CN108785657A - Application of histamine 1 polypeptide of element in preparing the composite material for promoting large skin defect reparation - Google Patents
Application of histamine 1 polypeptide of element in preparing the composite material for promoting large skin defect reparation Download PDFInfo
- Publication number
- CN108785657A CN108785657A CN201810725789.5A CN201810725789A CN108785657A CN 108785657 A CN108785657 A CN 108785657A CN 201810725789 A CN201810725789 A CN 201810725789A CN 108785657 A CN108785657 A CN 108785657A
- Authority
- CN
- China
- Prior art keywords
- polypeptide
- hst1
- composite material
- histamine
- skin defect
- 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.)
- Granted
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/1703—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0014—Skin, i.e. galenical aspects of topical compositions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
- A61L26/0009—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form containing macromolecular materials
- A61L26/0023—Polysaccharides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
- A61L26/0009—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form containing macromolecular materials
- A61L26/0028—Polypeptides; Proteins; Degradation products thereof
- A61L26/0047—Specific proteins or polypeptides not covered by groups A61L26/0033 - A61L26/0042
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
- A61L26/0061—Use of materials characterised by their function or physical properties
- A61L26/008—Hydrogels or hydrocolloids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
- A61L26/0061—Use of materials characterised by their function or physical properties
- A61L26/009—Materials resorbable by the body
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/02—Local antiseptics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
- A61L2300/252—Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/404—Biocides, antimicrobial agents, antiseptic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/41—Anti-inflammatory agents, e.g. NSAIDs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/412—Tissue-regenerating or healing or proliferative agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
- A61L2300/602—Type of release, e.g. controlled, sustained, slow
- A61L2300/604—Biodegradation
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Dermatology (AREA)
- Communicable Diseases (AREA)
- Inorganic Chemistry (AREA)
- Rheumatology (AREA)
- Dispersion Chemistry (AREA)
- Marine Sciences & Fisheries (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Pain & Pain Management (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Oncology (AREA)
- Materials For Medical Uses (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses application of plain 1 polypeptide of histamine in preparing the composite material for promoting large skin defect reparation.It is found that histamine element 1 (Hst1) polypeptide has in the present invention and promotes cell adherence, blood vessel metaplasia and the characteristic for inhibiting inflammatory reaction.The Hst1 polypeptides can be carried on a variety of biomaterials, can efficiently promote the healing of large skin defect with dressing, injection, paste, pulvis, hydrogel, film, sponge, the fiber scaffold material of the compound preparation of bioactive materials etc.；Wherein, large skin defect includes skin ulcer etc. caused by wound, burn, tumor resection or diabetes.Hst1 polypeptides are humanized's polypeptide in the present invention, have good biocompatibility and biological safety, prepared by Hst1 polypeptides large skin defect repair materials is promoted to have important medical value and good industrialization prospect.
Description
Technical field
The invention belongs to biomedical sector, more particularly to plain 1 polypeptide of histamine promotes large skin defect to repair in preparation
Application in multiple composite material.
Background technology
Large area skin full-thickness defects are common in skin ulcer etc. caused by wound, burn, tumor resection and diabetes.Greatly
The skin full-thickness defects of area can not self-heal, need to go self skin graft, skin flap transplantation, but there are sources to have for above method
The deficiencies of limiting, needing second operation.And there are immunological rejection equivalent risks for allosome skin graft, flap.Therefore, a large amount of artificial dermis implantation
Object is used for defect of skin reparation, however these materials do not obtain ideal therapeutic effect finally.Defect of skin is treated not
On the one hand ideal is that sufficient oxygen cannot be provided for newborn tissue because lacking vascularity in large defect skin
And nutrient；In addition, excessive inflammatory reaction and cell chemotaxis, cell adhesion are poor, defect of skin healing can be also influenced, is caused
Healing delay.
The speed of wound healing of oral cavity tissue will be significantly faster than that the speed of wound healing at other positions of whole body, gingiva tissue
It is twice that speed is repaired in skin injury to repair speed, and can effectively reduce the formation of scar, one of major reason
It may be albumen, polypeptide in oral cavity to have the function of promoting defect of skin reparation.Histamine element is mankind's Parotid and submandibular gland point
One group secreted is rich in the cationic polypeptide of histidine, and length is 7~38 amino acid residues.Histamine element 1,3,5 is wherein most heavy
3 kinds wanted account for the 85~90% of histamine element total content.In recent years, histamine element 1 (Hst1) is goed deep into biomedical sector
Research, have and promote cell adherence, stretching, extension, migration, blood vessel metaplasia, many-sided effect such as anti-inflammatory, but Hst1 whether can be with
Relevant report is had no applied to large skin defect reparation.Rarely seen 1 patent application of histamine element at present：Application No. is
201580061786.0, the patent application of entitled " saliva Statherin peptide " discloses that histamine element is applied to treatment tooth
Demineralization.Therefore, in order to promote large area skin wound repair, the problems such as wound repair inflammatory reaction and vascularization deficiency are solved,
The defect of skin repair materials based on Hst1 polypeptides are developed, efficiently promote the reparation of widespread skin defect to have important
Application value.
Invention content
The primary purpose of the present invention is that the shortcomings that overcoming the prior art and deficiency, provide plain 1 polypeptide of histamine and are preparing rush
Application into the composite material of large skin defect reparation.
