is chitosan, hyaluronic acid, gelatin and sodium carboxymethyl cellulose.
The most according to claim 1 based on natural polymer MULTILAYER COMPOSITE medical dressing and preparation method thereof, its feature exists It is single one or several in chitosan, hyaluronic acid, gelatin and sodium carboxymethyl cellulose in described second layer natural polymer sublayer Plant and be combined layer by layer.
4. according to described in claim 1 and 2 based on natural polymer MULTILAYER COMPOSITE medical dressing and preparation method thereof, its feature It is described sodium alginate molecular weight Mw=2 × 103-40×103g·mol-1, chitosan molecule amount Mw=1 × 104-3× 104g·mol-1, hyaluronan molecule amount Mw=8 × 105-12×105g·mol-1, gelatine molecular weight Mw=6 × 104-30× 104g·mol-1, sodium carboxymethyl cellulose molecular weight Mw=1.8 × 104—2.8×104g·mol-1
The most according to claim 1 based on natural polymer MULTILAYER COMPOSITE medical dressing and preparation method thereof, its feature exists In the cryogenic temperature-80 described in above-mentioned steps (3)~-10 DEG C, vacuum 1~600Pa, cooling time 12~48h.
The most according to claim 1 based on natural polymer MULTILAYER COMPOSITE medical dressing and preparation method thereof, its feature exists One or more in cross-linking agent solution is the ethanol solution of the aqueous solution of calcium chloride, calcium chloride described in above-mentioned steps (3).
The most according to claim 1 based on natural polymer MULTILAYER COMPOSITE medical dressing and preparation method thereof, its feature exists Medical dressing in described preparation is multilamellar natural polymer composite sponge, and this dressing can be used for biomedicine technical field.
CN201610621172.XA 2016-07-29 2016-07-29 Based on natural polymer MULTILAYER COMPOSITE medical dressing and preparation method thereof Pending CN106110367A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201610621172.XA CN106110367A (en) 2016-07-29 2016-07-29 Based on natural polymer MULTILAYER COMPOSITE medical dressing and preparation method thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201610621172.XA CN106110367A (en) 2016-07-29 2016-07-29 Based on natural polymer MULTILAYER COMPOSITE medical dressing and preparation method thereof

Publications (1)

Publication Number Publication Date
CN106110367A true CN106110367A (en) 2016-11-16

Family

ID=57255127

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201610621172.XA Pending CN106110367A (en) 2016-07-29 2016-07-29 Based on natural polymer MULTILAYER COMPOSITE medical dressing and preparation method thereof

Country Status (1)

Country Link
CN (1) CN106110367A (en)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108066807A (en) * 2018-02-07 2018-05-25 苏州元禾医疗器械有限公司 The preparation method of the absorption styptic dressing of high imbibition ability
CN110448714A (en) * 2019-09-23 2019-11-15 南通大学 A kind of antibacterial chitosan of moisture absorption/sodium alginate intertexture type dressing and preparation method
WO2020062282A1 (en) * 2018-09-30 2020-04-02 成都远山原力生物科技有限公司 Low-temperature preservation solution for cells, sodium alginate gel, cell gel, preparation method, use method and application thereof
CN114177346A (en) * 2021-12-24 2022-03-15 中国人民解放军军事科学院军事医学研究院 Hemostatic composition, hemostatic patch and application thereof
CN114681654A (en) * 2020-12-31 2022-07-01 广州迈普再生医学科技股份有限公司 Absorbable sponge dressing with wound repair function and preparation method thereof

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1774272A (en) * 2000-12-07 2006-05-17 株式会社日本组织工程 Substrate for tissue regeneration, material for transplantation, and processes for producing these
WO2010084481A1 (en) * 2009-01-23 2010-07-29 Royal College Of Surgeons In Ireland Layered scaffold suitable for osteochondral repair
CN102258801A (en) * 2011-06-27 2011-11-30 武汉纺织大学 Sponge calcium alginate medical dressing, and preparation method

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1774272A (en) * 2000-12-07 2006-05-17 株式会社日本组织工程 Substrate for tissue regeneration, material for transplantation, and processes for producing these
WO2010084481A1 (en) * 2009-01-23 2010-07-29 Royal College Of Surgeons In Ireland Layered scaffold suitable for osteochondral repair
CN102258801A (en) * 2011-06-27 2011-11-30 武汉纺织大学 Sponge calcium alginate medical dressing, and preparation method

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108066807A (en) * 2018-02-07 2018-05-25 苏州元禾医疗器械有限公司 The preparation method of the absorption styptic dressing of high imbibition ability
WO2020062282A1 (en) * 2018-09-30 2020-04-02 成都远山原力生物科技有限公司 Low-temperature preservation solution for cells, sodium alginate gel, cell gel, preparation method, use method and application thereof
CN110448714A (en) * 2019-09-23 2019-11-15 南通大学 A kind of antibacterial chitosan of moisture absorption/sodium alginate intertexture type dressing and preparation method
CN110448714B (en) * 2019-09-23 2022-02-25 南通大学 Moisture-absorbing and bacteriostatic chitosan/sodium alginate interwoven dressing and preparation method thereof
CN114681654A (en) * 2020-12-31 2022-07-01 广州迈普再生医学科技股份有限公司 Absorbable sponge dressing with wound repair function and preparation method thereof
CN114177346A (en) * 2021-12-24 2022-03-15 中国人民解放军军事科学院军事医学研究院 Hemostatic composition, hemostatic patch and application thereof
CN114177346B (en) * 2021-12-24 2023-05-26 中国人民解放军军事科学院军事医学研究院 Hemostatic composition and hemostatic patch and application thereof

Similar Documents

Publication Publication Date Title
Patil et al. Silk fibroin and silk-based biomaterial derivatives for ideal wound dressings
CN106110367A (en) Based on natural polymer MULTILAYER COMPOSITE medical dressing and preparation method thereof
CN102258801B (en) Sponge calcium alginate medical dressing, and preparation method
CN109045349A (en) A kind of hydrogel skin wound dressing and preparation method thereof that antibacterial heal-promoting closes
CN104491914A (en) Porous complex gel-nanofiber oxygen permeation dressing and preparation method thereof
Jing et al. Marine polysaccharides: Green and recyclable resources as wound dressings
CN102319448A (en) Antibacterial aquagel material for preparing medical wound dressing and preparation method thereof
CN101020077A (en) Prepn process of collagen-based surface wound repairing membrane possessing tissue induction
CN104888279A (en) Collagen/silk fibroin composite support and manufacturing method and application thereof
CN104004221A (en) Method for preparing polycaprolactone-keratin composite porous scaffolds
CN109731121A (en) A kind of preparation method of the cellulose containing mesoporous silicon oxide and chitosan combine dressing
CN1775302A (en) Chitose-gelatine sponge wound dressing preparing method
Balusamy et al. Electrospun nanofibrous materials for wound healing applications
CN107296978A (en) A kind of spongy hemostatic material in medical use of organism
Sun et al. Chitin-glucan composite sponge hemostat with rapid shape-memory from Pleurotus eryngii for puncture wound
CN102648987B (en) Asymmetric double-crosslinked composite material, as well as preparation method and application of same
Li et al. Construction of porous structure-based carboxymethyl chitosan/sodium alginate/tea polyphenols for wound dressing
CN109260502A (en) A kind of fibroin hyaluronic acid mandruka and its preparation method and application
CN105497964A (en) Fucoidin-alginate sponge and preparation method thereof
CN108452366B (en) Cod skin gelatin composite hemostatic dressing and preparation method thereof
CN104497345A (en) Preparation method of hyaluronic acid-chitosan degradable dressing
CN103131037B (en) Preparation of natural polymer base hemostasis dressing
CN105056279A (en) Double-layer polyurethane-based collagen-compounded dressing
Zhang et al. Water-retaining and separable adhesive hydrogel dressing for wound healing without secondary damage
CN102389584B (en) Preparation method of konjac sponge medical dressing

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
RJ01 Rejection of invention patent application after publication
RJ01 Rejection of invention patent application after publication

Application publication date: 20161116