CN107281277A - Promote the preparation method of the temperature-sensitive hydrogel of wound healing - Google Patents
Promote the preparation method of the temperature-sensitive hydrogel of wound healing Download PDFInfo
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- 239000000017 hydrogel Substances 0.000 title claims abstract description 53
- 238000002360 preparation method Methods 0.000 title claims abstract description 35
- 230000029663 wound healing Effects 0.000 title claims abstract description 22
- 229920001661 Chitosan Polymers 0.000 claims abstract description 20
- 241000155589 Pteroxygonum Species 0.000 claims abstract description 12
- 239000002023 wood Substances 0.000 claims abstract description 10
- 229960002901 sodium glycerophosphate Drugs 0.000 claims abstract description 5
- REULQIKBNNDNDX-UHFFFAOYSA-M sodium;2,3-dihydroxypropyl hydrogen phosphate Chemical compound [Na+].OCC(O)COP(O)([O-])=O REULQIKBNNDNDX-UHFFFAOYSA-M 0.000 claims abstract description 5
- 239000002994 raw material Substances 0.000 claims abstract description 3
- 238000003756 stirring Methods 0.000 claims description 19
- 239000000843 powder Substances 0.000 claims description 18
- 150000001875 compounds Chemical class 0.000 claims description 15
- KANLKAYGXGSUJC-UHFFFAOYSA-N 2,3-dihydroxypropyl dihydrogen phosphate;sodium Chemical compound [Na].OCC(O)COP(O)(O)=O KANLKAYGXGSUJC-UHFFFAOYSA-N 0.000 claims description 14
- 241000209094 Oryza Species 0.000 claims description 14
- 235000007164 Oryza sativa Nutrition 0.000 claims description 14
- 235000009566 rice Nutrition 0.000 claims description 14
- 238000002156 mixing Methods 0.000 claims description 11
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 10
- 229910052708 sodium Inorganic materials 0.000 claims description 10
- 239000011734 sodium Substances 0.000 claims description 10
- 244000138993 panchioli Species 0.000 claims description 9
- 238000009835 boiling Methods 0.000 claims description 7
- 238000000227 grinding Methods 0.000 claims description 7
- 239000012535 impurity Substances 0.000 claims description 7
- 235000021419 vinegar Nutrition 0.000 claims description 7
- 239000000052 vinegar Substances 0.000 claims description 7
- 239000000203 mixture Substances 0.000 claims description 5
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 claims description 4
- 230000015556 catabolic process Effects 0.000 claims description 3
- 229910000397 disodium phosphate Inorganic materials 0.000 claims description 2
- 235000019800 disodium phosphate Nutrition 0.000 claims description 2
- 238000007654 immersion Methods 0.000 claims description 2
- 239000001488 sodium phosphate Substances 0.000 claims description 2
- AWUCVROLDVIAJX-UHFFFAOYSA-N glycerol 1-phosphate Chemical compound OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 claims 1
- 239000000499 gel Substances 0.000 abstract description 8
- 230000000694 effects Effects 0.000 abstract description 4
- 230000001737 promoting effect Effects 0.000 abstract description 4
- 230000000844 anti-bacterial effect Effects 0.000 abstract description 3
- 238000000034 method Methods 0.000 abstract description 3
- 231100001083 no cytotoxicity Toxicity 0.000 abstract description 3
- 230000000845 anti-microbial effect Effects 0.000 abstract description 2
- 230000009969 flowable effect Effects 0.000 abstract description 2
- 230000003020 moisturizing effect Effects 0.000 abstract description 2
- 230000035699 permeability Effects 0.000 abstract description 2
- 241000522195 Dalbergia Species 0.000 abstract 1
- 230000002085 persistent effect Effects 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 59
- 238000012360 testing method Methods 0.000 description 7
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- OMEBXAYMRCYOTB-UHFFFAOYSA-N [P].OCC(O)CO Chemical compound [P].OCC(O)CO OMEBXAYMRCYOTB-UHFFFAOYSA-N 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 238000010521 absorption reaction Methods 0.000 description 4
- 230000008859 change Effects 0.000 description 4
- 229910052739 hydrogen Inorganic materials 0.000 description 4
- 239000001257 hydrogen Substances 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
- 206010052428 Wound Diseases 0.000 description 3
- 208000027418 Wounds and injury Diseases 0.000 description 3
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 230000003115 biocidal effect Effects 0.000 description 3
