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CN105816911B - A kind of reparation gel containing growth factor and preparation method thereof - Google Patents

A kind of reparation gel containing growth factor and preparation method thereof Download PDF

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Publication number
CN105816911B
CN105816911B CN201610375170.7A CN201610375170A CN105816911B CN 105816911 B CN105816911 B CN 105816911B CN 201610375170 A CN201610375170 A CN 201610375170A CN 105816911 B CN105816911 B CN 105816911B
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growth factor
gel
water
soluble polymer
cellulose derivative
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CN105816911A (en
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王海波
王中元
张慧芳
黄强
于志敏
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Hubei Bingbing Pharmaceutical Industry (Group) Co., Ltd.
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BINGBING PHARMACEUTICAL Co Ltd WUHAN
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L26/00Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
    • A61L26/0061Use of materials characterised by their function or physical properties
    • A61L26/0066Medicaments; Biocides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L26/00Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
    • A61L26/0009Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form containing macromolecular materials
    • A61L26/0014Chemical 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L26/00Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
    • A61L26/0009Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form containing macromolecular materials
    • A61L26/0023Polysaccharides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L26/00Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
    • A61L26/0061Use of materials characterised by their function or physical properties
    • A61L26/008Hydrogels or hydrocolloids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/404Biocides, antimicrobial agents, antiseptic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/412Tissue-regenerating or healing or proliferative agents
    • A61L2300/414Growth factors

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Materials Engineering (AREA)
  • Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Dispersion Chemistry (AREA)
  • Medicinal Preparation (AREA)

Abstract

The invention belongs to field of medicaments, specifically related to a kind of reparation gel containing growth factor and preparation method thereof, including 0.001~0.02% growth factor, 0.05~1% alkaline polysaccharide, 0.5~2% cellulose derivative water-soluble polymer, 0.05~2% natural plant polyose, the natural water-soluble copolymer of 0.01~1% exocellular polysaccharide class, 0.1~2% carbomer, 12~40% NMFs, 0.05~4%pH conditioning agents, 0.01 2% hyaluronic acid, 0.6~3% cutaneous permeable agent, 0.1~0.3% penetrating agent and balance deionized water.The present invention, which repairs gel, has an excellent fungistatic effect, good moisture pick-up properties, and it can significantly improve the cure rate of the surface of a wound and shorten the healing time of the surface of a wound, and be capable of the formation of prevention of scar.

Description

A kind of reparation gel containing growth factor and preparation method thereof
Technical field
The invention belongs to field of medicaments, and in particular to a kind of reparation gel containing growth factor and preparation method thereof.
Background technology
Skin is made up of epidermis, corium and hypodermis, and its function is to protect in-vivo tissue to be damaged from the external world;Carry out new Old metabolism such as absorbs, perspired, sebum secreted and row rush down waste;Skin can also adjust body temperature, impression pain, tactile, pressure, warm, cold etc. Stimulate, and have immunization.People in life inevitably by the different wound of various weights, ask its be wound, from Operation wound is often can hardly be avoided after right disaster and illness.When skin injury reaches to a certain degree, because fibroproliferative is anti- Should, skin ultrastructure will be come to an end with cicatrization.Various body surface scars can all destroy original skin integrity, damage and hold Looks, the injury of body and mind is brought to patient.It is always medical science neck that its appearance destruction caused how is treated while wound repair One of the important subject in domain.
The development of current new pattern compress and application, dermatoplasty, gene therapy, culture cell transplantation and artificial skin grafting dermepenthesis, The application of Porcine HGF and TCM Therapy all occur in that new technology.Traditional dressing can keep the drying of the surface of a wound well Property, but can not effectively prevent the surface of a wound from being infected, and easily be sticked together with planing surface, may cause during removal the surface of a wound again by Damage;New synthesis type dressing has good elasticity and gas permeability, but hygroscopicity is bad, may cause to form hydrops at the surface of a wound And cause the breeding of bacterium.There is certain repulsion immune response applied to clinical tissue engineering product, therapeutic effect is not good enough.
Based on the defect in traditional wound dressing performance, in recent years, the modern wound dressing of polytype is developed, its In wound dressing containing growth factor have become medical dressing field development new highlight.It not only overcomes traditional dressing performance Single shortcoming, and the addition of growth factor also makes dressing add wound healing, improve the work(of wound healing effect Effect.
Chinese patent application 201410438877.9 discloses a kind of wound repair gel containing hexagonal mesoporous silicon and its system Preparation Method, the composition of the invention includes:Hexagonal mesoporous silicon, basic fibroblast growth factor FGF-21, chitosan, surface are lived Property agent, cosurfactant, glycerin monostearate, carbomer, pH adjusting agent and deionized water.The present invention utilizes hexagonal mesoporous Silicon carrying active substance and active ingredient, can improve its stability, and reach slow release effect;Growth factor can stimulate cell to move The synthesis of dynamic, merisis and intercellular protein, promotes capillary of skin generation and tissue growth, is conducive to scar repairing; Chitosan is inhibited to various bacteria, also with good film forming, is conducive to wound healing and hemostasis;This is simultaneously Glycerin monostearate in system also acts as the effect of skin care.It is, using carbomer as thickener, to be gathered using shell in the invention Gel is repaired in the growth factor-loaded hexagonal mesoporous silicon formation of sugar parcel, the reparation Growth in Gel factor and glycan substrate it Between not exclusively run through, growth factor, which is difficult to ooze out, reaches that skin surface repairs skin, and repairing effect is good;Due to carbomer gel Viscosity it is larger, it is difficult to smear, use feeling is not good.
Therefore, the technical problem existed for above-mentioned prior art, needs a kind of repairing effect of proposition badly notable, it is easy to smear The reparation gel containing growth factor.
The content of the invention
In order to solve technical problem present in above-mentioned prior art, it is an object of the invention to provide one kind containing growth because Reparation gel of son and preparation method thereof, the reparation gel has excellent repairing effect and fungistatic effect, good hygroscopicity Can and it tend to smear out, it can significantly improve the cure rate of the surface of a wound and shorten the healing time of the surface of a wound, and be capable of prevention of scar Formed.
The invention provides a kind of reparation gel containing growth factor, include the component of following mass percent:0.001~ 0.02% growth factor, the growth factor is selected from recombinant human epidermal growth factor and/or recombination human basic fibroblast cell is given birth to The long factor;
0.05~1% alkaline polysaccharide, the alkaline polysaccharide is selected from chitosan and/or chitosan derivatives;
0.5~2% cellulose derivative water-soluble polymer, the cellulose derivative water-soluble polymer, which is selected from, to be modified One or more in nano micro crystal cellulose, sodium carboxymethylcellulose and hydroxyethyl cellulose;
0.05~2% natural plant polyose, the natural plant polyose is in konjac glucomannan, carragheen and algaroba glue It is one or more of;
The natural water-soluble copolymer of 0.01~1% exocellular polysaccharide class, the water-soluble polymerization of the exocellular polysaccharide class Thing is selected from xanthans or gellan gum;
0.1~2% carbomer;
12~40% NMFs, the NMF is selected from polyalcohols;
0.05~6%pH conditioning agents, the one kind or several of the pH adjusting agent in triethanolamine, citric acid and tartaric acid Kind;
0.6~6% cutaneous permeable agent, the cutaneous permeable agent is selected from Tween 80 and/or azone;
0.1~0.3% penetrating agent, the one kind or several of the penetrating agent in polyethylene glycol, polypropylene glycol and polyglycereol Kind;
0.01-2% hyaluronic acids;
40~70% deionized waters.
Preferably, the growth factor is by recombinant human epidermal growth factor and recombination human basic fibroblast growth factor By 1:0.5~1 weight is than composition.
Preferably, the growth factor is by recombinant human epidermal growth factor and recombination human basic fibroblast growth factor By 1:1 weight is than composition.
Preferably, the NMF is selected from glycerine.
Preferably, the cellulose derivative water-soluble polymer is by modified Nano microcrystalline cellulose and carboxymethyl cellulose Sodium presses 1:0.2~0.5 weight is than composition.
Preferably, the cellulose derivative water-soluble polymer is by modified Nano microcrystalline cellulose and carboxymethyl cellulose Sodium presses 1:0.5 weight is than composition.
Preferably, the natural water-soluble copolymer of the exocellular polysaccharide class presses 1 by xanthans and gellan gum:1~3 weight Than composition.
Preferably, the natural water-soluble copolymer of the exocellular polysaccharide class presses 1 by xanthans and gellan gum:1.5 weight Than composition.
Preferably, the pH adjusting agent is selected from triethanolamine.
Preferably, the alkaline polysaccharide is selected from carboxymethyl chitosan, the molecular weight of the carboxymethyl chitosan for 2~4 × 103, substitution value is 80~90%.
Preferably, the natural plant polyose is selected from algaroba glue.
Preferably, the cutaneous permeable agent is selected from Tween 80.
Preferably, the penetrating agent is selected from polyethylene glycol.
Correspondingly, present invention also offers the preparation method of the above-mentioned reparation gel containing growth factor, it includes following step Suddenly:
A) take 0.05~1% alkaline polysaccharide to be added in deionized water, be mixed evenly, obtain 0.5~1wt% alkalescence Polysaccharide solution, takes 0.5~2% cellulose derivative water-soluble polymer to be added in deionized water, is mixed evenly, obtains 0.1~1wt% cellulose derivative water-soluble polymer solution;Above two solution is well mixed, is swelled, alkalescence is obtained Polysaccharide/cellulose derivative water-soluble polymer support;
B 0.1~2% carbomer) is taken, is added to while stirring in deionized water, 12~24h is swelled, above-mentioned alkalescence is added Polysaccharide/cellulose derivative water-soluble polymer support, stirs 10~15min, continuously adds 0.05~2% natural plants many Sugar, the natural water-soluble copolymer of 0.01~1% exocellular polysaccharide class, 12~40% NMFs, 0.6~6% cutaneous permeable agent, 0.01-2% hyaluronic acids and 0.1~0.3% penetrating agent, stir 20~35min, add pH adjusting agent regulation pH be 6.0~ 7.0, obtain plural gel;
C) take 0.001~0.02% growth factor to be dissolved in deionized water and be configured to growth factor solution, growth factor is molten Liquid is added to above-mentioned steps B) gained plural gel in, be well mixed, be stored at room temperature 2~5h, produce.
Alkaline polysaccharide is 2~4 × 10 from molecular weight3, substitution value is 80~90% carboxymethyl chitosan, and it is water-soluble Height, with preferable antibiotic property, moisture absorbability and moisture retentivity, film forming and biocompatibility, but its antibiotic property and mechanical strength are still So fail to reach requirement.
Inventor has found to add cellulose derivative water-soluble polymer, is preferably added to modified Nano microcrystalline cellulose and is formed Carboxymethyl chitosan/cellulose derivative water-soluble polymer support, can be obviously improved carboxymethyl chitosan antibacterial ability and Mechanical strength.Trace it to its cause and may is that addition cellulose derivative water-soluble polymer can strengthen carboxymethyl chitosan gel With the interface compatibility of other matrix, and growth factor and carboxymethyl chitosan gel is set to form connect altogether anti-completely through getting up Bacterium gel, keeps wound to dry.The huge specific surface area of cellulose derivative water-soluble polymer can improve gel and wound Contact area so that antibacterial effect can be played preferably, and addition cellulose derivative water-soluble polymer can make water-setting The structure of glue formation is more fluffy, prevents hydrogel in the larger ice crystal of follow-up (- 15 DEG C) generations of freezing by bursting by freezing.
But because the addition of cellulose derivative water-soluble polymer causes the viscosity of gel rapidly to rise, spreading property Difference, adds carbomer, can neutralize the acidity of carboxymethyl chitosan, stretches its strand disperse and is formed in great swelling state Gel so that the hydrogel formed is homogeneous, it is easy to smear, no greasy feeling is good with skin and mucosa coupling effect.Three assists Same synergy, assigns the excellent anti-microbial property of gel, good spreading property.The addition of sodium carboxymethylcellulose causes gel in guarantor There is preferable hygroscopicity, it can adsorb the surface of a wound and suppurate while holding above-mentioned characteristic, it cooperates with cellulose derivative water-soluble poly Compound can stablize the drying for keeping the surface of a wound, improve repairing effect.
Hydrogel can further be improved by adding the natural water-soluble copolymer of natural plant polyose and exocellular polysaccharide class Sense of touch.Because the addition of above-mentioned high molecular polymer makes carbomer-carboxymethyl chitosan-cellulose derivative water-soluble polymer The viscosity increase of gel, causes moisture holding capacity to rise, the nutritional ingredient inside gel fails to be exuded to up to skin surface, therefore add Enter penetrating agent penetrating agent, be preferably added to polyethylene glycol, the growth factor of inside can be promoted successfully to be exuded to up to surface of a wound surface hair The effect of waving, so as to improve the healing time of the surface of a wound.And hyaluronic acid can promote absorption of the skin to growth factor, accelerate to repair The surface of a wound damages
NMF is added, the healing of wound face can be promoted, the formation of prevention of scar mitigates wound pain.Each component is mutual Synergistic, forming one has excellent wound repairing ability, an antibacterial ability, the reparation gel of good moisture pick-up properties, and its is easy In smearing, with control trauma surface infestation, accelerate the effect that wound healing, prevention of scar are formed.
Compared with prior art, reparation gel of the invention has the advantage that:
1) present invention can improve the cure rate of the surface of a wound by repairing gel made from the rational proportion of component, shorten the surface of a wound Healing time, while avoiding the drawback such as drug resistance, suprainfection, allergic reaction triggered using antibiotic.
2) good hygroscopicity of the present invention, can absorb the diffusate of the surface of a wound, it is allowed to which free gas permeates, while metabolite can lead to Gel discharge is crossed, and then improves the microenvironment of lesion, promotes the reparation of wound and the surface of a wound.
3) present invention has excellent biocidal property, with control trauma surface infestation, accelerates wound healing, prevention of scar shape Into effect.
Embodiment:
Below by way of the description of embodiment, the invention will be further described, but this is not the limit to the present invention System, those skilled in the art are according to the basic thought of the present invention, and various modifications may be made or improves, but without departing from this The basic thought of invention, within the scope of the present invention.
The embodiment of the present invention 1~7 of table 1 repairs gel component and its consumption (being calculated in mass percent)
Modified Nano microcrystalline cellulose of the present invention is made by following steps:
S1:In the nitration mixture aqueous solution that cellulosic material is added to organic acid and inorganic acid, cellulosic material is in mixed acid liquid In solid content be 0.05g/mL, in 60 DEG C react 12h, obtain nano micro crystal cellulose suspension;
S2:Above-mentioned suspension is moved into reactor, 5mol ammonium persulfates are added at 90 DEG C, 20min is stirred, weighs methyl Octadecyl acrylate is soluble in water, is instilled with the drop rate of per second 2 drops in reactor, reacts 6h at 60 DEG C, obtain methyl The crude product of octadecyl acrylate-nano micro crystal cellulose polymer, wherein octadecyl methacrylate and nanometer The mol ratio of microcrystalline cellulose is 1:2;
S3:At room temperature toward adding ethyl acetate in above-mentioned crude product, extractive reaction 36h, then rotary evaporation at 50 DEG C Instrument extracting 80min removes ethyl acetate, obtains modified Nano microcrystalline cellulose.
The embodiment of the present invention 1~7 repairs the preparation method of gel:
A) take alkaline polysaccharide to be added in deionized water, be mixed evenly, obtain alkaline polysaccharide solution, take cellulose to derive Thing water-soluble polymer is added in deionized water, is mixed evenly, and obtains cellulose derivative water-soluble polymer solution;Will Above two solution is well mixed, and is swelled, is obtained alkaline polysaccharide/cellulose derivative water-soluble polymer support;
B carbomer) is taken, is added to while stirring in deionized water, 24h is swelled, above-mentioned alkaline polysaccharide/cellulose is added and spreads out Biological water dissolubility polymer support, stirs 15min, continuously adds natural plant polyose, the water-soluble of exocellular polysaccharide class and gathers Compound, NMF, cutaneous permeable agent, hyaluronic acid and penetrating agent, stir 30min, and it is 7.0 to add pH adjusting agent regulation pH, Obtain plural gel;
C) take growth factor to be dissolved in deionized water and be configured to growth factor solution, growth factor solution is added to above-mentioned step Rapid B) in gained plural gel, it is well mixed, is stored at room temperature 3h, produces.
Comparative example 1, a kind of reparation gel containing growth factor
This comparative example 1 provide a kind of wound repair gel containing growth factor, its by following mass percent component Composition:0.01% growth factor, 1% carboxymethyl chitosan, 1% modified Nano microcrystalline cellulose, 1% sodium carboxymethylcellulose, 0.05% algaroba glue, 0.05% xanthans, 0.05% gellan gum, 1.5% carbomer, 10% glycerine, 2% triethanolamine, 1% Hyaluronic acid, 3% Tween 80,0.2% polyethylene glycol and excess water.
Preparation method refers to the preparation method of the embodiment of the present invention 4.
The difference of comparative example 1 and embodiment 4 is:Change modified Nano microcrystalline cellulose and sodium carboxymethylcellulose Proportioning, specially adds the consumption of sodium carboxymethylcellulose.
Stability test
Example 1~7 and the reparation gel of comparative example 1 are filling in undercoating sealing aluminum pipe, and sealing is placed in 2 DEG C~8 Tested at DEG C, gel is detected respectively at 0th month, 1 month, 3 months, 6 months, 9 months, 12 months, 18 the end of month Outward appearance, loading amount, pH value, biological activity (%) and total number of bacteria.Testing result is as follows:Embodiment 1~7 and the sample of comparative example 1 Outward appearance, pH, loading amount, total number of bacteria and the biological activity (%) of product meet the requirements within each sealed stage.
Bacteriostatic test
Subjects:The embodiment of the present invention 1~7 and the gained of comparative example 1 repair gel.
Test method:Gel is determined to bacteria to be tested (Escherichia coli, gold using AGP test paper disk method and colony counting method Staphylococcus aureus, Acinetobacter baumannii, pseudomonas aeruginosa, coagulase-negative staphylococci) fungistatic effect.Prepare Containing 108The bacteria suspension of/mL bacteria to be tested, is spread evenly across the nutrient agar planar surface of solidification, each μ of flat board 100 L;Gel is aseptically uniformly applied to a diameter of 0.3cm, on the filter paper that sterilizing, drying is crossed, the gel prepared is filtered The scraps of paper (using sterilizing filter paper piece as blank control) are affixed on the flat board of coated test strain, and scraps of paper repeat number is on each flat board 4, in 37 DEG C of incubated 24h, take contact surface culture to make gradient dilution, take the above-mentioned dilution bacteria suspensions of 1mL in flat board, use fine jade Fat pour plate, is mixed, it is to be solidified after be inverted in 37 DEG C of incubated 24h, calculate total plate count, the computational methods of total plate count With reference to GB 47892-2010, fungistatic effect is shown in Table 2.
Bacteriostasis rate (%)=(blank control total plate count-gel total plate count)/blank control total plate count * 100
The bacteriostatic test result of table 2
As seen from Table 2, the embodiment of the present invention 1~7 repair gel to the bacteriostasis rate of the normal infectious bacteria of the surface of a wound 90% with On, each group is optimal to the fungistatic effect of Escherichia coli and staphylococcus aureus;Above-mentioned 8 groups of fungistatic effect sorts from high to low For:The > comparative examples 1 of 7 > embodiments of embodiment 4 > embodiments, 6 > embodiments, 5 > embodiments, 2 > embodiments, 3 > embodiments 1, it is real 4 groups of bacteriostasis rate highests to bacteria to be tested of example are applied, its fungistatic effect is best.Comparative example 1 is fine due to changing modified Nano crystallite The proportioning of dimension element and sodium carboxymethylcellulose, the fungistatic effect that its gained repairs gel has compared with embodiment 4 significantly will be low, and contrast The fungistatic effect of embodiment 2 and embodiment 4 can be seen that, when modified Nano microcrystalline cellulose is pressed with sodium carboxymethylcellulose in formula 1:The fungistatic effect of gel can be significantly improved when 0.5 weight is than compounding, this is probably because the proportioning can farthest increase The contact area of big gel and the surface of a wound, so as to improve the fungistatic effect of gel;Comparative example 1 and embodiment 2 understand that modification is received Rice microcrystalline cellulose and sodium carboxymethylcellulose compounding and modified Nano microcrystalline cellulose, sodium carboxymethylcellulose and ethoxy are fine The plain three's compounding of dimension is compared, and the former can more improve the fungistatic effect of gel;Comparative example 2 is understood with embodiment 3, is used alone Algaroba glue is compared with by konjac glucomannan, algaroba glue compounding use, and the gelling performance formed is more preferable;Comparative example 4 and reality Apply example 7 to understand, polyethylene glycol is used alone as penetrating agent compared with by polyethylene glycol and polyglycereol compounding use, the former can carry The bacteriostasis of high gel, polyethylene glycol, which is used alone, as penetrating agent in this explanation can make nutritional ingredient inside gel more It hurry up, more effectively ooze out, play a role.
Summary experiment can show that the embodiment of the present invention 4 repairs gel prominent in terms of stability and fungistatic effect The performance gone out, therefore embodiment 4 is preferred embodiment.
Different carboxymethyl chitosans, cellulose derivative water-soluble polymer and carbomer are with comparison wound repair gel The influence of performance
This test example is control group with embodiment 4, there is provided 9 kinds of different carboxymethyl chitosans, cellulose derivatives are water-soluble Property polymer and carbomer proportioning reparation gel, be respectively labeled as 1. -9. group, investigate its stability to plural gel, The influence of sense organ and bacteriostasis property, with such as table 3.
The different carboxymethyl chitosans of table 3, cellulose derivative water-soluble polymer and carbomer proportioning
Note:Stability test, antibacterial test reference stability test and bacteriostatic test method of testing.
Stability, organoleptic properties and bacteriostasis property according to the reparation gel obtained by said ratio is detected, it is right As a result it is analyzed as follows:
Organoleptic properties analysis shows, each proportioning gained all transparent semi-solid of gel outward appearance, homogeneous exquisiteness has light Pool, is coated with refrigerant sense;The denseness of gel is reduced afterwards as the rise of carbomer addition first increases, and is added with carboxymethyl chitosan The increase of dosage and decrease, the change of cellulose derivative water-soluble polymer addition on the denseness influence of gel not Greatly, and denseness height is unfavorable for painting exhibition, compare each group, finally show that 1% carboxymethyl chitosan, 1% cellulose derivative are water-soluble Polymer and 1.5% carbomer compounding gained repair gel and have more preferable sensory effects;
Stability analysis shows that each proportioning gained gel is after hermetically storing 18 months, no layering and syneresis phenomenon, But mildew situation is shown, as the addition of carboxymethyl chitosan, carbomer and cellulose derivative water-soluble polymer is higher, Gel is less susceptible to mildew, and storage-stable is better.
Bacteriostasis property analysis shows, the fungistatic effect of gel is with cellulose derivative water-soluble polymer and carboxymethyl shell The increase of glycan addition and improve, the addition of carbomer influences little to the fungistatic effect of gel.
Therefore, comprehensive three indexs, draw with 1% cellulose derivative water-soluble polymer, 1.5% cellulose derivative Water-soluble polymer and 1.5% carbomer compounding gained, which repair gel, has more excellent bacteriostasis property, organoleptic properties and steady It is qualitative.
Clinical test
1st, data and method
1.1 general information:Jingzhou City of Hubei Province in May, 2009 is in May, 2012 burned patient 150, man 80, female 70,7~70 years old age, average age 35 ± 2 years old;It is divided into according to burn and scald reason:Boiling water burn 68, fire wound 82; It is divided into according to burn and scald degree:Deep II degree of burn and scald 90, III degree of burn and scald 60.
1.2 packets and medication
Packet:Above-mentioned II degree of depth burn and scald 90 patient is randomly divided into 5 groups, every group of 18 people, each group medication is as follows:
4 groups of embodiment:The outer reparation gel for putting the preparation of the embodiment of the present invention 4 on the skin;
5 groups of embodiment:The outer reparation gel for putting the preparation of the embodiment of the present invention 5 on the skin;
6 groups of embodiment:The outer reparation gel for putting the preparation of the embodiment of the present invention 6 on the skin;
7 groups of embodiment:The outer reparation gel for putting the preparation of the embodiment of the present invention 7 on the skin;
1 group of comparative example:Put reparation gel prepared by comparative example 1 of the present invention on the skin outside;
Above-mentioned III degree of burn and scald, 60 patients are divided into 5 groups, every group of 12 people, each group medication is as follows:
4 groups of embodiment:The outer reparation gel for putting the preparation of the embodiment of the present invention 4 on the skin;
5 groups of embodiment:The outer reparation gel for putting the preparation of the embodiment of the present invention 5 on the skin;
6 groups of embodiment:The outer reparation gel for putting the preparation of the embodiment of the present invention 6 on the skin;
7 groups of embodiment:The outer reparation gel for putting the preparation of the embodiment of the present invention 7 on the skin;
1 group of comparative example:Put reparation gel prepared by comparative example 1 of the present invention on the skin outside;
Medication:Under sterile working, by the surface of a wound routine disinfection of boiling hot burn, first with the Iodophor and physiology salt of low concentration Water simply cleans the surface of a wound, removes attachment and the elephant skin that come off, the high blister tap of tension force, residual epithelium is kept as far as possible, is cut Except coming off or downright bad epidermis, the thorough debridement of infective wound surface row applies to outside the surface of a wound or sprays corresponding decoction, every 3~4 hours of daytime 1 time, daily coating 3~4 times.After medication fully exposure the surface of a wound, can not cover, prevent that, into water, winter notes warming, each group according to Burn and scald area determines dosage, by can whole flap coverages be defined.
1.3 recovery from illness criterions of therapeutical effect:Swelling disappears after medication, and pain disappears, and the surface of a wound has epidermis without infection, subcrustal healing Growth, the surface of a wound is repaired or all repaired substantially.Recovery from illness number in 7d, 14d, 21d is recorded after medication, 14d cure rates, 14d is calculated Recovery from illness number/case total number of persons × 100% in cure rate=14d;When time needed for defining the complete epithelialization of the surface of a wound is healing Between, the healing time of each patient is recorded, and t inspections are carried out to healing time and is compared;Record the surface of a wound scar of burned patient Situation, records patient's number of cases of scar, calculates scar rate, patient's number of cases/case total number of persons of scar rate=scar × 100%;Applied statistics software is analyzed, with p<0.05 has significant difference, and result of the test is shown in Table 4.
1.4 result of the test.
The result of the test of table 4
As shown in Table 4, in deep II degree for the treatment of and III degree of burn and scald, the embodiment of the present invention 1~3 is repaired gel and achieved Excellent effect, particularly has significant progress in terms of improving 14d cure rates and shortening healing time;From present invention implementation Example 1~3 is repaired from the point of view of the scar rate of gel for treating burn and scald, with the exacerbation of burn and scald degree, deep II degree of present invention treatment with III degree of burn and scald scar rate is extremely low, it is clear that the present invention repairs gel staying after treatment burn and scald and expectation is achieved in scar problem Less than technique effect;And summary indices, it is found that the therapeutic effect of the embodiment of the present invention 4 is optimal.

Claims (6)

1. a kind of reparation gel containing growth factor, it is characterised in that be made up of the component of following mass percent:
0.001~0.02% growth factor, the growth factor be selected from recombinant human epidermal growth factor and/or recombination human basic into Fibroblast growth factor;
0.05~1% alkaline polysaccharide, the alkaline polysaccharide is selected from carboxymethyl chitosan, and the molecular weight of the carboxymethyl chitosan is 2~4 × 103, substitution value is 80~90%;
0.5~2% cellulose derivative water-soluble polymer, the cellulose derivative water-soluble polymer is micro- by modified Nano Crystalline cellulose and sodium carboxymethylcellulose press 1:0.2~0.5 weight is than composition;
0.05~2% natural plant polyose, the natural plant polyose is selected from algaroba glue;
The natural water-soluble copolymer of 0.01~1% exocellular polysaccharide class, the natural water-soluble copolymer of the exocellular polysaccharide class by Xanthans and gellan gum press 1:1~3 weight is than composition;
0.1~2% carbomer;
12~40% NMFs, the NMF is selected from polyalcohols;
0.05~6%pH conditioning agents, one or more of the pH adjusting agent in triethanolamine, citric acid and tartaric acid;
0.6~6% cutaneous permeable agent, the cutaneous permeable agent is selected from Tween 80 and/or azone;
0.1~0.3% penetrating agent, one or more of the penetrating agent in polyethylene glycol, polypropylene glycol and polyglycereol;
0.01~2% hyaluronic acid;
40~70% deionized waters.
2. the reparation gel as claimed in claim 1 containing growth factor, it is characterised in that the growth factor is by recombined human table Skin growth factor and recombination human basic fibroblast growth factor press 1:0.5~1 weight is than composition.
3. the reparation gel as claimed in claim 1 containing growth factor, it is characterised in that the NMF is selected from glycerine.
4. the reparation gel as claimed in claim 1 containing growth factor, it is characterised in that the pH adjusting agent is selected from three ethanol Amine.
5. the reparation gel as claimed in claim 1 containing growth factor, it is characterised in that the penetrating agent is selected from poly- second two Alcohol.
6. a kind of preparation method of the reparation gel containing growth factor, it is characterised in that comprise the following steps:
A) take 0.05~1% alkaline polysaccharide to be added in deionized water, be mixed evenly, obtain 0.5~1wt% alkaline polysaccharide Solution, takes 0.5~2% cellulose derivative water-soluble polymer to be added in deionized water, is mixed evenly, obtain 0.1~ 1wt% cellulose derivative water-soluble polymer solution;Above two solution is well mixed, is swelled, obtain alkaline polysaccharide/ Cellulose derivative water-soluble polymer support;
B) take 0.1~2% carbomer, be added to while stirring in deionized water, be swelled 12~24h, add above-mentioned alkaline polysaccharide/ Cellulose derivative water-soluble polymer support, stirs 10~15min, continuously adds 0.05~2% natural plant polyose, 0.01 Natural water-soluble copolymer, 12~40% NMFs, 0.6~6% cutaneous permeable agent, the 0.01-2% of~1% exocellular polysaccharide class Hyaluronic acid and 0.1~0.3% penetrating agent, stir 20~35min, and it is 6.0~7.0 to add pH adjusting agent regulation pH, must be answered Close gel;
C) take 0.001~0.02% growth factor to be dissolved in deionized water and be configured to growth factor solution, by growth factor solution plus Enter to above-mentioned steps B) gained plural gel in, be well mixed, be stored at room temperature 2~5h, produce.
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