Supercharge Your Innovation With Domain-Expert AI Agents!

A kind of stable leuprolide acetate and its application

A technology of leuprolide acetate and leuprolide, which is applied in the direction of specific peptides, medical preparations with non-active ingredients, medical preparations containing active ingredients, etc. Membrane, low bioavailability and other problems, to achieve better therapeutic effect, improve insulin resistance and high biological activity

Active Publication Date: 2022-03-29
浙江湃肽生物股份有限公司南京分公司
View PDF5 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] However, because LHRH-A is a water-soluble peptide drug, it is not easy to pass through biofilm, unstable in the gastrointestinal tract, and easily degraded by digestive enzymes. The bioavailability of oral, nasal, rectal, and vaginal routes is extremely low, respectively. <0.1%, 1%, <1%, 1~5%
And it is unstable in body fluids, with a short half-life of only 16 hours, so it is not suitable to be made into oral preparations and ordinary injections

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • A kind of stable leuprolide acetate and its application
  • A kind of stable leuprolide acetate and its application
  • A kind of stable leuprolide acetate and its application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0057] A method for improving the stability of leuprolide acetate:

[0058] Preparation of Leuprolide Conjugates

[0059] Dissolve the protected leuprolide in DMSO (solid-to-liquid ratio: 2.1 g: 1 mL), adjust the pH to 5.6, add 7-methoxy-2-oxobenzopyran-4-acetic acid N-butyl Imide ester, reacted at 36°C for 13h, followed by cation exchange chromatography (19.5mM PBS pH 6.4, sodium chloride gradient: 0.1, 0.3, 0.5M) purification, dialysis, and lyophilization to obtain leuprolide coupling thing. Wherein, the molar ratio of leuprolide acetate and 7-methoxy-2-oxobenzopyran-4-acetic acid N-succinimide ester is 1: 1.2;

[0060] Take the protected couple and add the volume ratio TFA:Tis:H 2 In a solution of O=95.5:2:2.5, stirred at room temperature for 6 h, precipitated with isopropyl ether, filtered, purified by Sephadex Superdex 200 column chromatography, concentrated, and freeze-dried to obtain a leuprolide conjugate.

[0061] A salt

[0062] Get leuprolide conjugate and be d...

Embodiment 2

[0070] Preparation of PLA-co-PEG-Mal copolymer:

[0071] S1: Dehydration of polyethylene glycol, take toluene and add polyethylene glycol, reflux and azeotrope at 106°C for 4.5 hours, evaporate toluene and water under reduced pressure to obtain purified polyethylene glycol;

[0072] S2: Use xylene as the reaction solvent, add L-lactide, heat and stir to dissolve, add the catalyst stannous octoate, then add purified polyethylene glycol drop by drop, control the reaction temperature at 128°C, stir for 18 hours; then reduce Xylene was removed by pressure distillation, chloroform was added to dissolve, methanol was precipitated, filtered, and after 4 cycles of vacuum drying, intermediate M was obtained; wherein the mass ratio of L-lactide to polyethylene glycol was 1:0.12; the catalyst octanoic acid The addition of stannous is 1.7% of monomer quality;

[0073] S3: Dissolve intermediate M in dichloromethane, add acid-binding agent pyridine, then add maleic anhydride, react at 62°C...

Embodiment 3

[0082] The difference between a method for improving the stability of leuprolide acetate and Example 2: using modified PLA-co-PEG-Mal copolymer instead of PLA-co-PEG-Mal copolymer.

[0083] The difference between the preparation of modified PLA-co-PEG-Mal copolymer and the preparation of PLA-co-PEG-Mal copolymer in Example 2: adding 2',3'-dihydro-2',3'- Dihydroxysafrole; the mass ratio of L-lactide to 2',3'-dihydro-2',3'-dihydroxysafrole is 1:0.73. The molecular weight of the copolymer is 35.2 kDa.

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

PropertyMeasurementUnit
molecular weightaaaaaaaaaa
molecular weightaaaaaaaaaa
molecular weightaaaaaaaaaa
Login to View More

Abstract

The invention discloses a stable leuprolide acetate and an application thereof, and relates to the technical field of polypeptide drug preparation. The method for improving the stability of leuprolide acetate comprises: modifying the imidazolyl group on the histidine at the 2-position of the leuprolide structure to obtain a leuprolide conjugate; then salifying to obtain a polypeptide containing compensatory ions solution, ultra-low temperature vacuum freeze-drying to obtain a stable polypeptide product; or, using PLA-co-PEG-Mal copolymer to modify the hydroxyl group on the side chain of the serine residue of the leuprolide conjugate to obtain its conjugate . The leuprolide prepared by the invention has more excellent stability, significantly increases the drug sustained-release action time and prolongs the half-life; and has higher biological activity; meanwhile, it also has certain effects on hyperuricemia combined with insulin resistance. Therapeutic efficacy.

Description

technical field [0001] The invention belongs to the technical field of polypeptide medicine preparation, and in particular relates to a stable leuprolide acetate and an application thereof. Background technique [0002] Peptide drugs have a short half-life in the human body, and the products are unstable and easily degraded. At present, most of them are injections. Methods to improve the stability of peptides include chemical modification, ring formation, etc. In recent years, making peptide drugs into slow-release microspheres has become a research topic. Hot spot, the purpose is to increase the drug action time and reduce the decay rate of the drug in the body. The amino acid structure of polypeptide itself is easy to degrade, and is sensitive to humidity, light, heat, acid, alkali, and oxidation. Peptide drugs contain a small amount of water and compensation ions, etc., which affect the stability of the drug and make the drug easy to degrade. [0003] Leuprolide acetate ...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Patents(China)
IPC IPC(8): C07K7/23C07K1/107A61K38/09A61K47/54A61K47/60A61P5/50A61P19/06
CPCC07K7/23A61K47/545A61K47/60A61P19/06A61P5/50A61K38/00
Inventor 刘慧敏魏祝宇潘海良吴潇钿
Owner 浙江湃肽生物股份有限公司南京分公司
Features
  • R&D
  • Intellectual Property
  • Life Sciences
  • Materials
  • Tech Scout
Why Patsnap Eureka
  • Unparalleled Data Quality
  • Higher Quality Content
  • 60% Fewer Hallucinations
Social media
Patsnap Eureka Blog
Learn More

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2025 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com