Injection for protecting ischemic myocardium and preparation method thereof

A technique for myocardial and injection, which can be applied to medical preparations without active ingredients, medical preparations containing active ingredients, and pharmaceutical formulas, etc. It can solve the problems of poor water solubility, low oral bioavailability, and low drug concentration. Avoid systemic side effects, improve bioavailability, increase effective concentration

Active Publication Date: 2020-07-28
FUWAI HOSPITAL CHINESE ACAD OF MEDICAL SCI & PEKING UNION MEDICAL COLLEGE
View PDF2 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] However, currently marketed N-suberoylanilide hydroxamic acid preparations are limited to antitumor oral dosage forms
Due to the poor water solubility of N-suberoylanilide hydroxamic acid, and the obvious first-pass metabolic elimination of N-suberoylanilide hydroxamic acid after oral administration, its oral bioavailability is very low, and it cannot be used in cardiovascular and other related diseases. Form effective therapeutic concentrations in adipose tissue
In addition, N-suberoylanilide hydroxamic acid can only play a therapeutic role as a prototype, and its metabolites are inactive, so chemical derivatization cannot be used to improve its oral bioavailability
In addition, oral N-suberoylanilide hydroxamic acid can cause systemic side effects if taken before cardiac interventional procedures
[0008] The problems mentioned above in the prior art have greatly limited the clinical application of N-suberoylanilide hydroxamic acid, especially its in ischemia / reperfusion During cardioprotection, because effective local drug concentrations cannot be achieved in cardiac tissue prior to cardiac intervention
Therefore, there is an urgent need to develop a new pharmaceutical dosage form of N-suberoylanilide hydroxamic acid to solve the excessive local drug concentration in the heart tissue of N-suberoylanilide hydroxamic acid in the process of ischemic myocardial protection. low problem

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
  • Injection for protecting ischemic myocardium and preparation method thereof
  • Injection for protecting ischemic myocardium and preparation method thereof
  • Injection for protecting ischemic myocardium and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0105] 1. Prescription 1

[0106] Name of raw material Prescription volume (g) N-suberoylanilide hydroxamic acid 15 Soy lecithin 10 Soybean Oil for Injection 100 Tween 80 3 Oleic acid 0.5 glycerin 12.5 Water for Injection Appropriate amount

[0107] Makes 500ml.

[0108] 2. Process:

[0109] Weigh the prescribed amount of N-suberoylanilide hydroxamic acid, add Tween-80 and glycerin, heat to 80°C, add about 100ml of water, until the raw material drug is dissolved, add soybean lecithin, shear (6000rpm) and mix evenly, Prepare the water phase; weigh oleic acid and soybean oil for injection, and mix them uniformly to form the oil phase; mix the oil and water phases at 70° C. for 30 minutes at high speed shear (6000 rpm) to produce colostrum. The colostrum is homogenized under the pressure of 800bar, circulated 6 times, filled into ampoules, sealed, and sterilized at 115°C for 30 minutes.

Embodiment 2

[0111] 1. Prescription 2

[0112] Name of raw material Prescription volume (g) N-suberoylanilide hydroxamic acid 15 Soy lecithin 5 Soybean Oil for Injection 75 Poloxamer 188 3 Oleic acid 0.75 glycerin 12.5 Water for Injection Appropriate amount

[0113] Makes 500ml.

[0114] 2. Process:

[0115] Weigh the prescribed amount of N-suberoylanilide hydroxamic acid, add poloxamer 188 and glycerin, heat to 80°C, add about 100ml of water, until the raw material drug is dissolved, add soybean lecithin, shear (6000rpm) and mix well , to make a water phase; weigh oleic acid and soybean oil for injection, and mix them uniformly to make an oil phase; the oil-water two phases are mixed at a high speed (5000rpm) at 80°C for 40 minutes to make colostrum. Homogenize the colostrum under the pressure of 700bar, circulate 6 times, put it into an ampoule, seal it, and sterilize it at 115°C for 30 minutes.

Embodiment 3

[0117] 1. Prescription 3

[0118] Name of raw material Prescription volume (g) N-suberoylanilide hydroxamic acid 15 Soy lecithin 12.5 Soybean Oil for Injection 50 Macrogol 15 Hydroxystearate 5 Oleic acid 0.25 glycerin 11.5 Water for Injection Appropriate amount

[0119] Makes 500ml

[0120] 2. Process:

[0121] Weigh the prescribed amount of N-suberoylanilide hydroxamic acid, add polyethylene glycol 15 hydroxystearate and glycerin, heat to 80°C, add about 100ml of water, until the raw material is dissolved, add soybean lecithin, cut (5000rpm) mixed evenly to make the water phase; weighed oleic acid and soybean oil for injection, mixed evenly to make the oil phase; the oil-water two phases were mixed under high pressure shear (6000rpm) for 40 minutes at 80°C to make colostrum. The colostrum is homogenized under the pressure of 800bar, circulated 6 times, filled into ampoules, sealed, and sterilized at 115°C for 30 mi...

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

No PUM Login to view more

Abstract

The invention relates to an injection for protecting ischemic myocardium and a preparation method thereof. In parts by mass, the emulsion for injection comprises: 1-5 parts of N-suberoylanilide hydroxamic acid; 0.2-12.5 parts of emulsifier 2-100 parts of injection oil; 0.02-5 parts of solubilizer; 0.03-0.4 parts of oleic acid; 0.4-12.5 parts of glycerin, and the balance of water for injection. The injection emulsion can be effectively used to improve the local drug concentration of N-suberoylanilide hydroxamic acid in cardiovascular and other lipophilic organs and / or tissues before cardiac interventional surgery, and increase the concentration of N-suberoylanilide hydroxamic acid. It can reduce the systemic side effects, effectively protect the myocardium in the state of ischemia or reperfusion injury, and reduce or avoid the occurrence of myocardial infarction. At the same time, the injection emulsion also provides a new alternative dosage form for the application of N-suberoylanilide hydroxamic acid in the treatment of cancer.

Description

technical field [0001] The invention belongs to the field of pharmaceutical preparations, and relates to an injection for protecting ischemic myocardium and a preparation method thereof, in particular to an emulsion for injection containing N-suberoylanilide hydroxamic acid for protecting ischemic myocardium and its preparation method. Background technique [0002] Histone deacetylase inhibitors (histone deacetylase inhibitors, HDACI) are a class of compounds that interfere with the function of histone deacetylases. research reports. [0003] It is known that N-suberoylanilide hydroxamic acid (SAHA, see formula I below for chemical structure) as a histone deacetylase (HDAC) inhibitor can induce cell differentiation and block cell cycle , Induce cell regulation and play a therapeutic role. In vitro studies have shown that N-suberoylanilide hydroxamic acid at nanomolar concentrations (IC 50 <86nmol / L) can inhibit HDAC 1, HDAC 2 and HDAC 3 (type I) and HDAC 6 (type II) e...

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): A61K31/167A61K47/26A61K47/10A61K47/14A61P9/10A61P35/00
CPCA61K47/10A61K47/14A61K47/26A61K9/0019A61K31/167A61P9/10A61P35/00A61K9/107A61K47/12A61K47/24A61K9/10A61K47/44
Inventor 唐熠达楚娜秦艳
Owner FUWAI HOSPITAL CHINESE ACAD OF MEDICAL SCI & PEKING UNION MEDICAL COLLEGE
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap