CN105801881A - Hyaluronic acid silica gel and preparation method thereof - Google Patents

Hyaluronic acid silica gel and preparation method thereof Download PDF

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Publication number
CN105801881A
CN105801881A CN201610214952.2A CN201610214952A CN105801881A CN 105801881 A CN105801881 A CN 105801881A CN 201610214952 A CN201610214952 A CN 201610214952A CN 105801881 A CN105801881 A CN 105801881A
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molecular weight
hyaluronate sodium
hyaluronic acid
weight ranges
sodium
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CN105801881B (en
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丁利营
王倩
丁军
李俊明
李红艳
王艳
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Tianjin Cachet Technology Co ltd
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Tianjin Jiashitang Medical Technology Co ltd
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    • CCHEMISTRY; METALLURGY
    • C08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08JWORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J3/00Processes of treating or compounding macromolecular substances
    • C08J3/02Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques
    • C08J3/03Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques in aqueous media
    • C08J3/075Macromolecular gels
    • CCHEMISTRY; METALLURGY
    • C08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08LCOMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L83/00Compositions of macromolecular compounds obtained by reactions forming in the main chain of the macromolecule a linkage containing silicon with or without sulfur, nitrogen, oxygen or carbon only; Compositions of derivatives of such polymers
    • C08L83/04Polysiloxanes
    • CCHEMISTRY; METALLURGY
    • C08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08JWORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J2383/00Characterised by the use of macromolecular compounds obtained by reactions forming in the main chain of the macromolecule a linkage containing silicon with or without sulfur, nitrogen, oxygen, or carbon only; Derivatives of such polymers
    • C08J2383/04Polysiloxanes
    • CCHEMISTRY; METALLURGY
    • C08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08JWORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J2405/00Characterised by the use of polysaccharides or of their derivatives not provided for in groups C08J2401/00 or C08J2403/00
    • C08J2405/08Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof
    • CCHEMISTRY; METALLURGY
    • C08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08LCOMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L2205/00Polymer mixtures characterised by other features
    • C08L2205/02Polymer mixtures characterised by other features containing two or more polymers of the same C08L -group
    • C08L2205/025Polymer mixtures characterised by other features containing two or more polymers of the same C08L -group containing two or more polymers of the same hierarchy C08L, and differing only in parameters such as density, comonomer content, molecular weight, structure
    • CCHEMISTRY; METALLURGY
    • C08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08LCOMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L2205/00Polymer mixtures characterised by other features
    • C08L2205/03Polymer mixtures characterised by other features containing three or more polymers in a blend

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Medicinal Chemistry (AREA)
  • Polymers & Plastics (AREA)
  • Organic Chemistry (AREA)
  • Dispersion Chemistry (AREA)
  • Cosmetics (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The invention discloses a hyaluronic acid silica gel and a preparation method thereof, wherein the hyaluronic acid silica gel is prepared from the following components in parts by mass: 10 to 50 percent of polydimethylsiloxane, 1 to 10 percent of emulsifier, 1 to 20 percent of glycerin, 0.01 to 10 percent of sodium hyaluronate and 28.99 to 69 percent of purified water. The hyaluronic acid silica gel provided by the invention can effectively inhibit excessive proliferation of fibroblasts, and simultaneously provides a wet environment for scars, so that the formation of scars is inhibited. The effect of repairing scars is remarkable. Meanwhile, the hyaluronic acid silica gel provided by the invention is simple in preparation method and low in production cost.

Description

A kind of hyaluronic acid Silica hydrogel and preparation method
Technical field
The present invention relates to a kind of biomedicine field, relate generally to a kind of hyaluronic acid Silica hydrogel group that cicatrix is had repair Compound and preparation thereof.
