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CN-121987560-A - Nerve regulation composite gel constructed based on programmed assembly and preparation method thereof

CN121987560ACN 121987560 ACN121987560 ACN 121987560ACN-121987560-A

Abstract

The invention relates to the technical field of biomedical materials, in particular to a nerve regulation composite gel constructed based on programmed assembly and a preparation method thereof, which comprises the following steps of preparing an active unit by selecting and mixing 3-5 parts of suberect spatholobus stem, 2-3 parts of dried orange peel, 2-3 parts of Chinese angelica, 2 parts of radix bupleuri, 2 parts of costustoot, 1-1.5 parts of astragalus mongholicus, 1-1.5 parts of bighead atractylodes rhizome, 1 part of poria cocos and 1 part of rhizoma alismatis, adding at least one of 1 part of radix salviae miltiorrhizae and 1 part of ligusticum wallichii, and adopting low-temperature composite enzymolysis combined with microwave auxiliary extraction or ultrasonic auxiliary extraction technology.

Inventors

  • GONG YIHAN

Assignees

  • 金华资御品牌管理有限公司

Dates

Publication Date
20260508
Application Date
20260304

Claims (10)

  1. 1. The nerve regulation composite gel constructed based on programmed assembly is characterized by being prepared by cyclic freezing-thawing physical crosslinking of multisource synergistic nano functional body dispersion liquid and modified sodium hyaluronate solution; The multisource synergistic nano functional body dispersion liquid is prepared by programmed assembly of a plant source active oligomer and a synthetic oligomer according to the mass ratio of 7:3-9:1, wherein the plant source active oligomer is prepared by taking 3-5 parts of suberect spatholobus stem, 2-3 parts of dried orange peel, 2-3 parts of Chinese angelica, 2 parts of radix bupleuri, 2 parts of costustoot, 1-1.5 parts of astragalus membranaceus, 1-1.5 parts of bighead atractylodes rhizome, 1 part of poria cocos and 1 part of rhizoma alismatis as raw materials or adding at least one of 1 part of salvia miltiorrhiza and 1 part of ligusticum wallichii as raw materials through low-temperature composite enzymolysis combined with microwave-assisted extraction or ultrasonic-assisted extraction, under the conditions of-50 ℃ and 0.08MPa, and the synthetic oligomer is prepared by vacuum freeze drying under the conditions of acetyl hexapeptide or acetyl hexapeptide and palmitoyl pentapeptide-4, and the purity of the synthetic oligomer is not lower than 95 percent; The modified sodium hyaluronate is prepared by modifying sodium hyaluronate by at least one of octyl glycidyl ether, palmitoyl, stearyl and decyl glycidyl ether, the substitution degree of the modified sodium hyaluronate is 0.12-0.20, the concentration is 1.5-2.2%, the volume ratio of the multi-source synergistic nano functional body dispersion liquid to the modified sodium hyaluronate solution is 1:8-1:10, the cyclic freezing-thawing physical crosslinking is carried out for 1.5-2.5 hours at-20 ℃ to-18 ℃ and the thawing for 1 hour at 25 ℃ is a crosslinking cycle, and the crosslinking cycle is repeated for 2-4 times.
  2. 2. The neuromodulation composite gel as in claim 1, wherein the plant-derived active oligomer is prepared from 3 parts of spatholobus stem, 2 parts of dried orange peel, 2 parts of Chinese angelica, 2 parts of bupleurum, 2 parts of costustoot, 1 part of astragalus root, 1 part of bighead atractylodes rhizome, 1 part of poria cocos, 1 part of alisma orientale, or from 4-5 parts of suberect spatholobus stem, 3 parts of dried orange peel, 2-3 parts of angelica, 2 parts of bupleurum, 2 parts of costustoot, 1.5 parts of astragalus root, 1-1.5 parts of bighead atractylodes rhizome, 1 part of poria cocos, 1 part of alisma orientale and 1 part of salvia miltiorrhiza and 1 part of ligusticum wallichii, wherein when the synthetic oligomer is a compound of acetyl hexapeptide and palmitoyl pentapeptide-4, the mass ratio of the acetyl hexapeptide to palmitoyl pentapeptide-4 is 1:1.
  3. 3. The preparation method of the nerve modulation composite gel based on programmed assembly construction is characterized by comprising the following steps of: (1) The preparation of an active unit comprises the steps of mixing 3-5 parts of suberect spatholobus stem, 2-3 parts of dried orange peel, 2-3 parts of Chinese angelica, 2 parts of radix bupleuri, 2 parts of costustoot, 1-1.5 parts of astragalus membranaceus, 1-1.5 parts of bighead atractylodes rhizome, 1 part of poria cocos and 1 part of rhizoma alismatis, or adding at least one of 1 part of radix salviae miltiorrhizae and 1 part of rhizoma ligustici wallichii, mixing, and extracting by adopting low-temperature compound enzymolysis combined with microwave-assisted extraction or ultrasonic-assisted extraction technology, wherein compound enzyme used for the low-temperature compound enzymolysis comprises cellulase and pectase or papain, the additive amount of the compound enzyme is 2-2.5% of the total mass of raw materials, and the extract is subjected to vacuum freeze-drying under the conditions of 50 ℃ below zero and 0.08MPa after the interception treatment of a 10kDa ultrafiltration membrane, preparing a synthetic oligomer by adopting a solid-phase synthesis method, wherein the synthetic oligomer is prepared by adopting a compound of acetyl hexapeptide or acetyl hexapeptide and palmitoyl pentapeptide-4, and the purity of the synthetic oligomer is not lower than 95% after deprotection and purification treatment; (2) The preparation method comprises the steps of programmed assembly, namely mixing a plant source active oligomer and a synthetic oligomer according to a mass ratio of 7:3-9:1, dissolving the mixture in a phosphate buffer solution with a pH value of 7.4, preparing a mixed solution with a total concentration of 5 mg/mL-6 mg/mL, pre-incubating for 1.5 hours-2 hours under the conditions of 18 ℃ to 22 ℃ and 120rpm, and then heating the mixed solution to 25 ℃ to 28 ℃ and mainly incubating for 4 hours-5 hours under the conditions of 150 rpm-160 rpm to obtain a multi-source synergistic nano-functional dispersion; (3) The gel construction comprises the steps of uniformly mixing multisource synergistic nano functional body dispersion liquid and modified sodium hyaluronate solution according to a volume ratio of 1:8-1:10, wherein a modifier of the modified sodium hyaluronate is at least one of octyl glycidyl ether, palmitoyl, stearoyl and decyl glycidyl ether, the substitution degree of the modified sodium hyaluronate is 0.12-0.20, the concentration is 1.5-2.2%, the modified sodium hyaluronate is crosslinked by adopting a cyclic freezing-thawing physical crosslinking method, freezing is carried out for 1.5-2.5 hours at-20 ℃ to-18 ℃ for 1 hour, thawing is carried out for 1 hour at 25 ℃ for one crosslinking cycle, and repeating for 2-4 times to obtain the neuromodulation composite gel.
  4. 4. The method according to claim 3, wherein in the step (1), the mass ratio of the cellulase to the pectase is 1:1, and when the complex enzyme contains papain, the mass ratio of the cellulase, the pectase to the papain is 2:1:1.
  5. 5. The method according to claim 3, wherein in the step (1), when the synthetic oligomer is a complex of acetyl hexapeptide and palmitoyl pentapeptide-4, the mass ratio of acetyl hexapeptide to palmitoyl pentapeptide-4 is 1:1.
  6. 6. A method according to claim 3, wherein in step (2), the pre-incubation conditions are 20 ℃, 120rpm, 2 hours, or 18 ℃, 120rpm, 1.5 hours, or 22 ℃, 120rpm, 2 hours, and the main incubation conditions are 25 ℃, 150rpm, 4 hours, or 28 ℃, 160rpm, 4.5 hours, or 25 ℃, 150rpm, 5 hours.
  7. 7. The method according to claim 3, wherein in the step (3), the modifying agent of the modified sodium hyaluronate is one of octyl glycidyl ether, palmitoyl, stearyl, decyl glycidyl ether, or a combination of octyl glycidyl ether and palmitoyl.
  8. 8. The method of claim 3, wherein in step (3), the concentration of the modified sodium hyaluronate is 1.6%, 1.8%, 2.0% or 2.2%, and the volume ratio of the multi-source synergistic nano-functional dispersion to the modified sodium hyaluronate solution is 1:8, 1:9 or 1:10.
  9. 9. The method according to claim 3, wherein in the step (3), the cycle of the physical cross-linking method of freezing at-20 ℃ for 2 hours is repeated 3 times.
  10. 10. A neuromodulation composite gel prepared according to the method of any of claims 3 to 9.

