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A kind of ph-responsive hydrogel biological carrier and its application

A biological carrier and hydrogel technology, applied in the field of pharmacy, can solve the problems of tumorigenesis, easy inactivation of PDGF-BB, short half-life of PDGF-BB, etc.

Active Publication Date: 2022-05-20
BIO-BANK CORP
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] Wound repair and tissue regeneration diseases require growth factors to maintain a certain concentration in the diseased area for a long time, but PDGF-BB has a short half-life (<2min) and is easily degraded by proteases, and there are a lot of proteases in chronic wound beds, which makes PDGF-BB more effective. Easy to inactivate
Generally, multiple high-dose administrations are used to maintain the drug concentration, but there is a risk of tumorigenesis

Method used

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  • A kind of ph-responsive hydrogel biological carrier and its application
  • A kind of ph-responsive hydrogel biological carrier and its application
  • A kind of ph-responsive hydrogel biological carrier and its application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0030] Example 1. Preparation of pH-responsive hydrogel biocarriers

[0031] figure 1 A schematic diagram of the preparation of PDGF-BB pH-responsive hydrogel is given, where A is methacrylic anhydride, B is sodium hyaluronate, 1 is the first crosslinking agent GDMA, and 2 is the second crosslinking agent AI102. The preparation steps are described in detail below.

[0032] 1. Preparation of Methacrylated Hyaluronic Acid (m-HA)

[0033] Sodium hyaluronate (HA) and methacrylic anhydride (MA) undergo esterification to synthesize methacrylate derivatives of hyaluronic acid. The specific steps include the following:

[0034] (1) Weigh 2g of sodium hyaluronate (HA) powder, dissolve it in 100mL of deionized water, and stir overnight in a refrigerator at 4°C to fully dissolve the powder.

[0035] (2) Adjust the pH of the HA solution by adding 5 mol / L sodium hydroxide to keep the pH of the reaction between 8 and 9, then slowly add 1.6 mL of methacrylic anhydride to the HA solution a...

Embodiment 2

[0060] Example 2. Characterization of m-HA hydrogel loaded with platelet-derived growth factor

[0061] 1. Characterization of hydrogel morphology

[0062] The hydrogel samples that had reached equilibrium swelling were placed in a lyophilizer at -50°C for 48 hours. The obtained samples were frozen and brittle in liquid nitrogen, and then sprayed with gold. The cross-sectional morphology was observed with a scanning electron microscope (SEM). Figure 5 Scanning electron microscopy images of pH-responsive hydrogels with different crosslinker ratios. It can be seen that the larger the proportion of cross-linking agent, the smaller the pore size, indicating the higher the degree of cross-linking. When the molar ratio of GDMA to AI102 is 1:2, the degree of cross-linking is maximum.

[0063] 2. Characterization of swelling rate of hydrogel

[0064] Swellability tests were performed using the freeze-dried hydrogel scaffolds. The hydrogel sample was punched with a hole punch to m...

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Abstract

The invention discloses a pH-responsive hydrogel biocarrier. The pH-responsive hydrogel biocarrier is made of sodium hyaluronate and methacrylic anhydride in the presence of a photoinitiator and irradiated with a 365nm ultraviolet laser. The hydroxyl group on the side chain of sodium hyaluronate is polymerized by photocrosslinking and esterification to form a methacrylate derivative of hyaluronic acid. The invention also discloses a pH-responsive hydrogel biological carrier loaded with the therapeutic protein PDGF‑BB. The invention adopts the method of in-situ free radical polymerization to synthesize, the reaction conditions are mild, and the biological activity of PDGF-BB will not be affected; PDGF-BB is wrapped in the hydrogel to avoid exposure to the enzyme environment, and the PDGF-BB is improved. Stability of BB biological activity.

Description

technical field [0001] The invention discloses a hydrogel biological carrier, which belongs to the technical field of pharmacy. Background technique [0002] Platelet-derived growth factor (PDGF) is a cationic glycoprotein that is heat-resistant, acid-resistant, and easily hydrolyzed by proteases. It can be secreted by a variety of cells, such as: platelets, fibroblasts, macrophages, etc. PDGF has four monomers PDGF-A, PDGF-B, PDGF-C and PDGF-D, and these monomers are connected by disulfide bonds to form a dimer form. Among them, PDGF-BB, the dimer form of PDGF-B, acts as a mitosis promoter, which can stimulate the proliferation and migration of fibroblasts and smooth muscle cells, and promote the production of macrophages and the secretion of growth factors. It is more effective in wound repair, tissue regeneration, bone and tooth regeneration, and joint repair. Especially in wound repair, it is the only growth factor approved by the US Food and Drug Administration (FDA) ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C08F299/00C08F251/00C08F222/20C08F2/48A61K9/06A61K38/18A61K47/36A61P17/02
CPCC08F299/00C08F251/00C08F2/48A61K38/1858A61K9/06A61K47/36A61P17/02C08F222/103
Inventor 赵兴卉翟俊辉杜红王轲珑
Owner BIO-BANK CORP
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