CN109589447A - A kind of preparation method and applications of medical injectable antibacterial composite in-situ hydrogel - Google Patents
A kind of preparation method and applications of medical injectable antibacterial composite in-situ hydrogel Download PDFInfo
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- CN109589447A CN109589447A CN201811342904.7A CN201811342904A CN109589447A CN 109589447 A CN109589447 A CN 109589447A CN 201811342904 A CN201811342904 A CN 201811342904A CN 109589447 A CN109589447 A CN 109589447A
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- hydrogel
- fibroin albumen
- solution
- povidone iodine
- fibroin
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- 239000000017 hydrogel Substances 0.000 title claims abstract description 102
- 239000002131 composite material Substances 0.000 title claims abstract description 22
- 238000011065 in-situ storage Methods 0.000 title claims abstract description 14
- 238000002360 preparation method Methods 0.000 title claims abstract description 13
- 230000000844 anti-bacterial effect Effects 0.000 title description 9
- 108010022355 Fibroins Proteins 0.000 claims abstract description 78
- 229920000153 Povidone-iodine Polymers 0.000 claims abstract description 49
- 229960001621 povidone-iodine Drugs 0.000 claims abstract description 49
- 239000007788 liquid Substances 0.000 claims abstract description 40
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 36
- CPKVUHPKYQGHMW-UHFFFAOYSA-N 1-ethenylpyrrolidin-2-one;molecular iodine Chemical compound II.C=CN1CCCC1=O CPKVUHPKYQGHMW-UHFFFAOYSA-N 0.000 claims abstract description 32
- 239000008367 deionised water Substances 0.000 claims abstract description 16
- 229910021641 deionized water Inorganic materials 0.000 claims abstract description 16
- 239000000843 powder Substances 0.000 claims abstract description 10
- 238000009963 fulling Methods 0.000 claims abstract description 8
- 238000007711 solidification Methods 0.000 claims abstract description 8
- 230000008023 solidification Effects 0.000 claims abstract description 8
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 62
- 229910052740 iodine Inorganic materials 0.000 claims description 62
- 239000011630 iodine Substances 0.000 claims description 62
- 239000000243 solution Substances 0.000 claims description 41
- 239000000499 gel Substances 0.000 claims description 7
- 238000000034 method Methods 0.000 claims description 7
- 238000004108 freeze drying Methods 0.000 claims description 6
- 239000012460 protein solution Substances 0.000 claims description 3
- 238000011049 filling Methods 0.000 claims description 2
- 238000013268 sustained release Methods 0.000 description 25
- 239000012730 sustained-release form Substances 0.000 description 25
- 238000005259 measurement Methods 0.000 description 15
- 238000010586 diagram Methods 0.000 description 13
- 206010052428 Wound Diseases 0.000 description 11
- 208000027418 Wounds and injury Diseases 0.000 description 11
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 10
- 235000019345 sodium thiosulphate Nutrition 0.000 description 10
- 238000004448 titration Methods 0.000 description 10
- 230000000845 anti-microbial effect Effects 0.000 description 9
- 230000000052 comparative effect Effects 0.000 description 9
- 241000894006 Bacteria Species 0.000 description 8
- 241000191967 Staphylococcus aureus Species 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 239000000463 material Substances 0.000 description 8
- 241000589517 Pseudomonas aeruginosa Species 0.000 description 7
- 238000002474 experimental method Methods 0.000 description 7
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 7
- 239000002994 raw material Substances 0.000 description 6
- 241000305071 Enterobacterales Species 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 5
- 230000001186 cumulative effect Effects 0.000 description 5
- 238000001514 detection method Methods 0.000 description 5
- 235000013399 edible fruits Nutrition 0.000 description 5
- 238000000605 extraction Methods 0.000 description 5
- 238000002156 mixing Methods 0.000 description 5
- 238000004321 preservation Methods 0.000 description 5
- 239000003814 drug Substances 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- 206010048038 Wound infection Diseases 0.000 description 3
- 239000012620 biological material Substances 0.000 description 3
- 230000015556 catabolic process Effects 0.000 description 3
- 238000006731 degradation reaction Methods 0.000 description 3
- 239000000645 desinfectant Substances 0.000 description 3
- 238000007599 discharging Methods 0.000 description 3