Description

Nerve regulation composite gel constructed based on programmed assembly and preparation method thereof Technical Field The invention relates to the technical field of biomedical materials, in particular to a nerve regulation composite gel constructed based on programmed assembly and a preparation method thereof. Background The nerve regulation biomedical material has important application value in clinical scenes such as nerve repair, fibrosis intervention and the like, and the performance of the material directly influences the treatment effect and the biological safety. At present, gel materials in the related art have a plurality of technical bottlenecks. In the aspect of ingredient compounding, the existing products mostly adopt single plant source extracts or synthetic peptide ingredients, and lack of cooperative design of multi-source active substances, so that the nerve regulation activity is limited, and the dual requirements of nerve cell protection and anti-fibrosis are difficult to meet at the same time. In the assembly process, the traditional technology depends on simple mechanical mixing or single condition incubation, and directional and ordered combination of active ingredients cannot be realized, so that the active ingredients are unevenly dispersed and have poor stability, and further the slow release effect and bioavailability are affected. In the aspect of crosslinking mode, chemical crosslinking method is still mainstream, although gel mechanical property can be improved, residual crosslinking agent is easy to cause cytotoxicity, biocompatibility is reduced, and clinical application safety is limited. In the extraction process, the traditional modes of high-temperature water boiling, simple solvent extraction and the like have low efficiency, active oligomers in plant source raw materials are difficult to fully release, and the subsequent purification treatment is insufficient, so that the purity of active ingredients is low, the impurity content is high, and the function of the material is further influenced. In addition, the existing gel has the problems of unbalanced mechanical property and injectability, too fast or too slow degradation rate and the like, cannot adapt to the actual requirements of physiological environments in vivo, and restricts the popularization and application of the gel in high-end biomedical scenes. Therefore, developing a nerve regulation composite gel with synergistic components, advanced process, safety and high efficiency has important practical significance and market value. Disclosure of Invention The invention aims at providing a nerve modulation composite gel constructed based on programmed assembly and a preparation method thereof. The invention further aims to provide a nerve modulation composite gel constructed based on programmed assembly, which is prepared by circulating freezing-thawing physical crosslinking of multisource collaborative nanometer functional body dispersion liquid and modified sodium hyaluronate solution; The multisource synergistic nano functional body dispersion liquid is prepared by programmed assembly of a plant source active oligomer and a synthetic oligomer according to the mass ratio of 7:3-9:1, wherein the plant source active oligomer is prepared by taking 3-5 parts of suberect spatholobus stem, 2-3 parts of dried orange peel, 2-3 parts of Chinese angelica, 2 parts of radix bupleuri, 2 parts of costustoot, 1-1.5 parts of astragalus membranaceus, 1-1.5 parts of bighead atractylodes rhizome, 1 part of poria cocos and 1 part of rhizoma alismatis as raw materials or adding at least one of 1 part of salvia miltiorrhiza and 1 part of ligusticum wallichii as raw materials through low-temperature composite enzymolysis combined with microwave-assisted extraction or ultrasonic-assisted extraction, under the conditions of-50 ℃ and 0.08MPa, and the synthetic oligomer is prepared by vacuum freeze drying under the conditions of acetyl hexapeptide or acetyl hexapeptide and palmitoyl pentapeptide-4, and the purity of the synthetic oligomer is not lower than 95 percent; The modified sodium hyaluronate is prepared by modifying sodium hyaluronate by at least one of octyl glycidyl ether, palmitoyl, stearyl and decyl glycidyl ether, the substitution degree of the modified sodium hyaluronate is 0.12-0.20, the concentration is 1.5-2.2%, the volume ratio of the multi-source synergistic nano functional body dispersion liquid to the modified sodium hyaluronate solution is 1:8-1:10, the cyclic freezing-thawing physical crosslinking is carried out for 1.5-2.5 hours at-20 ℃ to-18 ℃ and the thawing for 1 hour at 25 ℃ is a crosslinking cycle, and the crosslinking cycle is repeated for 2-4 times. Preferably, the plant source active oligomer is prepared from 3 parts of suberect spatholobus stem, 2 parts of dried orange peel, 2 parts of Chinese angelica, 2 parts of radix bupleuri, 2 parts of costustoot, 1 part of astragalus membranaceus, 1 part of bighead