Another object of the present invention is to provide plain 1 polypeptides of histamine to prepare the drug for promoting large skin defect reparation
In application.
The purpose of the invention is achieved by the following technical solution：(Hst1) polypeptide of histamine element 1 is preparing promotion Large Area Skin
Application in the composite material of skin defect repair.
The amino acid sequence of described histamine element 1 (Hst1) polypeptide is selected from following any sequence：
(1) such as SEQ ID NO.1 (DSPHEKRHHGYRRKFHEKHHSHREFPFYGDYGSNYLYDN amino acid shown in)
Sequence；
(2) polypeptide containing amino acid sequence some or all of in SEQ ID NO.1；
(3) to amino acid sequence shown in SEQ ID NO.1 carry out the substitutions of one or more amino acid, missing and/or
What addition (insertion) was obtained, there is the amino acid sequence of at least 80% homology with amino acid sequence shown in SEQ ID NO.1
Row.
The dosage of described histamine element 1 (Hst1) polypeptide is 10~1000 μ g/ days/people, 1 times a week；Applied to clinic
Dosage and dosage range need to combine many factors, include the size of administering mode, carrier, the physical condition of patient and defect
Deng.
The large skin defect includes skin ulcer etc. caused by wound, burn, tumor resection or diabetes.
The composite material is the composite material being made of (Hst1) polypeptide of histamine element 1 and carrier；The shape of composite material
Formula can be dressing, spray, hydrogel and plaster etc.；The Chitosan-Thiolated Polymers hydrogel for preferably loading Hst1 polypeptides, bears
It carries the collagen sponge of Hst1 polypeptides or loads the polyglycolic acid porous fiber film of Hst11 polypeptides；The use of the composite material
Mode is by dressing, spray, hydrogel, and plaster etc. directly sprays or be covered in wound or tissue surface.
The carrier is good biocompatibility and does not influence the carrier of polypeptide active, including degradable natural macromolecule, is closed
At macromolecule and bioceramic；Natural material and its derivative are specifically included, high molecular material and its derivative are synthesized, and
One or more of bioceramic.
The natural material include chitosan, hyaluronate, sodium alginate, cellulose, starch, lignin, collagen,
Gelatin and carragheen etc..
The synthesis high molecular material includes polylactic acid, polyglycolic acid, polycaprolactone, polyhydroxyalkanoates, poly- silica
Alkane and polyurethane etc..
The bioceramic includes hydroxyapatite, calcium monohydrogen phosphate, tricalcium phosphate, calcium octahate phosphate and calcium sulfate etc..
The dressing includes (Hst1) polypeptide of histamine element 1 and film or sponge etc..
The Chitosan-Thiolated Polymers hydrogel of the load Hst1 polypeptides is prepared preferably by following method：
(I) Chitosan-Thiolated Polymers (CS-SH) are dissolved into the water of pH=8, sodium β-glycerophosphate is then added and adjusts pH
=7, obtain CS-SH hydrogels；
(II) Hst1 polypeptide solutions are added in CS-SH hydrogels, are stirred evenly, obtain the sulfydryl of load Hst1 polypeptides
Change aquagel；
Chitosan-Thiolated Polymers (CS-SH) described in step (I) are prepared preferably by following method：
Chitosan is dissolved in aqueous acetic acid, 1- ethyls -3- (3- DimethylAminopropyls)-carbodiimides is then added
Hydrochloride (EDAC) and n-hydroxysuccinimide (NHS), are protected from light are stirred to react 15min at ambient temperature, are then added half
Cystine (Cys) adjusts pH to 5~6, then is protected from light is stirred to react 5 hours at ambient temperature, dialyses, and freeze-drying obtains mercapto
Base chitosan (CS-SH).
The aqueous acetic acid is the aqueous acetic acid of a concentration of 0.5% (v/v).
The dosage of the chitosan is pressed to be calculated per 100mL aqueous acetic acid proportioning 1g chitosans.
The dosage of 1- ethyls -3- (3- the DimethylAminopropyls)-carbodiimide hydrochlorides (EDAC) presses final concentration
It is calculated for 50mmol/L.
The dosage of the n-hydroxysuccinimide (NHS) is calculated by final concentration of 50mmol/L.
The molar ratio of the chitosan and cysteine is 1:1.
The conditioning agent of the pH is NaOH solution；The preferably NaOH solution of 1mol/L.
The dialysis is realized preferably by following steps：Successively with the HCl solution of pH=5.0, contain 1% (w/v)
The HCl solution of NaCl, pH=5.0 and the HCl solution of pH=5.0 are protected from light dialysis 3 days.
The CS-SH hydrogels that CS-SH hydrogels described in step (I) are a concentration of 5% (w/v).
A concentration of 125mg/mL of Hst1 polypeptide solutions described in step (II).
Hst1 polypeptide solutions and the volume ratio of CS-SH hydrogels described in step (II) are preferably 1：9.
The collagen sponge of the load Hst1 polypeptides includes collagen sponge and Hst1 aqueous solutions；Wherein collagen sponge passes through
Following method is prepared：
(a) type i collagen is dissolved in aqueous acetic acid and obtains collagen solution, be then freeze-dried collagen solution, obtained
Mandruka film；
(b) mandruka film is placed in ammonia atmosphere 30 minutes, is then washed to neutrality, freeze-drying, sterilizing obtain
To collagen sponge.
The collagen solution that collagen solution described in step (a) is a concentration of 3wt%.