- 230000036760 body temperature Effects 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 238000002834 transmittance Methods 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 2
- 239000001506 calcium phosphate Substances 0.000 description 2
- 239000011557 critical solution Substances 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000001879 gelation Methods 0.000 description 2
- 150000004676 glycans Chemical class 0.000 description 2
- 230000002209 hydrophobic effect Effects 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 239000012567 medical material Substances 0.000 description 2
- QNILTEGFHQSKFF-UHFFFAOYSA-N n-propan-2-ylprop-2-enamide Chemical compound CC(C)NC(=O)C=C QNILTEGFHQSKFF-UHFFFAOYSA-N 0.000 description 2
- 229920001282 polysaccharide Polymers 0.000 description 2
- 239000005017 polysaccharide Substances 0.000 description 2
- 230000001954 sterilising effect Effects 0.000 description 2
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- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
- 229940078499 tricalcium phosphate Drugs 0.000 description 2
- 229910000391 tricalcium phosphate Inorganic materials 0.000 description 2
- 235000019731 tricalcium phosphate Nutrition 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 241000238421 Arthropoda Species 0.000 description 1
- 229920002101 Chitin Polymers 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- FOIXSVOLVBLSDH-UHFFFAOYSA-N Silver ion Chemical compound [Ag+] FOIXSVOLVBLSDH-UHFFFAOYSA-N 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
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- 229940088710 antibiotic agent Drugs 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 238000013475 authorization Methods 0.000 description 1
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- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
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- 230000037396 body weight Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
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- 238000007796 conventional method Methods 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000003292 glue Substances 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 239000004816 latex Substances 0.000 description 1
- 229920000126 latex Polymers 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 230000029052 metamorphosis Effects 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 229920005615 natural polymer Polymers 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 238000011056 performance test Methods 0.000 description 1
- 238000005375 photometry Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 239000003223 protective agent Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/716—Glucans
- A61K31/722—Chitin, chitosan
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/56—Materials from animals other than mammals
- A61K35/63—Arthropods
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/70—Polygonaceae (Buckwheat family), e.g. spineflower or dock
- A61K36/704—Polygonum, e.g. knotweed
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Biotechnology (AREA)
- Mycology (AREA)
- Microbiology (AREA)
- Medical Informatics (AREA)
- Botany (AREA)
- Alternative & Traditional Medicine (AREA)
- Engineering & Computer Science (AREA)
- Insects & Arthropods (AREA)
- Inorganic Chemistry (AREA)
- Molecular Biology (AREA)
- Medicines Containing Plant Substances (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention discloses the preparation method for the temperature-sensitive hydrogel for promoting wound healing, using chitosan, Girald Pteroxygonum Root, courage, dalbergia wood, sodium glycero-phosphate as raw material, it is flowable colloidal solution at ambient temperature to be made, and in a heated condition, immobilising gel, as temperature-sensitive hydrogel can be changed into.The preparation method science of the temperature-sensitive hydrogel for the promotion wound healing that the present invention is provided, technique is simple, and products obtained therefrom has effect that is antibacterial, promoting wound healing, stop blooding, there is good moisturizing, gas permeability, no cytotoxicity, good antimicrobial effect, persistent.
Description
Technical field
The present invention relates to medical material field, more particularly to promote the preparation method of the temperature-sensitive hydrogel of wound healing.
