Unlock instant, AI-driven research and patent intelligence for your innovation.

Polymorphic substance of type 5 phosphodiesterase inhibitor, and preparation method and application thereof

A type of phosphodiesterase and phosphodiesterase technology, applied in the field of medicine, can solve the problems of bioavailability to be improved, burden on patients, and low solubility

Active Publication Date: 2021-11-05
JINAN MEILUWEI BIOTECH CO LTD +1
View PDF3 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The inventor has studied it in the early stage and found that there is a mesylate crystal form in it. However, the inventor found that the sildenafil analog and It is known that the solubility of mesylate salt is not good, especially, the solubility of the sildenafil analogue in water is <0.01mg / mL, which is an insoluble compound, and its bioavailability needs to be improved
Solubility is one of the most important properties in drug discovery, and compounds with low solubility can have many negative effects, including: low solubility limits drug absorption and reduces oral bioavailability; low solubility prevents intravenous formulation; drug formulation development Difficult; the resulting preparation requires frequent high-dose administration, which will increase the burden on patients, etc.

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
  • Polymorphic substance of type 5 phosphodiesterase inhibitor, and preparation method and application thereof
  • Polymorphic substance of type 5 phosphodiesterase inhibitor, and preparation method and application thereof
  • Polymorphic substance of type 5 phosphodiesterase inhibitor, and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0125] 1. Selection of solvent: According to the solubility of the compound of formula I, the compound of formula I is insoluble at room temperature in methanol, acetonitrile and acetone, and has better solubility in tetrahydrofuran. The following 8 solvents and combinations are screened out to screen out the most suitable for forming various formula I salts. solvent. The 8 solvents and combinations are: methanol, acetone, acetonitrile, tetrahydrofuran, methanol / water (v / v=9:1), acetone / water (v / v=9:1), acetonitrile / water (v / v =9:1), tetrahydrofuran / water (v / v=9:1). The results are shown in Table 1:

[0126] Table 1

[0127]

[0128] Because the compound of formula I is insoluble at room temperature in methanol, acetonitrile and acetone, and its solubility is better in tetrahydrofuran, so in the 1st, 2, 3 and 5, 6, 7 columns of table 1, the solution before the compound of formula I is mixed with acid begins to be is cloudy, while in columns 4 and 8 the solution is clea...

Embodiment 2

[0140] Embodiment 2 pharmacokinetic test

[0141]1. The purpose of this example is to give SD rats the hydrochloride of the compound of formula I and the mesylate of the compound of formula I (derived from Preparation Examples 1 and 3) by single intragastric administration (PO) respectively, before administration and Plasma was collected at 0.25, 0.5, 0.75, 1, 2, 4, 8 and 24 hours post-dose. Liquid chromatography tandem mass spectrometry (LC-MS / MS) analysis method was used to quantitatively determine the concentration of the compound of formula I in SD rat plasma. Through WinNonlin 6.4 software, the pharmacokinetic parameters were calculated according to the non-compartmental model.

[0142] 2. Instrument: liquid chromatography tandem mass spectrometer (LCMSMS-025): the chromatograph is a Shimadzu liquid chromatograph (Japan), consisting of LC-30AD binary pump, SIL-30AC autosampler, CTO-20A column temperature Box, CBM-20A system controller and CBM-20A degasser; mass spectr...

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
melting pointaaaaaaaaaa
decomposition temperatureaaaaaaaaaa
melting pointaaaaaaaaaa
Login to View More

Abstract

The invention provides a polymorphic substance of a type 5 phosphodiesterase inhibitor as well as a preparation method and application of the polymorphic substance. The polymorphic substance of the type 5 phosphodiesterase inhibitor is hydrochloride, mesylate, sulfate and the like of a compound shown in a formula I, and Cu-K[alpha] rays are used for measuring that the hydrochloride of the compound shown in the formula I has diffraction characteristic peaks at the following 2[theta] angles: 6.089+ / -0.2 degrees, 7.189+ / -0.2 degrees, 8.711+ / -0.2 degrees, 9.191+ / -0.2 degrees, 12.284+ / -0.2 degrees and 23.954+ / -0.2 degrees. Compared with a compound shown in a formula I and other known polycrystals, the polymorphic substance of the type 5 phosphodiesterase inhibitor has the advantages of better solubility, quicker effect, longer half-life period and better bioavailability.

Description

technical field [0001] The invention relates to the field of medicine, in particular to polymorphs of type 5 phosphodiesterase inhibitors and their preparation methods and applications. Background technique [0002] Erectile dysfunction (ED) refers to the persistent inability to achieve and / or maintain a sufficient erection for a satisfactory sexual life. According to statistics, currently about 150 million men worldwide suffer from ED symptoms of varying degrees, and it is estimated that the number of patients will double by 2025. Phosphodiesterase type 5 (PDE5) inhibitors are currently the most mature drugs for the treatment of ED. There are five drugs of this type that have been approved for marketing today, namely Sildenafil, Tadanafil, Vardenafil, Udenafil and Mironafil ( Mirodenafil). These compounds have a strong selective inhibitory effect on phosphodiesterase, which has attracted widespread attention and become a new research hotspot. Relevant studies have carri...

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): C07D487/04A61K31/519A61P15/10A61P13/08A61P13/10A61P13/00A61P9/10A61P9/04A61P11/06A61P11/00A61P25/28
CPCC07D487/04A61P13/08A61P13/10A61P9/10A61P9/04A61P11/06A61P11/00A61P25/28C07B2200/13A61P15/00A61P9/12A61P25/00
Inventor 王靖林于瑞梅魏兆民穆振强张宪生
Owner JINAN MEILUWEI BIOTECH CO LTD