The aqueous acetic acid that aqueous acetic acid described in step (a) is a concentration of 1% (v/v).
Mandruka film described in step (a) is diameter 5mm, height 2mm, 90% or more porosity mandruka
Film.
The concentration of the Hst1 aqueous solutions is preferably 40 μ g/mL.
The polyglycolic acid porous fiber film of the load Hst11 polypeptides include polyglycolic acid (PGA) fiber multihole film and
Hst1 aqueous solutions；Wherein, polyglycolic acid (PGA) fiber multihole film is prepared preferably by electrostatic spinning.
The concentration of the Hst1 aqueous solutions is preferably 40 μ g/mL.
Application of (Hst1) polypeptide of histamine element 1 in preparing the drug for promoting large skin defect reparation.
The administering mode of the drug of the described promotion large skin defect reparation is local administration, hypodermic injection, intradermal
Injection, intramuscular injection or intravenous injection.
The drug of the promotion large skin defect reparation can also contain a kind of either at least two pharmaceutically
Acceptable carrier.
The carrier be preferably sustained release agent, excipient, filler, adhesive, wetting agent, disintegrant, sorbefacient,
Absorption carrier or surfactant etc..
Various dosage forms are made in the conventional method that this field can be used in the drug of the promotion large skin defect reparation,
Including pulvis, injection etc..
The present invention has the following advantages and effects with respect to the prior art：
(1) present invention discover that histamine element 1 (histatin1, Hst1) polypeptide, which has, promotes cell adherence, blood vessel metaplasia and suppression
The characteristic of inflammatory reaction processed.Experiment in vitro confirms that Hst1 polypeptides can promote mescenchymal stem cell adherency, stretching, extension, blood vessel metaplasia, move
It moves, inhibit inflammatory reaction, raise the vascularization factor of stem cell and mescenchymal stem cell-endothelial cell is activated to form blood vessel sample group
It knits, promotes vascularization ability to improve 2.8 times compared with blank control group, illustrate that Hst1 polypeptides can effectively facilitate repairing for defect of skin
It is multiple.After zoopery confirms that Hst1 polypeptides are subcutaneously injected, rat skin defect healing rate can be accelerated, defect of skin healing compared with
Control group is fast.Experiment in vivo confirms that the materials such as hydrogel, film, cream and sponge of Hst1 polypeptides and complex group Hst1 can promote greatly
The healing rate of mouse defect of skin：Hst1 polypeptide loading chitosans hydrogel can efficiently promote the healing of rat skin defect,
At 7 days, defect of skin repaired 82%, and control group has only repaired 51%.
(2) the Hst1 polypeptides that the present invention applies are humanized's polypeptide, have good biocompatibility and biological safety,
Do not find that animal has acute toxic reaction, and without side effects such as immunological rejections, while in tumor formation observation, 1 polypeptides of Hst1 are without bright
Aobvious Tumor formation.
(3) large skin defect reparation difficulty is primarily due to difficult cell adherence, vascularization deficiency and wound repair
Inflammatory reaction, the Hst1 polypeptides that the present invention applies have antiphlogistic antibacterial effect, efficiently promote wound healing.
(4) the Hst1 polypeptides that the present invention applies can be carried on a variety of biomaterials, be with a wide range of applications, such as
Hst1 polypeptides are compound with bioactive materials, prepare dressing, injection, paste, pulvis, hydrogel, film, sponge, fibrous framework material
Material etc. can efficiently promote the healing of large skin defect, have important medical value；And Hst1 polypeptide combined artificial materials
It prepares simply, it is cheap.Therefore, being prepared using Hst1 polypeptides promotes large skin defect repair materials to have good industry
Change foreground.
Description of the drawings
Fig. 1 is Effect study result figures of the Hst1 to mescenchymal stem cell adherency, stretching, extension；Wherein, figure A fills between being Hst1 pairs
The effect of matter stem cell adherency；Figure B is the effect that Hst1 stretches mescenchymal stem cell.
Fig. 2 is the cell activity schematic diagram of Chitosan-Thiolated Polymers injection aquagel in embodiment 1.
Fig. 3 is HUVECs cell seedings in embodiment 1 in the microscope figure of Chitosan-Thiolated Polymers injection aquagel；Its
In, figure A is hydrogel；It is load Hst1 hydrogels to scheme B.
Fig. 4 is reparation result figure when Hst1 polypeptides repair rat skin defect 7 days in embodiment 2；Wherein, scheme A skins
Repair figure；Figure B is skin repair ration statistics figure.
Fig. 5 is the reparation result figure that Chitosan-Thiolated Polymers injection aquagel repairs rat skin defect in embodiment 3；Its
In, scheme A skin repair figures；Figure B is skin repair ration statistics figure.
Fig. 6 is masson colored graph of the collagen sponge to the reparation of rat skin defect for loading Hst1 polypeptides.
Fig. 7 is that the polyglycolic acid porous fiber film of load Hst1 polypeptides in embodiment 5 is applied to promote rat skin defect
The substantially figure repaired.
Specific implementation mode
With reference to embodiment, the present invention is described in further detail, and embodiments of the present invention are not limited thereto.
Each raw material used in following embodiments and reagent can be obtained from commercially available in addition to particularly pointing out.
It is Hst1 polypeptides pulvis (Tao Pu biotech firms synthesize by Shanghai), amino acid sequence that embodiment, which is related to Hst1 polypeptides,
It is classified as：DSPHEKRHHGYRRKFHEKHHSHREFPFYGDYGSNYLYDN (the 2nd serine is phosphorylated).
Embodiment 1：Hst1 polypeptides promote cell adherence, stretching, extension and the research at blood vessel
(1) by mesenchymal stem cell (being purchased from Cyagen Biosciences Inc (USA), lot number 170221I31)
It is inoculated in 96 orifice plates, density is per hole 5 × 103A mesenchymal stem cell (BMSCs), 50 μ l of addition contain final concentration of
The serum free medium (a-MEM, Gibco) of 10 μM of Hst1 polypeptides, control group be simple serum free medium (a-MEM,
Gibco), phalloidin after culture 1.5h, 3h observes cell adherence and stretching, extension situation.
(2) BMSCs is inoculated in 96 orifice plates, density is per hole 5 × 103A cell, 50 μ l of addition contain final concentration of
Serum free medium culture 1d (day), 3d and the 5d of 10 μM of Hst1 polypeptides, then in each time point by 90 μ l culture solutions (a-
MEM, Gibco) and 10 μ l CCK-8 solution (Japanese colleague chemistry) be added in each hole, and be incubated 2h at 37 DEG C again.
From taking out 100 μ l reaction solutions in each hole of 24 well culture plates and being transferred in 96 clean orifice plates, spectral luminosity enzyme mark is utilized
Instrument measures absorbance of the solution at 450nm.
(3) aquagel containing Hst1 polypeptides is laid in 96 orifice plates, per hole 40ul, a concentration of 125mg/mL,
BMSCs is inoculated in 96 orifice plates, density is per hole 5 × 103A cell, control group are to be cultivated 3 days without Hst1 polypeptide water-settings
Afterwards, micro- sem observation cell adherence, stretching, extension situation.Wherein, the aquagel containing Hst1 polypeptides (loads Hst1 polypeptides
Chitosan-Thiolated Polymers hydrogel) preparation method it is as follows：
1. the preparation method of Chitosan-Thiolated Polymers injection aquagel：
The aqueous acetic acid that 1g chitosans are dissolved in 100mL 0.5% (v/v) is weighed, final concentration of 50mmol/L is separately added into
1- ethyls -3- (3- DimethylAminopropyls)-carbodiimide hydrochloride (EDAC) and n-hydroxysuccinimide (NHS), room
Temperature is protected from light and is stirred to react 15min, then Cys adds in reaction system to (molar ratio of chitosan and cysteine is 1:1),
PH to 5~6 is adjusted with 1mol/L NaOH solutions, room temperature is protected from light and is stirred to react 5 hours；Successively with pH=5.0HCl solution, contain
The pH=5.0HCl solution and pH=5.0HCl solution of 1% (w/v) NaCl is protected from light dialysis 3 days, is finally freeze-dried, obtains sulfydryl
Change chitosan (CS-SH) sample, 4 DEG C of preservations.
2. CS-SH is added in the deionized water solution of pH=8, fully after dissolving, it is finally configured to the CS- of 5% (w/v)
Then SH solution is added sodium β-glycerophosphate and adjusts final pH=7 or so at room temperature, obtains CS-SH hydrogels；
3. according to the volume ratio of CS-SH hydrogels and Hst1 polypeptide solutions (a concentration of 125mg/mL of Hst1 polypeptide solutions)
It is 9:1 addition stirs and evenly mixs, you can obtains gel precursor liquid (the Chitosan-Thiolated Polymers hydrogel of load Hst1 polypeptides).
(4) result
Cell adherence, stretching, extension, vascularization the result shows that, Hist1 is obviously promoted BMSCs adherency, and cell adherence quantity exists
1.5h and 3h is 2.4 times and 1.8 times of control group (Con) respectively；Hist1 remarkably promotes BMSCs stretching, extensions, cytochrome oxidase isozymes ratio
It is 2 times of control group and 1.5 times (see Fig. 1) respectively in 1.5h and 3h.
CCK-8 is experiments have shown that Hst1 polypeptides have good cell compatibility, and cell activity is 1,3,5d, with control group
Equal no difference of science of statistics (see Fig. 2).
As a result show that load Hst1 polypeptide hydrogels can be obviously promoted the stretching, extension of BMSCs cells (see Fig. 3).
Embodiment 2：Hst1 polypeptides promote the research of rat skin defect repair
(1) SD rat large skin defect models are built
By SD rats (250~300g of weight, is purchased from Nanfang Medical Univ's animal experimental center by totally 5) with 3% (w/v)
Yellow Jackets intraperitoneal injection anesthesia after, prostrate is in operating table, fixing limbs, back shaving, 1% (w/v) iodine disinfection paving
Towel.Skin puncher does the round full thickness dermal of 5mm diameters in back side, in postoperative 3d, injects gentamicin (injection daily
Amount is 4mg/kg) prevent infection, injection Carprofen (injection volume 12.5mg/kg) eases pain, and cage is divided normally to feed.
(2) reparation of the Hst1 polypeptides to rat skin defect
Using SD rat own controls, side is experimental group, and preprepared Hst1 polypeptides pulvis implantation skin is lacked
(it is covered in wound surface) at damage, each defect point inserts about 100 μ g Hst1 polypeptide pulvis, and uses gauze covering wrapping.Separately
Side is control group, not specially treated.Whole experiment process observes the activity of animal in order to avoid dressing without needing to change dressing daily
It falls off.