Background technology
Chitosan is the alkaline polysaccharide that nature is uniquely largely present, and is one kind sun that chitin is formed after deacetylated
Nonionic polysaccharide.Chitosan is widely present in the cell membrane of the shell of arthropod, fungi and yeast, and stock number is enriched very much,
There is biodegradable simultaneously, good biocompatibility, the characteristic such as nontoxic, antibacterial, have in chitosan molecule substantial amounts of
Hydroxyl and amino, are easily modified by sulphation, and complex can be combined to form with metal ion, form a series of new chitosan derivative
Thing, is provided with more biological functions, therefore obtained in-depth study in medical science, field of biology and be widely applied.
Silver ion is in early stage just by its excellent antibiotic and sterilizing performance is by people institute extensive concern, and it is in medical material and anti-biotic material
Had broad application prospects Deng field.Temperature sensitive type water gel refers to produce stimuli responsive with the change of ambient temperature
The intellectual material of property.There is a certain proportion of hydrophilic and hydrophobic grouping, the change of temperature can in temperature sensitive type water gel structure
To influence the hydrogen bond action between the hydrophobic effect of these groups and macromolecular chain, so as to influence its metamorphosis.With synthesis high score
Son is compared, and natural polymer gel has the advantages that hypotoxicity, biocompatibility and degradability.Thermo-sensitive aquagel
Different physical aspects can be according to temperature change.It is liquid under normal temperature, into after tissue, the gelation under body temperature effect
And be fixed in local organization.Chitosan only keeps solution state under sour environment, when pH value is increased to 6.2, and shell gathers
Sugar juice starts to precipitate, if adding sodium glycero-phosphate, the system can keep solution state in neutral conditions, system tool
There is temperature sensitivity, solution state is kept below body temperature, gel can be formed when temperature is increased to body temperature.It has bio-compatible
Property good, degradation time in vivo and setting time the advantages of be adjustably controlled, led bioengineering, field of medicaments in engineering etc.
Obtain extensive concern.
The A of Authorization Notice No. CN 104984401（Application number 201510434128.3）Chinese patent literature disclose one
The preparation method of temperature-sensitive hydrogel/tricalcium phosphate material is planted, this method steps flow chart includes temperature-sensitive hydrogel is molten at low temperature
Solution, by a certain percentage addition tricalcium phosphate powder, mixing material are arbitrarily moulding into any desired shape.Publication No. CN
103004757 A（Application number 201210571657.4）Chinese patent literature disclose a kind of porous temperature-sensitive hydrogel slow release formulation
And preparation method thereof.The present invention loads medicine-feeding using the porous temperature-sensitive hydrogel of poly-N-isopropyl acrylamide as carrier in gel
Thing, using the temperature sensitive properties of poly-N-isopropyl acrylamide, to realize the control release to medicine.When temperature is less than water-setting
During the LCST of glue, insoluble drug release is very slow, and when temperature is higher than its LCST, rate of release is accelerated.
The content of the invention
For problem of the prior art, it is an object of the invention to provide a kind of system of the temperature-sensitive hydrogel of promotion wound healing
Preparation Method, the temperature-sensitive hydrogel is at ambient temperature flowable colloidal solution, and in a heated condition, can be changed into and not flow
Gel, and with good bacteriostasis, has a broad antifungal spectrum, no cytotoxicity, beneficial to wound healing.
