Tuesday, 4 July 2017




Novel crystalline forms I, II and III of ponesimod . Useful as a selective sphingosine-1-phosphate receptor-1 (S1P1) receptor agonist, for the treatment of psoriasis. Appears to be first filing from Crystal Pharmatech claiming ponesimod. Johnson & Johnson , following its acquisition of Actelion , is developing ponesimod (phase III clinical trial), a S1P1 agonist, for the treatment of autoimmune disorders. 

Applicants:CRYSTAL PHARMATECH CO., LTD. [CN/CN]; B4-101, Biobay, 218 Xinghu Street,
Suzhou Industrial Park Suzhou, Jiangsu 215123 (CN)
Inventors:CHEN, Minhua; (CN).
ZHANG, Yanfeng; (CN).
LI, Jiaoyang; (CN).
ZHANG, Xiaoyu; (CN)

Most of the family members of the product case ( WO2005054215 ) of ponesimod expire in European countries until November, 2023 and in the US by December, 2024 with US154 extension.

Disclosed are crystalline forms 1, 2, and 3 of a selective S1P1 receptor agonist, namely Ponesimod, and a method for preparing the same. An X-ray powder diffraction pattern of the crystalline form 1 has characteristic peaks at 2 theta values of 18.1° ± 0.2°, 14.6° ± 0.2°, and 11.3° ± 0.2°. An X-ray powder diffraction pattern of the crystalline form 2 has characteristic peaks at 2 theta values of 3.8° ± 0.2°, 10.8° ± 0.2°, and 6.1° ± 0.2°. An X-ray powder diffraction pattern of the crystalline form 3 has characteristic peaks at 2 theta values of 12.2° ± 0.2°, 6.2° ± 0.2°, and 5.6° ± 0.2°. Compared with existing crystalline forms, the present invention has better stability and a greatly increased solubility, and is more suitable for development of a pharmaceutical preparation containing Ponesimod

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Ponesimod (compound of formula I) is a selective S1P1 receptor antagonist developed by Actelion. The drug was used to treat moderate to severe chronic plaque psoriasis in the two medium-term trial was successful, and will carry out the treatment of psoriasis in 3 clinical trials.

The present invention discloses a process for the preparation of a compound of formula I, which is disclosed in patent CN 102177144B, which is an amorphous form prepared by the process of CN100567275C, and discloses a process for the preparation of a compound of formula I, crystalline form C, crystalline form III, Type II. The results show that the crystallinity of crystalline form III is poor and it is converted to crystalline form II at room temperature. The crystalline form II is difficult to repeat and prepare a certain amount of propionic acid. The thermodynamics stability of crystalline form A is inferior to that of crystal form C. In contrast, For the crystal form suitable for the development of the drug, the solubility of the crystalline form C is not ideal.

Example 1
Preparation of Ponesimod Form 1:
48.1 mg of Ponesimod was added to 0.40 mL of 1,4-dioxane and the filtrate was filtered. To the solution was stirred at room temperature, 1.20 mL of n-heptane was added dropwise to precipitate the crystals and stirred overnight. The supernatant was filtered off by centrifugation Liquid to obtain Ponesimod crystal form 1.

Image result for CRYSTAL PHARMATECH CHEN, Minhua

    Follow "'2014' Suzhou International Elite Entrepreneurship Week" with interest Over 88 billion venture capital investment helps your pioneering dreams come true

    Since 2009, there have been 1267 overseas high-level talent projects settled in Suzhou through International Elite Entrepreneurship Week and 54 talents have been introduced and fostered for the national "Thousand Talents Plan". Among these 53 talents, Dr. Chen Minhua, the founder of Suzhou Crystal Pharmatech Co., Ltd., was deeply impressed by thoughtful services in Suzhou for innovative pioneering talents when he recalled the development in Suzhou. "Investment and financing services are placed with particular importance. Everything is thoroughly considered for fear that enterprise
      In 2010, Chen Minhua quitted his job in a well-known pharmaceutical company in the United States and returned with his core 4-people R&D team. He founded Crystal Pharmatech Co., Ltd. in Suzhou Biobay through the Entrepreneurship Week. Till 2013, Crystal Pharmatech has made profits year by year. The yearly output value in 2013 reached 18 million Yuan, while the profits reached as high as 4 million Yuan. His clients involve half of top 20 pharmaceutical companies globally. Chen Minhua longs to fill the vacancy of drug crystals in China and take the lead in the international drug crystal research. Chen Minhua introduced that government service is an integral part to his growth. "Since it was settled down, Suzhou public sector organized several investment and financing activities and offered training and services in various aspects like the mode of financing, finance docking and enterprise strategic investment, which laid a solid foundation for Crystal Pharmatech's capital expansion", said by Chen Minhua.

      To help high-level talents solve financial difficulty, Suzhou lays stress on the docking of science & technology and finance. The person in charge of the Municipal Science and Technology Bureau said that Suzhou guides and integrates social capital for equity investment of hi-tech enterprises at the start-up stage via the guiding funds set up by the government and follow-up investment, etc, thus evolving the venture capital investment cluster based on Shahu Equity Investment Center. After the national "Thousand Talents Plan" venture capital investment center was set up, pioneering talents and venture capital are further converging here. As of the end of 2013, there are 270 effective organizations engaged in various venture capital investment in Suzhou that manage the funds in excess of 88 billion Yuan. 30 million Yuan will be appropriated from the municipal science and technology fund budget for the newly established FOF of Angel Investment this year, so as to take avail of social capital for the development of small and medium-sized hi-tech enterprises.

