CN108042845A - A kind of albumin based aquagel dressing and preparation method thereof - Google Patents
A kind of albumin based aquagel dressing and preparation method thereof Download PDFInfo
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- CN108042845A CN108042845A CN201810055504.1A CN201810055504A CN108042845A CN 108042845 A CN108042845 A CN 108042845A CN 201810055504 A CN201810055504 A CN 201810055504A CN 108042845 A CN108042845 A CN 108042845A
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- albumin
- functional group
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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
- A61L26/0028—Polypeptides; Proteins; Degradation products thereof
- A61L26/0047—Specific proteins or polypeptides not covered by groups A61L26/0033 - A61L26/0042
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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
- A61L26/0019—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form containing macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
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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
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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
- 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
- A61L2400/00—Materials characterised by their function or physical properties
- A61L2400/06—Flowable or injectable implant compositions
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Abstract
The present invention describes a kind of albumin based aquagel dressing and preparation method thereof.Albumin powder is dissolved in the buffer solution that pH scopes are 6.0 ~ 11.0；Hydrophilic polymer containing electrophilic functional group is dissolved in pure water；Albumin solution is mixed into post-crosslinking with the hydrophilic polymer containing electrophilic functional group and forms hydrogel.Gelation time is less than 20 minutes after two kinds of solution mixing, and tissue adhesion strength is more than 50kPa, and equilibrium moisture content is more than 90%.The albumin based aquagel dressing of the present invention has adjustable gelation time, can be prepared into injectable type wound dressing, and with good tissue adhesion strength, can form fitting skin and the aerogel dressing of wound shape.Aerogel dressing in the present invention has high-moisture-retention, can be that wound location maintains moist environment, have facilitation to wound repair.
Description
Technical field
The invention belongs to biomedicine, material technology, wound repair and medical instruments fields, and in particular to a kind of white egg
White based aquagel dressing, while the invention further relates to the preparation method and applications of the aerogel dressing.
Background technology
China has tens million of person-times because of contingency or operation cause skin injury every year, and with aging of population
Aggravation, the chronic wounds such as closely related pressure sore and ulcer also gradually increase with the elderly.Skin wound healing is a complexity
Biological process, comprising a series of biological event, mainly including inflammation, regeneration and reconstructed tissue.Moisten ring
Border be conducive to epithelial tissue it is newborn with collage synthesis so as to which acceleration of wound heals, therefore hydrogel material can be due to high-moisture-retention
The repairing environment that suitably moistens of surface of a wound maintenance, can effectively relieve pain, accelerating wound healing speed, be it is a kind of be suitable for it is various
The wound of type repairs dressing.
Hydrophilic polymer contains multiple hydrophilic radicals to be a series of（Such as hydroxyl, carboxyl, amido and polyethylene oxide chain
Section）Polymer, these polymer can dissolve under the action of hydrophilic radical in water or with good water absorbing properties.Parent
Aqueous polymer has preferable biocompatibility, has been widely used in biomedical sector.Such as artificial synthesized polyethylene glycols
Hydrogel（PEG）With good biocompatibility, and its properity can be modified and adjusted by chemical method
Section, to meet the needs of different situations.These excellent performances based on PEG, the PEG group water-setting built by a variety of crosslinking technologicals
Glue product has been successfully applied to clinic.
Albumin is the albumen for being found and being studied earliest, is enriched in body burden, especially pronounced in serum.White egg
There are multiple binding sites on white surface, with metal ion such as Cu2+, Zn2+And aliphatic acid, amino acid and drug etc. have very strong
Combination.Therefore the most important physiological action of albumin is exactly to combine these substances in blood and carry it to targeting machine
Body or tissue.Simultaneously because albumin can coupled ion, can adjust and maintain the pH of body and the osmotic pressure of blood plasma.It is many
Drug is sent to the in vivo disease location of people, so as to improve having for drug by research also using seralbumin as pharmaceutical carrier
Effect property.It has been reported that human serum albumins or bovine serum albumin(BSA) can be by inhibiting elastoser（One kind is in chronic inflammation
The factor of the high expression of disease wound）Activity promote the chronic wounds to heal（Advances in Experimental Medicine
and Biology, 2012, 733: 155-164.）For the patient of serious burn, exogenous supplement albumin can change
Kind local blood circulation, supplies local organization protein, adjusts osmotic pressure and eliminates granulation tissue oedema.