Technical background
Cicatrix is that the reason such as physics, biochemistry causes human body skin soft tissue major injury the most normally not repair, Turning by fibrous tissue replacement, staying and affecting function affects again the local symptom of outward appearance.Cicatrix growth exceedes certain limit, just Various complication can occur, the destruction of such as profile and functional activity obstacle etc., bring the huge human body painful and spiritual to patient Misery, the cicatrix especially burnt, scald, leave over after severe trauma.Several years of scar hyperplasia phase almost allow patient's hardship not May say.The atrophy phase then makes again patient changed beyond recognition, dysfunction, causes the great body of patient, heart double combination obstacle.Along with The progress of modern society, likes to be beautiful and not only represents a kind of right, also illustrates that a kind of respect to oneself, and cicatrix is drainer for plastic surgery One of modal problem in outpatient service, except the impact of outward appearance, in fact has many cicatrixes to have and painful scratches where it itches, aches Pain and dry and cracked, produces scar contracture if unfortunate, more can affect that extremities joint is movable or the normal function of face, these scars further The treatment of trace non-positive especially can not.
Existing market is the Silica hydrogel scar plaster or Silica hydrogel made with single polysiloxanes mostly, but this series products is to cicatrix Repair simply passively locks water, does not have the moisture-keeping functions that actively absorbs water, and cicatrix repairing effect is not ideal enough.
Summary of the invention
It is an object of the invention to overcome the deficiencies in the prior art, it is provided that a kind of hyaluronic acid Silica hydrogel that can effectively remove scar.
Second object of the present invention is to provide the preparation method of a kind of preparation technology simple hyaluronic acid Silica hydrogel.
Technical scheme is summarized as follows:
A kind of hyaluronic acid Silica hydrogel, is made up of following component by quality: polydimethylsiloxane 10%-50%, emulsifying agent 1%-10%, Glycerol 1%-20%, hyaluronate sodium 0.01%-10% and purified water 28.99%-69%.
Described compositions includes following composition by mass percentage: polydimethylsiloxane 30%, emulsifying agent 4%, glycerol 10%, Hyaluronate sodium 0.3% and purified water 55.7%.
Described hyaluronate sodium is 1:(1~4 by mass ratio): the molecular weight ranges of (1~20) is 1000000~2000000 Macromolecule hyaluronate sodium, the Middle molecule hyaluronate sodium of molecular weight ranges 100000~400000 and molecular weight ranges exist The micromolecule hyaluronic acid sodium composition of 5000~10000.
Described hyaluronate sodium by the molecular weight ranges that mass ratio is 1:4:10 1400000~1600000 macromolecule transparent Matter acid sodium, the Middle molecule hyaluronate sodium of molecular weight ranges 200000~300000 and molecular weight ranges 7000~8000 little Numerator sodium hyaluronate forms.
Described emulsifying agent is octyldimethyl siloxanes ethyoxyl glucoside, PEG-9 polydimethylsiloxanes ethyl poly dimethyl silicon Oxygen alkane, lauryl KF-6028 and polyglycereol-3 disiloxane polydimethylsiloxane In one.
The preparation method of a kind of hyaluronic acid Silica hydrogel, comprises the steps:
1) weigh raw material by mass percentage: polydimethylsiloxane 10%-50%, emulsifying agent 1%-10%, glycerol 1%-20%, Hyaluronate sodium 0.01%-10% and purified water 10%-87.99%;
2) use vacuum homogeneous emulsifying machine, polydimethylsiloxane and emulsifying agent be placed in the oil phase tank of vacuum homogeneous emulsifying machine, Low whipping speed is heated to 80 90 DEG C under conditions of being 10-20 rev/min, keep 10-20 minute at 80 90 DEG C, obtain oil phase;
3) hyaluronate sodium, purified water and glycerol are put in the aqueous phase tank of described vacuum homogeneous emulsifying machine, under agitation, heating To 80-90 DEG C, keep 10-20 minute at 80 90 DEG C, obtain aqueous phase;
4) by oil phase and aqueous phase homogenizing 500-800 second under vacuum;
5) it is cooled to room temperature, obtains a kind of hyaluronic acid Silica hydrogel.
Described step (1) is: weigh raw material by mass percentage: polydimethylsiloxane 30%, emulsifying agent 4%, glycerol 10%, Hyaluronate sodium 0.3% and purified water 55.7%.
Described hyaluronate sodium is 1:(1~4 by mass ratio): the molecular weight ranges of (1~20) is 1000000~2000000 Macromolecule hyaluronate sodium, the Middle molecule hyaluronate sodium of molecular weight ranges 100000~400000 and molecular weight ranges exist The micromolecule hyaluronic acid sodium composition of 5000~10000.