- 230000001408 fungistatic effect Effects 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 206010059866 Drug resistance Diseases 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 230000035876 healing Effects 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000011282 treatment Methods 0.000 description 2
- 238000002604 ultrasonography Methods 0.000 description 2
- 208000030453 Drug-Related Side Effects and Adverse reaction Diseases 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 241000726221 Gemma Species 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- 208000037581 Persistent Infection Diseases 0.000 description 1
- 241000295644 Staphylococcaceae Species 0.000 description 1
- 206010070863 Toxicity to various agents Diseases 0.000 description 1
- 208000030961 allergic reaction Diseases 0.000 description 1
- 230000002924 anti-infective effect Effects 0.000 description 1
- 239000002473 artificial blood Substances 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 244000052616 bacterial pathogen Species 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000001523 electrospinning Methods 0.000 description 1
- 230000009881 electrostatic interaction Effects 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 229940069328 povidone Drugs 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- 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
- A61L26/0052—Mixtures of macromolecular compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/74—Synthetic polymeric materials
- A61K31/785—Polymers containing nitrogen
- A61K31/787—Polymers containing nitrogen containing heterocyclic rings having nitrogen as a ring hetero atom
- A61K31/79—Polymers of vinyl pyrrolidone
-
- 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
- A61K47/42—Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein
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- 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
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
- A61K9/0024—Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- 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
- A61L26/0066—Medicaments; Biocides
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- 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
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- 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
- A61P31/04—Antibacterial agents
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J3/00—Processes of treating or compounding macromolecular substances
- C08J3/02—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques
- C08J3/03—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques in aqueous media
- C08J3/075—Macromolecular gels
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- 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
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- A61L2300/10—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing inorganic materials
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- 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
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
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- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J2439/00—Characterised by the use of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a single or double bond to nitrogen or by a heterocyclic ring containing nitrogen; Derivatives of such polymers
- C08J2439/04—Homopolymers or copolymers of monomers containing heterocyclic rings having nitrogen as ring member
- C08J2439/06—Homopolymers or copolymers of N-vinyl-pyrrolidones
Abstract
The invention discloses a kind of preparation methods of fibroin albumen-povidone iodine composite hydrogel in situ, which comprises fibroin albumen freeze-dried powder is dissolved in deionized water, after fulling shake, silk fibroin water solution of the concentration 5~30% is made；A certain amount of medical povidone iodine is extracted with the volume ratio of silk fibroin water solution and Betagen Solution 1:3~1:5, and fibroin albumen deionized water solution is deposited in syringe respectively with the medical Betagen Solution extracted；Two syringes are docked using double end female Luer, form blended liquid by repeatedly mutually pushing away solution, the blended liquid forms fibroin albumen-povidone iodine composite in-situ hydrogel by solidification in 2~8 hours.
Description
Technical field
The present invention relates to biomaterials and field of biomedicine, more particularly to one kind is with natural fibroin albumen and people
Work synthesis antibacterial agent povidone iodine based on prepare Injectable silk fibroin-povidone iodine composite in-situ hydrogel method and
Its application in regeneration and restoration, hand postoperative surgical site and wound prevention infection, the surface of a wound or deep infection treatment.
