Wednesday 27 December 2017

NEW PATENTS 27 DEC 2017

27 DEC 2017
11new patents,

Sr no
Patent number
name
company
INDICATION
REMARKS, WAIT FOR STR TO APPEAR
1
WO-2017218957
FUNAPIDE
TEVA
PAIN
Funapide.svg
2
WO-2017218920
FUNAPIDE
TEVA
PAIN
Funapide.svg
3
WO-2017216805

VORTIOXETINE
INDIVIDUAL
Major depressive disorder
Vortioxetine.svg






4
WO-2017216761

ETINOSTAT
DR REDDYS
Breast tumor
Entinostat.svg
5
WO-2017216661
BREXPIPRAZOLE
JUBILANT

Major depressive disorder; Schizophrenia

Brexpiprazole.svg
6
WO-2017216025

EMPESERTIB
BAYER
CANCER
Image result for EMPESERTIB
7
WO-2017215617

OZANIMOD
CRYSTAL
Multiple sclerosis; Ulcerative colitis
Ozanimod.svg
8
PEXIDARTINIB
CRYSTAL
Giant cell bone tumor
Pexidartinib.svg
9
WO-2017215110

CILASTATIN
SOOCHOW
Bacterial infection
Cilastatin.svg
10
WO-2017215019

LEDIPASVIR
CHENGDU
Hepatitis C virus infection
Ledipasvir.svg
11
WO-2017216709

EMTRICITABINE/LAMUVIDINE 
NELSON M M UNIV

HIV infection; Hepatitis B virus infection
Emtricitabine skeletal.svg Lamivudine structure.svg
12





Tuesday 26 December 2017

Pexidartinib, New Patent, WO 2017215521, Crystal Pharmatech Co Ltd

Image result for CRYSTAL PHARMACEUTICAL (SUZHOU) CO., LTD
Pexidartinib, New Patent, WO, 2017215521, Crystal Pharmatech Co Ltd
(WO2017215521) PLX3397 HYDROCHLORIDE CRYSTAL FORM, PREPARATION METHOD THEREFOR AND USE THEREOF
https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2017215521
CRYSTAL PHARMACEUTICAL (SUZHOU) CO., LTD
INVENTORS
CHEN, Minhua; (CN).
ZHANG, Yanfeng; (CN).
ZOU, Po; (CN).
ZHANG, Xiaoyu; (CN)
Novel crystalline forms of PLX3397 hydrochloride (designated as Forms CS2 and CS3), processes for their preparation and compositions comprising them are claimed. Also claim is their use for treating giant cell tumor of the tendon sheath.
The present invention relates to a PLX3397 hydrochloride crystal form, a preparation method therefor and use thereof. The PLX3397 hydrochloride crystal form has higher solubility, larger particle size, and good stability, especially better mechanical stability, is favorable for separation of products in subsequent production, provides a better choice for preparing PLX3397-containing pharmaceutical preparations, and is very important to medicinal development.
front page image
Pexidartinib (PLX3397) is a new drug used to treat tenosynovial giant cell tumor (TGCT). Tenoid sheath giant cell tumor is a rare type of tendon sheath cancer. At present, the disease is usually treated surgically by surgical resection, and the surgical treatment of the disease may lead to the deterioration of dysfunction and serious complications. And since TGCTs have multiple types, which typically occur at bone tissue and joints, the advent of new interventional therapies is urgently needed in the clinic. The PLX3397 is currently in Phase III clinical trials and has received the FDA's breakthrough drug therapy certification. The structural formula of PLX3397 is shown in formula (I).
 
Example 1 Preparation of monohydrochloride form CS2

[0112]
Weigh 101.6 mg of PLX3397 solids in a 5 mL glass vial and add 2 mL of n-heptane at 5 ° C. Under magnetic stirring, 440 μL of 0.6 mol / L diluted hydrochloric acid was added and the reaction was carried out for 40 min. The mixture was filtered and dried to obtain an off-white solid.

[0113]
Upon testing, the solid obtained in this example is the monohydrochloride form CS2. The XRPD pattern is shown in Figure 1, and the XRPD data is shown in Table 1. The resulting solid was monohydrochloride salt of PLX3397 as determined by ion chromatography. 1 H NMR is shown in FIG. 4.

[0114]
When differential scanning calorimetry was used, the endothermic peak began to form when heated to about 72 ° C. When heated to around 227 ° C, the endothermic peak started to appear. The DSC is shown in FIG. 2.

[0115]
When subjected to thermogravimetric analysis, crystalline form CS2 has a mass loss gradient of about 8.3% when heated to 137 ° C, the TGA of which is shown in FIG. 3. Form CS2 is hydrate.
[Figure 0009]   
Fig. 1 H NMR chart of crystalline form CS3 in Example 3. Fig
//////////////Pexidartinib, New Patent, WO 2017215521, Crystal Pharmatech Co Ltd

Monday 18 December 2017

IMIGLIPTIN, NEW PATENT, WO 2017211293, XUANZHU PHARMA CO., LTD.


(WO2017211293) CRYSTALLINE FORM OF SUCCINATE USED AS DIPEPTIDYL PEPTIDASE-4 INHIBITOR 
WO-2017211293, 
XUANZHU PHARMA CO., LTD. [CN/CN]; 2518, Tianchen Street, National High-Tech Development Zone Jinan, Shandong 250101 (CN)
SHU, Chutian; (CN)


https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2017211293&recNum=1&tab=PCTDocuments&maxRec=&office=&prevFilter=&sortOption=&queryString=

front page image


The present invention relates to a crystalline form of a succinate used as a dipeptidyl peptidase-4 inhibitor, and a manufacturing method, pharmaceutical composition, and application thereof. The invention specifically relates to a dipeptidyl peptidase-4 inhibitor compound as represented by formula (1), a crystalline form of a succinate, wherein the succinate is an (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, and a manufacturing method, pharmaceutical composition, and application thereof.




Example 1: Preparation of the succinate salt form I of the compound of formula (1)
[0056]

[0057]
The compound of formula (1) (44.6 g, 0.12 mol) was added to a 2 L round bottom flask and suspended in 1593 mL of acetonitrile. The mixture was heated to 80 ° C. and dissolved in free form. Immediately after the addition of 15.4 g A white solid precipitated, maintained at 80 ℃ for 1 hour and then cooled to room temperature, filtered and the filter cake was dried in vacuo at 40 ℃ for 10 hours, weighed 57.6g, yield 98.3%. The succinate salt Form I was tested by XRPD.
[0058]
Example 2: Preparation of the succinate salt form I of the compound of formula (1) II
[0059]
A quantity of succinate salt of the compound of formula (1) was weighed into glass vials in a total of 26 parts. A total of 26 vials of methanol, ethanol, isopropanol, isobutanol, 2-butanone, tetrahydrofuran, acetonitrile, methyl tert-butyl ether, acetone, water, toluene, Isopropyl acetate, n-propanol, isoamyl alcohol, butyl acetate, ethyl formate, 1,4-dioxane, n-butanol, pentane, heptane, cyclohexane, Ketone, xylene, isobutyl acetate, diethyl ether). After stirring, ultrasound and other means to make the sample fully dissolved. Subsequently, about 2 mL of liquid was removed from each bottle and filtered into 26 reagent tubes numbered 1-26. The resulting 26 filtrates were distributed in two 96-well plates. One or two of the above 1-13 solvents are sequentially added into the first 96-well plate, one or two of the above-mentioned 14-26 kinds of solvents are sequentially added into the second 96-well plate, Zha Kong sealing film sealed, placed in a fume hood, the natural environment to dry. Wherein Form I is obtained in the following mixed solvent, and Form I is also precipitated in the methyl isobutyl ketone in the remaining solution after plating.
[0060]
The solvent used to prepare succinate salt Form I was prepared
[0061]
[Table 0001]
Mixed solventsSolvent 1Solvent 2
1Methyl isobutyl ketoneEther
2XyleneEther
3Isobutyl acetateEther
4EtherEther
51,4-dioxanePentane
61,4-dioxaneHeptane
71,4-dioxaneCyclohexane
81,4-dioxaneMethyl isobutyl ketone
91,4-dioxaneXylene
101,4-dioxaneIsobutyl acetate
11Butyl acetateEther
12Butyl acetate1,4-dioxane
[0062]
Example 3: Preparation of the succinate salt form II of the compound of formula (1)
[0063]
Take 8 parts of the compound of formula (1), 200mg each, placed in a 10mL round bottom flask, add the solvent in the following table to each solvent, warmed until the solvent is refluxed, after dissolving it, add 69mg (1.1eq) succinic acid and cool to At room temperature, the solid precipitated and was filtered. The resulting solid was subjected to XRPD testing as succinate crystal form II.
[0064]
[Table 0002]
Feeding amountSolvent and ratio
2mLTetrahydrofuran
3mLacetone
5.5mLAcetonitrile: water = 10: 1
2mLMethanol
4mLEthanol
1mLEthanol: water = 10: 1
2mLIsopropanol: water = 19: 1
2mLIsopropyl alcohol: water = 9: 1

New patents, 19 DEC 2017



Sr no
Patent number
name
company
INDICATION
REMARKS, WAIT FOR STR TO APPEAR
1
WO-2017212390

LANREOTIDE
EMCURE

Acromegaly; Carcinoid syndrome; Gigantism; Neuroendocrine tumor

Lanreotide.svg
2
WO-2017212030
ASTAXANTHIN
DEINOVE
Aging; Cancer; Cardiovascular disease; Central nervous system disease; Diabetes mellitus; Inflammatory disease
Skeletal formula of astaxanthin
3
WO-2017211820
DEOXYCHOLIC ACID
BIONICE
Cholelithiasis; Hepatitis; Liver disease; Primary biliary cirrhosis
Skeletal formula of deoxycholic acid






4
WO-2017211788

PALBOCICLIB
KHS
Metastatic breast cancer
Palbociclib.svg
5
WO-2017211777

NINTEDANIB
OLON
Idiopathic pulmonary fibrosis; Small-cell lung cancer
Nintedanib
6
WO-2017211733
SUVOREXANT
ENANTIA
Insomnia
Suvorexant.svg
7
WO-2017211325

TENOFOVIR
SHANGHAI

HIV infection; Hepatitis B virus infection

Tenofovir alafenamide structure.svg
8
WO-2017211293
IMIGLIPTIN
XUANGHU
Hyperglycemia; Hyperlipidemia; Insulin resistance; Non-insulin dependent diabetes
Image result for IMIGLIPTIN
9
WO-2017211248

COPANLISIB
SHENZEN
Cancer; Cardiovascular disease; Inflammatory disease; Neurodegenerative disease
Copanlisib.svg
10
WO-2017211246
ALCAFTADINE
SHENZEN
Allergy; Nasal congestion
Alcaftadine.svg
11
WO-2017211245

RIBOCICLIB
SHENZEN
Glioma; Leukemia; Pancreas tumor
Ribociclib skeletal.svg
12
WO-2017211268

ABEMACICLIB
SHANGHAI
Autoimmune disease; Cancer; Inflammatory disease
Abemaciclib.svg