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

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...

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 methods, or difficult to make preparations for intravenous administration, which greatly limits the clinical application of drugs

At present, commonly used technologies such as co-solvent solubilization, cyclodextrin inclusion, liposome, micronization, and emulsion have certain limitations. Fine inclusion has special requirements on the size of drug molecules; liposomes have problems of low drug loading and poor stability; micronization has no obvious effect on increasing bioavailability; emulsions require drugs to have a higher Solubility

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