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A kind of crystal form of fatty acid bile acid conjugate and its preparation method and application

A crystal form and compound technology, applied in the field of the crystal form of fatty acid bile acid conjugates and its preparation, can solve the problems of harsh packaging and storage conditions, increased drug production costs, unfavorable production and application, etc., to reduce material storage and quality Control costs, facilitate drug absorption, and avoid the effects of pretreatment

Active Publication Date: 2022-05-17
CRYSTAL PHARMA CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] Patent CN100386339C discloses the preparation method of compound (I), and there is no disclosure of any other solid form. The applicant of the present invention repeats the method in patent CN100386339C to obtain an amorphous solid (solid in the prior art), and further research finds that the resulting amorphous The solid has high hygroscopicity, and the equilibrium weight gain is 2.44% under 80% relative humidity, and the stability is poor
Highly hygroscopic APIs have strict requirements on packaging and storage conditions, resulting in an increase in the production cost of the drug, which is not conducive to production and application

Method used

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  • A kind of crystal form of fatty acid bile acid conjugate and its preparation method and application
  • A kind of crystal form of fatty acid bile acid conjugate and its preparation method and application
  • A kind of crystal form of fatty acid bile acid conjugate and its preparation method and application

Examples

Experimental program
Comparison scheme
Effect test

preparation example 1

[0127] Weigh a certain amount of compound (I) solid in a glass vial, add a certain volume of solvent, as shown in Table 1A, make a suspension, stir at room temperature, centrifuge, dry, collect the solid, and mark the obtained solid as Samples 1-a, 1-b, 1-c.

[0128] Table 1A

[0129]

[0130] After testing, samples 1-a, 1-b, and 1-c were all crystal forms CS3. Wherein the XRPD data of sample 1-a are as Figure 1A , as shown in Table 1B, samples 1-b, 1-c have the same or similar XRPD pattern as sample 1-a.

[0131] Table 1B

[0132]

[0133]

[0134] The TGA of crystal form CS3 is as Figure 1B As shown, it has a mass loss gradient of about 0.3% when heated to 120 °C.

[0135] DSC of crystal form CS3 such as Figure 1C As shown, it has an endothermic peak, and the endothermic peak begins to appear around 111 °C.

[0136] NMR of crystal form CS3 Figure 1D As shown, the NMR data are: 1 HNMR (400MHz, DMSO) δ11.95(s, 1H), 7.53(d, J=7.0Hz, 1H), 4.12(d, J=3.3Hz, 1...

preparation example 2

[0138] Weigh 15.6 mg of compound (I) as a solid, dissolve it in 0.5 mL of chloroform, filter to obtain the filtrate, add 2.0 mL of toluene dropwise to the above 0.2 mL of filtrate, stir until a solid appears, collect the solid by centrifugation, and dry to obtain sample 1- d, after detection, sample 1-d is crystal form CS3.

preparation example 3

[0140] Weigh a certain mass of compound (I) solid, dissolve it in a certain volume of positive solvent in Table 1C, filter to obtain the filtrate, add a certain volume of filtrate to the anti-solvent in Table 1C, if there is solid precipitation, continue to stir until there is A large number of solids were precipitated, and the solids were collected by centrifugation and dried to obtain samples 1-e and 1-f; after testing, samples 1-e and 1-f were all crystal forms CS3.

[0141] Table 1C

[0142]

[0143]

[0144] Crystal form CS3 stability study:

[0145] As the most critical active ingredient in a drug, it is very important for the crystal form to have good physical and chemical stability. The crystal form has good physical stability, which ensures that the raw material drug is not easily transformed into other crystal forms during storage and preparation process, thereby ensuring that the quality of the sample is consistent and controllable.

[0146] Take 2 samples o...

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Abstract

The present invention relates to a new crystal form of compound (I) and its preparation method and use. The crystalline form CS3, crystalline form CS2, crystalline form CS5, and crystalline form CS8 of compound (I) provided by the present invention have the advantages of solubility, stability, melting point, hygroscopicity, particle size, bioavailability, processing performance, purification, and fluidity. , adhesion, stability in formulations, and in vitro dissolution have advantages in at least one aspect, providing a new and better option for the preparation of pharmaceutical formulations containing compound (I), which is of great significance for drug development .

Description

technical field [0001] The invention relates to the technical field of pharmaceutical crystals. Specifically, it relates to a crystal form of a fatty acid bile acid conjugate and its preparation method and use, and belongs to the field of medicine. Background technique [0002] Aramchol is a fatty acid bile acid conjugate, specifically an amide conjugate of eicosanic acid and 3-aminocholic acid. Aramchol can effectively inhibit the activity of stearoyl-CoA desaturase 1 (Stearoyl-CoA Desaturase 1, SCD1), which is related to the regulation of fatty acid metabolism. Aramchol inhibits SCD1, reduces fatty acid synthesis, and increases β-oxidation at the same time, leading to an overall reduction in triglyceride and fatty acid ester liver storage, thereby effectively reducing liver fat content and improving metabolic parameters related to fatty liver disease. It is developed for fatty liver disease and non-alcoholic steatohepatitis, and the research and development company is Ga...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07J41/00C07J9/00C07C229/26A61K31/575A61P1/04
CPCA61K31/575A61P1/04C07J41/0005C07B2200/13A61P9/10
Inventor 陈敏华张炎锋黄春香张晓宇
Owner CRYSTAL PHARMA CO LTD
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