Described hyaluronate sodium by the molecular weight ranges that mass ratio is 1:4:10 1400000~1600000 macromolecule transparent Matter acid sodium, the Middle molecule hyaluronate sodium of molecular weight ranges 200000~300000 and molecular weight ranges 7000~8000 little Numerator sodium hyaluronate forms.
Described emulsifying agent is octyldimethyl siloxanes ethyoxyl glucoside, PEG-9 polydimethylsiloxanes ethyl poly dimethyl silicon Oxygen alkane, lauryl KF-6028 and polyglycereol-3 disiloxane polydimethylsiloxane In one.
A kind of hyaluronic acid Silica hydrogel of the present invention, it is possible to effectively suppression fibroblast hyper-proliferative, provides moist for cicatrix simultaneously Environment, thus suppress the formation of cicatrix.The effect repairing cicatrix is notable.Meanwhile, prepared by the hyaluronic acid Silica hydrogel of this present invention Method is simple, and production cost is relatively low.
Detailed description of the invention
Below by specific embodiment, the present invention is further illustrated.
Embodiment 1
A kind of hyaluronic acid Silica hydrogel, is made up of following component by quality: polydimethylsiloxane 10%, PEG-9 poly dimethyl silicon Oxygen ethyl polydimethylsiloxane (emulsifying agent) 10%, glycerol 1%, hyaluronate sodium 10% and purified water 69%.
The hyaluronate sodium of the present embodiment by the molecular weight ranges that mass ratio is 1:2:8 1000000~1200000 macromolecule Hyaluronate sodium, the Middle molecule hyaluronate sodium of molecular weight ranges 300000~400000 and molecular weight ranges are 5000~7000 Micromolecule hyaluronic acid sodium composition.
Embodiment 2
A kind of hyaluronic acid Silica hydrogel, is made up of following component by quality: polydimethylsiloxane 50%, and lauryl PEG-9 gathers Dimethyl silica ethyl polydimethylsiloxane (emulsifying agent) 1%, glycerol 20%, hyaluronate sodium 0.01% and purified water 28.99%.
The hyaluronate sodium of the present embodiment by the molecular weight ranges that mass ratio is 1:1:1 1800000~2000000 macromolecule Hyaluronate sodium, the Middle molecule hyaluronate sodium of molecular weight ranges 100000~200000 and molecular weight ranges are 8000~10000 Micromolecule hyaluronic acid sodium composition.
Embodiment 3
A kind of hyaluronic acid Silica hydrogel, is made up of following component by quality: polydimethylsiloxane 30%, octyldimethyl silica Alkane ethyoxyl glucoside (emulsifying agent) 4%, glycerol 10%, hyaluronate sodium 0.3% and purified water 55.7%.
The hyaluronate sodium of the present embodiment by the molecular weight ranges that mass ratio is 1:4:10 1400000~1600000 macromole Amount hyaluronate sodium, the Middle molecule hyaluronate sodium of molecular weight ranges 200000~300000 and molecular weight ranges are 7000~8000 Micromolecule hyaluronic acid sodium composition.
Embodiment 4
A kind of hyaluronic acid Silica hydrogel, is made up of following component by quality: polydimethylsiloxane 25%, polyglycereol-3 two silica Alkane polydimethylsiloxane (emulsifying agent) 7%, glycerol 12%, hyaluronate sodium 4% and purified water 52%.
The hyaluronate sodium of the present embodiment by the molecular weight ranges that mass ratio is 1:4:20 1700000~1800000 macromole Amount hyaluronate sodium, the Middle molecule hyaluronate sodium of molecular weight ranges 200000~400000 and molecular weight ranges are 6000~8000 Micromolecule hyaluronic acid sodium composition.
Embodiment 5
The preparation method of a kind of hyaluronic acid Silica hydrogel, comprises the steps:
1) raw material is weighed by embodiment 1;
2) use vacuum homogeneous emulsifying machine, polydimethylsiloxane and emulsifying agent be placed in the oil phase tank of vacuum homogeneous emulsifying machine, Low whipping speed is heated to 85 DEG C under conditions of being 20 revs/min, keeps 15 minutes at 85 DEG C, obtains oil phase;
3) hyaluronate sodium, purified water and glycerol are put in the aqueous phase tank of described vacuum homogeneous emulsifying machine, under agitation, heating To 80 DEG C, keep 20 minutes at 80 DEG C, obtain aqueous phase;
4) by oil phase and aqueous phase homogenizing 500 seconds under vacuum;
5) it is cooled to room temperature, obtains a kind of hyaluronic acid Silica hydrogel.
