PCI (percutaneous coronary intervention) postoperative thrombus prevention and treatment pharmacological model construction method based on mesylate amine silver lactone B intervention
A pharmacological model using silver amine lactone mesylate B addresses the lack of effective models for PCI-related thrombosis and restenosis, ensuring safe and effective drug evaluation and treatment through comprehensive clinical studies and international standards.
Patent Information
- Application Number
- CN202310790482.4
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2023-06-30
- Publication Date
- 2024-12-31
AI Technical Summary
The development of an effective animal model for subacute thrombosis after PCI is lacking in China, and existing treatments for coronary artery restenosis and thrombosis post-PCI face issues like drug resistance, adverse reactions, and low tolerance, necessitating improved methods for drug evaluation and treatment.
A pharmacological model is constructed using silver amine lactone mesylate B, involving metabolite research, radioisotope pharmacokinetics, microreaction technology, and clinical studies to evaluate safety and efficacy, incorporating international evaluation standards for PCI-related thrombosis prevention and restenosis.
Provides a robust pharmacological model for evaluating drugs to prevent restenosis and thrombosis post-PCI, enhancing new drug development by ensuring safety and efficacy through rigorous clinical trials and evaluation methods.
Smart Images
Figure CN119215037A_ABST
Abstract
Description
Technical Field
[0001] The present invention belongs to the field of biomedicine technology, and specifically relates to a method for constructing a pharmacological model for preventing and treating thrombosis after PCI based on the intervention of silver amine mesylate B. Background Art
[0002] Percutaneous coronary intervention (PCI) is currently the main method for treating coronary heart disease, which has significantly reduced the incidence and mortality of cardiovascular events. However, the incidence of coronary artery thrombosis and vascular restenosis after this type of surgery is as high as 30% to 60%, which has become a serious obstacle to the further development of coronary heart disease treatment.
[0003] Based on the mechanism of silver amine lactone mesylate B in antagonizing PAF and its good efficacy in antiplatelet aggregation, it can be used to prevent thrombotic diseases. Percutaneous coronary intervention (PCI) significantly reduces the incidence and mortality of cardiovascular events, but the incidence of coronary artery restenosis after surgery is as high as 30% to 60%. This large postoperative population requires long-term or even lifelong oral antithrombotic drugs.
[0004] Currently, clopidogrel (Plavix) and aspirin are commonly used in clinical treatment of such diseases. Long-term use of the former can lead to drug resistance, resulting in loss of efficacy, the risk of myocardial infarction, and the serious adverse reaction of spontaneous bleeding; the latter has the adverse reaction of serious gastrointestinal mucosal damage, and patients with long-term medication have low tolerance. The development of silver amine lactone mesylate B for this indication has a very broad application prospect because of its high anticoagulant effect, no bleeding risk, good safety, and high tolerance. It can effectively prevent the formation of thrombus and restenosis of blood vessels after PCI treatment.
[0005] The animal model of subacute thrombosis after PCI has not yet been fully developed in China. The present invention provides a pharmacological model for the prevention and treatment of thrombosis after PCI based on the intervention of silver amine mesylate B. After successful application, it will provide a new method for evaluating drugs to prevent restenosis after PCI and improve the level of new drug development in China. Summary of the invention
[0006] The purpose of the present invention is to provide a method for constructing a pharmacological model for the prevention and treatment of thrombosis after PCI based on the intervention of silver amine mesylate lactone B, which will provide a new method for evaluating drugs to prevent restenosis after PCI and improve the level of domestic new drug development.
[0007] To achieve the above object, the present invention provides the following technical solutions:
[0008] A method for constructing a pharmacological model for the prevention and treatment of thrombosis after PCI based on the intervention of silver amine lactone mesylate B, comprising the following steps: metabolite research, based on radioisotope pharmacokinetic research, confirming that the main metabolites need to study their synthesis process in the next step, and obtaining metabolites in batches through microreaction technology for activity research.
[0009] It also includes the following steps: completing Phase I clinical studies, including single-dose, multiple-dose, in vivo drug-drug interactions, and pharmacokinetic studies in healthy elderly people and special populations.
[0010] It also includes the following steps: introducing the American cerebrovascular disease classification standards, using internationally recognized objective evaluation systems such as the Rankin scale, Barthel index, and NIHSS score, designing strict case selection indicators, and examining the clinical treatment of patients with a stroke course of 6-72 hours.
[0011] The following steps are also included: single-dose escalation, placebo-controlled, randomized double-blind, tolerability and pharmacokinetics phase I clinical study of several healthy subjects, to evaluate the safety, tolerability and pharmacokinetic characteristics of single-dose injection of silver amine lactone mesylate B in healthy subjects. Screening and verification of multiple efficacy indicators, preliminary pharmacodynamic studies combined with pharmacokinetic characteristics, to guide the establishment of objective efficacy indicators for phase II clinical trials.
[0012] Compared with the prior art, the present invention has the following beneficial effects:
[0013] The animal model of subacute thrombosis after PCI has not yet been fully developed in China. The present invention provides a pharmacological model for the prevention and treatment of thrombosis after PCI based on the intervention of silver amine mesylate B. After successful application, it will provide a new method for evaluating drugs to prevent restenosis after PCI and improve the level of new drug development in China. BRIEF DESCRIPTION OF THE DRAWINGS
[0014] Figure 1 It is the technical roadmap of the present invention. DETAILED DESCRIPTION
[0015] The following will be combined with the accompanying drawings of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.
[0016] Embodiment 1.
[0017] A method for constructing a pharmacological model for the prevention and treatment of thrombosis after PCI based on the intervention of silver amine lactone mesylate B, comprising the following steps: metabolite research, based on radioisotope pharmacokinetic research, confirming that the main metabolites need to study their synthesis process in the next step, and obtaining metabolites in batches through microreaction technology for activity research.
[0018] It also includes the following steps: completing Phase I clinical studies, including single-dose, multiple-dose, in vivo drug-drug interactions, and pharmacokinetic studies in healthy elderly people and special populations.
[0019] It also includes the following steps: introducing the American cerebrovascular disease classification standards, using internationally recognized objective evaluation systems such as the Rankin scale, Barthel index, and NIHSS score, designing strict case selection indicators, and examining the clinical treatment of patients with a stroke course of 6-72 hours.
[0020] The following steps are also included: single-dose escalation, placebo-controlled, randomized double-blind, tolerability and pharmacokinetics phase I clinical study of several healthy subjects, to evaluate the safety, tolerability and pharmacokinetic characteristics of single-dose injection of silver amine lactone mesylate B in healthy subjects. Screening and verification of multiple efficacy indicators, preliminary pharmacodynamic studies combined with pharmacokinetic characteristics, to guide the establishment of objective efficacy indicators for phase II clinical trials.
[0021] During the preclinical research stage, quality standards and stability studies were conducted on the raw materials and preparations of silver amine lactone mesylate B, and quality standards were formulated: identification was carried out using chemical precipitation reaction, color development reaction, HPLC and infrared absorption spectroscopy; inspection items included acidity, clarity and color of the solution, related substances, water, bacterial endotoxins, ignition residues, heavy metals, residual solvents, etc.; content determination and related substance inspection were carried out using high performance liquid chromatography; key impurities were qualitatively and quantitatively detected using LC-MS / MS and IT-TOF.
Claims
1. A method for constructing a pharmacological model for the prevention and treatment of thrombosis after PCI based on the intervention of silver amine lactone mesylate B, characterized in that The process includes the following steps: metabolite research, based on radioisotope pharmacokinetic research, confirm the main metabolites, the next step is to study their synthesis process, and obtain metabolites in batches through microreaction technology for activity research.
2. The method for constructing a pharmacological model for the prevention and treatment of thrombosis after PCI based on the intervention of silver amine mesylate lactone B according to claim 1, characterized in that: It also includes the following steps: completing Phase I clinical studies, including single-dose, multiple-dose, in vivo drug-drug interactions, and pharmacokinetic studies in healthy elderly people and special populations.
3. The method for constructing a pharmacological model for preventing and treating thrombosis after PCI based on the intervention of silver amine mesylate lactone B according to claim 1, characterized in that: It also includes the following steps: introducing the American cerebrovascular disease classification standards, using internationally recognized objective evaluation systems such as the Rankin scale, Barthel index, and NIHSS score, designing strict case selection indicators, and examining the clinical treatment of patients with a stroke course of 6-72 hours.
4. The method for constructing a pharmacological model for preventing and treating thrombosis after PCI based on the intervention of silver amine mesylate lactone B according to claim 1, characterized in that: The following steps are also included: single-dose escalation, placebo-controlled, randomized double-blind, tolerability and pharmacokinetics phase I clinical study of several healthy subjects, to evaluate the safety, tolerability and pharmacokinetic characteristics of single-dose injection of silver amine lactone mesylate B in healthy subjects. Screening and verification of multiple efficacy indicators, preliminary pharmacodynamic studies combined with pharmacokinetic characteristics, to guide the establishment of objective efficacy indicators for phase II clinical trials.