Postoperative 0d (same day after operation) and 7d, surface of a wound situation is recorded using digital camera.Experimental result is as shown in Figure 4.
Image analysis software (Image J) measure defect of skin area prompt using Hst1 obviously accelerate defect of skin reparation speed, 7
It when histamine element 1 repair about 75% skin area, and control group (Con) has only repaired 51%.Wherein, wound healing area
It is calculated with following formula：
P=[(I-R)/I] × 100%；
In formula：I is initial skin defect area, and R is the defect of skin area of particular point in time.
Embodiment 3：It loads Hst1 polypeptide Chitosan-Thiolated Polymers hydrogels and promotes rat skin defect repair
(1) the preparation method is the same as that of Example 1 for the Chitosan-Thiolated Polymers hydrogel of load Hst1 polypeptides.
(2) reparation of the load Hst1 polypeptide Chitosan-Thiolated Polymers hydrogels to rat skin defect
Using SD rats (model building method is with embodiment 1) own control, side is experimental group, and injection load Hst1 is more
Peptide Chitosan-Thiolated Polymers hydrogel, by the hydrogel for loading Hst1 polypeptide Chitosan-Thiolated Polymers, (every defect of skin injects 40ul
Hydrogel) it is injected at SD rat skins defect (Ф=5mm)；The other side is control group；Wherein, control group (Con) refuses spy
Different processing.The results are shown in Figure 5, shows that loading Hst1 polypeptide Chitosan-Thiolated Polymers is obviously promoted skin repair.
Embodiment 4：The collagen sponge for loading Hst1 polypeptides is applied to promote rat skin defect repair.
(1) preparation of the collagen sponge of load Hst1 polypeptides
1. the preparation of mandruka film：Type i collagen (Mingrang Biological Science & Technology Co., Ltd., Sichuan Prov.) is dissolved in 1% (v/v) acetic acid
After aqueous solution, 3% (wt%) collagen solution is prepared, a diameter of 5mm is obtained after freeze-drying, is highly the mandruka film of 2mm,
90% or more porosity；Then it is placed 30 minutes in ammonia atmosphere, is washed to neutrality；After being finally freeze-dried, sterilizing, low temperature
It is sealed；
2. the preparation of Hst1 solution：By 250 μ g Hst1 polypeptides pulvis 2mL sterile deionized water dispersing and dissolvings.
(2) reparation of the collagen sponge of load Hst1 polypeptides to rat skin defect
Using SD rats (model building method is with embodiment 1) own control, side is experimental group, will be preprepared
Mandruka film is implanted at (being covered in wound surface) defect of skin (Ф=5mm), and Hst1 solution is then added, and (diameter 5mm is more
Hole sponge membrane loads 40 μ l Hst1 solution)；The other side is pure collagen (simple mandruka film) control group.
As a result, it has been found that material part is degraded after 5 days, neoplastic skin is covered to entire defective region, compared with control group (Con),
Experimental group neoplastic skin is finer and close, closer to normal skin tissue (see Fig. 6).
Embodiment 5：The polyglycolic acid porous fiber film for loading Hst1 polypeptides is applied to promote rat skin defect repair.
Polyglycolic acid (PGA) fiber multihole film (fibre diameter about 100nm, membrane porosity 95% prepared by electrostatic spinning；
Its synthetic method refers to：Min Suk Lee,Taufiq Ahmad,Jinkyu Lee,Hassa n K.Awada,Yadong
Wang,Kyobum Kim,Heungsoo Shin and Hee Seok Yan g,Dual delivery of growth
factors with coacervate-coated poly(lactic-co-glycolic acid)nanofiber
improves neovascularization in a mouse skin flap model,Bioma terials,10.1016/
J.biomaterials.2017.01.036,124, (65-77), (2017)) moist heat sterilization.
Using SD rats (model building method is with embodiment 1), 250~300g of weight is totally 5, big purchased from southern medical courses in general
Learn animal experimental center.It is control with itself, side is experimental group, is implanted into PGA fiber multihole films, is implanted into rat side
At defect of skin (Ф=5mm), by 250 μ g Hst1 polypeptides pulvis 2mL sterile deionized water dispersing and dissolvings, then often place adds
Enter 40 μ L Hst1 solution (containing 5 μ g Hst1)；Other side blank control.
As a result, it has been found that experimental group skin repair 78% after 7 days, and blank control group is only 50% (see Fig. 7).
To sum up, find that Hst1 polypeptides can be obviously promoted the reparation of large skin defect in the present invention, by itself and a variety of lifes
Hydrogel, film, cream and sponge of object Material cladding etc. can obtain similar promotion defect of skin repair.Hst1 polypeptides
Can be natural polypeptides or synthesis polypeptide, can also be whole amino acid sequences or individual, multiple amino acid substitution, missing and
It is inserted into the polypeptide and homologue of variation, because the change of partial amino-acid has no effect on its substantial function.Composite material is in addition to upper
It states except material, other composite materials such as degradable natural macromolecule, synthesis macromolecule and bioceramic can also promote greatly
Mouse defect of skin reparation, such as chitosan, hyaluronate, sodium alginate, cellulose, starch, lignin, collagen, gelatin, OK a karaoke club
The natural materials such as glue and its derivative, polylactic acid, polyglycolic acid, polycaprolactone, polyhydroxyalkanoates, polysiloxanes, polyurethane
Deng synthesis high molecular material and its derivative, the biologies such as hydroxyapatite, calcium monohydrogen phosphate, tricalcium phosphate, calcium octahate phosphate, calcium sulfate
Ceramics, and composite material etc. that the above material is formed.
