CN-121971377-A - Poria cocos peel triterpene modified product sodium alginate hydrogel dressing with stage-specific repair function, and preparation method and application thereof

CN121971377ACN 121971377 ACN121971377 ACN 121971377ACN-121971377-A

Abstract

The invention relates to the technical field of biological medicine. The invention provides a poria peel triterpene modified product-sodium alginate hydrogel dressing with a stage-specific repair function, and a preparation method and application thereof. According to the preparation method, three poria peel triterpene differentiation modified products (PCTT/SD, PCNT/SD and PCWT) are obtained through a solid dispersion technology or a salifying technology, and after the poria peel triterpene differentiation modified products are loaded on hydrogel, clear and complementary stage-specific treatment advantages are shown in a complex wound healing process, namely PCNT/SD/Gel strongly regulate early inflammation and accelerate initial repair, PCTT/SD/Gel remarkably promote middle-stage collagen synthesis and deposition, and PCWT/Gel efficiently drive later-stage epithelialization, angiogenesis and tissue remodeling. The invention realizes accurate time sequence regulation of the wound healing process, provides an innovative treatment strategy for difficult-to-heal wounds such as diabetic foot ulcers and the like, and obviously improves the added value of poria cocos skin byproducts.

Inventors

ZAN JUNFENG
LIU JUNFENG
WANG PING
YU YUNAN
CHEN MINGZHI

Assignees

湖北中医药大学

Dates

Publication Date: 20260505
Application Date: 20260313

Claims (10)

1. A poria peel triterpene modified product-sodium alginate hydrogel dressing with a stage-specific repair function is characterized by comprising a three-dimensional porous network structure sodium alginate hydrogel matrix and poria peel triterpene differential modified products dispersed in the sodium alginate hydrogel matrix; The poria peel triterpene differentiation modified product is at least one selected from the group consisting of poria peel total triterpene solid dispersion with polyvinylpyrrolidone as a carrier, poria peel neutral triterpene solid dispersion with polyvinylpyrrolidone as a carrier, and poria peel triterpene acid salt.
2. The poria cocos peel triterpene modified product-sodium alginate hydrogel dressing according to claim 1, wherein the preparation method of the poria cocos peel total triterpene solid dispersion taking polyvinylpyrrolidone as a carrier is as follows: mixing Poria skin with alcohol, heating and reflux extracting to obtain extractive solution, concentrating the extractive solution, and drying to obtain Poria skin total triterpene compound; Mixing the poria peel total triterpene compound with polyvinylpyrrolidone, adding an alcohol solvent, continuously mixing, heating and evaporating the alcohol solvent, and drying to obtain a poria peel total triterpene solid dispersion taking polyvinylpyrrolidone as a carrier; the preparation method of the poria peel neutral triterpene solid dispersion taking polyvinylpyrrolidone as a carrier comprises the following steps: dripping alcohol solution of total triterpene compounds of Poria skin into aqueous solution of alkali metal hydroxide, reacting, and distilling under reduced pressure to remove alcohol to obtain concentrated aqueous solution; Filtering the concentrated aqueous solution, and separating to obtain a precipitate, wherein the precipitate is the poria cocos peel neutral triterpene compound; Mixing the poria peel neutral triterpene compound with polyvinylpyrrolidone, adding an alcohol solvent, continuously mixing, heating and evaporating the alcohol solvent, and drying to obtain a poria peel neutral triterpene solid dispersion taking polyvinylpyrrolidone as a carrier; The preparation method of the poria peel triterpenoid acid salt comprises the following steps: dripping alcohol solution of total triterpene compounds of Poria skin into aqueous solution of alkali metal hydroxide, reacting, and distilling under reduced pressure to remove alcohol to obtain concentrated aqueous solution; filtering the concentrated aqueous solution, collecting filtrate, concentrating the filtrate, and drying to obtain the poria peel triterpenic acid salt.
3. The poria cocos peel triterpene modified product-sodium alginate hydrogel dressing according to claim 2, wherein the mass ratio of the poria cocos peel total triterpene compound to the polyvinylpyrrolidone in the poria cocos peel total triterpene solid dispersion taking the polyvinylpyrrolidone as a carrier is 1 (4-12); the weight ratio of the poria peel neutral triterpene compound to the polyvinylpyrrolidone in the poria peel neutral triterpene solid dispersion taking the polyvinylpyrrolidone as a carrier is 1 (4-12).
4. The poria cocos peel triterpene modified product-sodium alginate hydrogel dressing according to claim 3, wherein the mass ratio of the poria cocos peel total triterpene compound to polyvinylpyrrolidone is 1:9; the mass ratio of the poria Pi Zhongxing triterpenoids to the polyvinylpyrrolidone is 1:9.
5. The poria cocos peel triterpene modified product-sodium alginate hydrogel dressing according to claim 2, wherein the sodium alginate hydrogel matrix is formed by crosslinking sodium alginate, a calcium ion source and an anhydride lactone crosslinking agent.
6. The poria cocos peel triterpene modified product-sodium alginate hydrogel dressing according to claim 5, wherein said calcium ion source is calcium carbonate; The anhydride lactone cross-linking agent is D-glucono-delta-lactone; The alkali metal hydroxide is sodium hydroxide.
7. A method for preparing the poria cocos peel triterpene modified product-sodium alginate hydrogel dressing according to any one of claims 1 to 6, which is characterized by comprising the following steps: dissolving sodium alginate in water to form a solution, adding a calcium ion source, and stirring to obtain a pre-gel solution; adding the poria peel triterpene differential modification product into the pre-gel solution, stirring, adding an anhydride lactone cross-linking agent, continuously stirring, and performing ultrasonic degassing to obtain a mixed solution; standing and crosslinking the mixed solution to obtain the poria peel triterpene modified product-sodium alginate hydrogel dressing.
8. The preparation method of the poria cocos peel triterpene modified product-sodium alginate hydrogel dressing according to claim 7, wherein sodium alginate is dissolved in water to form sodium alginate solution, and the mass fraction of the sodium alginate solution is 1-5%; the volume mass ratio of the sodium alginate solution to the calcium ion source to the poria peel triterpene differentiation modified product to the anhydride lactone cross-linking agent is (10-20) mL (24-34) mg (1-200) mg (36-51) mg.
9. An application of the poria cocos peel triterpene modified product-sodium alginate hydrogel dressing according to any one of claims 1-6 or the poria cocos peel triterpene modified product-sodium alginate hydrogel dressing prepared by the preparation method according to any one of claims 7-8 in preparation of medicines or cosmeceuticals for promoting skin wound healing.
10. Use according to claim 9, wherein the hydrogel dressing comprising a solid dispersion of a neutral triterpene from the skin of Poria with polyvinylpyrrolidone as carrier is used for the preparation of a medicament or cosmeceutical for inhibiting inflammatory reactions in the early stages of wound healing; Use of a hydrogel dressing comprising a solid dispersion of total triterpene from exodermis Poria with polyvinylpyrrolidone as carrier for the preparation of a medicament or cosmeceutical for promoting collagen synthesis and deposition during the proliferation phase of wound healing; use of a hydrogel dressing comprising a pachyman triterpenate in the manufacture of a medicament or cosmeceutical for promoting epithelial regeneration, angiogenesis and tissue remodeling during a wound healing remodeling stage.

Description

Poria cocos peel triterpene modified product sodium alginate hydrogel dressing with stage-specific repair function, and preparation method and application thereof Technical Field The invention relates to the technical field of biological medicine, in particular to a preparation method and application of a poria cocos peel triterpene modified product-sodium alginate hydrogel dressing. Background Healing of skin wounds is a highly ordered and complex biological process classically divided into hemostatic, inflammatory, proliferative and remodelling phases. The ideal wound dressing should not only provide a moist healing environment, absorb exudates, protect the wound surface, but also actively intervene and promote this dynamic repair process. Hydrogels are ideal substrates for modern wound care dressings due to their high water content, good biocompatibility, three-dimensional network structure similar to extracellular matrix. Sodium Alginate (SA) can be used as natural anionic polysaccharide, and can be gently crosslinked through divalent cations to form hydrogel, so that the hydrogel is high in safety and wide in source, and is mature in application in the field of dressing. Meanwhile, searching for components with multi-target repairing activity from traditional Chinese medicines is a research hotspot of wound surface treatment. The dried sclerotium skin of Poria cocos (i.e. "Poria cocos skin") is a major by-product of its processing process and is often discarded. Modern researches show that Poria Pi Fu contains triterpenes (such as pachymic acid, dehydro-deltoid acid, etc.), has remarkable anti-inflammatory, antioxidant, fibroblast proliferation promoting and collagen synthesis promoting effects, and has great wound therapeutic potential. However, the direct application of poria peel triterpenes to external dressings faces two major technical bottlenecks, first, the solubility barrier. The poria peel triterpene component has extremely strong hydrophobicity, is difficult to be directly and uniformly dispersed in a hydrophilic hydrogel network, and causes low loading rate, uneven distribution, abrupt release or incomplete release, and seriously influences the bioavailability and the curative effect of the poria peel triterpene component. Second, the uniformity of efficacy matches the timing issues. Wound healing is dynamic, and different pharmacological actions are required at different stages (e.g. early anti-inflammatory, mid-term collagen synthesis promotion, late epithelial regeneration promotion and tissue remodeling). The simple triterpene extract or simple mixture may have various activities, but cannot realize accurate and sequential regulation and control of different healing stages on a time axis, and has limited curative effect. Disclosure of Invention The invention provides a poria peel triterpene modified product-sodium alginate hydrogel dressing with a stage-specific repair function, which comprises a three-dimensional porous network structure sodium alginate hydrogel matrix and a poria peel triterpene differential modified product dispersed in the sodium alginate hydrogel matrix, wherein the poria peel triterpene differential modified product is at least one selected from a poria peel total triterpene solid dispersion taking polyvinylpyrrolidone as a carrier, a poria peel neutral triterpene solid dispersion taking polyvinylpyrrolidone as a carrier and a poria peel triterpene acid salt. The invention also provides an application of the poria cocos peel triterpene modified product-sodium alginate hydrogel dressing or the poria cocos peel triterpene modified product-sodium alginate hydrogel dressing prepared by the preparation method in preparation of medicines or cosmeceuticals for promoting skin wound healing. Compared with the prior art, the invention has the advantages that three poria peel triterpene differential modified products (PCTT/SD, PCNT/SD and PCWT) obtained by different modified paths are obtained by carrying out physicochemical modification on the solid dispersion technology (taking polyvinylpyrrolidone K30 as a carrier and the medicine-carrying mass ratio of 1:4-1:12) or the salifying technology, and then the three poria peel triterpene differential modified products are compounded with sodium alginate solution through calcium ion crosslinking, so that a series of compound hydrogel dressing is constructed, and in a complex wound healing model in vivo, the compound hydrogel dressing does not show similar or fuzzy healing promotion effect, but shows clear, differentiated and complementary 'stage-specific repair function'. This finding constitutes the core of the invention, and is embodied in: 1. differentiation (early stage) of the therapeutic effect the hydrogel dressing (PCNT/SD/Gel) containing the solid dispersion of neutral triterpene in pachyma skin shows the strongest anti-inflammatory activity in early healing stage (0-5 days), and can rapidly inhibit inflammatory factors