Background technique
Hydrogel is a kind of polymer with three-dimensional net structure, and property is soft, is able to maintain certain shape, can absorb
Large quantity of moisture and be swollen, and be still able to maintain original structure and be not dissolved, permeability and biocompatibility are good, have class extracellular
Medium property is often applied to biomedical, field of tissue engineering technology, such as pharmaceutical carrier, tissue filling agent, artificial blood plasma, contact
Glasses, tissue engineering bracket material and wound dressing etc..Nowadays, researcher utilizes natural and artificial synthesized polymer system
Standby hydrogel has become the pith in research organizational project and medicament slow release application.The hydrogel of a variety of materials synthesis has
Different advantages, but can also have respective deficiency, such as degradation is not easy to control, mechanical property is low, carrying medicament is unstable, material
Material preparation complexity etc., it is difficult to meet actual clinical demand.In recent years, biomedical and field of tissue engineering technology research direction will be different
The compound fibroin albumen of biomaterial, prepare novel biomaterial-silk fibroin hydrogel.Fibroin albumen composite hydrogel
Because its excellently biocompatibility, the slow degree of stable solution, excellent mechanical strength the advantages that cause the attention of researcher, tool
There is wide potential applicability in clinical practice.
Fibroin albumen is the macromolecular fibre albumen extracted from natural silk, can be added by the methods of electrospinning, ultrasound
Work is at the multiple materials form such as film, microballoon, porous support, nano particle and hydrogel.Fibroin albumen can be by changing solution
PH value, saltout, the methods of ultrasound prepares silk fibroin hydrogel.This is because fibroin molecule is from thermodynamically unstable
Random coil structure be changed into stable beta sheet conformation, eventually lead to the formation of silk fibroin hydrogel network, hydrogen bond and
Electrostatic interaction has played stabilization to silk fibroin hydrogel network structure.Simple silk fibroin hydrogel still remains
Shortcoming: mechanical performance is poor when fibroin albumen concentration is low, and degradation rate is too fast, the burst drug release etc. of embedding；Fibroin albumen
The drug release that embeds when high is not exclusively etc..Therefore, researcher makes by other biomedical materials in conjunction with fibroin albumen
Standby hydrogel can have better performance than simple silk fibroin hydrogel.
Wound infection is important always health care issues, because it is high-incidence in the wounds such as wound, burn and operation
Rate should cause the attention of clinical position and medical research.The bacteria levels in wound are reduced to the hair for reducing wound infection
Raw rate and the normally healing for accelerating wound are most important.Povidone iodine as antibacterial agent, be widely used in skin, mucous membrane and
The local anti-infective of wound is treated, and extensive antimicrobial spectrum, atomic small drug resistance and toxicity are possessed.
Summary of the invention
The technical problem to be solved by the present invention is to prepare a kind of medical Injectable in-situ using shirtsleeve operation method
Fibroin albumen-povidone iodine composite hydrogel and its application in field of biomedicine.
To solve the technical problems to be solved by the invention, it is multiple that the present invention provides a kind of fibroin albumen-povidone iodine in situ
The preparation method of Heshui gel, which comprises
Fibroin albumen freeze-dried powder is dissolved in deionized water, after fulling shake, fibroin egg of the concentration 5~30% is made
White water solution；
A certain amount of medical povidone is extracted with the volume ratio of silk fibroin water solution and Betagen Solution 1:3~1:5
Iodine, and fibroin albumen deionized water solution is deposited in syringe respectively with the medical Betagen Solution extracted；
Two syringes are docked using double end female Luer, form blended liquid by repeatedly mutually pushing away solution, described is total to
Mixed liquid forms fibroin albumen-povidone iodine composite in-situ hydrogel by solidification in 2-8 hours.
In one embodiment, the Betagen Solution available iodine content is 0.45~0.55%.
In one embodiment, the time that the silk fibroin powder of the freeze-drying is completely dissolved under room temperature is 10-30 points
Clock.
In one embodiment, after Betagen Solution and silk fibroin protein solution suck two syringes respectively, quickly mutually
Inject emitter 10-20 times or 40 seconds or more.
In one embodiment, the blended liquid solidifies to form the silk fibroin hydrogel during, can will be abundant
The blended liquid being mixed to get is put into a container, can be also placed directly in the syringe of side, and the empty injection of the other side is removed
Device and connector inject or for smearing filling.
Fibroin albumen in situ-povidone iodine composite hydrogel of the invention is safe and non-toxic, without obvious allergic reaction: this is compound
In biomaterial, the fibroin albumen of application is a kind of good material of biocompatibility, and medical povidone iodine is a kind of clinic
Common disinfectant, extensive clinical application confirm that its is safe and non-toxic.Simple silk fibroin protein solution is not easy shape under natural conditions
At hydrogel, after medical povidone iodine is added, it can promote fibroin albumen and form hydrogel.
The present invention controls povidone iodine in effective concentration ratio due to using the medical povidone iodine of disinfectant, energy
Enough make composite hydrogel that there is potent anti-microbial property.Since medical povidone iodine has extensive antimicrobial spectrum, to gram sun
Property bacterium, Gram-negative bacteria, gemma, fungi etc. all have it is good kill effect, and be not likely to produce drug resistance, therefore pass through above-mentioned
The fibroin albumen that method is prepared-povidone iodine composite hydrogel also has antibacterial, the effect of local treatment infection.According to configuration
Practical situations, when mixed povidone iodine ratio increases, the anti-microbial property of the composite hydrogel enhances therewith.In needle
To common wound infection pathogenic bacteria, such as Escherichia coli, staphylococcus aureus and pseudomonas aeruginosa, when fibroin albumen with
When mixed povidone iodine ratio increases to 1:3, composite hydrogel reaches 90% or more to the bacteriostasis rate of above 3 kinds of bacteriums.Its
Middle composite hydrogel is the most obvious to the fungistatic effect of staphylococcus aureus, in fibroin albumen and mixed povidone iodine ratio
When reaching 1:3 or so, bacteriostasis rate is up to 99%.Continuing to increase the povidone iodine ratio in mixture, antibacterial can be continued growing
Performance and duration.In configuration experiment, when fibroin albumen and mixed povidone iodine ratio reach 1:6 or so,
Composite hydrogel can still be formed.The present invention is by the good fibroin albumen of biocompatibility and the common disinfectant of clinical operation
Povidone iodine is compound to prepare hydrogel.Although the povidone iodine of high concentration has certain damage effect, system to body cell
When standby composite hydrogel, povidone iodine concentration is controlled, the effective iodine concentration for discharging composite hydrogel will not cause to damage to body
Wound.In compatibility experiments, when fibroin albumen and mixed povidone iodine ratio are in 1:5 or less, the composite hydrogel is to machine
Body hardly causes to damage.
The present invention mixes povidone iodine with fibroin albumen, hydrogel is formed, so as to keep in fluid environment
Form, the compound available iodine of slow release, and degradation time extend.The present invention can by the solubility of control silk fibroin water solution
Effectively to control the rate of release of povidone iodine available iodine, by repetition test discovery when the concentration of silk fibroin water solution is greater than
When 40%, available iodine is substantially reduced from the burst size in silk fibroin water solution, so that it is compound also to significantly reduce povidone iodine
The bactericidal effect of hydrogel.
For application prospect of the invention since the hydrogel raw material is simple, preparation method is convenient, can mass production, and performance
It is excellent, therefore possess the potentiality of clinical application.It can be applied to operative site or chronic infection focus implantation infected with prophylactic treatment,
Or the surface of a wound, wound are covered in play the role of antibacterial and promote healing as dressing.
Detailed description of the invention
Attached drawing is used to provide further understanding of the present invention, and constitutes part of specification, with reality of the invention
It applies example and is used together to explain the present invention, be not construed as limiting the invention.In the accompanying drawings:
Fig. 1 is the available iodine burst size schematic diagram of the embodiment of the present invention 1；
Fig. 2 is the available iodine Cumulative release amount curve synoptic diagram of the embodiment of the present invention 1；
Fig. 3 is the available iodine burst size schematic diagram of the embodiment of the present invention 2；
Fig. 4 is the available iodine Cumulative release amount curve synoptic diagram of the embodiment of the present invention 2；
Fig. 5 is the available iodine burst size schematic diagram of the embodiment of the present invention 3；
Fig. 6 is the available iodine Cumulative release amount curve synoptic diagram of the embodiment of the present invention 3；
Fig. 7 is the available iodine burst size schematic diagram of comparative example 1 of the present invention；
Fig. 8 is the available iodine Cumulative release amount curve synoptic diagram of comparative example 1 of the present invention；
Fig. 9 is the available iodine burst size schematic diagram of comparative example 2 of the present invention；
Figure 10 is the available iodine Cumulative release amount curve synoptic diagram of comparative example 2 of the present invention；
Figure 11 is directed to gold-coloured staphylococci bactericidal effect schematic diagram for the hydrogel of the embodiment of the present invention and comparative example；
Figure 12 is directed to Escherichia coli bactericidal effect schematic diagram for the hydrogel of the embodiment of the present invention and comparative example；
Figure 13 is directed to pseudomonas aeruginosa bactericidal effect schematic diagram for the hydrogel of the embodiment of the present invention and comparative example；
Specific embodiment
Embodiment of the present invention is further elaborated below in conjunction with attached drawing.
Embodiment 1
Fibroin albumen freeze-dried powder is dissolved in deionized water, after fulling shake 5-10 minutes, mass volume ratio is made
10% silk fibroin water solution, room temperature preservation.
Extraction available iodine content is the medical povidone iodine of 0.45~0.55% concentration.And by fibroin albumen deionized water solution
It is respectively that 1:1 is deposited in two syringes with volume ratio with the medical Betagen Solution extracted.Two syringes are made
It is docked with double end female Luer, by quickly repeatedly mutually pushing away solution about one minute or so, formation 1ML blended liquid,.The blending
Liquid forms fibroin albumen-povidone iodine in-situ hydrogel by solidification in 2-8 hours.The hydrogel is placed in the syringe of side
It is interior, slowly hydrogel is taken out from syringe.Aseptically, hydrogel is placed in PBS to the sustained release for carrying out available iodine
The measurement of amount.
The release of the outer available iodine of water gel uses sodium thiosulfate titration.The hydrogel of certain volume is immersed
In the PBS of 2ML, 2ML new PBS is replaced to original sustained release liquid again every 24 hours, and in 1/2/3/4/5/6/7/8/
The content of available iodine in 9/10/11/12 day measurement sustained release liquid.The results show that early period, available iodine burst size was larger, but do not formed
Burst release, the detection of number of days also has burst size later.Illustrate the ability that the hydrogel has slow release available iodine, specific experiment knot
Fruit as shown in the figure 1.
The degree that available iodine is discharged from hydrogel uses sodium thiosulfate titration.By certain volume
Hydrogel immerses in the PBS of 2ML, 2ML new PBS is replaced to original sustained release liquid again every 24 hours, and in 1/2/3/
The content of available iodine in 4/5/6/7/8/9/10/11/12 day measurement sustained release liquid.Have according in the povidone iodine in script raw material
The degree that the assay available iodine of effect iodine is discharged from hydrogel.Concrete outcome is referring to Fig. 2.
According to Figure 11 to 13, using the anti-microbial property of microdetermination hydrogel, staphylococcus aureus, big is chosen
Enterobacteria and pseudomonas aeruginosa.The results show that hydrogel can inhibit bacterial growth.
Embodiment 2
Fibroin albumen freeze-dried powder is dissolved in deionized water, after fulling shake 5-10 minutes, mass volume ratio is made
20% silk fibroin water solution, room temperature preservation.
