CN106822989A - It is a kind of to promote sprayable gel of wound healing and preparation method thereof - Google Patents

It is a kind of to promote sprayable gel of wound healing and preparation method thereof Download PDF

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Publication number
CN106822989A
CN106822989A CN201710196946.3A CN201710196946A CN106822989A CN 106822989 A CN106822989 A CN 106822989A CN 201710196946 A CN201710196946 A CN 201710196946A CN 106822989 A CN106822989 A CN 106822989A
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wound healing
pah
preparation
modified guar
gel
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陈令浩
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Qingdao Chenda Biotechnology Co Ltd
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Qingdao Chenda Biotechnology Co Ltd
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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
    • A61L26/0023—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
    • A61L26/0014—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form containing macromolecular materials obtained by reactions only involving carbon-to-carbon unsaturated bonds
    • 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
    • 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
    • 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
    • A61L2300/23—Carbohydrates
    • A61L2300/232—Monosaccharides, disaccharides, polysaccharides, lipopolysaccharides
    • 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
    • A61L2300/412—Tissue-regenerating or healing or proliferative agents

Abstract

Promote sprayable gel of wound healing and preparation method thereof the invention discloses a kind of, the preparation method is included modified guar and PAH stirring reaction in calcium chloride water.The sprayable gel gel gel of promotion wound healing prepared by preparation method of the invention is safe and non-stimulating, with good biocompatibility, for treatment of wounds, good water imbibition is so as to fully absorb the diffusate of wound, it is swelling after water suction to be able to maintain that surface of a wound physiological is moistened, and when total mass fraction is 5~10%, the viscosity of gel shows the plasticity feature for increasing and reducing with shear rate, it is particularly suitable for spraying to use, also there is good biocidal property under the concentration, so as to from bacterium infection, so as to effectively facilitate the healing of wound.

Description

It is a kind of to promote sprayable gel of wound healing and preparation method thereof
Technical field
The present invention relates to the preparation field of functional gel agent, in particular it relates to a kind of promote the sprayable solidifying of wound healing Jelly and preparation method thereof.
Background technology
Skin is the maximum organ of people's bulk area, is the mechanical barrier of body and the external world, various ulcer, wound or burnt degree Defect of skin is one of clinical common illness, and these symptoms may cause a series of problems of body, such as bacterium infection, The excessively loss etc. of moisture and protein.Research shows that skin wound healing is a pathophysiological process for complexity, is generally comprised Inflammatory phase, proliferation period and reinvent the phase.In wound healing process, when particularly damaging serious, tissue continuous anoxic, necrosis, sense The factors such as dye can all cause that the agglutination of wound extends, and healing is difficult.
Sponge product, sponge product are used the dressing for being conventionally used to wound healing can be absorbed more while flap coverage Wound fluid, be easily caused wound drying, and easily with wound adhesion, cause secondary damage, be unfavorable for the healing of wound. Doctor G.D.Winter et al. research has confirmed that wound heals faster in moist environment.In addition, traditional dressing Dressing biocompatibility and degradation-type all extreme differences.
Hydrogel is the gel with water as decentralized medium, with cross-linked network, and can keep certain shape, typically Absorbable larger water.As a kind of moist dressing, a large amount of wound fluids can be absorbed, keep surface of a wound moistening, subtracted significantly Lack the frequency of more change dressings, reduce the secondary injury to wound.But existing aerogel dressing, such as shitosan class water , there is the defects such as relatively costly, complex process in gel.In addition, existing dressing including traditional dressing or hydrogel etc. not With the effect of preferable bactericidal.
It is very high to there is viscosity in the existing gel for wound, is generally applied on skin using fashion of extrusion.Then Smoothened by cotton swab or finger etc., in-convenience in use, while also result in the waste of gel and produce safe and healthy The problems such as.In addition, being also contemplated that the problem of its stability for the gel of wound.
Therefore, this area need badly a kind of good stability, with fungistatic effect, promote wound healing gel.
The content of the invention
In view of the existing dressing for wound also has drawbacks described above, the present invention provides a kind of sprayable gel And preparation method thereof, gel prepared by the method can effectively facilitate wound healing, with good biocidal property and stability, And can be administered by the way of spraying.
