CN113018419A - Medical chitosan nano-microsphere for repairing wound surface and inhibiting scar and preparation method thereof - Google Patents

Medical chitosan nano-microsphere for repairing wound surface and inhibiting scar and preparation method thereof Download PDF

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CN113018419A
CN113018419A CN202110354951.9A CN202110354951A CN113018419A CN 113018419 A CN113018419 A CN 113018419A CN 202110354951 A CN202110354951 A CN 202110354951A CN 113018419 A CN113018419 A CN 113018419A
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microsphere
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杨洋
秦丽丽
薛建华
刘佳佳
虞俊波
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Affiliated Hospital of Nantong University
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/18Growth factors; Growth regulators
    • A61K38/1825Fibroblast growth factor [FGF]
    • AHUMAN NECESSITIES
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    • A61K31/7028Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
    • A61K31/7034Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
    • A61K31/704Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K9/1617Organic compounds, e.g. phospholipids, fats
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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    • A61K9/14Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605Excipients; Inactive ingredients
    • A61K9/1629Organic macromolecular compounds
    • A61K9/1641Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • A61P17/02Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like

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Abstract

The invention relates to the field of medicines, in particular to a medical chitosan nano microsphere for wound repair and scar inhibition and a preparation method thereof, aiming at the problems of poor wound repair treatment, incapability of inhibiting scars, low drug-loading rate, poor dispersibility and unstable size of nano microsphere particles of the existing medical chitosan nano microsphere, the following scheme is proposed at present: the feed comprises the following raw materials in parts by weight: 3-6 parts of chitosan, 4-8 parts of 1% acetic acid solution, 1-2 parts of ethanol, 30.1-0.2 part of ginsenoside Rg, 0.4-0.5 part of dopamine, 0.1-0.2 part of BFGF, 4-6 parts of emulsifier, 20-32 parts of liquid paraffin and 12-18 parts of cross-linking agent. The medical chitosan nano-microsphere prepared by the invention enhances the wound repair treatment effect and can inhibit the formation of scars, and meanwhile, the medical chitosan nano-microsphere has the advantages of high drug loading capacity and good dispersibility, and the size of the medical chitosan nano-microsphere particles is stable.

Description

Medical chitosan nano-microsphere for repairing wound surface and inhibiting scar and preparation method thereof
Technical Field
The invention relates to the field of medicines, in particular to a medical chitosan nano microsphere for wound repair and scar inhibition, and also relates to a preparation method of the medical chitosan nano microsphere for wound repair and scar inhibition.
Background
The nano microsphere material has excellent biocompatibility and adjustable biodegradability, can be used for embedding and releasing medicines, proteins and genes, and compared with frequent injection administration, the nano microsphere drug-loaded nano microsphere realizes the slow release of the medicines in vivo to achieve an ideal treatment effect, wherein the medical chitosan nano microsphere is a chitosan polymer purified by crab shells, and is prepared by removing N-acetyl and further processing to obtain the chitosan, has the biological characteristics of selectively promoting the growth of epithelial cells and endothelial cells and inhibiting the growth of fibroblasts, can promote tissue physiological repair, and is a common medical material in the fields of tissue engineering and regenerative medicine.
The existing medical chitosan nano microspheres cannot promote skin regeneration and rapid repair at the initial stage, inhibit excessive fibroblast proliferation at the later stage, and cannot inhibit generation of hyperplastic scars, the prepared medical chitosan nano microspheres have low force of promoting repair and scar healing of damaged skin tissues, the wound repair and treatment effects are influenced, chitosan is degraded in an acidic environment, the viscosity of an aqueous solution is reduced, and the medical chitosan nano microspheres prepared by the method have low drug-loading rate and poor dispersibility, and the size of medical chitosan nano microsphere particles is unstable.
Disclosure of Invention
Technical problem to be solved
Aiming at the defects brought forward by the background technology, the invention provides a medical chitosan nano microsphere for repairing a wound surface and inhibiting scars and a preparation method thereof, and solves the problems brought forward by the background technology.