      Meanwhile, Suzhou sets up the special compensation fund against credit risks and offers "Kedaitong" with "low threshold and low interest rate", so as to solve financial difficulty of small and medium-sized hi-tech enterprises and create favorable financing environment for the pioneering work of talents and corporate development. At present, the fund of credit risk pool has reached 500 million Yuan and "Kedaitong" loans of 8.52 billion Yuan have been granted for 1023 small and medium-sized hi-tech enterprises. Particularly, 120 pioneering enterprises that feature independent intellectual property, high content of technology and light assets were backed up with 1.314 billion Yuan, the special risk compensation fund of "Kedaitong", thus vigorously supporting innovation and pioneering work of leading talents in the science and technology community in Suzhou.

      Reporter Qian Yi
      Quoted from Suzhou Daily on July 6, 2014


Monday, 3 July 2017

Imigliptin dihydrochloride, Xuanzhu Pharma Co Ltd, NEW PATENT, WO 2017107945

Imigliptin dihydrochloride, Xuanzhu Pharma Co Ltd, NEW PATENT, WO 2017107945
Applicants:XUANZHU PHARMA CO.,LTD. [CN/CN]; 2518, Tianchen Street, National High-tech Development Zone Jinan, Shandong 250101 (CN)
Inventors:SHU, Chutian; (CN).
WANG, Zhenhua; (CN)
The present invention relates to a crystalline form of benzoate of a dipeptidyl peptidase-IV inhibitor, a method for preparing the same, a pharmaceutical composition,and a use thereof. Specifically, the present invention relates to a crystalline form of benzoate of a compound used as a dipeptidyl peptidase-IV inhibitor and represented by formula (1), namely (R)-2-((7-(3-aminopiperidine-1-yl)-3,5-dimethyl-2-oxo-2,3-dihydro-1H-imidazo(4,5-b)pyridine-1-yl)methyl)benzonitrile, a method for preparing the same, a pharmaceutical composition, and a use thereof.
Novel crystalline form I of imigliptin dihydrochloride as dipeptidyl peptidase IV inhibitor (DPP-IV) for the treatment of and/or prevention of non-insulin dependent diabetes, hyperglycemia and hyperlipidemia. In June 2017, KBP Biosciences and Xuanzhu Pharma , subsidiaries of Sihuan Pharmaceutical , are developing an imigliptin dihydrochloride (phase II clinical trial), a DPP-IV inhibitor and a hypoglycemic agent,, for the treatment of type II diabetes. Follows on from WO2013007167 , claiming similar composition.
Dipeptidyl peptidase-IV (DPP-IV) inhibitor is a new generation of oral type 2 diabetes treatment drugs, by enhancing the role of intestinal insulin to play a role, non-insulin therapy drugs. Compared with conventional drugs for the treatment of diabetes, DPP-IV inhibitors do not have weight gain and edema and other adverse reactions.
The compound (R) -2 - ((7- (3-aminopiperidin-1-yl) -3,5-dimethyl-2-oxo-2,3-dihydro- 1H-imidazo [4,5-b] pyridin-1-yl) methyl) benzonitrile (described in the specification as a compound of formula (1), as described in patent application PCT / CN2011 / 000068) Inhibitors of compounds, DPP-IV has a strong inhibitory effect and a high selectivity.

The study of crystal form plays an important role in drug development process. Application No. PCT / CN2012 / 078294 discloses the dihydrochloride crystal form I of the compound of formula (1), in order to meet the requirements of formulation, production and transportation , We further studied the crystal form of the compound of formula (1) in order to find a better crystal form.
Example 1 Preparation of benzoate form I of compound of formula (1)
40 g (0.1 mol) of the compound of the formula (1) was added to a 2 L round bottom flask, suspended in 1428 mL of acetonitrile, and the temperature was raised to 60 ° C. The free solution was dissolved, 14.3 g (0.1 mol) of benzoic acid was added, The precipitate was dried at 60 ° C for 1 hour and then allowed to stand at room temperature. The filter cake was dried in vacuo at 40 ° C for 10 hours and weighed 51.6 g in 97.4% yield. By XRPD test, for the benzoate crystal type Ⅰ.

////////////////Imigliptin dihydrochloride, Xuanzhu Pharma Co Ltd, NEW PATENT, WO 2017107945
CFDA Granted Approval of Phase II/III Clinical Trials for Imigliptin Hydrochloride
2016-08-04 15:25:37 Author:admin
        Phase II/ III Clinical Trials of Imigliptin Hydrochloride (KBP-3853) have been approved by CFDA; the Clinical Approval Numbers are 2016L05997 and 2016L06137.
        As we know, in Phase I study both single and multiple doses of Imigliptin Hydrochloride were safe and well tolerated in healthy volunteers and in Type 2 diabetes patients. Imigliptin Hydrochloride demonstrated good pharmacokinetic (PK) characteristics and exhibited dose-proportional plasma exposure. The potent and long duration inhibition of DPP-4 was validated in the PK/PD study. The results of Phase I study of Imigliptin Hydrochloride warranted its long-term safety and efficacy studies in Phase II/ III.
        Currently, the Imigliptin Hydrochloride team has completed the production of clinical trial drug product, as well as finalized the clinical protocols and the study sites. Phase II clinical trial of Imigliptin Hydrochloride will begin in the near future.
       The approval of Imigliptin Hydrochloride for the phase II/ III clinical trials represents another milestone in the SiHuan/ XuanZhu’s new drug discovery history. We enter into a new clinical stage of the development process, and we have many works remaining before us. It is still an urgent task for us to accelerate the clinical development, and to launch the drug product in the China market as soon as possible.