It was found by the inventors of the present invention that guar gum is oxidized modified, then with PAH under ultrasonication Scion grafting polymeric gel agent can be formed, gel stabilization, safe and non-stimulating, the suitable spraying of viscometric properties, while having good Good biocompatibility, for treatment of wounds, good water imbibition so as to fully absorb the diffusate of wound, water suction It is swelling afterwards to be able to maintain that surface of a wound physiological is moistened；The gel also has good biocidal property, so as to from bacterium infection.
To achieve these goals, the present invention provides a kind of preparation method of the sprayable gel for promoting wound healing, Wherein, the preparation method is included modified guar and PAH stirring reaction in calcium chloride water.
The preparation method of the sprayable gel of the promotion wound healing that the present invention is provided, can specifically include following step Suddenly：
1) guar gum is scattered in deionized water, is subsequently adding 30~45 DEG C of 4~8h of stirring reaction of sodium metaperiodate, reacted Dialysis obtains modified guar during liquid is transferred to the bag filter that molecular cut off is 4500；
2) by step 1) modified guar that obtains is added in calcium chloride water with PAH, and ultrasonically treated 10 ~30min, standing is promoted wound healing gel.
In the present invention, it is preferred in the case of, in step 1) in, the guar gum is 1 with the weight ratio of sodium metaperiodate:0.3 ~0.9；The oxidizability of the modified guar is 15~40%.In the case of further preferably, in step 1) in, the guar gum It is 1 with the weight ratio of sodium metaperiodate:0.5~0.7；The oxidizability of the modified guar is 20~30%.
The measure of oxidizability may be referred to the conventional method in this area in the present invention, and a certain amount of sodium iodide is dissolved in into pH= The mixed liquor of mass fraction 20% is made into 7 PBS.The amylodextrins of α 2 are dissolved in buffer solvent and prepare matter Amount fraction be 10% solution as indicator.Above-mentioned 2 kinds of solution is mixed in equal volume, and rapidly with modified guar react. There is oxidation-reduction reaction in the sodium metaperiodate not consumed in solution, the iodine for discharging occurs aobvious with starch indicator with sodium iodide Colour response and be in rufous.Record sodium metaperiodate consumption.Oxidizability (%)=808N/7m × 100%, wherein, N is periodic acid Sodium waste amount (mol), m is guar samples quality (g), and 808 is guar gum repeat unit molecular weight (g/mol), and the present invention makes Galactolipin and mannose ratio about 1 in guar gum repeat unit：1.5.
In the present invention, contain active carbonyl group in modified guar, scion grafting can be carried out with the amino in PAH, The extent of reaction scion grafting affects the property of product, it is preferable that in step 2) in, the modified guar and PAH Weight ratio is 1:0.01~0.05.The PAH is not particularly limited, in order that must react more smoothly, preferably The mean molecule quantity of the PAH of small-molecular-weight, such as PAH is 1000~3000.
Under the present invention, preferable case, in step 2) in, the ultrasonically treated supersonic frequency is 40~100KHz, is surpassed Acoustical power is 100~150W.
In step 2 of the invention) in, the mass fraction of calcium chloride water is preferably 2~3%, in step 2), it is described to change Property guar gum and PAH add solution after, total mass fraction be 5~10%.It is 5~10% to finally obtain mass fraction Gel.In terms of calcium chloride weight, the calcium chloride water is 0.5~2 with the weight ratio of modified guar:1.
The sprayable gel of promotion wound healing prepared by above-mentioned preparation method, the gel is safe and non-stimulating, has Good biocompatibility, for treatment of wounds, good water imbibition is inhaled so as to fully absorb the diffusate of wound After water it is swelling be able to maintain that surface of a wound physiological moisten, and total mass fraction be 5~10% when, intrinsic viscosity is 450 at room temperature Between~700cps, the viscosity of gel shows the plasticity feature for increasing and reducing with shear rate, and being particularly suitable for spraying makes With, also there is good biocidal property under the concentration, so that from bacterium infection, so as to effectively facilitate the healing of wound.
Specific embodiment
With reference to specific embodiment, the present invention is expanded on further.But these embodiments be only limitted to explanation the present invention without It is the further restriction to protection scope of the present invention.
Embodiment 1
1) guar gum 2g is scattered in 100ml deionized waters, is subsequently adding 35 DEG C of stirring reaction 6h of 1.2g sodium metaperiodates, Deionization dialysis obtains modified guar during reaction solution is transferred to the bag filter that molecular cut off is 4500；It is infrared to be displayed in 1725cm-1、2730cm-1、2820cm-1There is new absworption peak, the oxidizability for measuring modified guar is 24%.
2) by step 1) modified guar that obtains is added to mass fraction for 2% calcium chloride water with PAH In, the modified guar is 1 with the weight ratio of PAH:0.1, the modified guar and PAH (polyene After 2000) mean molecule quantity of propyl group amine to add solution, solution total mass fraction is 8%, ultrasonically treated 10~30min, institute Ultrasonically treated supersonic frequency is stated for 50kHz, standing is promoted wound healing gel A1.
Embodiment 2
1) guar gum 2g is scattered in 100ml deionized waters, is subsequently adding 30 DEG C of stirring reaction 6h of 1.4g sodium metaperiodates, Deionization dialysis obtains modified guar during reaction solution is transferred to the bag filter that molecular cut off is 4500；It is infrared to be displayed in 1725cm-1、2730cm-1、2820cm-1There is new absworption peak, the oxidizability for measuring modified guar is 28%.
2) by step 1) modified guar that obtains is added to mass fraction for 3% calcium chloride water with PAH In, the modified guar is 1 with the weight ratio of PAH:0.12, the modified guar and PAH (polyene After 3000) mean molecule quantity of propyl group amine to add solution, solution total mass fraction is 10%, ultrasonically treated 10~30min, institute Ultrasonically treated supersonic frequency is stated for 60kHz, standing is promoted wound healing gel A2.
Embodiment 3
1) guar gum 2g is scattered in 100ml deionized waters, is subsequently adding 45 DEG C of stirring reaction 5h of 1g sodium metaperiodates, instead Deionization dialysis obtains modified guar in answering liquid to be transferred to the bag filter that molecular cut off is 4500；It is infrared to be displayed in 1725cm-1、 2730cm-1、2821cm-1There is new absworption peak, the oxidizability for measuring modified guar is 20%.
2) by step 1) modified guar that obtains is added to mass fraction for 3% calcium chloride water with PAH In, the modified guar is 1 with the weight ratio of PAH:0.08, the modified guar and PAH (polyene After 2000) mean molecule quantity of propyl group amine to add solution, solution total mass fraction is 10%, ultrasonically treated 10~30min, institute Ultrasonically treated supersonic frequency is stated for 50kHz, standing is promoted wound healing gel A3.
Embodiment 4
1) guar gum 2g is scattered in 100ml deionized waters, is subsequently adding 30 DEG C of stirring reaction 5h of 1.8g sodium metaperiodates, Deionization dialysis obtains modified guar during reaction solution is transferred to the bag filter that molecular cut off is 4500；It is infrared to be displayed in 1725cm-1、2730cm-1、2820cm-1There is new absworption peak, the oxidizability for measuring modified guar is 38%.
2) by step 1) modified guar that obtains is added to mass fraction for 2% calcium chloride water with PAH In, the modified guar is 1 with the weight ratio of PAH:0.15, the modified guar and PAH (polyene After 2000) mean molecule quantity of propyl group amine to add solution, solution total mass fraction is 6%, ultrasonically treated 10~30min, institute Ultrasonically treated supersonic frequency is stated for 50kHz, standing is promoted wound healing gel A4.
Embodiment 5
1) guar gum 2g is scattered in 100ml deionized waters, is subsequently adding 35 DEG C of stirring reaction 6h of 0.6g sodium metaperiodates, Deionization dialysis obtains modified guar during reaction solution is transferred to the bag filter that molecular cut off is 4500；It is infrared to be displayed in 1724cm-1、2730cm-1、2821cm-1There is new absworption peak, the oxidizability for measuring modified guar is 13%.
2) by step 1) modified guar that obtains is added to mass fraction for 2% calcium chloride water with PAH In, the modified guar is 1 with the weight ratio of PAH:0.05, the modified guar and PAH (polyene After 3000) mean molecule quantity of propyl group amine to add solution, solution total mass fraction is 14%, ultrasonically treated 10~30min, institute Ultrasonically treated supersonic frequency is stated for 80kHz, standing is promoted wound healing gel A5.
Embodiment 6
1) guar gum 2g is scattered in 100ml deionized waters, is subsequently adding 35 DEG C of stirring reaction 5h of 2.2g sodium metaperiodates, Deionization dialysis obtains modified guar during reaction solution is transferred to the bag filter that molecular cut off is 4500；It is infrared to be displayed in 1725cm-1、2730cm-1、2820cm-1There is new absworption peak, the oxidizability for measuring modified guar is 55%.
2) by step 1) modified guar that obtains is added to mass fraction for 2% calcium chloride water with PAH In, the modified guar is 1 with the weight ratio of PAH:0.1, the modified guar and PAH (polyene After 2000) mean molecule quantity of propyl group amine to add solution, solution total mass fraction is 8%, ultrasonically treated 10~30min, institute Ultrasonically treated supersonic frequency is stated for 50kHz, standing is promoted wound healing gel A6.
Embodiment 7
1) guar gum 2g is scattered in 100ml deionized waters, is subsequently adding 35 DEG C of stirring reaction 6h of 1.2g sodium metaperiodates, Deionization dialysis obtains modified guar during reaction solution is transferred to the bag filter that molecular cut off is 4500；It is infrared to be displayed in 1725cm-1、2730cm-1、2820cm-1There is new absworption peak, the oxidizability for measuring modified guar is 25%.
2) by step 1) modified guar that obtains is added to mass fraction for 2% calcium chloride water with PAH In, the modified guar is 1 with the weight ratio of PAH:0.6, the modified guar and PAH (polyene After 2000) mean molecule quantity of propyl group amine to add solution, solution total mass fraction is 8%, ultrasonically treated 10~30min, institute Ultrasonically treated supersonic frequency is stated for 50kHz, standing is promoted wound healing gel A7.
Embodiment 8
1) guar gum 2g is scattered in 100ml deionized waters, is subsequently adding 30 DEG C of stirring reaction 5h of 1.2g sodium metaperiodates, Deionization dialysis obtains modified guar during reaction solution is transferred to the bag filter that molecular cut off is 4500；It is infrared to be displayed in 1725cm-1、2730cm-1、2820cm-1There is new absworption peak, the oxidizability for measuring modified guar is 24%.
2) by step 1) modified guar that obtains is added to mass fraction for 2% calcium chloride water with PAH In, the modified guar is 1 with the weight ratio of PAH:0.03, the modified guar and PAH (polyene After 2000) mean molecule quantity of propyl group amine to add solution, solution total mass fraction is 8%, ultrasonically treated 10~30min, institute Ultrasonically treated supersonic frequency is stated for 50kHz, standing is promoted wound healing gel A8.
Embodiment 9
1) guar gum 2g is scattered in 100ml deionized waters, is subsequently adding 30 DEG C of stirring reaction 5h of 1.2g sodium metaperiodates, Deionization dialysis obtains modified guar during reaction solution is transferred to the bag filter that molecular cut off is 4500；It is infrared to be displayed in 1725cm-1、2730cm-1、2820cm-1There is new absworption peak, the oxidizability for measuring modified guar is 24%.
2) by step 1) modified guar that obtains is added to mass fraction for 2% calcium chloride water with PAH In, the modified guar is 1 with the weight ratio of PAH:0.1, the modified guar and PAH (polyene After 2000) mean molecule quantity of propyl group amine to add solution, solution total mass fraction is 18%, ultrasonically treated 10~30min, institute Ultrasonically treated supersonic frequency is stated for 50kHz, standing is promoted wound healing gel A9.
Embodiment 10
1) guar gum 2g is scattered in 100ml deionized waters, is subsequently adding 30 DEG C of stirring reaction 5h of 1.2g sodium metaperiodates, Deionization dialysis obtains modified guar during reaction solution is transferred to the bag filter that molecular cut off is 4500；It is infrared to be displayed in 1725cm-1、2730cm-1、2820cm-1There is new absworption peak, the oxidizability for measuring modified guar is 24%.
2) by step 1) modified guar that obtains is added to mass fraction for 2% calcium chloride water with PAH In, the modified guar is 1 with the weight ratio of PAH:0.1, the modified guar and PAH (polyene After 2000) mean molecule quantity of propyl group amine to add solution, solution total mass fraction is 3%, ultrasonically treated 10~30min, institute Ultrasonically treated supersonic frequency is stated for 50kHz, standing is promoted wound healing gel A10.
Comparative example 1
1) guar gum 2g is scattered in 100ml deionized waters, is subsequently adding 35 DEG C of stirring reaction 7h of 1.2g sodium metaperiodates, Deionization dialysis obtains modified guar during reaction solution is transferred to the bag filter that molecular cut off is 4500；It is infrared to be displayed in 1725cm-1、2730cm-1、2820cm-1There is new absworption peak, the oxidizability for measuring modified guar is 25%.
2) by step 1) modified guar that obtains is added to mass fraction in 2% calcium chloride water, the total matter of solution Amount fraction is 8%, ultrasonically treated 10~30min, and the ultrasonically treated supersonic frequency is 50kHz, and standing obtains sticky mixing Thing D1.
Comparative example 2
Guar gum 2g and PAH are added to mass fraction in 2% calcium chloride water, guar gum and polyene The weight ratio of propyl group amine is 1:0.1, guar gum and PAH (mean molecule quantity of PAH is 2000) addition are molten After liquid, solution total mass fraction is 8%, ultrasonically treated 10~30min, and the ultrasonically treated supersonic frequency is 50kHz, is stood Obtain viscous mixture D2.
Comparative example 3
Guar gum 2g and PAH are added to mass fraction in 2% calcium chloride water, the modified Guar Glue is 1 with the weight ratio of PAH:0.1, the modified guar and the PAH (mean molecule of PAH After measuring 2000) to add solution, solution total mass fraction is 8%, and mechanical agitation mixes 2 hours, and standing obtains viscous mixture D3。
Test case 1
According to State Food and Drug Administration《Chemical induced irritation, anaphylaxis and hemolytic investigative technique are instructed Principle》(March 2005) is tested to the excitant and anaphylaxis of A1-A8 and D1, D2.
1) skin irritation test
Healthy new zealand rabbit 44, is divided into 11 groups, and rabbit age 6-8 month, 2.5 ± 0.2Kg of average weight removed animal backbone Both sides by hair, area about 100cm2, Continuous Observation 24h hours, see whether skin whether there is the phenomenons such as red and swollen, damage.
Damaged skin is tested：After determining above-mentioned epilating area skin situation without exception, every group of new zealand rabbit selects two at random, With warm water cleaning, iodophor disinfection, with aseptic syringe needle stroke " # " word to oozing of blood breakage white rabbit skin.About 0.5ml embodiments 1- is taken respectively A1-A8 and D1-D3 correspondence coating damaged skin in 8.Erasing tested material is gone with warm water after treatment 24h, phenomenon is observed and is simultaneously remembered Record, then repeats to smear identical medicament or auxiliary material, long run test and observation 7 days.1h, 4h, 48h and 72h after last coating, daily Observe and record the change and body performance of animal, such as breathing, central nervous system, four limbs movable and other poisoning manifestations and Change of body weight, skin, hair, eyes and mucous membrane etc..Test result is as shown in table 1.
Test result standard is：Erythema：Without erythema 0；Slight erythema (visible reluctantly) 1；Moderate erythema (clearly visible) 2； Severe erythema 3；Aubergine erythema forms 4 to slight eschar；Oedema：Without oedema 0；Mild edema (visible reluctantly) 1；Intermediate edema (substantially protuberance) 2；Severe edema's (cutaneous protuberance 1mm, profile understands) 3；Severe edema (more than cutaneous protuberance 1mm simultaneously has expansion) 4。
Table 1
Erythema Oedema Evaluate
A1 0 0 It is nonirritant
A2 0 0 It is nonirritant
A3 0 0 It is nonirritant
A4 0.5 0.25 Slight stimulation
A5 0.5 0 Slight stimulation
A6 1 1 Slight stimulation
A7 2 2 Moderate excitant
A8 0 0.25 Slight stimulation
D1 0 0 It is nonirritant
D2 2 2 Moderate excitant
D3 2 3 Strong and stimulating
2) skin allergy test
Select healthy guinea pig 110, male and female half and half, body weight 240-280g.Back both sides are removed by hair, face with clipper before experiment Product about 10cm2, observed after 24h and determine not damaged.Cavy stochastic averagina after treatment is divided into ten groups.
Process of the test：A1-A8, D1-D3 agent in embodiment 1-8 is taken into 1ml respectively uniformly to embrocate at the place of the 1st to 8 group On the skin surface of reason, about 2 × 2cm2.Continuously embrocate daily, continuous 7 days, and observe allergic situation.
Result of the test：1-6 groups and the 8th group, the 9th group (D1) each 10 guinea pig skins do not occur exception, and the 7th group equal Mild edema and visible erythema are occurred in that, is slight sensitization；And the 10th group (D2) and the 11st group (D3) occurs in that moderate or weight Degree erythema and Mild edema, are moderate sensitization.
Gel of the invention is can be seen that to wound skin safe from above-mentioned skin irritation and skin allergy test It is nonirritant and without sensitization, with good biocompatibility.
Test case 2
This test case is used to test the swelling behavior of gel A1-A10 and D1-D3 of the invention.
The method of testing of swelling behavior：Take A1-A10 and D1-D3 (about 2cm × 2cm), precise weight m0, then It is rapid to be soaked in deionized water 50ml to no longer absorbing water, it is rapid to weigh weight m with filter paper adsorption surface moisture1, it is swelling Rate=(m1-m0)/m0× 100%.Concrete outcome test result is as shown in table 2.
Table 2
A1 A2 A3 A4 A5 A6 A7 A8 A9 A10 D1 D2 D3
Swelling ratio (%) 1244 1210 1139 1162 947 982 1164 964 1276 920 811 697 702
From table 2 it can be seen that gel prepared by the method for the present invention has good water absorption and swelling, wound can be absorbed Mouth sepage, for the healing of wound provides good environment.
Test case 3
This test case is used to illustrate the biocidal property of gel of the invention.
Entered using ETEC (ATCC25922) and staphylococcus aureus (ATCC29213) in this test case Row test, the agar nutrient medium that culture medium is.The preparation method of culture medium：Take peptone 10g, beef extract 3g, sodium chloride 5g is dissolved in 1000ml distilled water, add 2ml mass fractions be 15% NaOH so that pH between 7.2~7.4, so 15~20g of agar is added afterwards, and heating is boiled, and dissolves agar, is then divided in erlenmeyer flask, 121 DEG C of 15 points of autoclavings Clock.
Specific method of testing：The bacteriostasis property of A1-A10 and D1-D3 is determined with Beating holes method, it is specifically, 2ml is dilute The suspension (10 released8Cfu/ml) it is added in the liquid culture medium of (50 DEG C) 200ml in water bath condition, and is well mixed, will 20ml is above-mentioned to be mixed with the media transfer of bacterium suspension (clump count is 10 to its solidification is made in culture dish6-107cfu/ml).With beating Hole device gets 3 holes on flat board, is evenly distributed, and away from side 1.5cm, is chosen agar block with sterilizing toothpick, flame back cover.Each 70 μ g testing samples are injected in hole, and culture 24 hours is carried out in 37 DEG C.Measure inhibition zone result as shown in table 3.
Table 3
From table 3 it can be seen that gel of the invention has very outstanding biocidal property, ensure wound from bacterium sense Dye.
Test case 4
This test case is used to illustrate influence of the gel of the invention for wound healing.
SD rats (120~150g, Shanghai Jia Ke bio tech ltd) 130 is chosen, is divided into ten groups.Specific experiment Method is：The 1cm by SD rat back backbones both sides, the circular incision line of one a diameter of 1cm of each mark, through iodophor disinfection skin After skin, prolong mark line with scissors and wipe out full thickness skin to deep fascia, form two circular wound faces.A1-A10 is applied respectively in left side And D1-D3 (each 200 μ g), right side only gauze covering wrapping.Every group each ten, Continuous Observation, and record wound area.As a result As shown in table 4.
Table 4
Test case 5
This test case carries out viscosimetric analysis using Brookfield LVT viscosimeters under different rotating speeds, and test temperature is 20 ℃.Result is as shown in table 5.
Table 5
Test case 6
Stability test：
Sample is placed in 40 DEG C ± 2 DEG C, is stored 6 months under conditions of relative temperature 75% ± 5%, and check afterwards in every month Its physical stability.Tested using hand sprayer, compressed air pressure control exists in 0.4Mpa, the control of gel flow 0.5ml/s.Wherein, A1-A6 and A10 can be pumped out in six months from hand sprayer, and gel is in stable condition, without substantially change Change.A7, A8 can not be pumped out from four month, and gel has a little clustering phenomena.A9 and D1 can not be pumped out from three month.D2、D3 Viscosity is excessive can not to be pumped out.
To sum up, the invention provides a kind of preparation method of the sprayable gel of promotion wound healing, prepared by the method Gel gel it is safe and non-stimulating, with good biocompatibility, for treatment of wounds, good water imbibition causes it The diffusate of wound can be fully absorbed, it is swelling after water suction to be able to maintain that surface of a wound physiological is moistened, and total mass fraction is 5 When~10%, between 450~700cps, the viscosity of gel shows to increase and drop with shear rate intrinsic viscosity at room temperature Low plasticity feature, is particularly suitable for spraying and uses, while the gel under the concentration also has good biocidal property, so that from Bacterium infection, so as to effectively facilitate the healing of wound.
The preferred embodiment of the present invention described in detail above, but, the present invention is not limited in above-mentioned implementation method Detail, in range of the technology design of the invention, various simple variants can be carried out to technical scheme, this A little simple variants belong to protection scope of the present invention.
It is further to note that each particular technique feature described in above-mentioned specific embodiment, in not lance In the case of shield, can be combined by any suitable means, in order to avoid unnecessary repetition, the present invention to it is various can The combination of energy is no longer separately illustrated.Additionally, any group can also be carried out between a variety of implementation methods of the invention Close, as long as it is without prejudice to thought of the invention, it should equally be considered as content disclosed in this invention.

Claims (9)

1. it is a kind of promote wound healing sprayable gel preparation method, it is characterised in that the preparation method include will change Property guar gum and PAH stirring reaction in calcium chloride water.
2. it is according to claim 1 promote wound healing sprayable gel preparation method, it is characterised in that the system Preparation Method specifically includes following steps：
1) guar gum is scattered in deionized water, is subsequently adding 30~45 DEG C of 4~8h of stirring reaction of sodium metaperiodate, reaction solution turns Dialysis obtains modified guar in entering the bag filter that molecular cut off is 4500；
2) by step 1) modified guar that obtains is added in calcium chloride water with PAH, ultrasonically treated 10~ 30min, standing is promoted wound healing gel.
3. it is according to claim 2 promote wound healing sprayable gel preparation method, it is characterised in that in step It is rapid 1) in, the weight ratio of the guar gum and sodium metaperiodate is 1:0.3~0.9；The oxidizability of the modified guar be 15~ 40%.
4. it is according to claim 3 promote wound healing sprayable gel preparation method, it is characterised in that in step It is rapid 1) in, the weight ratio of the guar gum and sodium metaperiodate is 1:0.5~0.7；The oxidizability of the modified guar be 20~ 30%.
5. it is according to claim 2 promote wound healing sprayable gel preparation method, it is characterised in that in step It is rapid 2) in, the weight ratio of the modified guar and PAH is 1:0.05~0.15.
6. it is according to claim 1 and 2 promote wound healing sprayable gel preparation method, it is characterised in that The mean molecule quantity of the PAH is 1000~3000.
7. it is according to claim 2 promote wound healing sprayable gel preparation method, it is characterised in that in step It is rapid 2) in, the ultrasonically treated supersonic frequency be 40~100kHz.
8. it is according to claim 2 promote wound healing sprayable gel preparation method, it is characterised in that in step It is rapid 2), after the modified guar and PAH add solution, total mass fraction is 5~10%.
9. prepared by the preparation method of the sprayable gel of the promotion wound healing according to claim 1-8 any one Promote the sprayable gel of wound healing.
CN201710196946.3A 2017-03-29 2017-03-29 It is a kind of to promote sprayable gel of wound healing and preparation method thereof Pending CN106822989A (en)

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101209354A (en) * 2007-12-25 2008-07-02 青岛博益特生物材料有限公司 Medical blood-stopping healing agent for wound-surface and using thereof
CN103910894A (en) * 2014-03-28 2014-07-09 西安交通大学 Preparation method of injectable natural polysaccharide self-healing hydrogel
CN104479150A (en) * 2014-10-29 2015-04-01 上海大学 Preparation method of multiple cross-linked polysaccharide injectable hydrogel
CN105833344A (en) * 2016-04-26 2016-08-10 青岛慧生惠众生物科技有限公司 Application of injectable hydrogel in preparing intraocular filling materials

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101209354A (en) * 2007-12-25 2008-07-02 青岛博益特生物材料有限公司 Medical blood-stopping healing agent for wound-surface and using thereof
CN103910894A (en) * 2014-03-28 2014-07-09 西安交通大学 Preparation method of injectable natural polysaccharide self-healing hydrogel
CN104479150A (en) * 2014-10-29 2015-04-01 上海大学 Preparation method of multiple cross-linked polysaccharide injectable hydrogel
CN105833344A (en) * 2016-04-26 2016-08-10 青岛慧生惠众生物科技有限公司 Application of injectable hydrogel in preparing intraocular filling materials

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