Embodiment 6
The preparation method of a kind of hyaluronic acid Silica hydrogel, comprises the steps:
1) raw material is weighed by embodiment 2;
2) use vacuum homogeneous emulsifying machine, polydimethylsiloxane and emulsifying agent be placed in the oil phase tank of vacuum homogeneous emulsifying machine, Low whipping speed is heated to 80 DEG C under conditions of being 10 revs/min, keeps 20 minutes at 80 DEG C, obtains oil phase;
3) hyaluronate sodium, purified water and glycerol are put in the aqueous phase tank of described vacuum homogeneous emulsifying machine, under agitation, heating To 90 DEG C, keep 20 minutes at 90 DEG C, obtain aqueous phase;
4) by oil phase and aqueous phase homogenizing 800 seconds under vacuum;
5) it is cooled to room temperature, obtains a kind of hyaluronic acid Silica hydrogel.
Embodiment 7
The preparation method of a kind of hyaluronic acid Silica hydrogel, comprises the steps:
1) raw material is weighed by embodiment 3;
2) use vacuum homogeneous emulsifying machine, polydimethylsiloxane and emulsifying agent be placed in the oil phase tank of vacuum homogeneous emulsifying machine, Low whipping speed is heated to 90 DEG C under conditions of being 15 revs/min, keeps 10 minutes at 90 DEG C, obtains oil phase;
3) hyaluronate sodium, purified water and glycerol are put in the aqueous phase tank of described vacuum homogeneous emulsifying machine, under agitation, heating To 85 DEG C, keep 10 minutes at 85 DEG C, obtain aqueous phase;
4) by oil phase and aqueous phase homogenizing 600 seconds under vacuum;
5) it is cooled to room temperature, obtains a kind of hyaluronic acid Silica hydrogel.
Embodiment 8
The preparation method of a kind of hyaluronic acid Silica hydrogel, comprises the steps:
1) raw material is weighed by embodiment 4;
2) use vacuum homogeneous emulsifying machine, polydimethylsiloxane and emulsifying agent be placed in the oil phase tank of vacuum homogeneous emulsifying machine, Low whipping speed is heated to 84 DEG C under conditions of being 17 revs/min, keeps 12 minutes at 84 DEG C, obtains oil phase;
3) hyaluronate sodium, purified water and glycerol are put in the aqueous phase tank of described vacuum homogeneous emulsifying machine, under agitation, heating To 83 DEG C, keep 18 minutes at 83 DEG C, obtain aqueous phase;
4) by oil phase and aqueous phase homogenizing 700 seconds under vacuum;
5) it is cooled to room temperature, obtains a kind of hyaluronic acid Silica hydrogel.
Embodiment 9
The preparation of matched group and preparation:
Compare 1 group: buy commercially available Silica hydrogel dressing (Shanghai food medicine prison tool (accurate) word 2012 the 2640953rd)
Compare 2 groups: the embodiment 12 in Chinese patent 2011103847533 (denomination of invention scar repair material) makes Scar repair material, its preparation method is as follows: be under agitation dissolved in 80g water by the chitosan lactate 4g of deacetylation 85%, Add the polyoxyethylene 20 sorbitan monolaurate 2g of emulsification, wetting agent glycerol 8g, mixing, obtain transparent gel Shape solution;Under army, kinematic viscosity is that the polydimethylsiloxane 50g of 100000cst joins in described gelatinous solution, Mix homogeneously, i.e. obtains a kind of scar repair material.
Compare 3 groups: take by quality: 30g polydimethylsiloxane, 4g octyldimethyl siloxanes ethyoxyl glucoside, 10g Glycerol, 0.3g molecular weight is the hyaluronate sodium of 1400000~1600000, and 55.7g purified water makes according to embodiment 7 Bright matter acid Silica hydrogel.
Compare 4 groups: take by quality: 30g polydimethylsiloxane, 4g octyldimethyl siloxanes ethyoxyl glucoside, 10g Glycerol, 0.3g molecular weight is the hyaluronate sodium of 200000~300000, and 55.7g purified water makes transparent according to embodiment 7 Matter acid sodium Silica hydrogel.
Compare 5 groups: take by quality: 30g polydimethylsiloxane, 4g octyldimethyl siloxanes ethyoxyl glucoside, 10g Glycerol, 0.3g molecular weight is the hyaluronate sodium of 6000~8000, and 55.7g purified water makes hyaluronic acid according to embodiment 7 Sodium Silica hydrogel.
Embodiment 10
Wettability test
Moist test direction principle is drawn with reference to " 2015 editions Chinese Pharmacopoeias (the 4th) " guideline 9103 medicine
1, take dry tool plug glass weighing botle (external diameter is 50mm, a height of 15mm) and be placed in suitable 25 DEG C ± 1 the previous day DEG C thermostatic drier (ammonium chloride or ammonium sulfate saturated solution are placed in bottom) or growth cabinet (design temperature is 25 DEG C ± 1 DEG C, Relative humidity is 80% ± 2%) in, precise weighing (m1)。
2. the hyaluronate sodium Silica hydrogel that prepared by Example 5-8, compare 1 group, compare 3 groups, compare 4 groups, compare 5 groups, Trehalose, hyaluronate sodium sodium are appropriate, put in above-mentioned weighing botle and are laid in weighing botle, and test sample thickness is typically about 1mm, Precise weighing (m2)。
Weighing botle is uncovered 3., and with bottle cap with being placed under the conditions of above-mentioned constant temperature and humidity 24 hours.
4. build weighing botle lid, precise weighing (m3)。
Percentage weight increase=(m3-m2)/(m2-m1) × 100%
5. draw moist feature description and draw defining of moist weightening finish.
Deliquescence: absorb enough water and divide formation liquid.
Great draw moist: draw wet weightening finish not less than 15%.
Have draw moist: draw wet weightening finish less than 15% but not less than 2%.
Slightly draw moist: draw wet weightening finish less than 2% but not less than 0.2%.
Nothing or moist almost without drawing: draw wet weightening finish less than 0.2%.
Table 1, draw moist experimental result
Percentage weight increase (%) Draw moist
Embodiment 5 12.15% Have draw moist
Embodiment 6 13.36% Have draw moist
Embodiment 7 15.16% Great draw moist
Embodiment 8 13.64% Have draw moist
Compare 1 group 1.67% Slightly draw moist
Compare 3 groups 8.19% Have draw moist
Compare 4 groups 7.61% Have draw moist
Compare 5 groups 6.38% Have draw moist
Trehalose 4.29% Have draw moist
Hyaluronate sodium 5.78% Have draw moist
Experiment shows, embodiment 7 is great draw moist, embodiment 5,6,8 groups, compare 3-5 group, trehalose and hyaluronate sodium Have and draw moist, and compare 1 group and slightly draw moist, it was demonstrated that simple Silica hydrogel patch does not have the moisture-retaining capacity of actively water suction.That is, The product of the present invention can actively absorb water moisturizing, repairs one moistening environment of offer for cicatrix.And can be found out by experiment Effective than other of embodiment 7.
Embodiment 11
CK skinanalysis apparatus is used to measure skin moisture-keeping degree.
Volunteer cleans arm, dries, and measures the basic value of now skin, takes test products 0.05g uniform application in 1cm2's On skin, measure 0h, 1h, 2h, 4h skin moisture-keeping.
Test and be divided into following groups:
Embodiment 5 groups;
Embodiment 6 groups;
Embodiment 7 groups;
Embodiment 8 groups;
Compare 1 group;
Compare 2 groups;
Compare 3 groups;
Compare 4 groups;
Compare 5 groups;
Table 2, moistening effect result of the test
*Compare with compareing 1 group, P < 0.01
As seen from Table 2, embodiment 5,6,7,8 groups is better than compareing 1,2,3,4,5 groups.
Embodiment 12
Inhibitory action to rabbit ear hypertrophic cicatrix.
Choosing 100 cleaning grade New Zealand large ear rabbits, male and female half and half, body weight 2.5-3kg, Changsha sky duty biotechnology is limited Company.White rabbit adaptability is fed 48 hours.Use Su Mian Xin 0.2ml/kg intramuscular injection anesthesia, rabbit ear facies ventralis skin 75% wine Essence sterilization, operates under stringent asepsis requirements, excises epidermis, corium and perichondrium, cartilage-preserving with skin biopsy apparatus and scalpel. Every ear prepares the standard wound surface of 6 diameter 2cm.Postoperative wound surface exposes, and treats its self-heal, the Hypertrophic scar of the rabbit ear after about 23 days Trace initially forms, and 100 white rabbits is randomly divided into 10 groups, is grouped as follows:
Embodiment 5 groups;
Embodiment 6 groups;
Embodiment 7 groups;
Embodiment 8 groups;
Compare 1 group;
Compare 2 groups;
Compare 3 groups;
Compare 4 groups;
Compare 5 groups;
Blank group.
Within postoperative 23 days, rise, partial smearing test products at hypertrophic cicatrix, every day 2 times, after postoperative 49 days, white rabbit put to death, Cut hypertrophic cicatrix tissue specimen.
One. cicatrix thickness measurement: the 21st, 28,35,42,49 days after surgery, record the size of hypertrophic cicatrix, color, Hardness, use slide gauge simultaneously, measure the thickness of cicatrix after being administered.
Table 3, cicatrix thickness measurement (mm)
Group 21 days 28 days 35 days 42 days 49 days
Compare 1 group 1.08 1.40 1.79* 1.92* 2.32*
Compare 2 groups 1.08 1.37 1.74* 1.89* 2.17*
Compare 3 groups 1.06 1.38 1.70* 1.87* 2.11*
Compare 4 groups 1.07 1.37 1.67* 1.83* 2.10*
Compare 5 groups 1.07 1.38 1.66* 1.85* 2.13*
Embodiment 5 groups 1.06 1.31 1.51*△ 1.60*△ 1.89*△
Embodiment 6 groups 1.07 1.32 1.50*△ 1.61*△ 1.88*△
Embodiment 7 groups 1.08 1.30 1.49*△ 1.59*△ 1.81*△
Embodiment 8 groups 1.05 1.32 1.51*△ 1.62*△ 1.87*△
Blank 1.08 1.57 2.34 2.98 3.27
* P < 0.01 is compared with blank;△ P < 0.05 with compare compared with in the of 1 group
Start that hypertrophic cicatrix occurs after each group rabbit ear wound surface postoperation recovery, and the lump constantly exceeding surface can be contacted, Hypertrophic Cicatrix initially forms the time and is about 21 days, it can be seen that embodiment 5,6,7,8 groups with compare 1,2,3,4,5 groups of equal energy Make rabbit ear hypertrophy thickness slow down (with blank ratio), but embodiment 9,10,11,12 groups becomes apparent from than each matched group effect.
Two. hydroxyproline determination: take postoperative 49 days rabbit ear scar tissue about 30mg and put in 50ml conical flask, add 6M salt Acid 10ml, is placed at electric drying oven with forced convection 105 DEG C hydrolysis 16 hours, adjusts pH to 6.8-6.9, by hydroxyproline test kit Be sequentially added into reagent solution, mixing, 60 DEG C of water-baths 15 minutes, after cooling, 3500 revs/min centrifugal 10 minutes, take supernatant and exist At 550nm, 1cm optical path, survey absorbance.Hydroxyproline content is calculated according to formula in test kit.
Hydroxyproline content in table 4, scar tissue
Group Hydroxyproline content
Compare 1 group 5.75±0.31*
Compare 2 groups 5.61±0.29*
Compare 3 groups 5.57±0.30*
Compare 4 groups 5.58±0.30*
Compare 5 groups 5.56±0.31
Embodiment 5 groups 4.30±0.23*△
Embodiment 6 groups 4.31±0.24*△
Embodiment 7 groups 4.28±0.21*△
Embodiment 8 groups 4.31±0.26*△
Blank 9.24±0.20
* P < 0.01 is compared with blank;△ P < 0.05 with compare compared with in the of 1 group
Hydroxyproline is one of collagen protein characteristic component, and it is excessive with fibroblast that the process of cicatrization is mainly collagen protein Increment, i.e. hydroxyproline content is the highest, and cicatrix is the most serious.Postoperative 49 days, table 4 showed 5,6,7,8 groups of hydroxyl dried meat of embodiment Histidine content the most relatively compare 1,2,3,4,5 groups the fewest, there is statistical significance.
