CN-121971369-A - Long-acting injection preparation based on alpha-lipoic acid derivative, and preparation method and application thereof

CN121971369ACN 121971369 ACN121971369 ACN 121971369ACN-121971369-A

Abstract

The invention provides a long-acting injection preparation based on alpha-lipoic acid derivatives, a preparation method and application thereof, wherein the preparation method of the long-acting injection preparation comprises the steps of taking alpha-lipoic acid as a carboxylic acid donor and N-hexylamine as a primary amine donor, and reacting in a system of EDC and NHS to generate N-N-hexyllipoamide; dissolving N-N-hexyl lipoamide and alpha-lipoic acid in dimethyl sulfoxide according to the mass ratio of 1:1 for reaction to obtain the long-acting injection preparation. The long-acting injection preparation can realize in-situ phase change and long-acting slow release of the medicine through solvent diffusion response, has good injectability and biocompatibility, can be used as a medicine delivery carrier, and is used for long-term treatment of chronic metabolic diseases.

Inventors

LIU JIANBO
LUO ZHENYU
WANG ZEFENG

Assignees

湖南师范大学

Dates

Publication Date: 20260505
Application Date: 20260407

Claims (10)

1. A method for preparing a long-acting injection preparation based on an alpha-lipoic acid derivative, which is characterized by comprising the following steps: s1, taking alpha-lipoic acid as a carboxylic acid donor and N-hexylamine as a primary amine donor, and reacting in a system of EDC and NHS to generate N-N-hexyllipoamide; S2, dissolving the N-N-hexyl lipoamide and alpha-lipoic acid in an organic solvent for reaction to obtain the long-acting injection preparation.
2. The method according to claim 1, wherein the reaction temperature in S1 is 20 ℃ to 50 ℃ and the reaction time is 12 h.
3. The preparation method according to claim 1, wherein the mass ratio of the N-hexyllipoamide to the α -lipoic acid in the S2 is 1:1.
4. The preparation method according to claim 1, wherein the reaction temperature in the step S2 is 20-50 ℃ and the reaction time is 4-24 hours.
5. The method according to claim 1, wherein the organic solvent in S2 is one or more of chloroform, dichloromethane, ethanol, isopropanol, propylene glycol and dimethyl sulfoxide.
6. A long-acting injectable formulation prepared by the method of any one of claims 1 to 5.
7. Use of the long-acting injectable formulation of claim 6 for the preparation of a drug delivery vehicle.
8. The application of claim 7, wherein the method of application comprises: And mixing the long-acting injection preparation with the medicine to form an injection preparation, so as to realize long-acting slow release of the medicine.
9. The method of claim 8, wherein the drug comprises one of a polypeptide drug, a protein drug, and a small molecule drug.
10. The use according to claim 8, wherein the medicament is semaglutin.

Description

Long-acting injection preparation based on alpha-lipoic acid derivative, and preparation method and application thereof Technical Field The invention belongs to the technical field of biomedical engineering, and particularly relates to a long-acting injection preparation based on an alpha-lipoic acid derivative, and a preparation method and application thereof. Background Alpha-lipoic acid is taken as a natural antioxidant, and has great application potential in the field of intelligent drug delivery by virtue of a unique five-membered ring disulfide bond structure. The molecule has the advantages of reduction sensitivity, excellent self-assembly capability and good biocompatibility, and meanwhile, the strong antioxidant activity can directly protect the drug activity and reduce the oxidative damage of organism tissues. Although α -lipoic acid has multiple advantages in drug delivery system construction, it has many bottlenecks in scale preparation, formulation stability, clinical transformation, and the like. At present, the design and synthesis of novel alpha-lipoic acid derivatives and the optimization of dynamic covalent chemical characteristics of the novel alpha-lipoic acid derivatives become a main research strategy for expanding the application of drug delivery. Long-acting injection preparations (LAIs) are an important leading direction in the current drug delivery field, have both convenience of injection administration and Long-acting sustained release durability, can realize the in-vivo on-demand, fixed-point and controllable release of the drug, are beneficial to maximizing the treatment effect, reducing toxic and side effects and remarkably improving the medication compliance of patients. The solvent diffusion response phase change is a mild and efficient physical gelation mechanism, solid or high-strength gel can be formed without complex chemical modification and additional crosslinking agent, the system is stable in molding, the risk of drug denaturation caused by environmental changes such as temperature, pH and the like can be avoided, and the solvent diffusion response phase change has good compatibility to bioactive molecules such as proteins, polypeptides and the like. Therefore, the construction of the long-acting injection preparation based on solvent diffusion response phase change is beneficial to promoting the development of an intelligent drug delivery system under a precise medical framework, and is expected to become an important platform for ultra-long-acting slow-release drug delivery. However, the conventional long-acting injection preparation generally has the problems of complex preparation process, poor injection performance, high drug burst risk, limited applicable drug loading types, poor patient compliance and the like. Disclosure of Invention The invention aims to overcome the defects in the prior art, and provides a long-acting injection preparation based on an alpha-lipoic acid derivative, a preparation method and application thereof, wherein the long-acting injection preparation based on the alpha-lipoic acid derivative can realize in-situ phase change and form a drug aggregate by means of solvent diffusion response, so that a target drug is efficiently entrapped and long-acting slow release is realized. The preparation has the advantages of excellent injectability, wide application range of drug loading, simple preparation process and easy large-scale popularization, is hopeful to break through the limitation of the existing drug delivery system, improves the compliance of patients and the clinical treatment effect, and can be used as a novel drug loading matrix for treating metabolic diseases such as obesity, diabetes and the like. In order to solve the technical problems, the invention provides a preparation method of the long-acting injection preparation, which comprises the following steps: S1, taking alpha-lipoic acid as a carboxylic acid donor and N-hexylamine as a primary amine donor, and reacting in a system of EDC and NHS to generate N-N-hexyllipoamide; S2, dissolving N-N-hexyl lipoamide and alpha-lipoic acid in dimethyl sulfoxide for reaction to obtain the long-acting injection. In the above preparation method, further, the reaction temperature in the step S1 is 20 ℃ to 50 ℃ and the reaction time is 12 h. According to the preparation method, further, the mass ratio of the N-N-hexyl lipoamide to the alpha-lipoic acid in the S2 is 1:1. According to the preparation method, further, the reaction temperature in the step S2 is 20-50 ℃, and the reaction time is 4-24 hours. In the above preparation method, further, the organic solvent in S2 is one or more of chloroform, dichloromethane, ethanol, isopropanol, propylene glycol and dimethyl sulfoxide. Based on a general technical conception, the invention also provides a long-acting injection prepared by the preparation method. Based on a general technical concept, the invention provides application of the long-act