The technical scheme is that：
Promote wound healing temperature-sensitive hydrogel preparation method, using chitosan, Girald Pteroxygonum Root, courage, dalbergia wood, sodium glycero-phosphate as
Raw material, is comprised the following steps that：
（1）Take ground courage to remove impurity, be placed in boiling vinegar and soak 20-30 minutes（It is preferred that：Immersion 25 minutes）, take out, with section
Girald Pteroxygonum Root and dalbergia wood mixing, add polished rice mix thoroughly, in the hot pot for being placed in 110 DEG C, stir-fry 10-24 minute, taking-up, weed out rice,
Pulverize and sieve, powder is made；
（2）Take chitosan powder breakdown mill 30-50 minutes（It is preferred that：Attrition grinding 35-45 minutes；More preferred：Crushed and ground
Mill 40 minutes）, with step（1）Gained powder is mixed, and is placed in homogenizer, quick stirring 15 minutes, and compound is made；
（3）By step（2）Gained compound is added into acetum, is stirred to being completely dissolved, and obtains mass concentration for 1-2%
Complex solution（It is preferred that：Obtain the complex solution that mass concentration is 1.5%）；
（4）To step（3）In gained complex solution, phosphoglycerol sodium solution is added dropwise, quickly stirs and measures pH
Value, and pH value is adjusted to 6.8-7.2 with the disodium phosphate soln of saturation；
（5）By step（4）Resulting solution is added in container, is used water-bath heated at constant temperature, when solution does not flow, that is, is formed temperature sensitive
Hydrogel.
The preparation method of described temperature-sensitive hydrogel, chitosan：Girald Pteroxygonum Root：Ground courage：The mass ratio of dalbergia wood is 15:4-6:2-
3:5-7（It is preferred that：Mass ratio is 15:5:2.5:6）.
The preparation method of described temperature-sensitive hydrogel, step（1）Stir-fry 14-20 minutes（It is preferred that：Stir-fry 17 minutes）.
The preparation method of described temperature-sensitive hydrogel, step（1）Also crushed 80-160 mesh sieves（It is preferred that：Crushed
100-140 mesh sieves；More preferred：Crushed 120 mesh sieves）.
The preparation method of described temperature-sensitive hydrogel, step（2）Mixing speed is 200-400 revs/min（It is preferred that：Stir
Speed is mixed for 250-350 revs/min；More preferred：Mixing speed is 300 revs/min）.
The preparation method of described temperature-sensitive hydrogel, step（3）The concentration of acetum is 0.08-0.2mol/L（It is preferred that
's：The concentration of acetum is 0.12-0.16mol/L；More preferred：The concentration of acetum is 0.14mol/L）.
The preparation method of described temperature-sensitive hydrogel, step（4）Add the body of phosphoglycerol sodium solution and complex solution
Product is than being 1:8-12（It is preferred that：The volume ratio for adding phosphoglycerol sodium solution and complex solution is 1:10）.
The preparation method of described temperature-sensitive hydrogel, step（4）The mass concentration of phosphoglycerol sodium solution is 52-60%（It is excellent
Choosing：The mass concentration of phosphoglycerol sodium solution is 54-58%；The mass concentration of more preferred phosphoglycerol sodium solution is
56%）.
The preparation method of described temperature-sensitive hydrogel, step（4）PH value is adjusted to 6.9-7.1（It is preferred that：Adjust pH value to
7.0）.
The preparation method of described temperature-sensitive hydrogel, step（5）The temperature of water-bath heated at constant temperature is 33-40 DEG C（It is preferred that
's：The temperature of water-bath heated at constant temperature is 35-38 DEG C；More preferred：The temperature of water-bath heated at constant temperature is 36.5 DEG C）.
The preparation method science of the temperature-sensitive hydrogel for the promotion wound healing that the present invention is provided, technique is simple, products obtained therefrom
With effect that is antibacterial, promoting wound healing, stop blooding, there are good moisturizing, gas permeability, no cytotoxicity, good antimicrobial effect is made
With lasting.In addition, excellent results of the invention are also manifested by：
1. products obtained therefrom of the present invention, while comprising chitosan and the characteristics of traditional Chinese medicine ingredients and advantage, with antibiotic property, promoting cell
Growth, promotes wound healing；
2. using chitosan as carrier in preparation process, adding traditional Chinese medicine ingredients, compound is made, chitosan divides as traditional Chinese medicine ingredients
Powder and protective agent, make in its uniform, stable distribution temperature-sensitive hydrogel system.