Cicatrix is effectively suppressed to generate by a kind of hyaluronic acid Silica hydrogel of the above-mentioned description of test present invention.
Embodiment 13
Clinical trial:
The selection of case: choose 306 example patients, wherein male 128 people, women 178 people altogether, the age be 7-66 year, adult 243 examples, child 63 example;Case is the cicatrix that acne infects, burns, scalds, wound or Post operation wound healing are formed.
Case is randomly divided into:
Embodiment 5 groups;
Embodiment 6 groups;
Embodiment 7 groups;
Embodiment 8 groups;
Compare 1 group;
Compare 2 groups;
Compare 3 groups;
Compare 4 groups;
Compare 5 groups.
Test products is applied on cicatrix for early, middle and late three times every day, massages until fully absorbing on cicatrix with finger;20 days It it is a course for the treatment of.
Skin lesion color score: crimson or scarlet companion's telangiectasis meter 3 points;Light red, disappear after pressing meter 2 points;It is the reddest, Some ash dark count 1 point;Normal skin tone meter 0 point.
The height scoring of skin lesion protuberance: height counts 4 points at more than 4mm;4mm >=highly > 2mm counts 3 points;2mm >=highly > 1mm Count 2 points;Highly≤1mm counts 1 point;Smooth or depression counts 0 point.
Skin lesion hardness is marked: normal meter 0 point, soft (skin is flexible under minimum resistance) counts 1 point;Submissive ( Energy amoebula under pressure) count 2 points;Hard (the most flexible, to be moved into bulk, pressure is had resistance) counts 3 points;Curved Bent (tissue such as rope form, cicatrix can be shunk back when stretching) meter 4 points;(the permanent cripetura of cicatrix causes maimed and distortion) of contracture Count 5 points.
Pruritus is marked: acutely or persistence pruritus with scratch meter 3 points;Often have but less violent, meter 2 points can be stood; Sometimes itch and count 1 point;Without meter 0 point of itching.
Touch a tender spot and mark: have the strongest " hyperpathia ", tenderness meter 3 points when touching;Pain is had when medium hyperpathia, pressing Feel but meter 2 points can be stood;The inconspicuous meter of pain 1 point when sometimes having pain, pressing;Painless meter 0 point.
By above-mentioned each index scoring addition be cicatrix order of severity overall score, overall score 1-5 is divided into slightly, 6-11 be divided into moderate, 12-18 is divided into severe.
Recruitment evaluation standard: overall score * 100% before curative effect index=(overall score after overall score-treatment before treatment)/treatment.Assessment By being almost recovered, four standards effective, effective, invalid.
Recovery from illness: therapeutic index >=90%;Effective: therapeutic index 70%-89%;Effective: therapeutic index 30%-69%;Invalid: to treat Effect index < 30%.Effective percentage by recovery from illness+effective+effectively in terms of.
Table 5, clinical test results
Group Case load Recovery from illness Effective Effectively Invalid Effective percentage
Compare 1 group 34 22 2 4 6 82.35%
Compare 2 groups 34 22 3 4 5 85.29%
Compare 3 groups 34 24 3 3 4 88.24%
Compare 4 groups 34 23 2 4 5 85.29%
Compare 5 groups 34 23 3 4 4 88.24%
Embodiment 5 groups 34 25 4 3 2 94.12%
Embodiment 6 groups 34 25 4 3 2 94.12%
Embodiment 7 groups 34 26 5 2 1 97.06%
Embodiment 8 groups 34 25 5 1 3 91.18%
The hyaluronate sodium Silica hydrogel of the present invention is relatively higher than matched group at the effective percentage for the treatment of cicatrix as can be seen from the above table, enters one Step illustrates that the hyaluronate sodium matched combined of different molecular weight effect in terms for the treatment of cicatrix is better than single a kind of hyaluronic acid Sodium, and reasonably proportion relation is the most crucial.

Claims (10)

1. a hyaluronic acid Silica hydrogel, is characterized in that being made up of following component by quality: polydimethylsiloxane 10%-50%, Emulsifying agent 1%-10%, glycerol 1%-20%, hyaluronate sodium 0.01%-10% and purified water 28.99%-69%.
Gel the most according to claim 1, is characterized in that described compositions includes following composition by mass percentage: poly-two Methylsiloxane 30%, emulsifying agent 4%, glycerol 10%, hyaluronate sodium 0.3% and purified water 55.7%.
Gel the most according to claim 1 and 2, is characterized in that described hyaluronate sodium is 1:(1~4 by mass ratio): The molecular weight ranges of (1~20) 1000000~2000000 macromolecule hyaluronate sodium, molecular weight ranges 100000~ The Middle molecule hyaluronate sodium of 400000 and molecular weight ranges form at the micromolecule hyaluronic acid sodium of 5000~10000.
Gel the most according to claim 3, is characterized in that described hyaluronate sodium is by the molecular weight model that mass ratio is 1:4:10 Be trapped among 1400000~1600000 macromolecule hyaluronate sodium, molecular weight ranges 200000~300000 Middle molecule transparent Matter acid sodium and molecular weight ranges form at the micromolecule hyaluronic acid sodium of 7000~8000.
Gel the most according to claim 1 and 2, is characterized in that described emulsifying agent is octyldimethyl siloxanes ethyoxyl Portugal Polyglycoside, KF-6028, the lauryl PEG-9 poly-diformazan of polydimethylsiloxanes ethyl One in radical siloxane and polyglycereol-3 disiloxane polydimethylsiloxane.
6. a preparation method for hyaluronic acid Silica hydrogel, is characterized in that comprising the steps:
1) weigh raw material by mass percentage: polydimethylsiloxane 10%-50%, emulsifying agent 1%-10%, glycerol 1%-20%, Hyaluronate sodium 0.01%-10% and purified water 10%-87.99%;
2) use vacuum homogeneous emulsifying machine, polydimethylsiloxane and emulsifying agent be placed in the oil phase tank of vacuum homogeneous emulsifying machine, Low whipping speed is heated to 80 90 DEG C under conditions of being 10-20 rev/min, keep 10-20 minute at 80 90 DEG C, obtain oil phase;
3) hyaluronate sodium, purified water and glycerol are put in the aqueous phase tank of described vacuum homogeneous emulsifying machine, under agitation, heating To 80-90 DEG C, keep 10-20 minute at 80 90 DEG C, obtain aqueous phase;
4) by oil phase and aqueous phase homogenizing 500-800 second under vacuum;
5) it is cooled to room temperature, obtains a kind of hyaluronic acid Silica hydrogel.
Method the most according to claim 6, is characterized in that described step (1) is: weigh raw material by mass percentage: poly- Dimethyl siloxane 30%, emulsifying agent 4%, glycerol 10%, hyaluronate sodium 0.3% and purified water 55.7%.
8., according to the method described in claim 6 or 7, it is characterized in that described hyaluronate sodium is 1:(1~4 by mass ratio): The molecular weight ranges of (1~20) 1000000~2000000 macromolecule hyaluronate sodium, molecular weight ranges 100000~ The Middle molecule hyaluronate sodium of 400000 and molecular weight ranges form at the micromolecule hyaluronic acid sodium of 5000~10000.
Method the most according to claim 8, is characterized in that described hyaluronate sodium is by the molecular weight model that mass ratio is 1:4:10 Be trapped among molecular weight ranges 1400000~1600000 macromolecule hyaluronate sodium, molecular weight ranges 200000~300000 Middle molecule hyaluronate sodium and molecular weight ranges 7000~8000 micromolecule hyaluronic acid sodium form.
10., according to the method described in claim 6 or 7, it is characterized in that described emulsifying agent is octyldimethyl siloxanes ethyoxyl Glucoside, KF-6028, lauryl PEG-9 polydimethylsiloxanes ethyl poly-two One in methylsiloxane and polyglycereol-3 disiloxane polydimethylsiloxane.
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