(II) technical scheme
In order to achieve the purpose, the invention provides the following technical scheme:
a medical chitosan nano microsphere for repairing a wound surface and inhibiting scars comprises the following raw materials in parts by weight: 3-6 parts of chitosan, 4-8 parts of 1% acetic acid solution, 1-2 parts of ethanol, 30.1-0.2 part of ginsenoside Rg, 0.4-0.5 part of dopamine, 0.1-0.2 part of BFGF, 4-6 parts of emulsifier, 20-32 parts of liquid paraffin and 12-18 parts of cross-linking agent.
Preferably, the feed comprises the following raw materials in parts by weight: 4-6 parts of chitosan, 5-8 parts of 1% acetic acid solution, 1-2 parts of ethanol, 30.15-0.2 part of ginsenoside Rg, 0.4-0.5 part of dopamine, 0.15-0.2 part of BFGF, 5-6 parts of emulsifier, 22-32 parts of liquid paraffin and 14-18 parts of cross-linking agent.
Preferably, the feed comprises the following raw materials in parts by weight: 5 parts of chitosan, 6 parts of 1% acetic acid solution, 1 part of ethanol, 30.15 parts of ginsenoside Rg, 0.4 part of dopamine, 0.15 part of BFGF, 4 parts of emulsifier, 26 parts of liquid paraffin and 14 parts of cross-linking agent.
Preferably, the weight part ratio of the ginsenoside Rg3 to the ginsenoside BFGF is 1: 1.
preferably, the emulsifier is sorbitan sesquioleate or glyceryl monostearate.
Preferably, the cross-linking agent is genipin or vanillin acetone.
The invention also provides a preparation method of the medical chitosan nano-microspheres for repairing the wound surface and inhibiting scars, which comprises the following steps:
preparation of an oil phase system of S1: measuring a certain amount of liquid paraffin, slowly adding the liquid paraffin into a round-bottom flask, adding a certain amount of emulsifier, and stirring the liquid in the round-bottom flask until the liquid paraffin is uniformly mixed to form an oil phase system to obtain an oil phase for later use;
preparation of an aqueous system of S2: weighing a certain amount of chitosan, dissolving the chitosan in a certain amount of 1% acetic acid solution, adding a certain amount of ethanol, and stirring for 1 hour by using an ultrasonic stirrer to form a water phase system to obtain a water phase for later use;
preparation of S3 emulsion: sucking the water phase by using a 1mL pipette, slowly and repeatedly dropping the water phase into the oil phase, and centrifugally stirring for 20-30 min under the centrifugal condition of 500-1000 rpm to obtain an emulsion water-in-oil emulsion;
s4 stirring: slowly adding quantitative ginsenoside Rg3, dopamine and BFGF into the emulsion, fully stirring for 1-1.5 h by using an ultrasonic stirrer, adding a cross-linking agent, and uniformly stirring;
s5 centrifugal separation: pouring the emulsion processed in the step S4 into a centrifuge tube, and centrifuging for 25min by using a centrifuge;
s6 one wash: adding 15mL of petroleum ether into a centrifugal tube, washing for 3 times, placing the centrifugal tube in a centrifugal machine, centrifuging for 20min at room temperature under the centrifugation condition of 1200rpm, standing for 6-8 min, and absorbing and removing the supernatant after layering;
s7 secondary washing: adding 15mL of acetone into the centrifuge tube treated in the step S6, washing for 3 times, placing the centrifuge tube in a centrifuge, centrifuging for 20min at room temperature under the centrifugation condition of 1200rpm, and standing for 6-8 min;
s8 drying and storing: and (4) absorbing and removing the supernatant fluid which is processed and layered in the step S7, freezing and drying to obtain the medical chitosan nano microspheres, collecting and storing in a dry environment.
(III) advantageous effects
Compared with the prior art, the invention provides the medical chitosan nano-microsphere for repairing the wound surface and inhibiting the scar and the preparation method thereof, and the medical chitosan nano-microsphere has the following beneficial effects:
ginsenoside Rg3 is immersed in dopamine aqueous solution, so that the surface is self-polymerized with a layer of polydopamine, and is used as a bridge and is doped with BFGF to the surface of the fiber in a matching way, so that the medical chitosan nano-microsphere is loaded with a micro-nano fiber support for inhibiting hypertrophic scars, the skin regeneration and rapid repair are promoted at the initial stage, the excessive proliferation of fiber cells is inhibited at the later stage so as to effectively inhibit the generation of hypertrophic scars, and the prepared medical chitosan nano-microsphere has the effects of promoting the repair and healing of damaged skin tissues and enhancing the wound repair and treatment effects.
The ethanol is doped to delay the reduction rate of the viscosity of the aqueous phase solution by inhibiting the degradation of chitosan in an acidic environment during the preparation of the aqueous phase, so that the medical chitosan nano-microsphere prepared by the method has the advantages of high drug loading and good dispersibility, and the size of the medical chitosan nano-microsphere particles is stable by matching with the doping of the cross-linking agent.
In conclusion, the medical chitosan nano-microspheres doped with the ginsenoside Rg3 are soaked in dopamine aqueous solution, so that a layer of polydopamine is gathered on the surface and used as a bridge, BFGF is doped on the surface of the fiber in a matching way, the medical chitosan nano-microspheres are loaded with the micro-nano fiber scaffold for inhibiting hypertrophic scars, the skin regeneration and rapid repair are promoted at the initial stage, the excessive proliferation of fiber cells is inhibited at the later stage, the generation of hypertrophic scars is effectively inhibited, the prepared medical chitosan nano-microspheres have the effects of promoting the repair and healing of damaged skin tissues, and the wound repair treatment effect is enhanced; the ethanol is doped to delay the reduction rate of the viscosity of the aqueous phase solution by inhibiting the degradation of chitosan in an acidic environment during the preparation of the aqueous phase, so that the medical chitosan nano-microsphere prepared by the method has the advantages of high drug loading and good dispersibility, and the size of the medical chitosan nano-microsphere particles is stable by matching with the doping of the cross-linking agent.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, rather than all embodiments, and all other embodiments obtained by a person of ordinary skill in the art without creative efforts based on the embodiments of the present invention belong to the protection scope of the present invention.
The first embodiment is as follows:
a medical chitosan nano microsphere for repairing a wound surface and inhibiting scars comprises the following raw materials in parts by weight: 3 parts of chitosan, 4 parts of 1% acetic acid solution, 1 part of ethanol, 30.1 parts of ginsenoside Rg, 0.4 part of dopamine, 0.1 part of BFGF, 4 parts of sorbitan sesquioleate, 20 parts of liquid paraffin and 12 parts of genipin.
A preparation method of medical chitosan nano-microspheres for wound repair and scar inhibition comprises the following steps:
preparation of an oil phase system of S1: weighing 20 parts of liquid paraffin, slowly adding the liquid paraffin into a round-bottom flask, adding 4 parts of sorbitan sesquioleate, and stirring the liquid in the round-bottom flask until the liquid paraffin is uniformly mixed to form an oil phase system to obtain an oil phase for later use;
preparation of an aqueous system of S2: weighing 3 parts of chitosan, dissolving the chitosan in 4 parts of 1% acetic acid solution, adding 1 part of ethanol, and stirring for 1 hour by using an ultrasonic stirrer to form a water phase system to obtain a water phase for later use;
preparation of S3 emulsion: sucking the water phase by using a 1mL pipette, slowly and repeatedly dropping the water phase into the oil phase, and centrifugally stirring for 20min under the centrifugal condition of 1000rpm to obtain an emulsion water-in-oil emulsion;
s4 stirring: slowly adding 0.1 part of ginsenoside Rg3, 0.4 part of dopamine and 0.1 part of BFGF into the emulsion, fully stirring for 1h by using an ultrasonic stirrer, then adding 12 parts of genipin, and uniformly stirring;
s5 centrifugal separation: pouring the emulsion processed in the step S4 into a centrifuge tube, and centrifuging for 25min by using a centrifuge;
s6 one wash: adding 15mL of petroleum ether into a centrifuge tube, washing for 3 times, placing the centrifuge tube in a centrifuge, centrifuging for 20min at room temperature under the centrifugation condition of 1200rpm, standing for 6min, and absorbing and removing the supernatant after layering;
s7 secondary washing: adding 15mL of acetone into the centrifuge tube treated in the step S6, washing for 3 times, placing the centrifuge tube in a centrifuge, centrifuging for 20min at room temperature under the centrifugation condition of 1200rpm, and standing for 6 min;
s8 drying and storing: and (4) absorbing and removing the supernatant fluid which is processed and layered in the step S7, freezing and drying to obtain the medical chitosan nano microspheres, collecting and storing in a dry environment.
Example two:
a medical chitosan nano microsphere for repairing a wound surface and inhibiting scars comprises the following raw materials in parts by weight: 4 parts of chitosan, 7 parts of 1% acetic acid solution, 2 parts of ethanol, 30.2 parts of ginsenoside Rg, 0.4 part of dopamine, 0.2 part of BFGF, 6 parts of glyceryl monostearate, 30 parts of liquid paraffin and 16 parts of genipin.
A preparation method of medical chitosan nano-microspheres for wound repair and scar inhibition comprises the following steps:
preparation of an oil phase system of S1: weighing 30 parts of liquid paraffin, slowly adding the liquid paraffin into a round-bottom flask, adding 6 parts of glyceryl monostearate, and stirring the liquid in the round-bottom flask until the liquid paraffin is uniformly mixed to form an oil phase system to obtain an oil phase for later use;
preparation of an aqueous system of S2: measuring 4 parts of chitosan, dissolving the chitosan in 7 parts of 1% acetic acid solution, adding 2 parts of ethanol, and stirring for 1 hour by using an ultrasonic stirrer to form a water phase system to obtain a water phase for later use;
preparation of S3 emulsion: sucking the water phase by using a 1mL pipette, slowly and repeatedly dropping the water phase into the oil phase, and centrifugally stirring for 25min under the centrifugal condition of 700rpm to obtain an emulsion water-in-oil emulsion;
s4 stirring: slowly adding 0.2 part of ginsenoside Rg3, 0.4 part of dopamine and 0.2 part of BFGF into the emulsion, fully stirring for 1.2h by using an ultrasonic stirrer, then adding 16 parts of genipin, and uniformly stirring;
s5 centrifugal separation: pouring the emulsion processed in the step S4 into a centrifuge tube, and centrifuging for 25min by using a centrifuge;
s6 one wash: adding 15mL of petroleum ether into a centrifuge tube, washing for 3 times, placing the centrifuge tube in a centrifuge, centrifuging for 20min at room temperature under the centrifugation condition of 1200rpm, standing for 7min, and absorbing and removing the supernatant after layering;
s7 secondary washing: adding 15mL of acetone into the centrifuge tube treated in the step S6, washing for 3 times, placing the centrifuge tube in a centrifuge, centrifuging for 20min at room temperature under the centrifugation condition of 1200rpm, and standing for 6 min;
s8 drying and storing: and (4) absorbing and removing the supernatant fluid which is processed and layered in the step S7, freezing and drying to obtain the medical chitosan nano microspheres, collecting and storing in a dry environment.
In the first embodiment and the second embodiment, the ginsenoside Rg3 is immersed in a dopamine aqueous solution, so that the surface is self-polymerized with a layer of polydopamine to serve as a bridge, BFGF is doped to the surface of the fiber in a matching way, the medical chitosan nano-microsphere is loaded with a micro-nano fiber scaffold for inhibiting hypertrophic scars, the skin regeneration and rapid repair are promoted at the initial stage, the excessive proliferation of fiber cells is inhibited at the later stage to effectively inhibit the generation of hypertrophic scars, and the prepared medical chitosan nano-microsphere has the effects of promoting the repair and healing of damaged skin tissues and enhancing the wound repair treatment effect; the ethanol is doped to delay the reduction rate of the viscosity of the aqueous phase solution by inhibiting the degradation of chitosan in an acidic environment during the preparation of the aqueous phase, so that the medical chitosan nano-microsphere prepared by the method has the advantages of high drug loading and good dispersibility, and the size of the medical chitosan nano-microsphere particles is stable by matching with the doping of the cross-linking agent.
Example three:
a medical chitosan nano microsphere for repairing a wound surface and inhibiting scars comprises the following raw materials in parts by weight: 5 parts of chitosan, 6 parts of 1% acetic acid solution, 1 part of ethanol, 30.15 parts of ginsenoside Rg, 0.4 part of dopamine, 0.15 part of BFGF, 4 parts of sorbitan sesquioleate, 26 parts of liquid paraffin, 14 parts of vanillin acetone, 8 parts of degradable medical polyurethane, 4 parts of high polymer material for promoting wound healing and 4 parts of micromolecular medicine with biological anti-inflammatory activity.
Preferably, the degradable medical polyurethane is preferably polyester PU (including PU materials with PCL and GA as soft segments and lysine diisocyanate as hard segments and with the degradation time of 7-14 days, PU materials with lysine diisocyanate cross-linked polylysine, PU materials with natural polymer carboxymethyl cellulose or hyaluronic acid as soft segments and lysine diisocyanate as hard segments), polyglycolide, copolymer of polylactide and polyglycolide, polycaprolactone-glycolide and polylysine, or a combination of two of them.
The high polymer material is one or two of sodium hyaluronate, zinc hyaluronate, alginate, modified alginate and alginate degraded into hexosamine and N-acetylglucosamine.
The small molecular drug is one or two combinations of polypeptides, amino acids and various anti-inflammatory drugs.
A preparation method of medical chitosan nano-microspheres for wound repair and scar inhibition comprises the following steps:
preparation of an oil phase system of S1: weighing 26 parts of liquid paraffin, slowly adding the liquid paraffin into a round-bottom flask, adding 4 parts of sorbitan sesquioleate, and stirring the liquid in the round-bottom flask until the liquid paraffin is uniformly mixed to form an oil phase system to obtain an oil phase for later use;
preparation of an aqueous system of S2: measuring 5 parts of chitosan, dissolving the chitosan in 6 parts of 1% acetic acid solution, adding 1 part of ethanol, and stirring for 1 hour by using an ultrasonic stirrer to form a water phase system to obtain a water phase for later use;
preparation of S3 emulsion: sucking the water phase by using a 1mL pipette, slowly and repeatedly dropping the water phase into the oil phase, and centrifugally stirring for 27min under the centrifugal condition of 850rpm to obtain an emulsion water-in-oil emulsion;
s4 stirring: slowly adding 0.15 part of ginsenoside Rg3, 0.4 part of dopamine, 0.15 part of BFGF, 8 parts of degradable medical polyurethane, 4 parts of high polymer material for promoting wound healing and 4 parts of micromolecule medicine with biological anti-inflammatory activity into the emulsion, fully stirring for 1.2 hours by using an ultrasonic stirrer, then adding 14 parts of vanillin acetone, and uniformly stirring;
s5 centrifugal separation: pouring the emulsion processed in the step S4 into a centrifuge tube, and centrifuging for 25min by using a centrifuge;
s6 one wash: adding 15mL of petroleum ether into a centrifuge tube, washing for 3 times, placing the centrifuge tube in a centrifuge, centrifuging for 20min at room temperature under the centrifugation condition of 1200rpm, standing for 7min, and absorbing and removing the supernatant after layering;
s7 secondary washing: adding 15mL of acetone into the centrifuge tube treated in the step S6, washing for 3 times, placing the centrifuge tube in a centrifuge, centrifuging for 20min at room temperature under the centrifugation condition of 1200rpm, and standing for 7 min;
s8 drying and storing: and (4) absorbing and removing the supernatant fluid which is processed and layered in the step S7, freezing and drying to obtain the medical chitosan nano microspheres, collecting and storing in a dry environment.
Example four
A medical chitosan nano microsphere for repairing a wound surface and inhibiting scars comprises the following raw materials in parts by weight: 6 parts of chitosan, 8 parts of 1% acetic acid solution, 2 parts of ethanol, 30.2 parts of ginsenoside Rg, 0.5 part of dopamine, 0.2 part of BFGF, 6 parts of glyceryl monostearate, 32 parts of liquid paraffin, 18 parts of vanillin acetone, 10 parts of degradable medical polyurethane, 4 parts of high polymer material for promoting wound healing and 5 parts of micromolecular medicine with biological anti-inflammatory activity.
Preferably, the degradable medical polyurethane is preferably polyester PU (including PU materials with PCL and GA as soft segments and lysine diisocyanate as hard segments and with the degradation time of 7-14 days, PU materials with lysine diisocyanate cross-linked polylysine, PU materials with natural polymer carboxymethyl cellulose or hyaluronic acid as soft segments and lysine diisocyanate as hard segments), polyglycolide, copolymer of polylactide and polyglycolide, polycaprolactone-glycolide and polylysine, or a combination of two of them.
The high polymer material is one or two of sodium hyaluronate, zinc hyaluronate, alginate, modified alginate and alginate degraded into hexosamine and N-acetylglucosamine.
The small molecular drug is one or two combinations of polypeptides, amino acids and various anti-inflammatory drugs.
A preparation method of medical chitosan nano-microspheres for wound repair and scar inhibition comprises the following steps:
preparation of an oil phase system of S1: weighing 32 parts of liquid paraffin, slowly adding the liquid paraffin into a round-bottom flask, adding 6 parts of glyceryl monostearate, and stirring the liquid in the round-bottom flask until the liquid paraffin is uniformly mixed to form an oil phase system to obtain an oil phase for later use;
preparation of an aqueous system of S2: measuring 6 parts of chitosan, dissolving the chitosan in 8 parts of 1% acetic acid solution, adding 2 parts of ethanol, and stirring for 1 hour by using an ultrasonic stirrer to form a water phase system to obtain a water phase for later use;
preparation of S3 emulsion: sucking the water phase by using a 1mL pipette, slowly and repeatedly dropping the water phase into the oil phase, and centrifugally stirring for 30min under the centrifugal condition of 500rpm to obtain an emulsion water-in-oil emulsion;
s4 stirring: slowly adding 0.2 part of ginsenoside Rg3, 0.5 part of dopamine, 0.2 part of BFGF, 10 parts of degradable medical polyurethane, 4 parts of high polymer material for promoting wound healing and 5 parts of micromolecule medicine with biological anti-inflammatory activity into the emulsion, fully stirring for 1.5h by using an ultrasonic stirrer, then adding 18 parts of vanillin acetone, and uniformly stirring;
s5 centrifugal separation: pouring the emulsion processed in the step S4 into a centrifuge tube, and centrifuging for 25min by using a centrifuge;
s6 one wash: adding 15mL of petroleum ether into a centrifuge tube, washing for 3 times, placing the centrifuge tube in a centrifuge, centrifuging for 20min at room temperature under the centrifugation condition of 1200rpm, standing for 8min, and absorbing and removing the supernatant after layering;
s7 secondary washing: adding 15mL of acetone into the centrifuge tube treated in the step S6, washing for 3 times, placing the centrifuge tube in a centrifuge, centrifuging for 20min at room temperature under the centrifugation condition of 1200rpm, and standing for 7 min;
s8 drying and storing: and (4) absorbing and removing the supernatant fluid which is processed and layered in the step S7, freezing and drying to obtain the medical chitosan nano microspheres, collecting and storing in a dry environment.
In the third embodiment and the fourth embodiment, the ginsenoside Rg3 is immersed in a dopamine aqueous solution, so that a layer of polydopamine is gathered on the surface, the polydopamine serves as a bridge, BFGF is doped on the surface of the fiber in a matching manner, the medical chitosan nano-microsphere is loaded with a micro-nano fiber scaffold for inhibiting hypertrophic scars, the skin regeneration and rapid repair are promoted at the initial stage, the excessive proliferation of fiber cells is inhibited at the later stage, the generation of hypertrophic scars is effectively inhibited, the prepared medical chitosan nano-microsphere has the effects of promoting the repair and healing of damaged skin tissues, and the wound repair treatment effect is enhanced; the ethanol is doped to delay the reduction rate of the viscosity of the aqueous phase solution by inhibiting the degradation of chitosan in an acidic environment during the preparation of the aqueous phase, so that the medical chitosan nano-microsphere prepared by the method has the advantages of high drug loading and good dispersibility, and the size of the medical chitosan nano-microsphere particles is stable by matching with the doping of the cross-linking agent.
Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that changes, modifications, substitutions and alterations can be made in these embodiments without departing from the principles and spirit of the invention, the scope of which is defined in the appended claims and their equivalents.

Claims (7)

1. The medical chitosan nano-microsphere for repairing the wound surface and inhibiting the scar is characterized by comprising the following raw materials in parts by weight: 3-6 parts of chitosan, 4-8 parts of 1% acetic acid solution, 1-2 parts of ethanol, 30.1-0.2 part of ginsenoside Rg, 0.4-0.5 part of dopamine, 0.1-0.2 part of BFGF, 4-6 parts of emulsifier, 20-32 parts of liquid paraffin and 12-18 parts of cross-linking agent.
2. The medical chitosan nano-microsphere for wound repair and scar inhibition according to claim 1, which is characterized by comprising the following raw materials in parts by weight: 4-6 parts of chitosan, 5-8 parts of 1% acetic acid solution, 1-2 parts of ethanol, 30.15-0.2 part of ginsenoside Rg, 0.4-0.5 part of dopamine, 0.15-0.2 part of BFGF, 5-6 parts of emulsifier, 22-32 parts of liquid paraffin and 14-18 parts of cross-linking agent.
3. The medical chitosan nano-microsphere for wound repair and scar inhibition according to claim 1, which is characterized by comprising the following raw materials in parts by weight: 5 parts of chitosan, 6 parts of 1% acetic acid solution, 1 part of ethanol, 30.15 parts of ginsenoside Rg, 0.4 part of dopamine, 0.15 part of BFGF, 4 parts of emulsifier, 26 parts of liquid paraffin and 14 parts of cross-linking agent.
4. The medical chitosan nano-microsphere for wound healing and scar inhibition according to claim 1, wherein the weight ratio of the ginsenoside Rg3 to the BFGF is 1: 1.
5. the medical chitosan nano-microsphere for wound healing and scar inhibition according to claim 1, wherein the emulsifier is sorbitan sesquioleate or glyceryl monostearate.
6. A chitosan nanosphere for medical use in wound healing and scar inhibition according to claim 1, wherein the cross-linking agent is genipin or vanillin acetonide.
7. A preparation method of medical chitosan nano-microspheres for wound repair and scar inhibition is characterized by comprising the following steps:
preparation of an oil phase system of S1: measuring a certain amount of liquid paraffin, slowly adding the liquid paraffin into a round-bottom flask, adding a certain amount of emulsifier, and stirring the liquid in the round-bottom flask until the liquid paraffin is uniformly mixed to form an oil phase system to obtain an oil phase for later use;
preparation of an aqueous system of S2: weighing a certain amount of chitosan, dissolving the chitosan in a certain amount of 1% acetic acid solution, adding a certain amount of ethanol, and stirring for 1 hour by using an ultrasonic stirrer to form a water phase system to obtain a water phase for later use;
preparation of S3 emulsion: sucking the water phase by using a 1mL pipette, slowly and repeatedly dropping the water phase into the oil phase, and centrifugally stirring for 20-30 min under the centrifugal condition of 500-1000 rpm to obtain an emulsion water-in-oil emulsion;
s4 stirring: slowly adding quantitative ginsenoside Rg3, dopamine and BFGF into the emulsion, fully stirring for 1-1.5 h by using an ultrasonic stirrer, adding a cross-linking agent, and uniformly stirring;
s5 centrifugal separation: pouring the emulsion processed in the step S4 into a centrifuge tube, and centrifuging for 25min by using a centrifuge;
s6 one wash: adding 15mL of petroleum ether into a centrifugal tube, washing for 3 times, placing the centrifugal tube in a centrifugal machine, centrifuging for 20min at room temperature under the centrifugation condition of 1200rpm, standing for 6-8 min, and absorbing and removing the supernatant after layering;
s7 secondary washing: adding 15mL of acetone into the centrifuge tube treated in the step S6, washing for 3 times, placing the centrifuge tube in a centrifuge, centrifuging for 20min at room temperature under the centrifugation condition of 1200rpm, and standing for 6-8 min;
s8 drying and storing: and (4) absorbing and removing the supernatant fluid which is processed and layered in the step S7, freezing and drying to obtain the medical chitosan nano microspheres, collecting and storing in a dry environment.
CN202110354951.9A 2021-04-01 2021-04-01 Medical chitosan nano-microsphere for repairing wound surface and inhibiting scar and preparation method thereof Pending CN113018419A (en)

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Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103656728A (en) * 2013-11-01 2014-03-26 深圳清华大学研究院 Wound repairing material and preparation method thereof
CN105664239A (en) * 2016-03-23 2016-06-15 成都交大麦迪克科技有限公司 Preparation method of self-adhesive skin repairing hydrogel
CN107596431A (en) * 2017-09-29 2018-01-19 温州生物材料与工程研究所 A kind of natural glycan Quito functional microsphere and Preparation method and use
CN108144115A (en) * 2018-02-09 2018-06-12 重庆医科大学附属永川医院 A kind of sustained anti-microbial anti-inflammatory bone cement of injectable and preparation method thereof
CN108578418A (en) * 2018-04-16 2018-09-28 云南中医学院 A kind of composition of medicine for treating diabetes wound surface in refractory to treatment complication
CN108853573A (en) * 2018-07-17 2018-11-23 山东景仲生物科技有限公司 A kind of hydrogel for promoting early stage wound healing and mitigating cicatrization
CN109432488A (en) * 2018-12-14 2019-03-08 武汉理工大学 A kind of preparation method of chitosan/gelatin-compounded hemostatic microsphere
CN111317852A (en) * 2020-02-27 2020-06-23 吉林大学 Medical dressing compounded by chitosan and polypropylene carbonate and preparation method thereof
CN111632075A (en) * 2020-05-27 2020-09-08 广州赛琅生物技术有限公司 Exosome preparation for promoting skin wound healing and preparation method thereof
AU2020103311A4 (en) * 2020-11-09 2021-01-14 Southwest Petroleum University Hollow polymer microsphere profile control agent and preparation method thereof

Patent Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103656728A (en) * 2013-11-01 2014-03-26 深圳清华大学研究院 Wound repairing material and preparation method thereof
CN105664239A (en) * 2016-03-23 2016-06-15 成都交大麦迪克科技有限公司 Preparation method of self-adhesive skin repairing hydrogel
CN107596431A (en) * 2017-09-29 2018-01-19 温州生物材料与工程研究所 A kind of natural glycan Quito functional microsphere and Preparation method and use
CN108144115A (en) * 2018-02-09 2018-06-12 重庆医科大学附属永川医院 A kind of sustained anti-microbial anti-inflammatory bone cement of injectable and preparation method thereof
CN108578418A (en) * 2018-04-16 2018-09-28 云南中医学院 A kind of composition of medicine for treating diabetes wound surface in refractory to treatment complication
CN108853573A (en) * 2018-07-17 2018-11-23 山东景仲生物科技有限公司 A kind of hydrogel for promoting early stage wound healing and mitigating cicatrization
CN109432488A (en) * 2018-12-14 2019-03-08 武汉理工大学 A kind of preparation method of chitosan/gelatin-compounded hemostatic microsphere
CN111317852A (en) * 2020-02-27 2020-06-23 吉林大学 Medical dressing compounded by chitosan and polypropylene carbonate and preparation method thereof
CN111632075A (en) * 2020-05-27 2020-09-08 广州赛琅生物技术有限公司 Exosome preparation for promoting skin wound healing and preparation method thereof
AU2020103311A4 (en) * 2020-11-09 2021-01-14 Southwest Petroleum University Hollow polymer microsphere profile control agent and preparation method thereof

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
靖雅笋: "新型聚多巴胺功能材料的制备与生物医用研究", 《中国优秀硕士学位论文全文数据库 工程科技Ⅰ辑》 *

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