WO2017133542A1 - Composition pharmaceutique comprenant un dérivé pyridopyrimidine ou un sel de qualité pharmaceutique de ce dernier - Google Patents

Composition pharmaceutique comprenant un dérivé pyridopyrimidine ou un sel de qualité pharmaceutique de ce dernier Download PDF

Info

Publication number
WO2017133542A1
WO2017133542A1 PCT/CN2017/072213 CN2017072213W WO2017133542A1 WO 2017133542 A1 WO2017133542 A1 WO 2017133542A1 CN 2017072213 W CN2017072213 W CN 2017072213W WO 2017133542 A1 WO2017133542 A1 WO 2017133542A1
Authority
WO
WIPO (PCT)
Prior art keywords
pharmaceutical composition
composition according
acceptable salt
microcrystalline cellulose
disintegrant
Prior art date
Application number
PCT/CN2017/072213
Other languages
English (en)
Chinese (zh)
Inventor
卢韵
张新华
丁欢
张代美
Original Assignee
江苏恒瑞医药股份有限公司
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 江苏恒瑞医药股份有限公司 filed Critical 江苏恒瑞医药股份有限公司
Priority to CN201780000891.2A priority Critical patent/CN107405350A/zh
Publication of WO2017133542A1 publication Critical patent/WO2017133542A1/fr
Priority to HK18102971.9A priority patent/HK1243351A1/zh

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • 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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A61K47/38—Cellulose; Derivatives thereof

Definitions

  • the invention belongs to the field of pharmaceutical preparations, in particular to a method comprising 6-acetyl-8-cyclopentyl-5-methyl-2-((5-(piperidin-4-yl)pyridin-2-yl)amino) A composition of pyrido[2,3-d]pyrimidin-7(8H)-one or a pharmacologically acceptable salt thereof.
  • Breast cancer is one of the most common malignant tumors in women. It has a high incidence and is invasive, but the progress of the disease is slow.
  • the China Population Association released the "China Breast Diseases Investigation Report” in Beijing on February 1, 2010. The report shows that The mortality rate of breast cancer in urban areas in China has increased by 38.91%.
  • Breast cancer has become the most threatening disease for women.
  • At least 156 kinds of breast cancer drugs are currently under research and market, 68% of which are targeted therapeutic drugs.
  • Tumors were found to be abnormally associated with the cell cycle. Mutations in mitotic signaling proteins and defects in anti-mitotic signaling proteins in tumor cells lead to proliferation disorders. At the same time, most tumors have genomic instability (GIN) and genomic instability (CIN). These three basic cell cycle defects are caused directly or indirectly by the loss of control of CDKs. Cyclin Dependent Kinase (CDK) inhibitors are increasingly becoming a hot target.
  • CDK Cyclin Dependent Kinase
  • the second-generation drugs of greatest concern include the CDK4/6 inhibitor PD-0332991, jointly developed by Pfizer and Onyx, which inhibits the phosphorylation of Rb by inhibiting the activity of CDK4/6.
  • the E2F-Rb complex is retained in the cytosol to block the initiation of the cell cycle.
  • Clinical trial results (NCT00721409) showed that progression-free survival (PFS) was 7.5 months in patients treated with letrozole monotherapy, whereas no progress was observed in patients treated with letrozole and PD-0332991. The survival period was extended to 26.1 months, and this remarkable advantage has received wide attention.
  • WO2014183520 discloses a series of CDK4/6 inhibitors of the formula (I) which are structurally similar to PD-0332991, have significant CDK4/6 inhibitory activity and high selectivity, and are expected to be useful for a range of tumors. And can be used in combination with a range of existing anti-tumor agents, including the compound of formula A shown below, having the chemical name 6-acetyl-8-cyclopentyl-5-methyl-2-(5 -(piperidin-4-yl)pyridin-2-yl)amino)pyrido[2,3-d]pyrimidin-7(8H)-one:
  • the invention also provides a pharmaceutical composition having good stability.
  • the pharmaceutical composition provided by the present invention contains (6-acetyl-8-cyclopentyl-5-methyl-2-((5-(piperidin-4-yl)pyridin-2-yl)amino) as an active ingredient Pyrido[2,3-d]pyrimidin-7(8H)-one or a pharmacologically acceptable salt thereof, and a disintegrant which is a metal element-free disintegrant.
  • the metal element is an alkali metal or an alkaline earth metal such as sodium, potassium, calcium or magnesium.
  • the disintegrant contained in the composition is a low-substituted hydroxypropyl cellulose or a crospovidone.
  • One or more kinds thereof are not particularly limited, and may be from about 1 to 30% by weight, preferably from 8% to 15% by weight.
  • the pharmacologically acceptable salt of the active ingredient may preferably be selected from the isethionate of the active ingredient.
  • the active ingredient may be included in an amount ranging from 5% to 50%, preferably from 10% to 35%, more preferably from 25% to 35%, based on the total weight of the composition.
  • the pharmaceutical composition provided in the present invention further contains a filler containing mannitol.
  • the filler may contain, in addition to mannitol, one or more of microcrystalline cellulose, pregelatinized starch, and calcium hydrogen phosphate, preferably microcrystalline cellulose.
  • the filler is a mixture of mannitol and microcrystalline cellulose.
  • the content of the filler is not particularly limited and may be 20 to 90%, preferably 30% to 70%, more preferably 40% to 65%, based on the total weight of the pharmaceutical composition, most preferably 45%-60%.
  • the weight ratio of mannitol to microcrystalline cellulose is from 2:1 to 10:1, preferably from 2.5:1 to 5:1, most preferably from 2.5:1 to 3:1.
  • the ratio of mannitol to microcrystalline cellulose used is 3:1, which can significantly increase the stability of the sample as well as the rate and extent of dissolution.
  • the pharmaceutical composition provided in the present invention may further contain a binder, for example, the binder is one or more of polyvinylpyrrolidone, pregelatinized starch, hypromellose, and hydroxypropylcellulose.
  • the binder content is from about 0.5% to about 10%, preferably from about 0.5% to about 5%, based on the total weight of the composition.
  • the pharmaceutical compositions provided herein may further comprise one or more lubricants to aid in filling or compressing the capsules.
  • the lubricant may be selected from the group consisting of talc, magnesium stearate, zinc stearate, glyceryl behenate, and the like, based on the total weight of the composition.
  • the lubricant is present in an amount of from about 0.5% to about 5%.
  • composition comprising the following ingredients by weight:
  • ком ⁇ онент selected from one or two of low-substituted hydroxypropylcellulose or crospovidone;
  • binder selected from one or more of polyvinylpyrrolidone, pregelatinized starch, hypromellose;
  • lubricant selected from one or more of magnesium stearate, stearic acid, and glyceryl behenate.
  • compositions of the present invention can be prepared by methods conventional in the art, such as high shear wet granulation, dry granulation, one-step granulation, and the like, to prepare granules of the pharmaceutical composition, which are then compressed into tablets.
  • the composition of the present invention dissolves very rapidly and completely.
  • purified water is used as the dissolution medium, preferably 1000 ml of purified water, and at 37 ⁇ 0.5 ° C
  • the composition of the present invention was subjected to a dissolution test at a paddle speed of 50 rpm, and the dissolution rate was 80% or more in 40 minutes or 45 minutes, preferably 95% or more in 45 minutes or 60 minutes.
  • the pharmaceutical composition provided by the present invention improves the stability thereof by using a filler containing mannitol, and the composition of the present invention is placed in an environment of a temperature of 40 ° C and a relative humidity of 75% for one month. Then, the content of the relevant substance is not more than 1% as determined by HPLC.
  • Figure 1 shows the dissolution profiles of the tablets of Examples 1-5 in purified water.
  • Figure 2 shows the dissolution profiles of the tablets of Examples 6-9 in purified water.
  • Figure 3 shows the dissolution profiles of the tablets of Examples 1 and 10-12 in purified water.
  • Figure 4 shows the dissolution profiles of the tablets of Examples 10 and 13-14 in purified water.
  • 6-Acetyl-8-cyclopentyl-5-methyl-2-((5-(piperidin-4-yl)pyridin-2-yl)amino)pyrido[2,3-d]pyrimidine- 7(8H)-ketohydroxyethyl sulfonate hereinafter referred to as compound A
  • lactose lactose
  • microcrystalline cellulose low-substituted hydroxypropyl cellulose or crospovidone
  • croscarmellose sodium carboxymethyl Base starch sodium, according to the ratio in Table 1, wet granulation by high-speed shear granulator, 5% aqueous solution prepared with povidone K30 as wetting agent, wet granulation and drying of wet materials After treatment, dry granules (water content less than 3%) are dry granulated, and a prescribed amount of magnesium stearate is added and mixed well. The resulting total mixed granules were compressed into tablets.
  • Example 1 The tablets in Examples 1 to 5 were subjected to dissolution measurement according to the second method (paddle method) of the dissolution test of the second edition of the Chinese Pharmacopoeia 2015. 1000 ml of purified water was used as the dissolution medium, and the dissolution test was carried out at 37 ⁇ 0.5 ° C at a paddle speed of 50 rpm.
  • the results showed that in Examples 2 and 3, the dissolution of Compound A was slow and incomplete; in Example 4, Compound A was completely dissolved.
  • Example 5 Compound A was completely dissolved, and the dissolution rate was slower than that of the tablet of Example 1.
  • the dissolution data are shown in Table 2 below, and the dissolution curve is shown in Figure 1.
  • 6-Acetyl-8-cyclopentyl-5-methyl-2-((5-(piperidin-4-yl)pyridin-2-yl)amino)pyrido[2,3-d]pyrimidine- 7(8H)-ketohydroxyethyl sulfonate hereinafter referred to as compound A
  • compound A mannitol, microcrystalline cellulose, low-substituted hydroxypropyl cellulose, wetted by a high-speed shear granulator according to the ratio in Table 3.
  • the dissolution rates of the tablets of Examples 6 to 9 were measured according to the second method (paddle method) of the dissolution test of the Appendix 2 of the Chinese Pharmacopoeia. 1000 ml of purified water was used as the dissolution medium, and the dissolution test was carried out at 37 ⁇ 0.5 ° C at a paddle speed of 50 rpm. The results showed that in Examples 6 to 9, the compound A was completely eluted.
  • the dissolution data is shown in Table 4, and the dissolution curve is shown in Figure 2.
  • Compound A 6-Acetyl-8-cyclopentyl-5-methyl-2-((5-(piperidin-4-yl)pyridin-2-yl)amino)pyrido[2,3-d]pyrimidine- 7(8H)-ketohydroxyethyl sulfonate (hereinafter referred to as Compound A), lactose or mannitol, microcrystalline cellulose, low-substituted hydroxypropyl cellulose, according to the ratio in Table 5, using a high-speed shear granulator Wet granulation, 5% aqueous solution prepared with povidone K30 as a wetting agent, wet granules and drying treatment of wet materials, and then dry granules (water content less than 3%) are added and dried. Prescribe the amount of magnesium stearate and mix well. The resulting total mixed granules were compressed into tablets.
  • the dissolution rates of the tablets of Examples 1 and 10 to 12 were determined according to the second method (paddle method) of the dissolution test of the Chinese Pharmacopoeia 2015 edition. 1000 ml of purified water was used as the dissolution medium, and the dissolution test was carried out at 37 ⁇ 0.5 ° C at a paddle speed of 50 rpm. The results showed that in Examples 1 and 10, Compound A was completely dissolved; in Examples 11 and 12, the proportion of microcrystalline cellulose was gradually increased, and the dissolution rate of Compound A was gradually slowed compared with the tablet of Example 1. And the dissolution is not complete.
  • the dissolution data is shown in Table 6 below, and the dissolution profile is shown in Figure 3.
  • 6-Acetyl-8-cyclopentyl-5-methyl-2-((5-(piperidin-4-yl)pyridin-2-yl)amino)pyrido[2,3-d]pyrimidine- 7(8H)-ketohydroxyethyl sulfonate hereinafter referred to as compound A
  • compound A mannitol, microcrystalline cellulose, low-substituted hydroxypropyl cellulose, wetted by a high-speed shear granulator according to the ratio in Table 7.
  • Method granules respectively, a 5% aqueous solution prepared with povidone K30 and a 3% aqueous solution prepared with hypromellose E5, and a 13% aqueous solution prepared with pregelatinized starch as a wetting agent.
  • Wet and soft materials are wet granulated and dried, then dry granules (water content less than 3%) are dry granulated, and the prescribed amount of magnesium stearate is added and mixed uniformly. The resulting total mixed granules were compressed into tablets.
  • the dissolution rates of the tablets of Examples 10, 13, and 14 were determined according to the second method (paddle method) of the dissolution test of the Chinese Pharmacopoeia 2015 edition. 1000 ml of purified water was used as the dissolution medium, and the dissolution test was carried out at 37 ⁇ 0.5 ° C at a paddle speed of 50 rpm. The results showed that in Example 10, Compound A was completely dissolved; in Example 14, Compound A was incompletely eluted; in Example 13, Compound A was completely dissolved.
  • the dissolution data is shown in Table 8 below, and the dissolution profile is shown in Figure 4.
  • the examples 1 and 10 were placed in an environment of a temperature of 40 ° C and a relative humidity of 75% for 1 month, 2 months, and 3 months, and then the changes of the substances were measured by HPLC.
  • the results of the related substance test showed that the total amount of the starting substance related to the tablet in Example 1 was larger than the total amount of the related substance in the tablet of Example 10; after the tablet was placed in Example 1 for one month, the related substance was increased; After the tablets were placed for 1 month, 2 months, and 3 months, there was no significant change in the relevant substances (see Table 9).
  • Step 1 6-((6-(1-Butoxyvinyl)-8-cyclopentyl-5-methyl-7-carbonyl-7,8-dihydropyrido[2,3-d]pyrimidine Preparation of 2-yl)amino)-5',6'-dihydro-[3,4'-bipyridyl]-1'(2'H)-carboxylic acid tert-butyl ester
  • the reaction solution was cooled to room temperature, filtered, and the filter cake was washed with dichloromethane 17.
  • the filtrate was concentrated to dryness under reduced pressure at 65 °C.
  • the residue was dissolved in 137.50 g of dichloromethane, 56.25 g of purified water was added, and the mixture was partitioned and the aqueous phase was extracted with 68.75 g of dichloromethane.
  • the combined organic layers were dried with anhydrous sodium sulfate and filtered, and then filtered and evaporated.
  • Step 2 4-(6-((6-Acetyl-8-cyclopentyl-5-methyl-7-carbonyl-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl) Of amino)pyridin-3-yl)piperidine-1-carboxylic acid tert-butyl ester
  • the residual amount of the intermediate state (6-((6-(1-butoxyvinyl))-8-cyclopentyl-5-methyl-7-carbonyl-7,8-dihydropyrido[2, 3-d]pyrimidin-2-yl)amino)-5',6'-di Hydrogen-[3,4'-bipyridyl]-1 '(2'H)-carboxylic acid tert-butyl ester was removed from the n-butyl-protected but unreduced intermediate of the double bond) ⁇ 0.3%, and the reaction was terminated.
  • the reaction solution was cooled to room temperature, the system was replaced with argon and filtered, and the filter cake was washed with 37.50 g of dichloromethane.
  • the filtrate was concentrated to dryness under reduced pressure at 65 °C.
  • the residue was purged with argon gas and refluxed with 50 g of absolute ethanol for 0.5 h, and then cooled to room temperature with stirring, and stirred for about 4 h in an ice bath. Filter and filter cake was washed with cold anhydrous ethanol 12.50 g x 2 .
  • the obtained wet product was stirred with 31.25 g of dichloromethane, and the insoluble matter was filtered.
  • Step 3 6-Acetyl-8-cyclopentyl-5-methyl-2-((5-(piperidin-4-yl)pyridin-2-yl)amino)pyrido[2,3-d] Preparation of pyrimidine-7(8H)-ketohydroxyethyl sulfonate

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Inorganic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)

Abstract

La présente invention concerne une composition pharmaceutique comprenant un dérivé pyridopyrimidine ou un sel de qualité pharmaceutique de ce dernier. Spécifiquement, la composition comprend du 6-acétyl-8-cyclopentyl-5-méthyl-2-{[5-(pipéridine-4-yl)pyridine-2-yl]amino}pyrido[2,3-d]pyrimidine-7(8H)-one ou un sel de qualité pharmaceutique de ce dernier, et un désagrégeant. Le désagrégeant est un désagrégeant ne comprenant aucun élément métallique. La composition se dissout rapidement. Le procédé de préparation de la composition pharmaceutique de la présente invention est simple et plus approprié pour une production à l'échelle industrielle.
PCT/CN2017/072213 2016-02-04 2017-01-23 Composition pharmaceutique comprenant un dérivé pyridopyrimidine ou un sel de qualité pharmaceutique de ce dernier WO2017133542A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
CN201780000891.2A CN107405350A (zh) 2016-02-04 2017-01-23 一种含有吡啶并嘧啶类衍生物或其可药用盐的药物组合物
HK18102971.9A HK1243351A1 (zh) 2016-02-04 2018-03-01 一種含有吡啶並嘧啶類衍生物或其可藥用鹽的藥物組合物

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN201610080476 2016-02-04
CN201610080476.X 2016-02-04

Publications (1)

Publication Number Publication Date
WO2017133542A1 true WO2017133542A1 (fr) 2017-08-10

Family

ID=59500122

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2017/072213 WO2017133542A1 (fr) 2016-02-04 2017-01-23 Composition pharmaceutique comprenant un dérivé pyridopyrimidine ou un sel de qualité pharmaceutique de ce dernier

Country Status (4)

Country Link
CN (1) CN107405350A (fr)
HK (1) HK1243351A1 (fr)
TW (1) TWI737673B (fr)
WO (1) WO2017133542A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2020253808A1 (fr) * 2019-06-20 2020-12-24 江苏恒瑞医药股份有限公司 Composition pharmaceutique et son procédé de préparation
WO2022184113A1 (fr) * 2021-03-03 2022-09-09 苏州盛迪亚生物医药有限公司 Composition pharmaceutique comprenant un dérivé de pyridopyrimidine et son procédé de préparation

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014183520A1 (fr) * 2013-05-17 2014-11-20 上海恒瑞医药有限公司 Dérivé de miazines de tiophène, son procédé de préparation et ses applications médicales
WO2016169422A1 (fr) * 2015-04-22 2016-10-27 江苏恒瑞医药股份有限公司 Forme cristalline d'un inhibiteur de kinase dépendant des cyclines et procédé de préparation de celle-ci

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3501696A1 (de) * 1985-01-19 1986-07-24 Bayer Ag, 5090 Leverkusen Pyridopyrimidine, mehrere verfahren zu ihrer herstellung sowie ihre verwendung als arzneimittel

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014183520A1 (fr) * 2013-05-17 2014-11-20 上海恒瑞医药有限公司 Dérivé de miazines de tiophène, son procédé de préparation et ses applications médicales
WO2016169422A1 (fr) * 2015-04-22 2016-10-27 江苏恒瑞医药股份有限公司 Forme cristalline d'un inhibiteur de kinase dépendant des cyclines et procédé de préparation de celle-ci

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2020253808A1 (fr) * 2019-06-20 2020-12-24 江苏恒瑞医药股份有限公司 Composition pharmaceutique et son procédé de préparation
CN113993505A (zh) * 2019-06-20 2022-01-28 江苏恒瑞医药股份有限公司 一种药物组合物以及其制备方法
CN113993505B (zh) * 2019-06-20 2023-12-12 江苏恒瑞医药股份有限公司 一种药物组合物以及其制备方法
WO2022184113A1 (fr) * 2021-03-03 2022-09-09 苏州盛迪亚生物医药有限公司 Composition pharmaceutique comprenant un dérivé de pyridopyrimidine et son procédé de préparation

Also Published As

Publication number Publication date
TWI737673B (zh) 2021-09-01
TW201728329A (zh) 2017-08-16
CN107405350A (zh) 2017-11-28
HK1243351A1 (zh) 2018-07-13

Similar Documents

Publication Publication Date Title
AU2020203497B2 (en) Formulations of 2-(tert-butylamino)-4-((1R,3R,4R)-3-hydroxy-4-methycyclohexylamino)-pyrimidine-5-carboxamide
AU2015229214B2 (en) Pharmaceutical compositions of therapeutically active compounds
TWI706951B (zh) 一種週期素依賴性蛋白激酶抑制劑的羥乙基磺酸鹽、其結晶形式及製備方法
EP3279201A1 (fr) Inhibiteur de cdk, cristal eutectique d'inhibiteur de mek, et leur procédé de préparation
TW201638090A (zh) 一種週期素依賴性蛋白激酶抑制劑的結晶形式及其製備方法
WO2017133542A1 (fr) Composition pharmaceutique comprenant un dérivé pyridopyrimidine ou un sel de qualité pharmaceutique de ce dernier
TWI815820B (zh) ２－（５－（４－（２－嗎啉乙氧基）苯基）吡啶－２－基）－ｎ－芐乙醯胺之固態形式
CN107137409A (zh) 一种cdk4/6抑制剂与雌激素受体拮抗剂联合在制备治疗乳腺癌的药物中的用途
CN107028899B (zh) 一种含有吡啶并嘧啶类衍生物或其可药用盐的药物组合物
TW202016114A (zh) 抑制ｃｄｋ４／６活性化合物的晶型及其應用
CN110650960B (zh) Acalabrutinib的新晶型及其制备方法和用途
CN105407892B (zh) 一种化合物的药物组合物、其固体形式及它们的使用方法
CN114306255B (zh) 一种甲基酮类衍生物药物制剂及其制备方法
EP3650025A1 (fr) Composition pharmaceutique et sa méthode de préparation
CN111362871B (zh) 取代的吡啶-2-甲酰胺类化合物及其用途
CN113372345B (zh) 氘代杂环类激酶抑制剂
WO2020043078A1 (fr) Forme de sel et forme cristalline d'un nouveau composé azatricyclique et utilisation associée
WO2024040241A1 (fr) Formulations pharmaceutiques, processus de préparation et méthodes d'utilisation
CN117582438A (zh) 吡啶类衍生物的药物组合物、制备方法及用途
CN112220785A (zh) 一种pde4抑制剂药物组合物及其制备方法与用途
CN112300132A (zh) 芳基喹唑啉类dna-pk抑制剂
CN113272295A (zh) 含有哌嗪酮的喹唑啉二酮盐类化合物、其制备方法、药物组合物和用途

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: 17746862

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: 17746862

Country of ref document: EP

Kind code of ref document: A1