Nanosuspension of P2X7 receptor antagonist employing isoquinoline as basic skeleton and preparation method of nanosuspension

A technology of receptor antagonists and nanosuspensions, applied in the direction of anti-inflammatory agents, medical preparations with non-active ingredients, medical preparations containing active ingredients, etc., can solve the problem of limiting the clinical application of drugs and increasing the effect of bioavailability , drug precipitation and other issues, to achieve the effect of improving the in vitro dissolution rate, good application prospects, and increasing solubility

Inactive Publication Date: 2016-05-25
CHINA PHARM UNIV
View PDF6 Cites 3 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] As a newly developed fat-soluble drug, it is soluble in organic solvents such as methanol, acetone, chloroform, and acetonitrile, but hardly soluble in water. It belongs to the BCSII drug of the biopharmaceutical classification system, and its solubility in water is only 40μg.mL -1 (37°C), and water solubility is not affected by pH, resulting in lower oral bioavailability
[0005] Insoluble drugs are often difficult to achieve the bioavailability required for treating diseases after oral administration through traditional preparation

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
  • Nanosuspension of P2X7 receptor antagonist employing isoquinoline as basic skeleton and preparation method of nanosuspension
  • Nanosuspension of P2X7 receptor antagonist employing isoquinoline as basic skeleton and preparation method of nanosuspension
  • Nanosuspension of P2X7 receptor antagonist employing isoquinoline as basic skeleton and preparation method of nanosuspension

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0029] Weigh 100 mg of hydroxypropyl methyl cellulose and 10 mg of sodium lauryl sulfate and disperse in 100 mL of deionized water, make it fully dissolved by ultrasonic in a water bath, and use it as the water phase; weigh 100 mg of micronized crude drug and dissolve in 5 mL of methanol, vortex Rotate and mix well, as the organic phase. Under the condition of ice bath and high-speed stirring, slowly add the organic phase dropwise to the water phase, continue stirring for 2h, then rotate and evaporate at 40℃ to remove the organic solvent, and homogenize the resulting initial suspension at a pressure of 1200bar , Circulate for 10min, and get it. The average particle size of the nanosuspension prepared by this method is 188.4 nm, and the polydispersity coefficient PI is 0.47.

Embodiment 2

[0031] Weigh 200mg of polyvinylpyrrolidone K30 and 5mg of sodium lauryl sulfate and disperse in 100mL of deionized water, make it fully dissolved by ultrasonic in a water bath, as the water phase; Weigh 100mg of micronized crude drug in 3mL of methanol, vortex and mix, As the organic phase. Under the condition of ice bath and high-speed stirring, the organic phase was slowly added dropwise to the water phase, and then the organic solvent was removed by rotary evaporation at 40°C, and the resulting initial suspension was homogenized at a pressure of 800 bar under high pressure and circulated for 8 min. Immediately. The average particle size of the nanosuspension prepared by this method is 432.9 nm, and the polydispersity coefficient PI is 0.51.

Embodiment 3

[0033] Weigh 50 mg of sodium carboxymethyl cellulose and disperse in 100 mL of deionized water, make it fully dissolved by ultrasonic in a water bath, as the water phase; weigh 100 mg of the micronized crude drug in 5 mL of methanol, vortex and mix, as the organic phase. Under the condition of ice bath and high-speed stirring, the organic phase was slowly added dropwise to the water phase, and then the organic solvent was removed by rotary evaporation at 42°C. The resulting initial suspension was homogenized at a pressure of 1000 bar under high pressure and circulated for 5 minutes. Immediately. The average particle size of the nanosuspension prepared by this method is 559.2nm, and the polydispersity coefficient PI is 0.44.

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 sizeaaaaaaaaaa
The average particle sizeaaaaaaaaaa
The average particle sizeaaaaaaaaaa
Login to view more

Abstract

The invention discloses a nanosuspension of a P2X7 receptor antagonist employing isoquinoline as a basic skeleton and a preparation method of the nanosuspension, and belongs to the field of medicinal preparations. As a novel P2X7 receptor antagonist, the major indications are labour pains, inflammation, respiratory tract and airway diseases and obstacles and the like. The medicine is extremely difficult to dissolve in water, so that the clinical application is limited. The nanosuspension is prepared by an antisolvent precipitation method combined with a high pressure homogenization method; and the prescription and technology are optimized employing the particle sizes and a polydispersity index as indexes. The result shows that the particle sizes of the medicines in the prepared nanosuspension are 50-500nm; the nanosuspension is round in shape and uniform in distribution; the particle sizes are reduced; increase of the medicine solubility is facilitated; and the in vitro dissolubility is improved.

Description

Technical field [0001] The invention relates to the field of pharmaceutical preparations, in particular to a nano-suspension of a P2X7 receptor antagonist with isoquinoline as the basic skeleton and a preparation method thereof. Background technique [0002] The P2X7 receptor antagonist with isoquinoline as the basic skeleton involved in this patent is a new, oral, potent and selective P2X7 receptor antagonist. P2X7 receptors are ion channels gated by adenosine triphosphate, which are mainly expressed in cells of the immune system. In the process of inflammation, the P2X7 receptor antagonist can play an important role by regulating inflammatory cytokines (such as IL-1β). The main indications are: 1. Analgesia, such as acute, inflammatory and neuropathic pain, and chronic pain , Toothache, headache, etc.; 2. Inflammation-mediated and the diseases and disorders that cause them, such as arthritis, rheumatoid arthritis, osteoarthritis, etc.; 3. Neuroinflammation-mediated diseases an...

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
IPC IPC(8): A61K9/19A61K9/10A61K47/20A61K47/38A61K47/10A61K47/26A61K45/06A61P29/00A61P25/00A61P1/02A61P19/02A61P11/02A61P37/08A61P11/06A61P11/00A61P37/02
CPCA61K9/10A61K9/19A61K45/06A61K47/10A61K47/20A61K47/26A61K47/38
Inventor 周建平丁杨张旭
Owner CHINA PHARM UNIV
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