The above embodiment is a preferred embodiment of the present invention, but embodiments of the present invention are not by above-described embodiment
Limitation, it is other it is any without departing from the spirit and principles of the present invention made by changes, modifications, substitutions, combinations, simplifications,
Equivalent substitute mode is should be, is included within the scope of the present invention.
Sequence table
<110>Hangzhou Hui Bo Science and Technology Ltd.s
<120>Application of histamine 1 polypeptide of element in preparing the composite material for promoting large skin defect reparation
<160> 1
<170> SIPOSequenceListing 1.0
<210> 1
<211> 38
<212> PRT
<213>Artificial sequence (Artificial Sequence)
<220>
<223>Hst1 polypeptides
<400> 1
Asp Ser His Glu Lys Arg His His Gly Tyr Arg Arg Lys Phe His Glu
1 5 10 15
Lys His His Ser His Arg Glu Phe Pro Phe Tyr Gly Asp Tyr Gly Ser
20 25 30
Asn Tyr Leu Tyr Asp Asn
35
Claims (10)
1. application of histamine 1 polypeptide of element in preparing the composite material for promoting large skin defect reparation, which is characterized in that institute
The amino acid sequence for plain 1 polypeptide of histamine stated is selected from following any sequence：
(1) amino acid sequence as shown in SEQ ID NO.1；
(2) polypeptide containing amino acid sequence some or all of in SEQ ID NO.1；
(3) substitution of one or more amino acid carried out to amino acid sequence shown in SEQ ID NO.1, lacked and ored add
It is obtained, there is the amino acid sequence of at least 80% homology with amino acid sequence shown in SEQ ID NO.1.
2. plain 1 polypeptide of histamine according to claim 1 is in preparing the composite material for promoting large skin defect reparation
Application, it is characterised in that：
The large skin defect is skin ulcer caused by wound, burn, tumor resection or diabetes.
3. plain 1 polypeptide of histamine according to claim 1 is in preparing the composite material for promoting large skin defect reparation
Application, it is characterised in that：
The dosage of plain 1 polypeptide of the histamine is 10~1000 μ g/ days/people, 1 times a week.
4. plain 1 polypeptide of histamine according to claim 1 is in preparing the composite material for promoting large skin defect reparation
Application, it is characterised in that：
The composite material is the composite material being made of with carrier plain 1 polypeptide of histamine；The carrier be natural material and its
Derivative synthesizes high molecular material and its one or more of derivative and bioceramic；
The natural material be chitosan, hyaluronate, sodium alginate, cellulose, starch, lignin, collagen, gelatin or
Carragheen；
The synthesis high molecular material is polylactic acid, polyglycolic acid, polycaprolactone, polyhydroxyalkanoates, polysiloxanes or poly-
Urethane；
The bioceramic is hydroxyapatite, calcium monohydrogen phosphate, tricalcium phosphate, calcium octahate phosphate or calcium sulfate.
5. plain 1 polypeptide of histamine according to claim 4 is in preparing the composite material for promoting large skin defect reparation
Application, it is characterised in that：
The form of the composite material is dressing, spray, hydrogel or plaster, and occupation mode is that composite material is direct
Spray or be covered in wound/tissue surface.
6. plain 1 polypeptide of histamine according to claim 1 is in preparing the composite material for promoting large skin defect reparation
Application, it is characterised in that：
The composite material be load Hst1 polypeptides Chitosan-Thiolated Polymers hydrogel, load Hst1 polypeptides collagen sponge or
Load the polyglycolic acid porous fiber film of Hst11 polypeptides；
The Chitosan-Thiolated Polymers hydrogel of the load Hst1 polypeptides is prepared via a method which to obtain：
(I) Chitosan-Thiolated Polymers are dissolved into the water of pH=8, sodium β-glycerophosphate is then added and adjusts pH=7, obtains CS-
SH hydrogels；
(II) Hst1 polypeptide solutions are added in CS-SH hydrogels, are stirred evenly, obtain the sulfhydrylation shell of load Hst1 polypeptides
Glycan hydrogel；
The collagen sponge of the load Hst1 polypeptides includes collagen sponge and Hst1 aqueous solutions；Wherein, collagen sponge passes through such as
Lower section method is prepared：
(a) type i collagen is dissolved in aqueous acetic acid and obtains collagen solution, be then freeze-dried collagen solution, obtained porous
Sponge membrane；
(b) mandruka film is placed in ammonia atmosphere 30 minutes, is then washed to neutrality, freeze-drying, sterilizing obtain glue
Olynthus；
The polyglycolic acid porous fiber film of the load Hst11 polypeptides includes polyglycolic acid fiber perforated membrane and Hst1 water-soluble
Liquid.
7. plain 1 polypeptide of histamine according to claim 6 is in preparing the composite material for promoting large skin defect reparation
Application, which is characterized in that the Chitosan-Thiolated Polymers described in step (I) are prepared via a method which to obtain：
Chitosan is dissolved in aqueous acetic acid, 1- ethyls -3- (3- DimethylAminopropyls)-carbodiimides hydrochloric acid is then added
Salt and n-hydroxysuccinimide are protected from light are stirred to react 15min at ambient temperature, and cysteine is then added, and adjust pH to 5
~6, then be protected from light be stirred to react 5 hours at ambient temperature, it dialyses, freeze-drying obtains Chitosan-Thiolated Polymers；
The aqueous acetic acid is the aqueous acetic acid of concentration 0.5% (v/v)；
The dosage of described 1- ethyls -3- (3- the DimethylAminopropyls)-carbodiimide hydrochloride presses final concentration of 50mmol/L
It calculates；
The dosage of the n-hydroxysuccinimide is calculated by final concentration of 50mmol/L；
The molar ratio of the chitosan and cysteine is 1:1.
8. plain 1 polypeptide of histamine according to claim 6 is in preparing the composite material for promoting large skin defect reparation
Application, it is characterised in that：
The CS-SH hydrogels that CS-SH hydrogels described in step (I) are a concentration of 5% (w/v)；
A concentration of 125mg/mL of Hst1 polypeptide solutions described in step (II)；
The volume ratio of Hst1 polypeptide solutions and CS-SH hydrogels described in step (II) is 1：9；
The aqueous acetic acid that aqueous acetic acid described in step (a) is a concentration of 1% (v/v)；
The collagen solution that collagen solution described in step (a) is a concentration of 3wt%；
The concentration of the Hst1 aqueous solutions is 40 μ g/mL.
9. application of histamine 1 polypeptide of element in preparing the drug for promoting large skin defect reparation.
10. plain 1 polypeptide the answering in preparing the drug for promoting large skin defect reparation of histamine according to claim 9
With, it is characterised in that：
The administering mode of the drug of the promotion large skin defect reparation is hypodermic injection, intracutaneous injection, intramuscular injection
Or intravenous injection.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810725789.5A CN108785657B (en) | 2018-07-04 | 2018-07-04 | Application of histaminin 1 polypeptide in preparation of composite material for promoting repair of large-area skin defect |
| CN202210015023.4A CN114344449B (en) | 2018-07-04 | 2018-07-04 | Application of histamine 1 polypeptide in preparing composite material for promoting repair of large-area skin defect |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810725789.5A CN108785657B (en) | 2018-07-04 | 2018-07-04 | Application of histaminin 1 polypeptide in preparation of composite material for promoting repair of large-area skin defect |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202210015023.4A Division CN114344449B (en) | 2018-07-04 | 2018-07-04 | Application of histamine 1 polypeptide in preparing composite material for promoting repair of large-area skin defect |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN108785657A true CN108785657A (en) | 2018-11-13 |
| CN108785657B CN108785657B (en) | 2022-02-11 |
Family
ID=64074510
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810725789.5A Active CN108785657B (en) | 2018-07-04 | 2018-07-04 | Application of histaminin 1 polypeptide in preparation of composite material for promoting repair of large-area skin defect |
| CN202210015023.4A Active CN114344449B (en) | 2018-07-04 | 2018-07-04 | Application of histamine 1 polypeptide in preparing composite material for promoting repair of large-area skin defect |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202210015023.4A Active CN114344449B (en) | 2018-07-04 | 2018-07-04 | Application of histamine 1 polypeptide in preparing composite material for promoting repair of large-area skin defect |
Country Status (1)
| Country | Link |
|---|---|
| CN (2) | CN108785657B (en) |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110551201A (en) * | 2019-08-26 | 2019-12-10 | 杭州彗搏科技有限公司 | Novel cyclic peptide derived from bone morphogenetic protein 2, preparation method and application thereof |
| CN111420119A (en) * | 2020-04-16 | 2020-07-17 | 南通大学 | Method for covalently grafting active polypeptide for promoting nerve regeneration on material surface and application thereof |
| CN112316110A (en) * | 2020-11-12 | 2021-02-05 | 温州大学 | Pharmaceutical preparation for promoting skin wound repair and preparation method thereof |
| CN112851978A (en) * | 2021-01-05 | 2021-05-28 | 西北工业大学 | Self-healing tough lipopeptide surfactant hydrogel and preparation method thereof |
| CN114774357A (en) * | 2022-05-26 | 2022-07-22 | 杭州彗搏科技有限公司 | Application of polypeptide in preparation of product for promoting skin wound healing |
| WO2022178907A1 (en) | 2021-02-25 | 2022-09-01 | 杭州彗搏科技有限公司 | Use of polypeptide in promotion of cartilage regeneration or repair |
| CN115670965A (en) * | 2021-05-17 | 2023-02-03 | 杭州吾心科技有限公司 | Anti-inflammatory composition for skin effective in inhibiting IL-8, TNF-alpha and IL-6 |
