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CN-122005953-A - Drug mineralized gel and preparation method and application thereof

CN122005953ACN 122005953 ACN122005953 ACN 122005953ACN-122005953-A

Abstract

The invention relates to the technical field of biomedical gel material preparation, and discloses a drug mineralized gel, a preparation method and application thereof. The preparation method of the drug mineralized gel comprises the following steps of dropwise adding an aqueous solution of NaOH into an aqueous solution of alendronate to obtain a mixture, mixing the mixture with sodium hyaluronate to obtain a viscous liquid, dropwise adding the viscous liquid into an aqueous solution of CaCl 2 , stirring and mixing to obtain hydrogel, and incubating the hydrogel to obtain the drug mineralized gel. The drug mineralized gel prepared by the invention has excellent injectability, lubricating performance, long-acting drug slow-release capability and good biocompatibility, can be quickly glued after being injected into joint cavities, has the effects of lubricating joints and reducing friction, can relieve joint inflammation, effectively improves joint functions, and has extremely high application value in the field of osteoarthritis treatment.

Inventors

  • LIU DESHENG
  • DING DAN
  • YAN YUKE
  • LU YAOZHONG
  • WANG XIAOLONG

Assignees

  • 中国科学院兰州化学物理研究所

Dates

Publication Date
20260512
Application Date
20260225

Claims (10)

  1. 1. The preparation method of the drug mineralized gel is characterized by comprising the following steps: dripping an aqueous solution of hydroxide into an aqueous solution of alendronate sodium to obtain a mixture; mixing the mixture with sodium hyaluronate to obtain a viscous liquid; Dropwise adding the viscous liquid into a calcium source water solution, and stirring and mixing to obtain hydrogel; Incubating the hydrogel to obtain the drug mineralized gel.
  2. 2. The method of claim 1, wherein the hydroxide in the aqueous hydroxide solution comprises one or more of sodium hydroxide, potassium hydroxide, lithium hydroxide, and calcium hydroxide; the concentration of the hydroxide aqueous solution is 50-100 mg/mL.
  3. 3. The method according to claim 1, wherein the concentration of the alendronate sodium aqueous solution is 10-30 mg/mL.
  4. 4. The method of claim 1, wherein the calcium source in the aqueous solution of calcium source comprises one or more of calcium chloride, calcium nitrate, and calcium acetate; The concentration of the calcium source aqueous solution is 400-600 mg/mL.
  5. 5. The method according to claim 1, wherein the pH of the system is 7-8 during the preparation of the mixture.
  6. 6. The method according to claim 1, wherein the sodium hyaluronate has a number average molecular weight of 100 to 150 ten thousand; The mass concentration of the sodium hyaluronate in the viscous liquid is 30-60 mg/mL.
  7. 7. The method according to claim 1, wherein the incubation is performed at a temperature of 25 to 45 ℃ for a time of 0 to 7 hours.
  8. 8. The pharmaceutical mineralized gel prepared by the preparation method of any one of claims 1 to 7.
  9. 9. The use of the drug mineralized gel according to claim 8 in the preparation of biomedical gel materials.
  10. 10. The use according to claim 9, wherein the biomedical gel material comprises an injectable joint lubricant.

Description

Drug mineralized gel and preparation method and application thereof Technical Field The invention relates to the technical field of biomedical gel materials, in particular to a drug mineralization type gel and a preparation method and application thereof. Background Osteoarthritis is a common degenerative joint disease, mainly manifested by wear of articular cartilage, reduction of joint cavity lubricating fluid and joint inflammatory reaction, and clinical treatment often adopts the mode of injecting joint lubricant to relieve symptoms. The traditional joint lubricant such as hyaluronic acid gel can temporarily improve joint lubricating performance, but lacks of drug treatment effect and can not effectively relieve joint inflammation, and the simple drug injection treatment has short residence time in joint cavity, is easy to be rapidly metabolized and has limited treatment effect. The medicine slow-release type injectable gel combines the convenience of injectable materials and the long-acting property of medicine slow release, and becomes a research hot spot. However, the existing drug sustained-release gel adopts a physical embedding mode to load the drug, and has the problems of drug burst release, low loading capacity, poor stability and the like. Meanwhile, partial gel materials have poor biocompatibility, foreign body reaction is easy to be induced after the gel materials are injected into the joint cavity, and the gel forming speed and the mechanical property are difficult to match with the physiological environment requirements in the joint cavity. Therefore, the injectable gel with excellent lubricating performance, long-acting drug slow release capability and good biocompatibility is developed, and has important significance for effective treatment of osteoarthritis. Disclosure of Invention In view of the above, the present invention aims to provide a drug mineralized gel, and a preparation method and application thereof. The drug mineralized gel provided by the invention has excellent lubricating performance, long-acting drug release capacity and good biocompatibility, and has excellent therapeutic effect on osteoarthritis. In order to achieve the above object, the present invention provides the following technical solutions: The invention provides a preparation method of a drug mineralization type gel, which comprises the following steps: dripping an aqueous solution of hydroxide into an aqueous solution of alendronate sodium to obtain a mixture; mixing the mixture with sodium hyaluronate to obtain a viscous liquid; Dropwise adding the viscous liquid into a calcium source water solution, and stirring and mixing to obtain hydrogel; Incubating the hydrogel to obtain the drug mineralized gel. Preferably, the hydroxide in the hydroxide aqueous solution comprises one or more of sodium hydroxide, potassium hydroxide, lithium hydroxide and calcium hydroxide; the concentration of the hydroxide aqueous solution is 50-100 mg/mL. Preferably, the concentration of the alendronate sodium aqueous solution is 10-30 mg/mL. Preferably, the calcium source in the calcium source aqueous solution comprises one or more of calcium chloride, calcium nitrate and calcium acetate; The concentration of the calcium source aqueous solution is 400-600 mg/mL. Preferably, the pH value of the system in the preparation process of the mixture is 7-8. Preferably, the number average molecular weight of the sodium hyaluronate is 100-150 ten thousand; The mass concentration of the sodium hyaluronate in the viscous liquid is 30-60 mg/mL. Preferably, the temperature of the incubation is 25-45 ℃ and the time is 0-7 h. The invention also provides the drug mineralization type gel prepared by the preparation method of the technical scheme. The invention also provides application of the drug mineralized gel in preparing biomedical gel materials. Preferably, the biomedical gel material comprises an injectable joint lubricant. According to the invention, the alendronate sodium (ADA) and Ca 2+ are mixed to form ADA-Ca 2+ Metal Organic Framework (MOF) like crystals, the hydrogel (HA-ADA-Ca) is dynamically and mechanically changed in the incubation process, and Ca 2+ in the HA-ADA-Ca hydrogel and carboxylic acid groups (-COO-) of sodium Hyaluronate (HA) and phosphonic acid groups (-PO 32-) of alendronate sodium (ADA) are coordinated, and meanwhile, the deposition of calcium-phosphorus mineralization phase is promoted by the introduction of ADA through P-Ca interaction, so that the mechanical property and biological activity of the drug mineralization gel are endowed. The drug mineralized gel prepared by the invention has excellent lubricating performance, and due to the hydrophilicity of a polymer chain (sodium hyaluronate) and the capability of combining water in a gel network, the hydrogel can form a hydration film layer in the lubricating process, so that the friction coefficient is reduced, thereby achieving good lubricating effect, effectiv