Chinese patent CN105521521A discloses a kind of lung's sealing medical gel and preparation method and application, mentions
Application human serum albumins and hydrophilic polymer fast reaction under certain condition containing electrophilic functional group are used for wound
Bonding, hemostasis, antiseep or the application in preventing adhesion, but the gelation time of this gel, at 3 ~ 150 seconds, plastic is too fast,
It is unfavorable for the Clinical practice as skin wound dressing.At present there are many Hydrogels Wound dressing, mainly include seaweed acids,
Carboxymethyl cellulose class and the aerogel dressing that is loaded with drug etc..Traditional dressing before comparison, water-setting of the present invention
Glue dressing has high-moisture and superior water-retaining property, and with excellent tissue adhesion strength.
The present invention is based under weak basic condition, the amino on albumin surface and the polyethylene glycol containing electrophilic functional group
Can gel be formed with reaction in-situ.Using under the conditions of different concentration and pH, the amino on albumin surface is to containing electrophilic official
The nucleophilic attack for the polyethylene glycol that can be rolled into a ball is different, so that whole system has adjustable gelation time, as skin trauma
Dressing operates needs to adapt to different clinical practices.
The content of the invention
It is a kind of with adjustable gelation time, high-moisture and excellent tissue adhesion strength present invention aims at providing
Albumin based aquagel dressing.
A kind of albumin based aquagel dressing, main component are albumin and the hydrophilic polymer containing electrophilic functional group
Object.
Albumin based aquagel dressing of the present invention, the source of albumin can be that people, ox, horse, sheep, mouse etc. are dynamic
The seralbumin and recombination human serum albumin of object are preferably human serum albumins.
Above-mentioned albumin based aquagel dressing, hydrophilic polymer main body can be polyethylene glycol, polyethylene glycol oxide, poly- second
Enol is preferably polyethylene glycol, and hydrophilic polymer molecules amount is 1000~100000, is preferably 2000-50000, more preferably
3000-20000。
Above-mentioned albumin based aquagel dressing, electrophilic functional group be selected from dimaleoyl imino (- Mal), propionic aldehyde base (-
ALD), succinimdyl carbonate base (- SC), succinimide acetate groups (- SCM), succinimidyl propionate base (-
SPA), succinimidyl succinate base (- SS), succinimidyl glutarate base and succinimide decanedioic acid base etc., preferably
Functional group be succinimidyl succinate base sealing end, the number of each electrophilic functional group of hydrophilic polymer molecules is at 2
More than.
It is a further object of the present invention to provide a kind of preparation methods of albumin based aquagel dressing.
The preparation method of albumin based aquagel dressing provided by the invention, comprises the following steps：（1）Configuring pH scopes is
6.0 ~ 11.0 buffer solution, can optionally phosphate buffer solution, borate buffer solution, histidine buffer solution, bicarbonate
The combination etc. of sodium-sodium carbonate buffer, Tris- hydrochloric acid buffer solutions, diethanol amine buffer solution or above-mentioned buffer solution；
（2）Albumin powder is added in the buffer solution for being 6.0 ~ 11.0 in pH scopes, is configured to the white egg that concentration is 5%-45% (w/v)
White solution；（3）It weighs the hydrophilic polymer containing electrophilic functional group to be dissolved in purified water, is configured to concentration as 2.5%-25%
(w/v) the hydrophilic polymer aqueous solution of electrophilic functional group is contained；（4）Hydrophilic polymer containing electrophilic functional group is water-soluble
Liquid is mixed to form gel with albumin solution, the body of hydrophilic polymer aqueous solution and albumin solution containing electrophilic functional group
Product is than being 30:70 to 70:30.
Following methods detection may be employed in hydrogel of the present invention.