| WO2023092926A1 (en) * | 2021-11-25 | 2023-06-01 | 暨南大学 | New polypeptide for promoting tissue repair, and use thereof |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2023005945A1 (en) * | 2021-07-27 | 2023-02-02 | 杭州彗搏科技有限公司 | Cyclic peptide, preparation method therefor and use thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104958783A (en) * | 2015-06-19 | 2015-10-07 | 暨南大学 | Natural polysaccharide-based hydrogel and preparation method and application thereof in conjunctival repair |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102038976A (en) * | 2011-01-27 | 2011-05-04 | 浙江大学 | Regeneration material of dermis substitution for tissue engineering skin for loading rhGM-CSF and preparation method thereof |
-
2018
- 2018-07-04 CN CN201810725789.5A patent/CN108785657B/en active Active
- 2018-07-04 CN CN202210015023.4A patent/CN114344449B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104958783A (en) * | 2015-06-19 | 2015-10-07 | 暨南大学 | Natural polysaccharide-based hydrogel and preparation method and application thereof in conjunctival repair |
Non-Patent Citations (1)
| Title |
|---|
| 蒋艳等: ""富组蛋白１促皮肤创伤愈合的细胞学研究"", 《解放军护理杂志》 * |
Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110551201A (en) * | 2019-08-26 | 2019-12-10 | 杭州彗搏科技有限公司 | Novel cyclic peptide derived from bone morphogenetic protein 2, preparation method and application thereof |
| CN110551201B (en) * | 2019-08-26 | 2020-04-28 | 杭州彗搏科技有限公司 | Novel cyclic peptide derived from bone morphogenetic protein 2, preparation method and application thereof |
| CN111420119A (en) * | 2020-04-16 | 2020-07-17 | 南通大学 | Method for covalently grafting active polypeptide for promoting nerve regeneration on material surface and application thereof |
| CN112316110A (en) * | 2020-11-12 | 2021-02-05 | 温州大学 | Pharmaceutical preparation for promoting skin wound repair and preparation method thereof |
| CN112316110B (en) * | 2020-11-12 | 2023-06-23 | 温州大学 | Pharmaceutical preparation for promoting skin wound repair and preparation method thereof |
| CN112851978A (en) * | 2021-01-05 | 2021-05-28 | 西北工业大学 | Self-healing tough lipopeptide surfactant hydrogel and preparation method thereof |
| WO2022178907A1 (en) | 2021-02-25 | 2022-09-01 | 杭州彗搏科技有限公司 | Use of polypeptide in promotion of cartilage regeneration or repair |
| CN115670965A (en) * | 2021-05-17 | 2023-02-03 | 杭州吾心科技有限公司 | Anti-inflammatory composition for skin effective in inhibiting IL-8, TNF-alpha and IL-6 |
| CN115670965B (en) * | 2021-05-17 | 2024-04-19 | 杭州朝与暮品牌管理有限公司 | A skin anti-inflammatory composition effective in inhibiting IL-8, TNF-alpha and IL-6 |
| WO2023092926A1 (en) * | 2021-11-25 | 2023-06-01 | 暨南大学 | New polypeptide for promoting tissue repair, and use thereof |
| CN114774357A (en) * | 2022-05-26 | 2022-07-22 | 杭州彗搏科技有限公司 | Application of polypeptide in preparation of product for promoting skin wound healing |
Also Published As
| Publication number | Publication date |
|---|---|
| CN114344449B (en) | 2024-04-12 |
| CN108785657B (en) | 2022-02-11 |
| CN114344449A (en) | 2022-04-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN108785657A (en) | Application of histamine 1 polypeptide of element in preparing the composite material for promoting large skin defect reparation | |
| Chattopadhyay et al. | Collagen‐based biomaterials for wound healing | |
| Aramwit | Introduction to biomaterials for wound healing | |
| US7125960B2 (en) | Crosslinked elastin and process for producing the same | |
| CN103648536B9 (en) | Biocompatible and biodegradable gradient layer system for regenerative medicine and for tissue support | |
| CN105031740B (en) | A kind of biomimetic prosthetic skin with waterproof and breathable function and preparation method thereof | |
| Xiao et al. | Zwitterionic hydrogel for sustained release of growth factors to enhance wound healing | |
| WO1990013302A1 (en) | Novel materials and methods for guided tissue regeneration | |
| CN108837184A (en) | A kind of composite membrane and preparation method thereof for Guided Bone Regeneration | |
| Stie et al. | Protein materials as sustainable non-and minimally invasive strategies for biomedical applications | |
| Abtahi et al. | Resorbable membranes for guided bone regeneration: critical features, potentials, and limitations | |
| Lanka Mahesh et al. | Regeneration in periodontics: Collagen—A review of its properties and applications in dentistry | |
| Vijayan et al. | Lanthanum oxide nanoparticle-collagen bio matrix induced endothelial cell activation for sustained angiogenic response for biomaterial integration | |
| US10111982B2 (en) | Pepsinized collagen implants and biomedical uses thereof | |
| Dong et al. | Electrospun nanofibrous membranes of recombinant human collagen type III promote cutaneous wound healing | |
| Ghosh et al. | Bio mimicking of extracellular matrix | |
| Ma et al. | Periodontal guided tissue regeneration membranes: limitations and possible solutions for the bottleneck analysis | |
| Eshgh et al. | Nanocelluloses for tissue engineering and biomedical scaffolds | |
| KR102141950B1 (en) | A biodegradable scaffold composition having semi-IPN structure for tissue regeneration and a preparation method thereof | |
| Ramshaw et al. | Applications of collagen in medical devices | |
| Ding et al. | Novel Functional Dressing Materials for Intraoral Wound Care | |
| CN104940981B (en) | Biologically active external application dressing and preparation method thereof | |
| CN107982568A (en) | Degradable biological auxiliary material and its preparation method and application | |
| Ring et al. | Improved neovascularization of PEGT/PBT copolymer matrices in response to surface modification by biomimetic coating | |
| KR101456638B1 (en) | Composition comprising atelocollagen-coated bone powder for reproduction of bone and method for preparing the same |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |