WO2018196687A1 - Nouvelle forme cristalline de méthanesulfonate de lenvatinib et procédé de préparation correspondant - Google Patents

Nouvelle forme cristalline de méthanesulfonate de lenvatinib et procédé de préparation correspondant Download PDF

Info

Publication number
WO2018196687A1
WO2018196687A1 PCT/CN2018/083861 CN2018083861W WO2018196687A1 WO 2018196687 A1 WO2018196687 A1 WO 2018196687A1 CN 2018083861 W CN2018083861 W CN 2018083861W WO 2018196687 A1 WO2018196687 A1 WO 2018196687A1
Authority
WO
WIPO (PCT)
Prior art keywords
crystal form
mesylate
mesylate salt
preparation
ray powder
Prior art date
Application number
PCT/CN2018/083861
Other languages
English (en)
Chinese (zh)
Inventor
陈敏华
张炎锋
张龙
邹坡
黄春香
杨朝惠
张晓宇
Original Assignee
苏州科睿思制药有限公司
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 苏州科睿思制药有限公司 filed Critical 苏州科睿思制药有限公司
Priority to CN201880024174.8A priority Critical patent/CN110494423B/zh
Publication of WO2018196687A1 publication Critical patent/WO2018196687A1/fr

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen

Definitions

  • the invention relates to the field of chemical medicine, in particular to a new crystal form of levastatin mesylate and a preparation method thereof.
  • Levartinib is an oral multi-receptor tyrosine kinase (RTK) inhibitor developed by Japan Eisai Co., Ltd. for the treatment of invasive and differentiated thyroid cancer. It was acquired on February 13, 2015. Approved by the FDA, approved by the EMA on May 28, 2015.
  • the chemical name of leventinib is: 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide (hereinafter referred to as "compound (I) )"), its structural formula is as follows:
  • CN100569753C discloses crystal forms A, B, C, F, and I of methanesulfonate.
  • the solubility of crystal form A is inferior to that of crystal form C
  • form B is converted to crystal form C under conditions of high humidity or high temperature.
  • WO2016184436A1 discloses mesylate salt form M, which is disclosed in the patent as being more soluble in several biological media than the methanesulfonate salt form C disclosed in patent CN100569753C.
  • the invention provides a new crystal form 1 of methanesulfonate salt, the solubility of which is obviously superior to the prior art crystal form, and the preparation process of the crystal form 1 is simple and the cost is low, which is of great value for the optimization and development of the drug in the future.
  • the present invention provides the crystalline form 1 of the mesylate salt of the compound (I) (hereinafter referred to as "crystal form 1").
  • the X-ray powder diffraction of the Form 1 has characteristic peaks at diffraction angles 2 ⁇ of 7.4° ⁇ 0.2°, 14.8° ⁇ 0.2°, and 24.8° ⁇ 0.2°.
  • the X-ray powder diffraction of the Form 1 has a characteristic peak at one or more of the diffraction angle 2 ⁇ of 26.6° ⁇ 0.2°, 20.4° ⁇ 0.2°, and 25.8° ⁇ 0.2°. Further, the X-ray powder diffraction of the crystal form 1 has a characteristic peak at a diffraction angle 2 ⁇ of 26.6 ° ⁇ 0.2 °, 20.4 ° ⁇ 0.2 °, 25.8 ° ⁇ 0.2 °.
  • the X-ray powder diffraction of the Form 1 has a characteristic peak at one or more of the diffraction angle 2 ⁇ of 9.7° ⁇ 0.2°, 22.8° ⁇ 0.2°, and 23.3° ⁇ 0.2°. Further, the X-ray powder diffraction of the crystal form 1 has a characteristic peak at a diffraction angle 2 ⁇ of 9.7° ⁇ 0.2°, 22.8° ⁇ 0.2°, and 23.3° ⁇ 0.2°.
  • the X-ray powder diffraction of Form 1 is 7.4 ° ⁇ 0.2 °, 14.8 ° ⁇ 0.2 °, 24.8 ° ⁇ 0.2 °, 26.6 ° ⁇ 0.2 °, 20.4 ° ⁇ at diffraction angle 2 ⁇ 0.2°, 25.8° ⁇ 0.2°, 9.7° ⁇ 0.2°, 22.8° ⁇ 0.2°, 23.3° ⁇ 0.2°, 10.1 ⁇ °°, 11.2° ⁇ 0.2°, 19.3° ⁇ 0.2°, 27.1 ⁇ 0.2° There are characteristic peaks.
  • the X-ray powder diffraction pattern of Form 1 is shown in FIG.
  • the present invention also provides a method for preparing the crystal form 1, the preparation method comprising:
  • levastatin mesylate form B or form F in a mixed system of acetonitrile to water volume ratio of 92/8 to 80/20, stirring and decanting at -10 ° C to 25 ° C Obtain; or
  • the crystal form B and the crystal form F are the methanesulfonate crystal form B and the crystal form F disclosed in the patent CN100569753C.
  • the crystal form M is the methanesulfonate crystal form M disclosed in the patent WO2016184436A1.
  • the molar ratio of methanesulfonic acid to lavatinib free base in the method 1) is from 1/1 to 1.5/1, preferably 1/1.0.
  • the temperature described in the method 1) is preferably 5 °C.
  • the volume ratio of acetonitrile to water is preferably 88/12.
  • the temperature described in the method 2) is preferably 5 °C.
  • the present invention provides the crystal form 7 of the mesylate salt of the compound (I) (hereinafter referred to as "crystal form 7").
  • the X-ray powder diffraction of the Form 7 has characteristic peaks at diffraction angles 2 ⁇ of 5.3° ⁇ 0.2°, 18.5° ⁇ 0.2°, and 20.8° ⁇ 0.2°.
  • the X-ray powder diffraction of the crystal form 7 has a characteristic peak at one or more of the diffraction angle 2 ⁇ of 16.8° ⁇ 0.2°, 22.4° ⁇ 0.2°, and 24.3° ⁇ 0.2°.
  • the X-ray powder diffraction of the crystal form 7 has a characteristic peak at a diffraction angle 2 ⁇ of 16.8° ⁇ 0.2°, 22.4° ⁇ 0.2°, and 24.3° ⁇ 0.2°.
  • the X-ray powder diffraction of the crystal form 7 has a characteristic peak at one or more of the diffraction angle 2 ⁇ of 9.6° ⁇ 0.2°, 10.7° ⁇ 0.2°, and 19.3° ⁇ 0.2°.
  • the X-ray powder diffraction of the crystal form 7 has a characteristic peak at diffraction angles 2 ⁇ of 9.6° ⁇ 0.2°, 10.7° ⁇ 0.2°, and 19.3° ⁇ 0.2°.
  • the X-ray powder diffraction of Form 7 is 5.3 ° ⁇ 0.2 °, 9.6 ° ⁇ 0.2 °, 10.7 ° ⁇ 0.2 °, 16.8 ° ⁇ 0.2 °, 18.5 ° ⁇ at diffraction angle 2 ⁇
  • the X-ray powder diffraction pattern of Form 7 is as shown in FIG.
  • the present invention also provides a method for preparing the crystal form 7, which comprises adding mesylate to anhydrous acetonitrile using levatinib free base, and stirring at 0 ° C to 35 ° C. The reaction is obtained by crystallization.
  • the molar ratio of the methanesulfonic acid to the lavatinib free base is from 1/1 to 1.5/1, preferably 1/1.0.
  • the temperature is preferably 25 °C.
  • the "room temperature” means 10 ° C to 30 ° C.
  • the “stirring” is carried out by a conventional method in the art, such as magnetic stirring or mechanical stirring, and the stirring speed is 50 to 1800 rpm, preferably 300 to 900 rpm.
  • the “separation” is accomplished using conventional methods in the art, such as centrifugation or filtration.
  • the “centrifugation” operation was performed by placing the sample to be separated in a centrifuge tube and centrifuging at a rate of 10,000 rpm until the solids all settled to the bottom of the centrifuge tube.
  • the levavirinib and/or its salt as a raw material means a solid (crystalline or amorphous), semi-solid, wax or oil form.
  • the levavirinib and/or a salt thereof as a raw material is in the form of a solid powder.
  • crystal or “polymorph” means confirmed by the X-ray diffraction pattern characterization shown.
  • X-ray diffraction pattern will generally vary with the conditions of the instrument. It is particularly important to note that the relative intensities of the X-ray diffraction patterns may also vary with experimental conditions, so the order of peak intensities cannot be the sole or decisive factor. In fact, the relative intensity of the diffraction peaks in the XRPD pattern is related to the preferred orientation of the crystal.
  • the peak intensities shown here are illustrative and not for absolute comparison.
  • the experimental error of the peak angle is usually 5% or less, and the error of these angles should also be taken into account, and an error of ⁇ 0.2° is usually allowed.
  • the overall offset of the peak angle is caused, and a certain offset is usually allowed.
  • the X-ray diffraction pattern of one crystal form in the present invention is not necessarily identical to the X-ray diffraction pattern in the example referred to herein, and the "XRPD pattern is the same" as used herein does not mean absolutely the same.
  • the same peak position can differ by ⁇ 0.2° and the peak intensity allows for some variability.
  • Any crystal form having a map identical or similar to the characteristic peaks in these maps is within the scope of the present invention.
  • One skilled in the art will be able to compare the maps listed herein with a map of an unknown crystal form to verify whether the two sets of maps reflect the same or different crystal forms.
  • the mesylate salt form 1, Form 7 of the present invention is pure, unitary, and substantially free of any other crystal form.
  • substantially free when used to refer to a new crystalline form means that the crystalline form contains less than 20% by weight of other crystalline forms, especially less than 10% by weight of other crystalline forms, more Other crystal forms of 5% by weight, more preferably less than 1% by weight of other crystal forms.
  • Another object of the present invention is to provide a pharmaceutical composition comprising an effective amount of the mesylate salt form 1 and a pharmaceutically acceptable excipient.
  • the present invention provides the use of Form 1 in the manufacture of a tyrosinase inhibitor drug.
  • the present invention provides the use of Form 1 for the preparation of a pharmaceutical preparation for treating thyroid cancer.
  • the lovastatin mesylate salt form 1 of the present invention has the following beneficial properties:
  • the crystal form 1 provided by the invention has good solubility in simulated biological medium and pure water, especially in the artificial intestinal juice (FeSSIF) in the fed state, the solubility is 30 times higher than that in the prior art CN100569753 crystal form C, The solubility in simulated artificial gastric juice (SGF) and water is higher than 10 mg/mL.
  • Levartinib is a poorly soluble drug, and solubility is the rate-limiting factor of drug bioavailability. Therefore, a significant increase in the solubility of Form 1 will help to improve the bioavailability of levavirinib, thereby increasing the drug's drug-forming properties.
  • the efficacy of the drug while ensuring the efficacy of the drug, reducing the dose of the drug, thereby reducing the side effects of the drug and improving the safety of the drug.
  • the crystal form 1 provided by the invention has good physical and chemical stability.
  • the crystal form 1 of the present invention does not change crystal form at 25 ° C / 60% relative humidity for at least 1 week, and the crystal form purity hardly changes; at room temperature / 22.5% relative humidity, room temperature / 43.2% relative humidity, room temperature /
  • the crystal form did not change at 57.6% relative humidity, room temperature/75.3% relative humidity, and room temperature/97.5% relative humidity for at least 5 days.
  • Form 1 has good stability, ensuring that the drug substance is not easily converted into other crystal forms during the storage and formulation process, thereby ensuring consistent and controllable sample quality, which is of great significance for drug development.
  • Example 1 is an XRPD pattern of the mesylate salt form 1 prepared in Example 1.
  • Example 2 is an XRPD pattern of the mesylate salt form 1 prepared in Example 2.
  • Figure 5 is an XRPD pattern of the mesylate salt form 7 prepared in Example 8.
  • Figure 7 is a comparison chart of XRPD of the stability test of the methanesulfonate crystal form 1 in Example 11 (the figure above is before placing, the lower figure is placed after 25°C/60% humidity for one week)
  • Figure 8 is a comparison chart of XRPD of the methanesulfonate crystal form 1 stability test in Example 11 (from top to bottom, starting sample, 22.5% relative humidity, 43.2% relative humidity, 57.6% relative humidity, 75.3% relative) Humidity, sample placed at 97.5% relative humidity for five days)
  • Figure 10 is a TGA diagram of the mesylate salt form 1 prepared in Example 5.
  • Figure 11 is a DSC chart of the methanesulfonate salt form 1 prepared in Example 5.
  • test methods described are generally carried out under conventional conditions or conditions recommended by the manufacturer.
  • the X-ray powder diffraction pattern of the present invention was collected on a Panalytical Empyrean X-ray powder diffractometer.
  • the method parameters of the X-ray powder diffraction described in the present invention are as follows:
  • Scan range: from 3.0 to 40.0 degrees
  • the differential scanning calorimetry (DSC) map of the present invention was acquired on a TA Q2000.
  • the method parameters of the differential scanning calorimetry (DSC) described in the present invention are as follows:
  • thermogravimetric analysis (TGA) map of the present invention was taken on a TA Q5000.
  • the method parameters of the thermogravimetric analysis (TGA) described in the present invention are as follows:
  • levavirinib and/or a salt thereof according to the present invention can be obtained by a method disclosed in the prior art, for example, by the method disclosed in CN100569753C and WO2016184436A1.
  • the white solid obtained in this example was tested to be Form 1 of Levatinib mesylate.
  • the X-ray powder diffraction data is shown in Figure 1, Table 1.
  • the white solid obtained in this example was the crystalline form 1 of Levatinib mesylate, and its X-ray powder diffraction data is shown in Table 2, and its XRPD pattern is shown in FIG.
  • the white solid obtained in this example was tested to be Form 1 of Levatinib mesylate, and its XRPD pattern is shown in FIG.
  • the crystal form 8 has an XRPD pattern as shown in FIG.
  • the TGA of the crystal form is as shown in FIG. 10, and when it is heated to about 150 ° C, it has a mass loss gradient of about 11.2%; the DSC of the crystal form is as shown in FIG. 11 at 87 ° C, 91 ° C, and 117 ° C. An endothermic peak appeared near 162 ° C and 181 ° C; combined with TGA and DSC data, the crystalline form 1 of the present invention was a hydrate.
  • Form B of Leventinibethanesulfonate 5.0 mg was placed in a 1.5 mL glass vial, and 0.6 mL of a mixed solvent of acetonitrile and water (volume ratio of acetonitrile to water of 88/12) was added at 5 Magnetic stirring was carried out for 4 days at ° C to obtain a white solid, and XRPD was immediately detected, and the obtained white solid was methanesulfonate crystal form 1.
  • the white solid obtained in this example was tested to be Form 7 of Levatinib mesylate.
  • the X-ray powder diffraction pattern is shown in Fig. 5, and the data is shown in Table 3.
  • the mesylate salt form 1 of the present invention was placed under the condition of 25 ° C / 60% relative humidity for one week, and the crystal form change was sampled.
  • the XRPD comparison chart of the methanesulfonate crystal form 1 before and after the placement is shown in Fig. 7.
  • the above figure shows the purity of 99.73% after the one placed at 25 ° C / 60% humidity for one week. The purity was 99.74%), and the crystal form showed almost no change, indicating that Form 1 has good physicochemical stability.
  • the solid of the methanesulfonate crystal form 1 was placed at room temperature and humidity for five days, and the solid crystal form was measured.
  • the XRPD comparison chart is shown in Fig. 8 (from top to bottom, the starting sample, 22.5% relative humidity, 43.2% relative humidity, 57.6% relative humidity, 75.3% relative humidity, 97.5% relative humidity for five days).
  • SGF simulated artificial gastric juice
  • pure water pure water
  • the crystal form 1 of the present invention has higher solubility than the prior art crystal form C and crystal form M after being placed in SGF, FeSSIF and water for 24 hours, especially in FeSSIF, the solubility ratio is now There are technical crystal forms that are 30 times higher.
  • the results show that the solubility of the crystalline form 1 of the present invention meets the requirements of medicinal requirements and provides favorable conditions for drug development.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne une nouvelle forme cristalline d'un sel de méthanesulfonate de lenvatinib et un procédé de préparation correspondant, une composition pharmaceutique contenant la forme cristalline et l'utilisation de la forme cristalline dans la préparation d'un inhibiteur de tyrosinase et d'une préparation pharmaceutique pour le traitement du cancer de la thyroïde. La nouvelle forme cristalline de type méthanesulfonate de la présente invention présente des avantages économiques évidents et présente une ou plusieurs propriétés améliorées par rapport à l'état de la technique et est de grande valeur pour l'optimisation et la mise au point du médicament à l'avenir.
PCT/CN2018/083861 2017-04-25 2018-04-20 Nouvelle forme cristalline de méthanesulfonate de lenvatinib et procédé de préparation correspondant WO2018196687A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201880024174.8A CN110494423B (zh) 2017-04-25 2018-04-20 乐伐替尼甲磺酸盐的新晶型及其制备方法

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
CN201710277048 2017-04-25
CN201710277048.0 2017-04-25
CN201710903156.4 2017-09-29
CN201710903156 2017-09-29

Publications (1)

Publication Number Publication Date
WO2018196687A1 true WO2018196687A1 (fr) 2018-11-01

Family

ID=63918030

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2018/083861 WO2018196687A1 (fr) 2017-04-25 2018-04-20 Nouvelle forme cristalline de méthanesulfonate de lenvatinib et procédé de préparation correspondant

Country Status (2)

Country Link
CN (1) CN110494423B (fr)
WO (1) WO2018196687A1 (fr)

Cited By (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109867626A (zh) * 2019-04-18 2019-06-11 安礼特（上海）医药科技有限公司 一种甲磺酸仑伐替尼多晶型物及其制备方法
CN110256341A (zh) * 2019-06-27 2019-09-20 尚科生物医药（上海）有限公司 一种乐伐替尼甲磺酸盐晶型c的制备方法
CN110563644A (zh) * 2019-10-30 2019-12-13 北京赛思源生物医药技术有限公司 一种仑伐替尼甲磺酸盐的新晶型
CN110818634A (zh) * 2018-08-13 2020-02-21 上海博志研新药物技术有限公司 甲磺酸乐伐替尼的精制方法
CN111233762A (zh) * 2020-02-20 2020-06-05 天津理工大学 一种乐伐替尼与对羟基苯甲酸共晶及其制备方法
CN111574359A (zh) * 2019-02-19 2020-08-25 愈磐生物科技（苏州）有限公司 乐伐替尼-没食子酸共晶晶型及其应用
CN111689897A (zh) * 2019-03-13 2020-09-22 齐鲁制药有限公司 一种高纯度甲磺酸乐伐替尼晶型c的制备方法
CN111793027A (zh) * 2020-08-07 2020-10-20 天津理工大学 一种乐伐替尼与苯甲酸的共晶及其制备方法
US11059787B2 (en) 2019-11-12 2021-07-13 Shenzhen Bolan Pharmaceutical Co., Ltd Crystalline form of lenvatinib mesylate and methods thereof
CN113135853A (zh) * 2020-01-19 2021-07-20 重庆医药工业研究院有限责任公司 一种氟伐替尼或甲磺酸盐的晶型及其制备方法
CN114213322A (zh) * 2022-01-05 2022-03-22 中国药科大学 甲磺酸仑伐替尼没食子酸共晶及其制备方法
JP2022524011A (ja) * 2019-04-22 2022-04-27 ベイジン コンルンス ファーマシューティカル カンパニー リミテッド 化合物結晶形、その製造方法、医薬組成物及び使用
JP2023510684A (ja) * 2020-04-24 2023-03-15 成都苑東生物制薬股▲フン▼有限公司 レンバチニブメシル酸塩結晶形ｘｉ及びその調製方法

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113533544A (zh) * 2020-04-16 2021-10-22 先声药业有限公司 一种甲磺酸仑伐替尼的有关物质检测方法

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1890220A (zh) * 2003-12-25 2007-01-03 卫材株式会社 4－(3－氯－4－(环丙基氨基羰基)氨基苯氧基)－7－甲氧基－6－喹啉羧酰胺的盐或其溶剂合物的结晶及其制备方法
CN101233111A (zh) * 2005-06-23 2008-07-30 卫材R&D管理有限公司 4-（3-氯-4-（环丙基氨基羰基）氨基苯氧基）-7-甲氧基-6-喹啉羧酸酰胺的无定形盐及其制备方法
WO2016184436A1 (fr) * 2015-05-21 2016-11-24 苏州晶云药物科技有限公司 Nouvelle forme cristalline de sel de méthanesulfonate de lenvatinib et son procédé de préparation

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1890220A (zh) * 2003-12-25 2007-01-03 卫材株式会社 4－(3－氯－4－(环丙基氨基羰基)氨基苯氧基)－7－甲氧基－6－喹啉羧酰胺的盐或其溶剂合物的结晶及其制备方法
CN101233111A (zh) * 2005-06-23 2008-07-30 卫材R&D管理有限公司 4-（3-氯-4-（环丙基氨基羰基）氨基苯氧基）-7-甲氧基-6-喹啉羧酸酰胺的无定形盐及其制备方法
WO2016184436A1 (fr) * 2015-05-21 2016-11-24 苏州晶云药物科技有限公司 Nouvelle forme cristalline de sel de méthanesulfonate de lenvatinib et son procédé de préparation

Cited By (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110818634A (zh) * 2018-08-13 2020-02-21 上海博志研新药物技术有限公司 甲磺酸乐伐替尼的精制方法
CN111574359A (zh) * 2019-02-19 2020-08-25 愈磐生物科技（苏州）有限公司 乐伐替尼-没食子酸共晶晶型及其应用
CN111689897A (zh) * 2019-03-13 2020-09-22 齐鲁制药有限公司 一种高纯度甲磺酸乐伐替尼晶型c的制备方法
CN111689897B (zh) * 2019-03-13 2024-02-06 齐鲁制药有限公司 一种高纯度甲磺酸乐伐替尼晶型c的制备方法
CN109867626A (zh) * 2019-04-18 2019-06-11 安礼特（上海）医药科技有限公司 一种甲磺酸仑伐替尼多晶型物及其制备方法
JP2022524011A (ja) * 2019-04-22 2022-04-27 ベイジン コンルンス ファーマシューティカル カンパニー リミテッド 化合物結晶形、その製造方法、医薬組成物及び使用
CN110256341A (zh) * 2019-06-27 2019-09-20 尚科生物医药（上海）有限公司 一种乐伐替尼甲磺酸盐晶型c的制备方法
CN110563644A (zh) * 2019-10-30 2019-12-13 北京赛思源生物医药技术有限公司 一种仑伐替尼甲磺酸盐的新晶型
US11059787B2 (en) 2019-11-12 2021-07-13 Shenzhen Bolan Pharmaceutical Co., Ltd Crystalline form of lenvatinib mesylate and methods thereof
CN113135853A (zh) * 2020-01-19 2021-07-20 重庆医药工业研究院有限责任公司 一种氟伐替尼或甲磺酸盐的晶型及其制备方法
WO2021143954A3 (fr) * 2020-01-19 2021-08-26 重庆医药工业研究院有限责任公司 Forme cristalline de fluvatinib ou de méthanesulfonate de fluvatinib et son procédé de préparation
CN111233762A (zh) * 2020-02-20 2020-06-05 天津理工大学 一种乐伐替尼与对羟基苯甲酸共晶及其制备方法
CN111233762B (zh) * 2020-02-20 2021-12-28 天津理工大学 一种乐伐替尼与对羟基苯甲酸共晶及其制备方法
JP2023510684A (ja) * 2020-04-24 2023-03-15 成都苑東生物制薬股▲フン▼有限公司 レンバチニブメシル酸塩結晶形ｘｉ及びその調製方法
JP7466642B2 (ja) 2020-04-24 2024-04-12 成都苑東生物制薬股▲フン▼有限公司 レンバチニブメシル酸塩結晶形ｘｉ及びその調製方法
CN111793027B (zh) * 2020-08-07 2021-12-03 天津理工大学 一种乐伐替尼与苯甲酸的共晶及其制备方法
CN111793027A (zh) * 2020-08-07 2020-10-20 天津理工大学 一种乐伐替尼与苯甲酸的共晶及其制备方法
CN114213322A (zh) * 2022-01-05 2022-03-22 中国药科大学 甲磺酸仑伐替尼没食子酸共晶及其制备方法
CN114213322B (zh) * 2022-01-05 2023-11-07 中国药科大学 甲磺酸仑伐替尼没食子酸共晶及其制备方法

Also Published As

Publication number Publication date
CN110494423B (zh) 2022-04-26
CN110494423A (zh) 2019-11-22

Similar Documents

Publication Publication Date Title
WO2018196687A1 (fr) Nouvelle forme cristalline de méthanesulfonate de lenvatinib et procédé de préparation correspondant
WO2016184436A1 (fr) Nouvelle forme cristalline de sel de méthanesulfonate de lenvatinib et son procédé de préparation
ES2550771T3 (es) Sal de bismesilato etexilato de dabigatrán, formas en estado sólido y proceso para la preparación de las mismas
US10487064B1 (en) Crystalline forms of selective S1P1 receptor modulator and preparation method thereof
US10208065B2 (en) Crystalline free bases of C-Met inhibitor or crystalline acid salts thereof, and preparation methods and uses thereof
CN104470920A (zh) 固态形式的维罗菲尼胆碱盐
JP2020500912A (ja) ブロモドメインタンパク質阻害薬の結晶形及びその製造方法並びに用途
US9884856B2 (en) Crystal form of Dabrafenib mesylate and preparation method thereof
WO2018233437A1 (fr) Forme cristalline de baricitinib et procédé de préparation correspondant
CN114773342A (zh) Mrtx849化合物的晶型及其制备方法和用途
CN114605406A (zh) Amg510化合物的晶型及其制备方法和用途
WO2016177308A1 (fr) Cristaux de dimaléate d'un composé crotyle de quinazoline, leurs procédés de préparation et leurs utilisations
WO2019205812A1 (fr) Nouvelle forme cristalline de l'acalabrutinib, son procédé de préparation et son utilisation
CN110903239A (zh) 乐伐替尼甲磺酸盐的新晶型及其制备方法
US9458149B2 (en) Crystal form of dabrafenib and preparation method and use thereof
JP2020526593A (ja) Ｎ−フェニル−２−アミノピリミジン類化合物の結晶形、塩形態及びその製造方法
WO2018137670A1 (fr) Forme cristalline du médicament inhibiteur de protéine virale (vx-287), et son procédé de préparation et d'utilisation
US10544129B2 (en) Crystalline forms of AP26113, and preparation method thereof
CN104884128B (zh) 力格赛狄盐及其晶型、它们的制备方法和用途
WO2016155631A1 (fr) Nouvelle forme cristalline du topiroxostat et son procédé de préparation
WO2017152858A1 (fr) Forme cristalline de céritinib et procédé pour sa préparation
WO2023083293A1 (fr) Sel pharmaceutiquement acceptable d'éliglustat et forme cristalline de celui-ci
WO2023125419A1 (fr) Cristal d'adipate et son procédé de préparation
WO2019105217A1 (fr) Forme cristalline du galunisertib, son procédé de préparation et son utilisation
WO2016101912A1 (fr) Forme cristalline d'un sel d'un inhibiteur de kinase du récepteur du facteur de croissance épidermique et son procédé de préparation

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 18791916

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 18791916

Country of ref document: EP

Kind code of ref document: A1