Gelation time detects：Using the inverted method detection gelation time of test tube.By albumin solution with containing electrophilic function
The component solution of group is added in centrifuge tube, is put in 37 DEG C of thermostat water baths, using manual time-keeping, was tilted or was fallen every 5 seconds
Turn a centrifuge tube, the immobilising time is denoted as gelation time in centrifuge tube when solution.
Water content detects：This experiment is carried out using cylindric hydrogel sample.The height of each hydrogel sample is 10mm,
A diameter of 15mm.After hydrogel prepares, weigh example weight and be denoted as Wwet；It is re-weighed after sample is freeze-dried, is denoted as Wdry。
The water content of hydrogel sample can be calculated by the following formula：
Water content=(Wwet-Wdry) / Wwet ×100%
Sample after will be lyophilized impregnates 24 in phosphate buffer and as a child weighed again, is denoted as Wswell.
The equilibrium moisture content of hydrogel sample can be calculated by the following formula
Equilibrium moisture content=(Wswell-Wdry) / Wswell ×100%
Organize adhesion strength detection：This experiment uses standard（YY/T 0729.1-2009）It carries out.Fresh porcine skin is taken, is cut into
1cm × 15cm list structures are added dropwise after two kinds of solution are mixed afterwards on the skin corium of a piece of pigskin, in addition a piece of in covering
The skin corium of pigskin.Make hydrogel original position plastic, afterwards using the pressed bonded areas of 50g counterweights 1 minute, and measure bonded areas
Area.Afterwards by sample as the long axis direction that Impact direction is sample in the fixture of mechanics machine, is made, with 1mm/min
Speed be loaded onto destruction to sample, record load-deformation curve.
Another object of the present invention is to provide the application of above-mentioned albumin based aquagel dressing.
The Novel albumin based aquagel dressing of the present invention has adjustable gelation time, can be prepared into injectable type wound
Hinder dressing, and with good tissue adhesion strength, fitting skin and the aerogel dressing of wound shape can be formed.This hair
Aerogel dressing in bright and with high-moisture-retention, can be that wound location maintains moist environment, have to wound repair and promote
Into effect.
Description of the drawings
Fig. 1 is two kinds of hydrogel water content using the present invention and equilibrium moisture content.
Fig. 2 is two kinds of aquagel tissue adhesion strengths using the present invention.
Fig. 3 is using nude mice back wound shines before the Hydrogel In Treating of an example of the present invention, after treatment 7 days and 14 days
Piece.
Specific embodiment
Embodiment 1
The phosphate buffer solution that pH is 7.40 and 9.40 is prepared respectively, 1ml phosphate buffer solutions is taken to add in respectively afterwards white
0.2 gram of protein powder（20%, w/v）It is made to be dissolved into transparency liquid, is configured to the albumin phosphorus that pH is 7.40 and 9.40 respectively
Hydrochlorate buffer solution.The double amber imide succinic acid ester group polyethylene glycol 0.1g that molecular weight is 3500 is weighed, 1ml is dissolved in and goes
In ionized water, vortex makes its dissolving become transparence liquid.Afterwards respectively by 1ml pH be 7.40 and 9.40 albumin phosphoric acid
Salt buffer solution is mixed with isometric double amber imide succinic acid ester group polyglycol solution, and gelation time is respectively 18.7 points
Clock（When pH is 7.4）With 12 seconds（When pH is 9.4）.Two kinds of gels all have higher water content（As shown in Figure 1）.Tissue bonds
Detected intensities show that stress first increases up to maximum with strain, then is gradually reduced（As shown in Figure 2）.
Embodiment 2
The wound repair effect of the invention hydrogel is assessed using nude mice back chronic wounds model.Specific method is in nude mice
Back manufactures the surface of a wound of 1 diameter 1cm, and (20 mg kg-1 BW dilute 10 times, often to intravenous injection depomedrol delayed healings
Only 100 μ l).The hydrogel that pH in embodiment 1 is 7.4 is applied on wound.Using the dressing to chronic wounds carry out 7 days and
After treatment in 14 days, wound site has obtained apparent healing（As shown in Figure 3）.
Claims (6)
1. a kind of albumin based aquagel dressing, main component is albumin and the hydrophilic polymer containing electrophilic functional group.
2. albumin based aquagel dressing according to claim 1, it is characterised in that：The source of the albumin can be with
It is the seralbumin and recombination human serum albumin of the animals such as people, ox, horse, sheep, mouse, is preferably human serum albumins.
3. albumin based aquagel dressing according to claim 1, it is characterised in that：The hydrophilic polymer main body
Can be polyethylene glycol, polyethylene glycol oxide, polyvinyl alcohol, be preferably polyethylene glycol, hydrophilic polymer molecules amount for 1000~
100000, it is preferably 2000-50000, more preferable 3000-20000.
4. albumin based aquagel dressing according to claim 1, it is characterised in that：The electrophilic functional group is selected from horse
Carry out imide (- Mal), propionic aldehyde base (- ALD), succinimdyl carbonate base (- SC), succinimide acetate groups (-
SCM), succinimidyl propionate base (- SPA), succinimidyl succinate base (- SS), succinimidyl glutarate base and
Succinimide decanedioic acid base etc., preferred functional group block for succinimidyl succinate base, each hydrophilic polymer
The number of the electrophilic functional group of molecule is at 2 or more.
5. a kind of preparation method of albumin based aquagel dressing, comprises the following steps：（1）It is 6.0 ~ 11.0 to configure pH scopes
Buffer solution can optionally phosphate buffer solution, borate buffer solution, histidine buffer solution, sodium bicarbonate-carbonate delay
Rush combination of solution, Tris- hydrochloric acid buffer solutions, diethanol amine buffer solution or above-mentioned buffer solution etc.；（2）It is in pH scopes
Albumin powder is added in 6.0 ~ 11.0 buffer solution, is configured to the albumin solution that concentration is 5%-45% (w/v)；（3）Claim
The hydrophilic polymer containing electrophilic functional group is taken to be dissolved in purified water, it is 2.5%-25% (w/v) containing electrophilic to be configured to concentration
The hydrophilic polymer aqueous solution of functional group；（4）Hydrophilic polymer aqueous solution containing electrophilic functional group and albumin is molten
Liquid mixes, and the volume ratio of hydrophilic polymer aqueous solution and albumin solution containing electrophilic functional group is 30:70 to 70:30.
6. a kind of application of albumin based aquagel dressing in skin wound healing as described in claim 1 to 5.
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| CN201810055504.1A CN108042845A (en) | 2018-01-19 | 2018-01-19 | A kind of albumin based aquagel dressing and preparation method thereof |
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| CN201810055504.1A CN108042845A (en) | 2018-01-19 | 2018-01-19 | A kind of albumin based aquagel dressing and preparation method thereof |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111621038A (en) * | 2020-06-08 | 2020-09-04 | 中国科学院长春应用化学研究所 | Albumin hydrogel, and preparation method and application thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20110293692A1 (en) * | 2010-05-27 | 2011-12-01 | Steven Bennett | Hydrogel implants with varying degrees of crosslinking |
| CN105699199A (en) * | 2016-03-30 | 2016-06-22 | 杭州亚慧生物科技有限公司 | Bursting strength detection device of sealant for surgical operation |
| CN106769502A (en) * | 2016-12-02 | 2017-05-31 | 杭州亚慧生物科技有限公司 | A kind of surgical operation sealing agent BURSTING STRENGTH detection means |
-
2018
- 2018-01-19 CN CN201810055504.1A patent/CN108042845A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20110293692A1 (en) * | 2010-05-27 | 2011-12-01 | Steven Bennett | Hydrogel implants with varying degrees of crosslinking |
| CN105699199A (en) * | 2016-03-30 | 2016-06-22 | 杭州亚慧生物科技有限公司 | Bursting strength detection device of sealant for surgical operation |
| CN106769502A (en) * | 2016-12-02 | 2017-05-31 | 杭州亚慧生物科技有限公司 | A kind of surgical operation sealing agent BURSTING STRENGTH detection means |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111621038A (en) * | 2020-06-08 | 2020-09-04 | 中国科学院长春应用化学研究所 | Albumin hydrogel, and preparation method and application thereof |
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Application publication date: 20180518 |