Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Aqueous dispersion of camptothecin analogue-phospholipid complex and method for preparing same

A technology of phospholipid complex and camptothecin, which is applied in medical preparations with non-active ingredients, medical preparations containing active ingredients, liquid delivery, etc., can solve the problems of poor patient compliance and clinical use restrictions, and achieve toxic and side effects Small, highly targeted, and less residual effect

Inactive Publication Date: 2010-06-09
SHENYANG PHARMA UNIVERSITY
View PDF3 Cites 4 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, lipid-containing preparations generally cannot be used for severe acute liver damage, severe metabolic disorders, especially lipid metabolism disorders (lipid nephropathy, severe renal insufficiency, severe hyperlipidemia), thrombosis, jaundice, diabetes with ketone poisoning and Patients with sepsis and other patients, and the main indication of camptothecin drugs is liver cancer, and most patients are accompanied by liver dysfunction and jaundice symptoms, so the clinical use is limited to a certain extent. During long-term use, the patient's blood picture and fat clearance ability should be monitored; Phlebitis, vascular pain and bleeding tendency, venous thrombosis may occur, and the patient's compliance is poor
[0008] In summary, the currently existing preparations of camptothecin compounds all have limitations in different forms.

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
  • Aqueous dispersion of camptothecin analogue-phospholipid complex and method for preparing same
  • Aqueous dispersion of camptothecin analogue-phospholipid complex and method for preparing same
  • Aqueous dispersion of camptothecin analogue-phospholipid complex and method for preparing same

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0037] Disperse 50mg of 10-hydroxycamptothecin and 3 times the molar amount of egg yolk lecithin in 100ml of tetrahydrofuran at 40°C, blow in nitrogen, connect to a reflux device and stir for 1 hour, stop the reaction, remove the organic solvent by vacuum evaporation, add the additive containing Using 50ml of water for injection, hydration for 10min, washing the film ultrasonically in a water bath to obtain an aqueous dispersion, and treating it with a high-pressure homogenizer at 400bar for 10 cycles to obtain an aqueous dispersion of hydroxycamptothecin phospholipid complex with a particle size of 117±65nm.

[0038] The above preparation was added with 2% mannitol and 3% trehalose (w / v), and freeze-dried to obtain a freeze-dried product of a phospholipid complex aqueous dispersion. The average particle size after reconstitution is 118±59nm.

[0039] Dilute it with normal saline for injection to 0.2mg / ml, take 1ml and put it in a dialysis bag (molecular weight cut-off 7000), ...

Embodiment 2

[0041] Disperse 50 mg of 9-nitrocamptothecin and 2 times the molar amount of soybean lecithin in 100 ml of acetone at 40 ° C, pass through nitrogen gas, and stir for 1 hour at 40 ° C with a reflux device to stop the reaction. Additives were dispersed in water for injection with high-speed stirring for 30 minutes, evaporated ethanol under reduced pressure, and treated the coarse dispersion with a high-pressure homogenizer at 300 bar for 50 cycles to obtain an aqueous dispersion of 9-nitrocamptothecin phospholipid complex.

[0042] The above preparation was added with 10% trehalose and 2% mannitol, and freeze-dried to obtain a freeze-dried product of phospholipid complex aqueous dispersion.

Embodiment 3

[0044] Disperse 10 mg of 9-methoxycamptothecin and 5 times the molar amount of dipalmitoylphosphatidylcholine in 100 ml of dioxane at 50°C, blow in nitrogen, connect to a reflux device and stir at 50°C for 2 hours, stop Reaction, remove dioxane by evaporation under reduced pressure, add ether to dissolve 9-methoxycamptothecin phospholipid complex, inject 50ml of water for injection containing additives at 70°C and disperse at high speed for 1hr to evaporate ether, and the coarse dispersion is passed through the probe Ultrasound (power 500w) for 5 minutes to obtain an aqueous dispersion of 9-methoxycamptothecin phospholipid complex.

[0045] The above preparation was added with 5% lactose and 2% glycine, and freeze-dried to obtain a freeze-dried product of phospholipid complex aqueous dispersion.

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
particle diameteraaaaaaaaaa
Login to View More

Abstract

The invention belongs to the field of medicinal preparations, and relates to aqueous dispersion preparation of a camptothecin analogue-phospholipid complex and a method for preparing the same. The aqueous dispersion of the camptothecin analogue-phospholipid complex substantially consists of camptothecin analogue, phospholipid and water for injection of therapeutic effective dose, and each milliliter of aqueous dispersion comprises the following components: 0.001 to 5 mg of camptothecin analogue, 0.001 to 500 mg of phospholipid, 0 to 500 mg of additive and the balance of the water for injection. The aqueous dispersion of the camptothecin analogue-phospholipid complex provided by the invention has the advantages of active structure of a lactone ring of camptothecin, high medicament-loading rate, wide clinical application range, little toxic or side effect, long-circulation modification and freeze drying storage, good stability of the preparations, high medicament-to-phospholipid ratio, industrialized production and the like.

Description

technical field [0001] The invention belongs to the field of pharmaceutical preparations, and relates to an aqueous dispersion of camptothecin compound phospholipid complex and a preparation method thereof. The prepared aqueous dispersion of the camptothecin compound phospholipid complex helps the camptothecin compound to be administered in the active form of lactone ring closure, and compared with the existing commercially available preparations, it has the advantages of increasing curative effect, improving targeting, Prolong the residence time of drugs in the body, reduce the number of administrations, improve patient compliance, and have the advantages of stable storage. Background technique [0002] Camptothecin compounds are a kind of compounds with significant anticancer activity and wide anticancer spectrum extracted from the deciduous plant Camptotheca involucrataceae genus Eclipta, which is unique to my country. Among them, 10-camptothecin compounds It is the first...

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 Applications(China)
IPC IPC(8): A61K9/10A61K9/19A61K31/4745A61K47/24A61P35/00
Inventor 王东凯贺晓玲李翔
Owner SHENYANG PHARMA UNIVERSITY
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com