CN116510068A - Preparation method of liposome temperature-sensitive gel dressing with whitening effect - Google Patents
Preparation method of liposome temperature-sensitive gel dressing with whitening effect Download PDFInfo
- Publication number
- CN116510068A CN116510068A CN202310393064.1A CN202310393064A CN116510068A CN 116510068 A CN116510068 A CN 116510068A CN 202310393064 A CN202310393064 A CN 202310393064A CN 116510068 A CN116510068 A CN 116510068A
- Authority
- CN
- China
- Prior art keywords
- liposome
- sensitive gel
- temperature
- gel dressing
- whitening effect
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000002502 liposome Substances 0.000 title claims abstract description 69
- 230000002087 whitening effect Effects 0.000 title claims abstract description 27
- 238000002360 preparation method Methods 0.000 title claims abstract description 13
- MLSJBGYKDYSOAE-DCWMUDTNSA-N L-Ascorbic acid-2-glucoside Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)=C1O MLSJBGYKDYSOAE-DCWMUDTNSA-N 0.000 claims abstract description 50
- 229940067599 ascorbyl glucoside Drugs 0.000 claims abstract description 50
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 36
- 238000000034 method Methods 0.000 claims abstract description 15
- 239000002245 particle Substances 0.000 claims abstract description 13
- 229920001661 Chitosan Polymers 0.000 claims description 51
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 33
- 239000000243 solution Substances 0.000 claims description 31
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 30
- 238000003756 stirring Methods 0.000 claims description 27
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 claims description 20
- 229920002674 hyaluronan Polymers 0.000 claims description 20
- 229960003160 hyaluronic acid Drugs 0.000 claims description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 19
- 229960002901 sodium glycerophosphate Drugs 0.000 claims description 16
- 238000010438 heat treatment Methods 0.000 claims description 12
- 230000003113 alkalizing effect Effects 0.000 claims description 9
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 9
- 238000002156 mixing Methods 0.000 claims description 8
- 230000001105 regulatory effect Effects 0.000 claims description 8
- 238000006467 substitution reaction Methods 0.000 claims description 8
- 238000001291 vacuum drying Methods 0.000 claims description 8
- 238000005406 washing Methods 0.000 claims description 8
- 239000011259 mixed solution Substances 0.000 claims description 7
- FOCAUTSVDIKZOP-UHFFFAOYSA-N chloroacetic acid Chemical compound OC(=O)CCl FOCAUTSVDIKZOP-UHFFFAOYSA-N 0.000 claims description 4
- 229940106681 chloroacetic acid Drugs 0.000 claims description 4
- 238000001914 filtration Methods 0.000 claims description 2
- 239000000499 gel Substances 0.000 abstract description 34
- 239000000017 hydrogel Substances 0.000 abstract description 20
- 239000003814 drug Substances 0.000 abstract description 13
- 238000002347 injection Methods 0.000 abstract description 8
- 239000007924 injection Substances 0.000 abstract description 8
- 229940079593 drug Drugs 0.000 abstract description 5
- 230000000694 effects Effects 0.000 abstract description 4
- 239000002994 raw material Substances 0.000 abstract description 3
- 238000013268 sustained release Methods 0.000 abstract description 2
- 239000012730 sustained-release form Substances 0.000 abstract description 2
- 210000003491 skin Anatomy 0.000 description 30
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- 239000002253 acid Substances 0.000 description 8
- 239000007864 aqueous solution Substances 0.000 description 8
- 235000019441 ethanol Nutrition 0.000 description 8
- 230000036564 melanin content Effects 0.000 description 8
- KUBWXQUHENSKGC-UHFFFAOYSA-N 2-chloroacetic acid;ethanol Chemical compound CCO.OC(=O)CCl KUBWXQUHENSKGC-UHFFFAOYSA-N 0.000 description 7
- 230000001186 cumulative effect Effects 0.000 description 7
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 6
- 229960000583 acetic acid Drugs 0.000 description 6
- 239000008280 blood Substances 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 239000012362 glacial acetic acid Substances 0.000 description 6
- 229930182478 glucoside Natural products 0.000 description 6
- 150000008131 glucosides Chemical class 0.000 description 6
- 238000000338 in vitro Methods 0.000 description 6
- 230000004048 modification Effects 0.000 description 6
- 238000012986 modification Methods 0.000 description 6
- 230000007935 neutral effect Effects 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- 238000000746 purification Methods 0.000 description 6
- 230000007480 spreading Effects 0.000 description 6
- 238000003892 spreading Methods 0.000 description 6
- 238000000967 suction filtration Methods 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 239000008279 sol Substances 0.000 description 5
- 229960005070 ascorbic acid Drugs 0.000 description 3
- 235000010323 ascorbic acid Nutrition 0.000 description 3
- 239000011668 ascorbic acid Substances 0.000 description 3
- 230000021523 carboxylation Effects 0.000 description 3
- 238000006473 carboxylation reaction Methods 0.000 description 3
- XUMBMVFBXHLACL-UHFFFAOYSA-N Melanin Chemical compound O=C1C(=O)C(C2=CNC3=C(C(C(=O)C4=C32)=O)C)=C2C4=CNC2=C1C XUMBMVFBXHLACL-UHFFFAOYSA-N 0.000 description 2
- 230000036760 body temperature Effects 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 238000013270 controlled release Methods 0.000 description 2
- 239000002537 cosmetic Substances 0.000 description 2
- 238000004132 cross linking Methods 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 238000011068 loading method Methods 0.000 description 2
- 239000011148 porous material Substances 0.000 description 2
- 230000008591 skin barrier function Effects 0.000 description 2
- 241000700199 Cavia porcellus Species 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000010382 chemical cross-linking Methods 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 210000002510 keratinocyte Anatomy 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- 210000000434 stratum corneum Anatomy 0.000 description 1
- 230000009469 supplementation Effects 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 238000009827 uniform distribution Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
- A61L26/0061—Use of materials characterised by their function or physical properties
- A61L26/008—Hydrogels or hydrocolloids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
- A61L26/0009—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form containing macromolecular materials
- A61L26/0023—Polysaccharides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
- A61L26/0061—Use of materials characterised by their function or physical properties
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
- A61L26/0061—Use of materials characterised by their function or physical properties
- A61L26/0066—Medicaments; Biocides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
- A61L26/0061—Use of materials characterised by their function or physical properties
- A61L26/009—Materials resorbable by the body
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/428—Vitamins, e.g. tocopherol, riboflavin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
- A61L2300/602—Type of release, e.g. controlled, sustained, slow
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Abstract
The invention relates to the technical field of hydrogel dressing, and discloses a preparation method of a liposome temperature-sensitive gel dressing with a whitening effect. The ascorbyl glucoside liposome is prepared by an ethanol injection method and is embedded into the hydrogel, so that the hydrogel dressing capable of stably and controllably releasing the ascorbyl glucoside liposome on the skin for a long time is obtained. The raw materials of the invention have good biocompatibility, the obtained hydrogel has proper skin smearing and adhesion properties, the hydrogel can be adhered to the skin, and the hydrogel has good sustained release effect on drug-loaded liposome with the particle size of 100-120 nm, thereby improving the bioavailability of the drug.
Description
Technical Field
The invention relates to the technical field of hydrogel dressing, in particular to a preparation method of a liposome temperature-sensitive gel dressing with a whitening effect.
Background
With the improvement of the living standard and aesthetic standard of people, smooth and fair skin is more and more promoted by women in various countries, and the whitening functional component is greatly focused as a functional raw material of the whitening cosmetics, so that the development and application research of the whitening cosmetics are continuously in depth. The ascorbyl glucoside is taken as one of important derivatives of the ascorbic acid, has similar oxidation resistance and whitening efficacy as the ascorbic acid and more stable physicochemical properties, and is expected to be a substitute product of the ascorbic acid. The skin barrier formed by dense keratinocytes is present on the surface of the human skin and is generally difficult to pass through by hydrophilic ascorbyl glucoside. The key to the nutritional supplementation, skin condition improvement and skin disease prevention action of the active ingredient is the necessity of crossing the skin barrier to the corresponding site and maintaining a certain administration time.
Liposomes are microvesicles formed from cholesterol and phospholipids and having a bilayer structure, which have a high degree of structural similarity and physiological compatibility with the stratum corneum of the skin, and thus can improve the skin transport of functional factors. The functional factors are encapsulated inside by liposome or clamped in the lipoid film, so that the stability and bioavailability are improved. However, liposome solutions have limited routes of administration and, due to their flowability, are prone to rapid clearance and difficult to achieve sustained release on skin. Loading it onto the hydrogel is a perfect solution. Hydrogels are three-dimensional network structured materials formed by physical or chemical cross-linking. In one aspect, the porous structure of the hydrogel can serve as a liposome attachment carrier and transport channel; on the other hand, the adhesiveness of the hydrogel enables the hydrogel to be applied to the skin surface, and the drug release is controlled through the environmental response and the gel crosslinking degree, so that the long-term and stable release is realized, the drug utilization rate is greatly improved, and the hydrogel is widely applied to drug delivery systems.
Disclosure of Invention
The invention aims at solving the defects that water-soluble ascorbyl glucoside is difficult to absorb on skin and low in bioavailability, and provides a preparation method of a liposome temperature-sensitive gel dressing with a whitening effect, so that stable and effective absorption of ascorbyl glucoside on skin medicaments is realized, and the whitening effect is exerted.
The aim of the invention is achieved by the following technical scheme:
the preparation method of the liposome temperature-sensitive gel dressing with the whitening effect is characterized by comprising the following steps of:
step one: preparing carboxymethyl chitosan by modifying chitosan, and then mixing the carboxymethyl chitosan with hyaluronic acid solution, beta-sodium glycerophosphate and water and uniformly stirring to form a mixed solution;
step two: and adding the liposome loaded with the ascorbyl glucoside into the mixed solution, and heating to prepare the ascorbyl glucoside liposome temperature-sensitive gel dressing.
The chitosan is modified to be prepared into a solution, which specifically comprises the following steps:
stirring chitosan, dispersing in ethanol, adding sodium hydroxide aqueous solution for alkalization, dripping chloroacetic acid ethanol solutions with different concentrations, stirring and modifying in water bath, regulating pH, suction filtering, washing, purifying, and vacuum drying to obtain carboxymethyl chitosan with different carboxyl substitution degrees.
The mass ratio of the chitosan to the chloroacetic acid is 5:1 g-5:6 g.
The conditions for alkalization with sodium hydroxide were: alkalizing for 2-4 hours at 10-35 ℃.
The conditions for stirring and modifying under the water bath are as follows: modifying at 40-60 deg.c for 2-4 hr.
In the second step, the ascorbyl glucoside liposome exists in a temperature-sensitive gel dressing.
In the second step, the heating temperature is 10-50 ℃.
In the second step, the particle size of the liposome loaded with the ascorbyl glucoside is 100-580 nm.
In the second step, the concentration of the ascorbyl glucoside in the temperature-sensitive gel is 0.1-6 mg/mL.
Further, the preparation method of the liposome temperature-sensitive gel dressing with the whitening effect comprises the following steps of:
(1) Dispersing chitosan powder in 40mL absolute ethyl alcohol, stirring for 1 hour, adding 40mL40wt% sodium hydroxide solution, alkalizing for 3 hours at room temperature, dripping chloroacetic acid ethanol solution, stirring and modifying for 3 hours in a water bath at 50 ℃, adjusting pH to be neutral by glacial acetic acid after the reaction is finished, and obtaining carboxymethyl chitosan with different carboxylation degrees through suction filtration, washing, purification and vacuum drying;
(2) Preparing ascorbyl glucoside liposome by ethanol injection method, obtaining liposome with different particle diameters by a liposome extruder, and dialyzing to remove unencapsulated medicine;
(3) Preparing carboxymethyl chitosan, hyaluronic acid and beta-sodium glycerophosphate into aqueous solution with a certain concentration, stirring and dissolving, ultrasonically removing bubbles, adding an ascorbyl glucoside liposome solution, uniformly mixing, and heating at different temperatures to obtain an ascorbyl glucoside liposome temperature-sensitive gel dressing;
(4) The ascorbyl glucoside liposome temperature-sensitive gel dressing is applied to a guinea pig melanin deposition model induced by ultraviolet rays, and skin chromaticity and melanin content are measured to evaluate the whitening efficacy.