Extraction available iodine content is the medical povidone iodine of 0.45~0.55% concentration.And by fibroin albumen deionized water solution
It is respectively that 1:3 is deposited in two syringes with volume ratio with the medical Betagen Solution extracted.Two syringes are made
It is docked with double end female Luer, by quickly repeatedly mutually pushing away solution about one minute or so, formation 1ML blended liquid,.The blending
Liquid forms fibroin albumen-povidone iodine in-situ hydrogel by solidification in 2-8 hours.The hydrogel is placed in the syringe of side
It is interior, slowly hydrogel is taken out from syringe.Aseptically, hydrogel is placed in PBS to the sustained release for carrying out available iodine
The measurement of amount.
The release of the outer available iodine of water gel uses sodium thiosulfate titration.The hydrogel of certain volume is immersed
In the PBS of 2ML, 2ML new PBS is replaced to original sustained release liquid again every 24 hours, and in 1/2/3/4/5/6/7/8/
The content of available iodine in 9/10/11/12 day measurement sustained release liquid.The results show that early period, available iodine burst size was larger, but do not formed
Burst release, the detection of number of days also has burst size later.Illustrate the ability that the hydrogel has slow release available iodine, specific experiment knot
Fruit as shown in the figure 3.
The degree that available iodine is discharged from hydrogel uses sodium thiosulfate titration.By certain volume
Hydrogel immerses in the PBS of 2ML, 2ML new PBS is replaced to original sustained release liquid again every 24 hours, and in 1/2/3/
The content of available iodine in 4/5/6/7/8/9/10/11/12 day measurement sustained release liquid.Have according in the povidone iodine in script raw material
The degree that the assay available iodine of effect iodine is discharged from hydrogel.Concrete outcome is referring to Fig. 4.
According to Figure 11 to 13, using the anti-microbial property of microdetermination hydrogel, staphylococcus aureus, big is chosen
Enterobacteria and pseudomonas aeruginosa.The results show that hydrogel is up to 90% or more to the bacteriostasis rate of three kinds of target bacterias.
Embodiment 3
Fibroin albumen freeze-dried powder is dissolved in deionized water, after fulling shake 5-10 minutes, mass volume ratio is made
30% silk fibroin water solution, room temperature preservation.
Extraction available iodine content is the medical povidone iodine of 0.45~0.55% concentration.And by fibroin albumen deionized water solution
It is respectively that 1:5 is deposited in two syringes with volume ratio with the medical Betagen Solution extracted.Two syringes are made
It is docked with double end female Luer, by quickly repeatedly mutually pushing away solution about one minute or so, formation 1ML blended liquid,.The blending
Liquid forms fibroin albumen-povidone iodine in-situ hydrogel by solidification in 2-8 hours.The hydrogel is placed in the syringe of side
It is interior, slowly hydrogel is taken out from syringe.Aseptically, hydrogel is placed in PBS to the sustained release for carrying out available iodine
The measurement of amount.
The release of the outer available iodine of water gel uses sodium thiosulfate titration.The hydrogel of certain volume is immersed
In the PBS of 2ML, 2ML new PBS is replaced to original sustained release liquid again every 24 hours, and in 1/2/3/4/5/6/7/8/
The content of available iodine in 9/10/11/12 day measurement sustained release liquid.The results show that early period, available iodine burst size was larger, but do not formed
Burst release, the detection of number of days also has burst size later.Illustrate the ability that the hydrogel has slow release available iodine, specific experiment knot
Fruit is as shown in Figure 5.
The degree that available iodine is discharged from hydrogel uses sodium thiosulfate titration.By certain volume
Hydrogel immerses in the PBS of 2ML, 2ML new PBS is replaced to original sustained release liquid again every 24 hours, and in 1/2/3/
The content of available iodine in 4/5/6/7/8/9/10/11/12 day measurement sustained release liquid.Have according in the povidone iodine in script raw material
The degree that the assay available iodine of effect iodine is discharged from hydrogel.Concrete outcome is referring to Fig. 6.
According to Figure 11 to 13, using the anti-microbial property of microdetermination hydrogel, staphylococcus aureus, big is chosen
Enterobacteria and pseudomonas aeruginosa.The results show that hydrogel is up to 90% or more to the bacteriostasis rate of three kinds of target bacterias, wherein right
The bacteriostasis rate of staphylococcus aureus is up to 99%.
Comparative example 1
Fibroin albumen freeze-dried powder is dissolved in deionized water, after fulling shake 5-10 minutes, mass volume ratio is made
40% silk fibroin water solution, room temperature preservation.
Extraction available iodine content is the medical povidone iodine of 0.45~0.55% concentration.And by fibroin albumen deionized water solution
It is respectively that 1:5 is deposited in two syringes with volume ratio with the medical Betagen Solution extracted.Two syringes are made
It is docked with double end female Luer, by quickly repeatedly mutually pushing away solution about one minute or so, formation 1ML blended liquid,.The blending
Liquid forms fibroin albumen-povidone iodine in-situ hydrogel by solidification in 2-8 hours.The hydrogel is placed in the syringe of side
It is interior, slowly hydrogel is taken out from syringe.Aseptically, hydrogel is placed in PBS to the sustained release for carrying out available iodine
The measurement of amount.
The release of the outer available iodine of water gel uses sodium thiosulfate titration.The hydrogel of certain volume is immersed
In the PBS of 2ML, 2ML new PBS is replaced to original sustained release liquid again every 24 hours, and in 1/2/3/4/5/6/7/8/
The content of available iodine in 9/10/11/12 day measurement sustained release liquid.The results show that early period, available iodine burst size was larger, but do not formed
Burst release, the detection of number of days also has burst size later.Illustrate the ability that the hydrogel has slow release available iodine, specific experiment knot
Fruit is as shown in Figure 7.
The degree that available iodine is discharged from hydrogel uses sodium thiosulfate titration.By certain volume
Hydrogel immerses in the PBS of 2ML, 2ML new PBS is replaced to original sustained release liquid again every 24 hours, and in 1/2/3/
The content of available iodine in 4/5/6/7/8/9/10/11/12 day measurement sustained release liquid.Have according in the povidone iodine in script raw material
The degree that the assay available iodine of effect iodine is discharged from hydrogel.Concrete outcome is referring to Fig. 8.
According to Figure 11 to 13, using the anti-microbial property of microdetermination hydrogel, staphylococcus aureus, big is chosen
Enterobacteria and pseudomonas aeruginosa.The results show that hydrogel is lower to the bacteriostasis rate of three kinds of target bacterias.In conjunction with Fig. 7, shown in 8,
The drop for discharging from hydrogel, and then leading to fungistatic effect can not be divided again seeing as the increase available iodine of fibroin albumen concentration
It is low.
Comparative example 2
Fibroin albumen freeze-dried powder is dissolved in deionized water, after fulling shake 5-10 minutes, mass volume ratio is made
50% silk fibroin water solution, room temperature preservation.
Extraction available iodine content is the medical povidone iodine of 0.45~0.55% concentration.And by fibroin albumen deionized water solution
It is respectively that 1:5 is deposited in two syringes with volume ratio with the medical Betagen Solution extracted.Two syringes are made
It is docked with double end female Luer, by quickly repeatedly mutually pushing away solution about one minute or so, formation 1ML blended liquid,.The blending
Liquid forms fibroin albumen-povidone iodine in-situ hydrogel by solidification in 2-8 hours.The hydrogel is placed in the syringe of side
It is interior, slowly hydrogel is taken out from syringe.Aseptically, hydrogel is placed in PBS to the sustained release for carrying out available iodine
The measurement of amount.
The release of the outer available iodine of water gel uses sodium thiosulfate titration.The hydrogel of certain volume is immersed
In the PBS of 2ML, 2ML new PBS is replaced to original sustained release liquid again every 24 hours, and in 1/2/3/4/5/6/7/8/
The content of available iodine in 9/10/11/12 day measurement sustained release liquid.The results show that early period, available iodine burst size was larger, but do not formed
Burst release, the detection of number of days also has burst size later.Illustrate the ability that the hydrogel has slow release available iodine, specific experiment knot
Fruit is as shown in Figure 9.
The degree that available iodine is discharged from hydrogel uses sodium thiosulfate titration.By certain volume
Hydrogel immerses in the PBS of 2ML, 2ML new PBS is replaced to original sustained release liquid again every 24 hours, and in 1/2/3/
The content of available iodine in 4/5/6/7/8/9/10/11/12 day measurement sustained release liquid.Have according in the povidone iodine in script raw material
The degree that the assay available iodine of effect iodine is discharged from hydrogel.Concrete outcome referring to Fig.1 0.
According to Figure 11 to 13, using the anti-microbial property of microdetermination hydrogel, staphylococcus aureus, big is chosen
Enterobacteria and pseudomonas aeruginosa.The results show that hydrogel is lower to the bacteriostasis rate of three kinds of target bacterias.In conjunction with Fig. 7, shown in 8,
The drop for discharging from hydrogel, and then leading to fungistatic effect can not be divided again seeing as the increase available iodine of fibroin albumen concentration
It is low.
Aseptically material is cut, in order to Electronic Speculum observation.First by hydrogel be put into freeze dryer into
Row freeze-drying, lyophilisation condition are -80 DEG C, 1.9Pa, and freeze-drying time is 48 hours.The sample of freeze-drying is subjected to metal spraying, scanning electron microscope is seen
It examines.Povidone iodine is evenly distributed in aquogel system in granular form as the result is shown, and hydrogel is porous structure.
Specific Electronic Speculum result referring to Fig.1 1.
The above, specific implementation case only of the invention, scope of protection of the present invention is not limited thereto, any ripe
Those skilled in the art are known in technical specification of the present invention, modifications of the present invention or replacement all should be in the present invention
Protection scope within.
Claims (6)
1. a kind of preparation method of original position fibroin albumen-povidone iodine composite hydrogel, which is characterized in that the described method includes:
Fibroin albumen freeze-dried powder is dissolved in deionized water, after fulling shake, fibroin albumen water of the concentration 5~30% is made
Solution；
A certain amount of medical povidone iodine is extracted with the volume ratio of silk fibroin water solution and Betagen Solution 1:3~1:5, and
Fibroin albumen deionized water solution is deposited in syringe respectively with the medical Betagen Solution extracted；
Two syringes are docked using double end female Luer, form blended liquid, the blended liquid by repeatedly mutually pushing away solution
Fibroin albumen-povidone iodine composite in-situ hydrogel is formed by solidification in 2-8 hours.
2. preparation method shown according to claim 1, which is characterized in that the Betagen Solution available iodine content is 0.45
~0.55%.
3. preparation method shown according to claim 1, which is characterized in that the silk fibroin powder of the freeze-drying is complete under room temperature
The fully dissolved time is 10~30 minutes.
4. preparation method shown according to claim 1, which is characterized in that Betagen Solution is inhaled respectively with silk fibroin protein solution
After entering two syringes, quickly mutually inject emitter 10~20 times.
5. preparation method shown according to claim 1, which is characterized in that the blended liquid solidifies to form the fibroin albumen water
During gel, the blended liquid being sufficiently mixed can be put into a container, can also be placed directly within the syringe of side
In, the empty syringe and connector for removing the other side inject or for smearing filling.
6. a kind of original position fibroin albumen-povidone iodine composite hydrogel, the original position fibroin albumen-povidone iodine composite hydrogel
Preparation method preparation according to claims 1 to 5.
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