Embodiment
Technical scheme, but protection domain not limited to this are described in detail with reference to embodiment and experimental example.
Embodiment 1 promotes the preparation method of the temperature-sensitive hydrogel of wound healing, and step is as follows：
（1）Take ground courage 4g to remove impurity, be placed in boiling vinegar and soak 20 minutes, take out, mixed with the Girald Pteroxygonum Root 8g and dalbergia wood 10g of section
Close, add polished rice and mix thoroughly, in the hot pot for being placed in 110 DEG C, stir-fry 10 minutes, take out, weed out rice, crushed 80 mesh sieves, powder is made
End；
（2）Chitosan 30g attrition grindings are taken 30 minutes, with step（1）Gained powder is mixed, and is placed in homogenizer, with 200
Rev/min speed quickly stirring 15 minutes, compound is made；
（3）By step（2）Gained compound adds to concentration in 0.08mol/L acetum, to stir to being completely dissolved, obtain
To the complex solution that mass concentration is 1%；
（4）To step（3）In gained complex solution, the phosphoglycerol sodium solution that mass concentration is 52%, glycerine phosphorus is added dropwise
The volume ratio of acid sodium solution and complex solution is 1:8, quickly stir and pH value determination, and with the disodium hydrogen phosphate of saturation
Solution adjusts pH value to 6.8；
（5）By step（4）Resulting solution is added in container, with 33 DEG C of water-bath heated at constant temperature, when solution does not flow, i.e. shape
Into temperature-sensitive hydrogel.
Embodiment 2 promotes the preparation method of the temperature-sensitive hydrogel of wound healing, and step is as follows：
（1）Take ground courage 6g to remove impurity, be placed in boiling vinegar and soak 30 minutes, take out, Girald Pteroxygonum Root 12g and dalbergia wood 14g with section
Mixing, adds polished rice and mixes thoroughly, in the hot pot for being placed in 110 DEG C, stir-fry 24 minutes, take out, weed out rice, crushed 160 mesh sieves, and be made
Powder；
（2）Chitosan 30g attrition grindings are taken 50 minutes, with step（1）Gained powder is mixed, and is placed in homogenizer, with 400
Rev/min speed quickly stirring 15 minutes, compound is made；
（3）By step（2）Gained compound adds to concentration in 0.2mol/L acetum, to stir to being completely dissolved, obtain
To the complex solution that mass concentration is 2%；
（4）To step（3）In gained complex solution, the phosphoglycerol sodium solution that mass concentration is 60%, glycerine phosphorus is added dropwise
The volume ratio of acid sodium solution and complex solution is 1:12, quickly stir and pH value determination, and with the phosphoric acid hydrogen two of saturation
Sodium solution adjusts pH value to 7.2；
（5）By step（4）Resulting solution is added in container, with 40 DEG C of water-bath heated at constant temperature, when solution does not flow, i.e. shape
Into temperature-sensitive hydrogel.
Embodiment 3 promotes the preparation method of the temperature-sensitive hydrogel of wound healing, and step is as follows：
（1）Take ground courage 4g to remove impurity, be placed in boiling vinegar and soak 20 minutes, take out, mixed with the Girald Pteroxygonum Root 8g and dalbergia wood 10g of section
Close, add polished rice and mix thoroughly, in the hot pot for being placed in 110 DEG C, stir-fry 14 minutes, take out, weed out rice, crushed 100 mesh sieves, powder is made
End；
（2）Chitosan 30g attrition grindings are taken 35 minutes, with step（1）Gained powder is mixed, and is placed in homogenizer, with 250
Rev/min speed quickly stirring 15 minutes, compound is made；
（3）By step（2）Gained compound adds to concentration in 0.12mol/L acetum, to stir to being completely dissolved, obtain
To the complex solution that mass concentration is 1%；
（4）To step（3）In gained complex solution, the phosphoglycerol sodium solution that mass concentration is 54%, glycerine phosphorus is added dropwise
The volume ratio of acid sodium solution and complex solution is 1:8, quickly stir and pH value determination, and with the disodium hydrogen phosphate of saturation
Solution adjusts pH value to 6.9；
（5）By step（4）Resulting solution is added in container, with 35 DEG C of water-bath heated at constant temperature, when solution does not flow, i.e. shape
Into temperature-sensitive hydrogel.
Embodiment 4 promotes the preparation method of the temperature-sensitive hydrogel of wound healing, and step is as follows：
（1）Take ground courage 6g to remove impurity, be placed in boiling vinegar and soak 30 minutes, take out, Girald Pteroxygonum Root 12g and dalbergia wood 14g with section
Mixing, adds polished rice and mixes thoroughly, in the hot pot for being placed in 110 DEG C, stir-fry 20 minutes, take out, weed out rice, crushed 140 mesh sieves, and be made
Powder；
（2）Chitosan 30g attrition grindings are taken 45 minutes, with step（1）Gained powder is mixed, and is placed in homogenizer, with 350
Rev/min speed quickly stirring 15 minutes, compound is made；
（3）By step（2）Gained compound adds to concentration in 0.16mol/L acetum, to stir to being completely dissolved, obtain
To the complex solution that mass concentration is 2%；
（4）To step（3）In gained complex solution, the phosphoglycerol sodium solution that mass concentration is 58%, glycerine phosphorus is added dropwise
The volume ratio of acid sodium solution and complex solution is 1:12, quickly stir and pH value determination, and with the phosphoric acid hydrogen two of saturation
Sodium solution adjusts pH value to 7.1；
（5）By step（4）Resulting solution is added in container, with 38 DEG C of water-bath heated at constant temperature, when solution does not flow, i.e. shape
Into temperature-sensitive hydrogel.
Embodiment 5 promotes the preparation method of the temperature-sensitive hydrogel of wound healing, and step is as follows：
（1）Take ground courage 5g to remove impurity, be placed in boiling vinegar and soak 25 minutes, take out, Girald Pteroxygonum Root 10g and dalbergia wood 12g with section
Mixing, adds polished rice and mixes thoroughly, in the hot pot for being placed in 110 DEG C, stir-fry 17 minutes, take out, weed out rice, crushed 120 mesh sieves, and be made
Powder；
（2）Chitosan 30g attrition grindings are taken 40 minutes, with step（1）Gained powder is mixed, and is placed in homogenizer, with 300
Rev/min speed quickly stirring 15 minutes, compound is made；
（3）By step（2）Gained compound adds to concentration in 0.14mol/L acetum, to stir to being completely dissolved, obtain
To the complex solution that mass concentration is 1.5%；
（4）To step（3）In gained complex solution, the phosphoglycerol sodium solution that mass concentration is 56%, glycerine phosphorus is added dropwise
The volume ratio of acid sodium solution and complex solution is 1:10, quickly stir and pH value determination, and with the phosphoric acid hydrogen two of saturation
Sodium solution adjusts pH value to 7.0；
（5）By step（4）Resulting solution is added in container, with 36.5 DEG C of water-bath heated at constant temperature, when solution does not flow, i.e.,
Form temperature-sensitive hydrogel.
The present invention gained of test example 1 promotes the temperature-sensitive hydrogel of wound healing（Embodiment 5）Performance test：
1. lower critical solution temperature（LCST）Measure：
It is measured using absorption photometry, the change of the absorption photometric value of gel rubber system, LCST is recorded using absorption photometric instrument
Corresponding temperature when as absorption photometric value is undergone mutation.Temperature-sensitive hydrogel obtained by weighing the present invention, reaches balance at room temperature
Solvent swelling state, the temperature range of test is 30-40 DEG C.
Test result is as shown in table 1：
The test result of light transmittance under the different temperatures of table 1
As shown in Table 1, water-setting latex solution is at 32-34 DEG C, and light transmittance is mutated, and illustrates the rise with temperature, hydrogel
Swelling ratio rapid decrease, light transmittance reduction, that is, occur phase in version, thus its lower critical solution temperature be 33 DEG C.
The present invention gained of test example 2 promotes the temperature-sensitive hydrogel of wound healing（Embodiment 5）Clinical effectiveness experiment：
Subjects：Randomly select experiment and use small white mouse 50, body weight is between 250-300g, male 25, female 25.
Test method：Small white mouse is divided into two groups, experimental group 30 and control group 20, two groups of small white mouses are in sex, body
There was no significant difference in terms of weight, feeding time.Two groups of small white mouses are anaesthetized respectively, same area, shaving hair removal hair, in nothing is chosen
Skin surface is removed under the conditions of bacterium and the diameter 3cm surface of a wound is formed, and is taken after conventional method sterilization, experimental group uses institute of the present invention
Temperature-sensitive hydrogel emulsion is obtained, wound surface is applied to；Control group is using conventional temperature-sensitive hydrogel.Calculate the Primogel time and observe
The wound healing situation and infection conditions of two groups of small white mouses.
Result of the test：The result of the test of two groups of small white mouses is as shown in table 2：
As shown in Table 2, the gelation rate of present invention gained temperature-sensitive hydrogel is faster, more preferable to the healing effect of wound, can reduce
Amount of bleeding, and bacterium infection is prevented, the facilitation effect for wound healing is notable.
It should be pointed out that embodiment is the more representational example of the present invention, it is clear that skill of the invention
Art scheme is not limited to above-described embodiment, can also there is many variations.One of ordinary skill in the art, it is clearly public with institute of the invention
Written description open or according to file obtaining undoubtedly, it is considered as this patent scope of the claimed.
Claims (10)
1. promote wound healing temperature-sensitive hydrogel preparation method, it is characterised in that with chitosan, Girald Pteroxygonum Root, courage, drop
Fragrant, sodium glycero-phosphate is raw material, is comprised the following steps that：
（1）Take ground courage to remove impurity, be placed in boiling vinegar and soak 20-30 minutes（It is preferred that：Immersion 25 minutes）, take out, with section
Girald Pteroxygonum Root and dalbergia wood mixing, add polished rice mix thoroughly, in the hot pot for being placed in 110 DEG C, stir-fry 10-24 minute, taking-up, weed out rice,
Pulverize and sieve, powder is made；
（2）Take chitosan powder breakdown mill 30-50 minutes（It is preferred that：Attrition grinding 35-45 minutes；More preferred：Crushed and ground
Mill 40 minutes）, with step（1）Gained powder is mixed, and is placed in homogenizer, quick stirring 15 minutes, and compound is made；
（3）By step（2）Gained compound is added into acetum, is stirred to being completely dissolved, and obtains mass concentration for 1-2%
Complex solution（It is preferred that：Obtain the complex solution that mass concentration is 1.5%）；
（4）To step（3）In gained complex solution, phosphoglycerol sodium solution is added dropwise, quickly stirs and measures pH
Value, and pH value is adjusted to 6.8-7.2 with the disodium phosphate soln of saturation；
（5）By step（4）Resulting solution is added in container, is used water-bath heated at constant temperature, when solution does not flow, that is, is formed temperature sensitive
Hydrogel.
2. the preparation method of temperature-sensitive hydrogel as claimed in claim 1, it is characterised in that chitosan：Girald Pteroxygonum Root：Ground courage：Drop
Fragrant mass ratio is 15:4-6:2-3:5-7（It is preferred that：Mass ratio is 15:5:2.5:6）.
3. the preparation method of temperature-sensitive hydrogel as claimed in claim 1, it is characterised in that step（1）Stir-fry 14-20 minutes
（It is preferred that：Stir-fry 17 minutes）.
4. the preparation method of temperature-sensitive hydrogel as claimed in claim 1, it is characterised in that step（1）Also crushed 80-160
Mesh sieve（It is preferred that：Crushed 100-140 mesh sieves；More preferred：Crushed 120 mesh sieves）.
5. the preparation method of temperature-sensitive hydrogel as claimed in claim 1, it is characterised in that step（2）Mixing speed is 200-
400 revs/min（It is preferred that：Mixing speed is 250-350 revs/min；More preferred：Mixing speed is 300 revs/min）.
6. the preparation method of temperature-sensitive hydrogel as claimed in claim 1, it is characterised in that step（3）The concentration of acetum
For 0.08-0.2mol/L（It is preferred that：The concentration of acetum is 0.12-0.16mol/L；More preferred：Acetum it is dense
Spend for 0.14mol/L）.
7. the preparation method of temperature-sensitive hydrogel as claimed in claim 1, it is characterised in that step（4）Add sodium glycero-phosphate
The volume ratio of solution and complex solution is 1:8-12（It is preferred that：Add the volume of phosphoglycerol sodium solution and complex solution
Than for 1:10）.
8. the preparation method of temperature-sensitive hydrogel as claimed in claim 1, it is characterised in that step（4）Phosphoglycerol sodium solution
Mass concentration be 52-60%（It is preferred that：The mass concentration of phosphoglycerol sodium solution is 54-58%；More preferred phosphoglycerol
The mass concentration of sodium solution is 56%）.
9. the preparation method of temperature-sensitive hydrogel as claimed in claim 1, it is characterised in that step（4）PH value is adjusted to 6.9-
7.1（It is preferred that：PH value is adjusted to 7.0）.
10. the preparation method of temperature-sensitive hydrogel as claimed in claim 1, it is characterised in that step（5）Water-bath heated at constant temperature
Temperature be 33-40 DEG C（It is preferred that：The temperature of water-bath heated at constant temperature is 35-38 DEG C；More preferred：Water-bath constant temperature adds
The temperature of heat is 36.5 DEG C）.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108210891A (en) * | 2018-04-03 | 2018-06-29 | 广州赛莱拉干细胞科技股份有限公司 | Wound healing compositions |
| CN108354854A (en) * | 2018-04-24 | 2018-08-03 | 珀莱雅化妆品股份有限公司 | A kind of preparation method of the chitosan-based anti-acne hydrogel of temperature sensitive type used for cosmetic |
| CN111420117A (en) * | 2020-03-31 | 2020-07-17 | 陕西朗泰生物科技有限公司 | Preparation method of gel containing stem cell exosomes for skin wound repair |
| CN113018417A (en) * | 2021-03-29 | 2021-06-25 | 安徽工程大学 | Antibacterial drug material for promoting wound healing and preparation method thereof |
-
2016
- 2016-04-11 CN CN201610220078.3A patent/CN107281277A/en not_active Withdrawn
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108210891A (en) * | 2018-04-03 | 2018-06-29 | 广州赛莱拉干细胞科技股份有限公司 | Wound healing compositions |
| CN108354854A (en) * | 2018-04-24 | 2018-08-03 | 珀莱雅化妆品股份有限公司 | A kind of preparation method of the chitosan-based anti-acne hydrogel of temperature sensitive type used for cosmetic |
| CN111420117A (en) * | 2020-03-31 | 2020-07-17 | 陕西朗泰生物科技有限公司 | Preparation method of gel containing stem cell exosomes for skin wound repair |
| CN113018417A (en) * | 2021-03-29 | 2021-06-25 | 安徽工程大学 | Antibacterial drug material for promoting wound healing and preparation method thereof |
| CN113018417B (en) * | 2021-03-29 | 2023-05-16 | 安徽工程大学 | Antibacterial drug material for promoting wound healing and preparation method thereof |
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