Preferably, the mass ratio of the chitosan to the chloroacetic acid in the step (1) is 5:1 g-5:6 g, and the carboxylation degree of the carboxymethyl chitosan is 10-30%.
Preferably, the liposome in step (2) has a particle size of 100 to 580nm.
Preferably, the concentration of ascorbyl glucoside in the liposome in the step (2) is 0.1-6 mg/mL.
Preferably, the heating temperature in the step (3) is 10 to 50 ℃.
Preferably, the mass concentration ratio of the carboxymethyl chitosan to the hyaluronic acid in the step (3) is 1.6:0.01-1.6:1.6 wt%.
Compared with the prior art, the invention has the beneficial effects that:
(1) The invention provides a preparation method of a liposome temperature-sensitive gel dressing with a whitening effect, which takes carboxymethyl chitosan, hyaluronic acid and beta-sodium glycerophosphate as raw materials and has the advantages of biocompatibility, biodegradability and the like. The carboxymethyl chitosan and the hyaluronic acid can form an interpenetrating network structure with excellent dispersibility, hydroxyl and carboxyl on the chain provide a large number of hydrogen bonds, maintain certain gel strength and simultaneously have adhesion, and are favorable for smearing and adhering on skin. The carboxymethyl modification enhances the water solubility of chitosan, improves the solubility of chitosan in weak acid aqueous solution, and avoids the irritation of chitosan acid gel to skin.
(2) The liposome temperature-sensitive gel dressing with the whitening effect, which is obtained by the method, can regulate and control the gel low critical phase transition temperature to be close to the human body temperature of 37 ℃ by regulating the carboxyl substitution degree of carboxymethyl chitosan, so that the gel is in a solution state at room temperature, the uniform distribution of the liposome is facilitated, the gel is gelled in a short time after the gel contacts with the human body, and the administration of sites with any shape is realized.
(3) The liposome temperature-sensitive gel dressing with the whitening effect, which is obtained by the method, takes hydrogel as a carrier, and is embedded into the ascorbyl glucoside liposome, so that the drug loading rate and stability can be effectively improved. Meanwhile, gel pores with different sizes are formed according to the gel crosslinking degree, and the controlled release effect on liposomes with different particle sizes is achieved. In addition, the carboxymethyl chitosan and the hyaluronic acid can hydrate skin, promote skin penetration of the ascorbyl glucoside liposome serving as a whitening component, and achieve good whitening effect.
Drawings
FIG. 1. Degree of carboxyl substitution of carboxymethyl chitosan;
FIG. 2 is a view of the appearance and scanning electron microscope of the liposome temperature-sensitive hydrogel;
FIG. 3 lipid body temperature sensitive hydrogel spreadability;
FIG. 4 determination of gel temperature and gel time;
FIG. 5 cumulative skin release of ascorbyl glucoside in the gel;
fig. 6 skin chromaticity L values and skin color pictures;
FIG. 7 skin melanin content and section.
Detailed Description
The present invention will be further described in detail with reference to examples and comparative examples, without limiting the scope of the present invention.
Example 1
(1) Dispersing 5g of chitosan powder in 40mL of absolute ethyl alcohol, stirring for 1 hour, adding 40mL of 40wt% sodium hydroxide aqueous solution, alkalizing at room temperature and 25 ℃ for 3 hours, dripping 4mL of chloroacetic acid ethanol solution (0.5 g/mL), stirring in a water bath at 50 ℃ for modification for 3 hours, regulating pH to be neutral after the reaction is finished by glacial acetic acid, and carrying out suction filtration, washing, purification and vacuum drying to obtain carboxymethyl chitosan, wherein the substitution degree of carboxyl is 18.20+/-0.47 percent (shown in figure 1);
(2) Preparing ascorbyl glucoside liposome with particle diameter of 105.4nm by ethanol injection method, and dialyzing to remove unencapsulated medicine;
(3) Preparing carboxymethyl chitosan, hyaluronic acid, beta-sodium glycerophosphate and water into a solution, stirring and dissolving the solution, ultrasonically removing bubbles to obtain a mixed solution, adding an ascorbyl glucoside liposome solution, uniformly mixing the mixed solution, and heating the mixed solution at 37 ℃ for 300 seconds to obtain the ascorbyl glucoside liposome temperature-sensitive gel dressing. The mass percentage of carboxymethyl chitosan in the ascorbyl glucoside liposome temperature-sensitive gel dressing is 1.6wt%, the mass percentage of hyaluronic acid is 1wt%, the mass percentage of beta-sodium glycerophosphate is 13wt%, and the content of anti-blood acid glucoside is 0.5mg/mL;
(4) The hydrogel dressing had a spreading area of 57.2cm under a pressure of 500g 2 (FIG. 3), the cumulative in vitro skin release of ascorbyl glucoside was 35.20.+ -. 0.47. Mu.g/cm over 24 hours 2 (FIG. 5). In animal experiments, skin L values were 52.21 ±1.26 (fig. 6) and melanin content was 0.19±0.03% (fig. 7).
Example 2
(1) Preparing ascorbyl glucoside liposome with particle diameter of 108.2nm by ethanol injection method, and dialyzing to remove unencapsulated medicine;
(2) Preparing solution from carboxymethyl modified chitosan, hyaluronic acid, beta-sodium glycerophosphate and water, stirring for dissolving, ultrasonically removing bubbles, adding ascorbyl glucoside liposome solution, uniformly mixing, and heating at 37 ℃ for 40 seconds to obtain the ascorbyl glucoside liposome temperature-sensitive gel dressing. The weight percentage of chitosan in the temperature-sensitive gel dressing is 1.6 percent, the weight percentage of hyaluronic acid is 1 percent, the weight percentage of beta-sodium glycerophosphate is 13 percent, and the content of anti-blood acid glucoside is 0.5mg/mL;
(3) The spreading area of the hydrogel dressing under the pressure of 500g is 71.5cm 2 (FIG. 3), the cumulative in vitro skin release of ascorbyl glucoside was 15.30.+ -. 0.58. Mu.g/cm over 24 hours 2 (FIG. 5). In animal experiments, skin L values were 44.91 ±0.56 (fig. 6) and melanin content was 1.01±0.07% (fig. 7).
Example 3
(1) Dispersing 5g of chitosan powder in 40mL of absolute ethyl alcohol, stirring for 1 hour, adding 40mL of 40wt% sodium hydroxide aqueous solution, alkalizing at room temperature for 3 hours, dripping 4mL of chloroacetic acid ethanol solution (0.25 g/mL), stirring in a water bath at 50 ℃ for modification for 3 hours, regulating pH to be neutral by glacial acetic acid after the reaction, and carrying out suction filtration, washing, purification and vacuum drying to obtain carboxymethyl chitosan, wherein the substitution degree of carboxyl is 15.98+/-0.21 percent (shown in figure 1);
(2) Preparing ascorbyl glucoside liposome with particle diameter of 110.5nm by ethanol injection method, and dialyzing to remove unencapsulated medicine;
(3) Preparing carboxymethyl chitosan, hyaluronic acid, beta-sodium glycerophosphate and water into a solution, stirring and dissolving, ultrasonically removing bubbles, adding an ascorbyl glucoside liposome solution, uniformly mixing, and heating at 37 ℃ for 90 seconds to obtain the ascorbyl glucoside liposome temperature-sensitive gel dressing. The weight percentage of carboxymethyl chitosan in the temperature-sensitive gel dressing is 1.6 percent, the weight percentage of hyaluronic acid is 1 percent, the weight percentage of beta-sodium glycerophosphate is 13 percent, and the content of anti-blood acid glucoside is 0.5mg/mL;
(4) The hydrogel dressing had a spreading area of 81.9cm under a pressure of 500g 2 (FIG. 3), the cumulative in vitro skin release of ascorbyl glucoside was 20.24.+ -. 0.60. Mu.g/cm over 24 hours 2 (FIG. 5). In animal experiments, skin L values were 48.06±0.51 (fig. 6) and melanin content was 0.74±0.05% (fig. 7).
Example 4
(1) Dispersing 5g of chitosan powder in 40mL of absolute ethyl alcohol, stirring for 1 hour, adding 40mL of 40wt% sodium hydroxide aqueous solution, alkalizing at room temperature for 3 hours, dripping 4mL of chloroacetic acid ethanol solution (1.0 g/mL), stirring in a water bath at 50 ℃ for modification for 3 hours, regulating pH to be neutral by glacial acetic acid after the reaction, and carrying out suction filtration, washing, purification and vacuum drying to obtain carboxymethyl chitosan, wherein the substitution degree of carboxyl is 24.86+/-0.79 percent (shown in figure 1);
(2) Preparing ascorbyl glucoside liposome with particle diameter of 101.8nm by ethanol injection method, and dialyzing to remove unencapsulated medicine;
(3) Preparing carboxymethyl chitosan, hyaluronic acid, beta-sodium glycerophosphate and water into a solution, stirring and dissolving, ultrasonically removing bubbles, adding an ascorbyl glucoside liposome solution, uniformly mixing, and heating at 37 ℃ for 30 minutes to obtain the ascorbyl glucoside liposome sol dressing. The sol dressing comprises 1.6wt% of carboxymethyl chitosan, 1wt% of hyaluronic acid, 13wt% of beta-sodium glycerophosphate and 0.5mg/mL of anti-blood acid glucoside;
(4) The dressing had a spreading area of 109.5cm under a pressure of 500g 2 (FIG. 3), the cumulative in vitro skin release of ascorbyl glucoside was 25.26.+ -. 0.84. Mu.g/cm over 24 hours 2 (FIG. 5). Skin L values were 48.84±1.28 (fig. 6) and melanin content was 0.51±0.06% (fig. 7).
Example 5
(1) Dispersing 5g of chitosan powder in 40mL of absolute ethyl alcohol, stirring for 1 hour, adding 40mL of 40wt% sodium hydroxide aqueous solution, alkalizing at room temperature for 3 hours, dripping 4mL of chloroacetic acid ethanol solution (1.5 g/mL), stirring in a water bath at 50 ℃ for modification for 3 hours, regulating pH to be neutral by glacial acetic acid after the reaction, and carrying out suction filtration, washing, purification and vacuum drying to obtain carboxymethyl chitosan with the carboxyl substitution degree of 27.49 +/-0.41 percent (shown in figure 1);
(2) Preparing ascorbyl glucoside liposome with particle diameter of 115.4nm by ethanol injection method, and dialyzing to remove unencapsulated medicine;
(3) Preparing carboxymethyl chitosan, hyaluronic acid, beta-sodium glycerophosphate and water into a solution, stirring and dissolving, ultrasonically removing bubbles, adding an ascorbyl glucoside liposome solution, and heating at 37 ℃ for 30 minutes to obtain the ascorbyl glucoside liposome sol dressing. The sol dressing comprises 1.6wt% of carboxymethyl chitosan, 1wt% of hyaluronic acid, 13wt% of beta-sodium glycerophosphate and 0.5mg/mL of anti-blood acid glucoside;
(4) The dressing had a spreading area of 115.9cm under a pressure of 500g 2 (FIG. 3), the cumulative in vitro skin release of ascorbyl glucoside was 27.58.+ -. 1.42. Mu.g/cm over 24 hours 2 (FIG. 5). In animal experiments, the skin L values were 51.56±0.95 (fig. 6) and the melanin content was 0.45±0.04% (fig. 7).
Comparative example 1
(1) Dispersing 5g of chitosan powder in 40mL of absolute ethyl alcohol, stirring for 1 hour, adding 40mL of 40wt% sodium hydroxide aqueous solution, alkalizing at room temperature for 3 hours, dripping 4mL of chloroacetic acid ethanol solution (0.5 g/mL), stirring in a water bath at 50 ℃ for modification for 3 hours, regulating pH to be neutral by glacial acetic acid after the reaction, and carrying out suction filtration, washing, purification and vacuum drying to obtain carboxymethyl chitosan with carboxylation degree of 18.20+/-0.47 percent (shown in figure 1);
(2) Preparing ascorbyl glucoside liposome with particle size of 589.6nm by ethanol injection method, and dialyzing to remove unencapsulated medicine;
(3) Preparing carboxymethyl chitosan, hyaluronic acid, beta-sodium glycerophosphate and water into a solution, stirring and dissolving, ultrasonically removing bubbles, adding an ascorbyl glucoside liposome solution, uniformly mixing, and heating at 37 ℃ for 300 seconds to obtain the ascorbyl glucoside liposome sol dressing. The weight percentage of carboxymethyl chitosan in the temperature-sensitive gel dressing is 1.6 percent, the weight percentage of hyaluronic acid is 1 percent, the weight percentage of beta-sodium glycerophosphate is 13 percent, and the content of anti-blood acid glucoside is 6mg/mL;
(4) The hydrogel dressing had a spreading area of 57.2cm under a pressure of 500g 2 (FIG. 3), the cumulative in vitro skin release of ascorbyl glucoside was 9.33.+ -. 0.89. Mu.g/cm over 24 hours 2 . This is probably due to the entrapment effect of the small pore size gel matrix on the large particle size liposomes (fig. 2), thus producing a controlled release effect on the liposomes. In animal experiments, the skin L values were 40.91 ±1.22 and the melanin content was 1.25±0.13%.
Claims (9)
1. The preparation method of the liposome temperature-sensitive gel dressing with the whitening effect is characterized by comprising the following steps of:
step one: preparing carboxymethyl chitosan by modifying chitosan, and then mixing the carboxymethyl chitosan with hyaluronic acid solution, beta-sodium glycerophosphate and water and uniformly stirring to form a mixed solution;
step two: and adding the liposome loaded with the ascorbyl glucoside into the mixed solution, and heating to prepare the ascorbyl glucoside liposome temperature-sensitive gel dressing.
2. The preparation method of the liposome temperature-sensitive gel dressing with the whitening effect according to claim 1, which is characterized in that chitosan is modified to prepare a solution, and the preparation method specifically comprises the following steps:
stirring chitosan, dispersing in ethanol, adding sodium hydroxide solution for alkalization, dripping ethanol solutions of chloroacetic acid with different concentrations, stirring and modifying in water bath, regulating pH, suction filtering, washing, purifying, and vacuum drying to obtain carboxymethyl chitosan with different carboxyl substitution degrees.
3. The preparation method of the liposome temperature-sensitive gel dressing with the whitening effect according to claim 2, wherein the mass ratio of chitosan to chloroacetic acid is 5:1-5:6.
4. The method for preparing the liposome temperature-sensitive gel dressing with whitening effect according to claim 2, wherein the condition of alkalizing with sodium hydroxide is as follows: alkalizing for 2-4 hours at 10-35 ℃.
5. The method for preparing the liposome temperature-sensitive gel dressing with whitening effect according to claim 2, wherein the conditions for stirring and modifying under water bath are as follows: modifying at 40-60 deg.c for 2-4 hr.
6. The preparation method of the liposome temperature-sensitive gel dressing with the whitening effect according to claim 1, wherein in the second step, the mass concentration ratio of the carboxymethyl chitosan to the hyaluronic acid in the ascorbyl glucoside liposome temperature-sensitive gel dressing is 1.6:0.01-1.6:1.6 wt%.
7. The method for preparing a liposome temperature-sensitive gel dressing with whitening effect according to claim 1, wherein in the second step, the heating temperature is 10-50 ℃.
8. The method for preparing a liposome temperature-sensitive gel dressing with whitening effect according to claim 1, wherein in the second step, the particle size of the liposome loaded with the ascorbyl glucoside is 100-580 nm.
9. The method for preparing the liposome temperature-sensitive gel dressing with the whitening effect according to claim 1, wherein in the second step, the concentration of the ascorbyl glucoside in the ascorbyl glucoside liposome temperature-sensitive gel dressing is 0.1-6 mg/mL.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310393064.1A CN116510068A (en) | 2023-04-13 | 2023-04-13 | Preparation method of liposome temperature-sensitive gel dressing with whitening effect |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310393064.1A CN116510068A (en) | 2023-04-13 | 2023-04-13 | Preparation method of liposome temperature-sensitive gel dressing with whitening effect |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN116510068A true CN116510068A (en) | 2023-08-01 |
Family
ID=87393258
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202310393064.1A Pending CN116510068A (en) | 2023-04-13 | 2023-04-13 | Preparation method of liposome temperature-sensitive gel dressing with whitening effect |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN116510068A (en) |
-
2023
- 2023-04-13 CN CN202310393064.1A patent/CN116510068A/en active Pending
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP0224987B1 (en) | Drug delivery systems based on hyaluronan, derivatives thereof and their salts and method of producing same | |
| US9822243B2 (en) | Freeze-dried composition | |
| Sabbagh et al. | Recent progress in polymeric non-invasive insulin delivery | |
| KR101012289B1 (en) | Sheetless face mask using hydrogel and fabrication method thereof | |
| Anirudhan et al. | Deposition of gold-cellulose hybrid nanofiller on a polyelectrolyte membrane constructed using guar gum and poly (vinyl alcohol) for transdermal drug delivery | |
| FI118415B (en) | Collagen preparations for controlled release of active substances | |
| Tekade et al. | Biopolymer-based nanocomposites for transdermal drug delivery | |
| KR101032125B1 (en) | Method for producing porous moulded bodies containing alginate | |
| JP6519930B2 (en) | Water soluble hyaluronic acid gel and method for producing the same | |
| Noreen et al. | Natural polysaccharide-based biodegradable polymeric platforms for transdermal drug delivery system: A critical analysis | |
| KR20120033393A (en) | Hydrogel pack using chitosan and method of preparing the same | |
| CN112121032A (en) | Hydrogel patch for skin care and preparation method thereof | |
| Samiraninezhad et al. | Using chitosan, hyaluronic acid, alginate, and gelatin-based smart biological hydrogels for drug delivery in oral mucosal lesions: A review | |
| CN106390179B (en) | A kind of polyurethane sponge dressing and preparation method thereof with the hemostatic function that prevents adhesion | |
| CN110917120A (en) | Sticky antibacterial repairing material and preparation method and application thereof | |
| Parhi et al. | Applications of polysaccharides in topical and transdermal drug delivery: A recent update of literature | |
| CN116510068A (en) | Preparation method of liposome temperature-sensitive gel dressing with whitening effect | |
| Wijayadi et al. | Characterized and synthesis of chitosan nanoparticle as nanocarrier system technology | |
| Djekic et al. | Micro-and nanoscale drug delivery systems based on xanthan gum hydrogels | |
| CN114099710A (en) | Hyaluronic acid-cyclodextrin nano carrier for promoting skin retention of active substances | |
| Chahardoli et al. | Application of micro-and nanoengineering tragacanth and its water-soluble derivative in drug delivery and tissue engineering | |
| JP2004231604A (en) | Carrier sheet, sustained release preparation and method for producing the same | |
| Nayak et al. | Pharmaceutical applications of natural polymers | |
| JP6478132B2 (en) | Water-soluble hyaluronic acid gel and method for producing the same | |
| JP6512560B2 (en) | Water soluble hyaluronic acid gel and method for producing the same |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |