WO2022184113A1 - Composition pharmaceutique comprenant un dérivé de pyridopyrimidine et son procédé de préparation - Google Patents

Composition pharmaceutique comprenant un dérivé de pyridopyrimidine et son procédé de préparation Download PDF

Info

Publication number
WO2022184113A1
WO2022184113A1 PCT/CN2022/078916 CN2022078916W WO2022184113A1 WO 2022184113 A1 WO2022184113 A1 WO 2022184113A1 CN 2022078916 W CN2022078916 W CN 2022078916W WO 2022184113 A1 WO2022184113 A1 WO 2022184113A1
Authority
WO
WIPO (PCT)
Prior art keywords
cancer
pharmaceutical composition
lactose
pregelatinized starch
composition according
Prior art date
Application number
PCT/CN2022/078916
Other languages
English (en)
Chinese (zh)
Inventor
高玮
李锦�
Original Assignee
苏州盛迪亚生物医药有限公司
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 苏州盛迪亚生物医药有限公司, 江苏恒瑞医药股份有限公司 filed Critical 苏州盛迪亚生物医药有限公司
Priority to CN202280018385.7A priority Critical patent/CN116981446A/zh
Publication of WO2022184113A1 publication Critical patent/WO2022184113A1/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
    • A61K31/495—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
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/18—Antivirals for RNA viruses for HIV
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders

Definitions

  • the present disclosure belongs to the field of pharmaceutical preparations, and in particular relates to a pharmaceutical composition comprising pyridopyrimidine derivatives and a preparation method thereof.
  • TLRs Toll-like receptors
  • TLRs are an important class of receptors involved in innate immunity.
  • TLRs are monomeric, transmembrane, non-catalytic receptors that are typically expressed in sentinel cells such as macrophages and dendritic cells and can recognize structurally conserved molecules produced by microorganisms. Once these microbes breach physical barriers such as the skin or intestinal mucosa, they are recognized by TLRs, which in turn activate immune cell responses (Mahla, R S. et al., Front Immunol. 4:248 (2013)). The ability of the immune system to broadly recognize pathogenic microorganisms is partly due to the widespread presence of Toll-like immune receptors.
  • TLR8 is a member of a subgroup of TLRs (TLRs 3, 7, 8, and 9), restricted to the endosomal compartment of cells that specialize in recognizing non-hexogenic nucleic acids. TLR8 is mainly expressed in humans by monocytes, NK cells and myeloid dendritic cells (mDCs). TLR8 agonists can lead to the release of various pro-inflammatory cytokines, such as IL-6, IL-12, TNF- ⁇ and IFN- ⁇ .
  • WO2020007275A discloses a novel pyridopyrimidine derivative whose structure is shown in formula (I). The compound showed strong TLR8 agonism and improved in clinical efficacy and safety.
  • the purpose of the present disclosure is to provide a pharmaceutical composition with good mixing uniformity, particle fluidity and compressibility, and a simple preparation process, which is suitable for large-scale industrial production.
  • the present disclosure provides a pharmaceutical composition
  • a pharmaceutical composition comprising a compound represented by formula (I) or a pharmaceutically acceptable salt thereof and pregelatinized starch.
  • the pharmaceutical composition further contains a filler selected from one or more of lactose, microcrystalline cellulose, mannitol, calcium hydrogen phosphate and sucrose, preferably lactose, microcrystalline cellulose and mannitol, most preferably lactose.
  • a filler selected from one or more of lactose, microcrystalline cellulose, mannitol, calcium hydrogen phosphate and sucrose, preferably lactose, microcrystalline cellulose and mannitol, most preferably lactose.
  • the weight ratio of filler and pregelatinized starch is 10:1-1:1, preferably 9:1-2:1, non-limiting examples include: 9:1, 8:1 , 7:1, 6:1, 5:1, 4:1, 3:1, 2:1, or any value in between.
  • the content of the pregelatinized starch is 5%-45% based on the total weight of the composition, preferably 5%-35%, more preferably 10%-30%, non-limiting examples include: 10 %, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, or anything in between.
  • the content of the filler is 50%-90% based on the total weight of the composition, preferably 60%-88%, non-limiting examples include: 60%, 61%, 62%, 63% , 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80 %, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, or any value in between.
  • the pharmaceutical composition further comprises a disintegrant.
  • the disintegrant is selected from one or more of croscarmellose sodium, starch, sodium carboxymethyl starch and crospovidone, preferably croscarmellose Sodium.
  • the disintegrant is present in an amount of 1% to 10% based on the total weight of the composition.
  • the pharmaceutical composition further comprises a lubricant.
  • the lubricant is selected from one or more of talc, micronized silica gel and magnesium stearate, preferably talc and/or magnesium stearate.
  • the lubricant is present in an amount of 0.01% to 10% based on the total weight of the composition.
  • the active drug is present in an amount of 0.01%-10.0%, preferably 0.05%-5.0%, based on the total weight of the composition.
  • composition comprising:
  • 1-10wt% disintegrant which is selected from one or more of croscarmellose sodium, starch, sodium carboxymethyl starch and crospovidone;
  • the lubricant is selected from one or more of talc, micropowder silica gel and magnesium stearate;
  • the weight ratio of the lactose and pregelatinized starch is 10:1-1:1, preferably 9:1-2:1.
  • compositions described in the present disclosure are solid preparations, including tablets, pills or granules, preferably tablets.
  • the pharmaceutical composition in the present disclosure can be prepared by methods common in the art, including the steps of mixing the compound represented by formula (I) or a pharmaceutically acceptable salt thereof with a filler, and further including wet granulation and dry granulation of the mixture. , the step of direct pressing of the powder, preferably dry granulation.
  • the present disclosure also provides the use of the aforementioned pharmaceutical composition in the preparation of a medicament for treating infection caused by a virus, preferably hepatitis B virus, hepatitis C virus, influenza virus, herpes virus and HIV.
  • a virus preferably hepatitis B virus, hepatitis C virus, influenza virus, herpes virus and HIV.
  • the present disclosure also provides the use of the aforementioned pharmaceutical composition in the preparation of a medicament for regulating the immune system.
  • the present disclosure also provides the use of the aforementioned pharmaceutical composition in the preparation of a medicament for the treatment or prevention of tumors, wherein the tumor is selected from cancer, preferably selected from melanoma, lung cancer, liver cancer, basal cell carcinoma, kidney cancer, Myeloma, biliary tract cancer, brain cancer, breast cancer, cervical cancer, choriocarcinoma, colon cancer, rectal cancer, head and neck cancer, peritoneal tumor, fallopian tube cancer, endometrial cancer, esophageal cancer, gastric cancer, leukemia, lymphoma, sarcoma , neuroblastoma, oral cancer, ovarian cancer, pancreatic cancer, prostate cancer, testicular cancer, skin cancer and thyroid cancer.
  • cancer preferably selected from melanoma, lung cancer, liver cancer, basal cell carcinoma, kidney cancer, Myeloma, biliary tract cancer, brain cancer, breast cancer, cervical cancer, choriocarcinoma, colon cancer, rectal cancer, head and
  • the present disclosure prepares a pharmaceutical composition by using pregelatinized starch and lactose as fillers, which can help disperse active ingredients with low dosage and small particle size, and the prepared material particles have good mixing uniformity and fluidity, and can be compressible. meet the actual production needs.
  • Figure 1 is a pressure-hardness curve.
  • the compound of formula (I) was premixed with lactose, pregelatinized starch, microcrystalline cellulose and mannitol respectively according to the proportions in Table 1, passed through a 60-mesh sieve, and then mixed in a mixer. After mixing, samples were taken from different positions of the hopper to check the mixing uniformity.
  • the pregelatinized starch group has the highest content, the best dispersibility of active ingredients, and the best mixing uniformity.
  • Compound of formula (I) pregelatinized starch, lactose, microcrystalline cellulose, mannitol, croscarmellose sodium are premixed according to the composition and ratio in Table 3, and the premix is placed in a mixer Mixing in the middle, adding part of magnesium stearate and continuing to mix, carrying out dry granulation of the mixed material, adding the remaining amount of magnesium stearate after adjusting the particle size for total mixing to obtain pharmaceutical compositions of different filler formulations, sampling and testing Mixing uniformity, bulk density and particle size distribution of the blended particles, and finally the blended material is pressed into tablets.
  • the components were prepared according to the proportions in Table 7, and the pharmaceutical composition was prepared by the same method as in Example 2, and the mixing uniformity of the granules after blending was tested.
  • Composition 6 Compounds of formula (I) 0.3125 0.3125 0.3125 pregelatinized starch 20 / / lactose 77.2875 77.2875 / microcrystalline cellulose / 20 20 Mannitol / / 77.2875 Croscarmellose sodium 2 2 2 Magnesium stearate 0.40 0.40 0.40 total 100 100 100
  • Composition 4 and Composition 1 are different batches of the same formulation.
  • the components were prepared according to the proportions in Table 9, and the pharmaceutical composition was prepared by the same method as in Example 2, and the mixing uniformity of the materials after the total mixing was investigated.
  • the prepared pharmaceutical composition was compressed into tablets, and the hardness of the tablets was examined with a hardness tester, and a pressure-hardness curve was drawn according to the results (Fig. 1).

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Virology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Oncology (AREA)
  • Communicable Diseases (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Epidemiology (AREA)
  • Immunology (AREA)
  • AIDS & HIV (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Pulmonology (AREA)
  • Medicinal Preparation (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)

Abstract

L'invention concerne une composition pharmaceutique comprenant un dérivé de pyridopyrimidine représenté par la formule (I) et son procédé de préparation. La composition pharmaceutique contient un composé de formule (I) ou un sel pharmaceutiquement acceptable de celui-ci et de l'amidon prégélatinisé, et la composition a une bonne uniformité de mélange, une fluidité et une compressibilité satisfaisantes et est appropriée pour une production industrielle.
PCT/CN2022/078916 2021-03-03 2022-03-03 Composition pharmaceutique comprenant un dérivé de pyridopyrimidine et son procédé de préparation WO2022184113A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202280018385.7A CN116981446A (zh) 2021-03-03 2022-03-03 一种包含吡啶并嘧啶类衍生物的药物组合物及其制备方法

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN202110237135 2021-03-03
CN202110237135.X 2021-03-03

Publications (1)

Publication Number Publication Date
WO2022184113A1 true WO2022184113A1 (fr) 2022-09-09

Family

ID=83154729

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2022/078916 WO2022184113A1 (fr) 2021-03-03 2022-03-03 Composition pharmaceutique comprenant un dérivé de pyridopyrimidine et son procédé de préparation

Country Status (3)

Country Link
CN (1) CN116981446A (fr)
TW (1) TW202245782A (fr)
WO (1) WO2022184113A1 (fr)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2024125636A1 (fr) * 2022-12-16 2024-06-20 上海拓界生物医药科技有限公司 Polythérapie avec un modulateur de récepteur de type toll et un arn double brin

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101502495A (zh) * 2009-02-24 2009-08-12 江苏飞马药业有限公司 吡嘧司特钾片及其生产工艺
CN102512656A (zh) * 2011-12-27 2012-06-27 天津市嵩锐医药科技有限公司 盐酸喹那普利药物组合物
WO2017133542A1 (fr) * 2016-02-04 2017-08-10 江苏恒瑞医药股份有限公司 Composition pharmaceutique comprenant un dérivé pyridopyrimidine ou un sel de qualité pharmaceutique de ce dernier
CN107028899A (zh) * 2016-02-04 2017-08-11 江苏恒瑞医药股份有限公司 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
WO2020007275A1 (fr) * 2018-07-03 2020-01-09 江苏恒瑞医药股份有限公司 Dérivé de pyridopyrimidine, son procédé de préparation et son utilisation médicale
WO2020216247A1 (fr) * 2019-04-25 2020-10-29 青岛海尔洗衣机有限公司 Lave-linge/sèche-linge
WO2021136488A1 (fr) * 2020-01-02 2021-07-08 江苏恒瑞医药股份有限公司 Forme cristalline d'un dérivé de pyridopyrimidine et son procédé de préparation

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101502495A (zh) * 2009-02-24 2009-08-12 江苏飞马药业有限公司 吡嘧司特钾片及其生产工艺
CN102512656A (zh) * 2011-12-27 2012-06-27 天津市嵩锐医药科技有限公司 盐酸喹那普利药物组合物
WO2017133542A1 (fr) * 2016-02-04 2017-08-10 江苏恒瑞医药股份有限公司 Composition pharmaceutique comprenant un dérivé pyridopyrimidine ou un sel de qualité pharmaceutique de ce dernier
CN107028899A (zh) * 2016-02-04 2017-08-11 江苏恒瑞医药股份有限公司 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
WO2020007275A1 (fr) * 2018-07-03 2020-01-09 江苏恒瑞医药股份有限公司 Dérivé de pyridopyrimidine, son procédé de préparation et son utilisation médicale
WO2020216247A1 (fr) * 2019-04-25 2020-10-29 青岛海尔洗衣机有限公司 Lave-linge/sèche-linge
WO2021136488A1 (fr) * 2020-01-02 2021-07-08 江苏恒瑞医药股份有限公司 Forme cristalline d'un dérivé de pyridopyrimidine et son procédé de préparation

Also Published As

Publication number Publication date
CN116981446A (zh) 2023-10-31
TW202245782A (zh) 2022-12-01

Similar Documents

Publication Publication Date Title
JP6876758B2 (ja) ブルトンチロシンキナーゼの阻害剤を含む剤形組成物
KR101475971B1 (ko) 신규 제약 조성물
JP2009519326A5 (fr)
JP2016074698A (ja) 好ましくはポサコナゾールおよびｈｐｍｃａｓを含む固体分散物中の経口用薬学的組成物
TW201000472A (en) New solid pharmaceutical formulations comprising BIBW 2992
KR20140096124A (ko) 고융점 소수성 화합물을 위한, 개선된 생체이용률을 갖는 약학 조성물
WO2022184113A1 (fr) Composition pharmaceutique comprenant un dérivé de pyridopyrimidine et son procédé de préparation
WO2018199282A1 (fr) Composition pharmaceutique contenant de l'enzalutamide pouvant être administrée par voie orale
CN104546770A (zh) 一种阿齐沙坦的口腔崩解片及其制备方法
KR20190005939A (ko) 아세트아미노펜 제제의 제조 방법
KR20220004098A (ko) Tlr7 작용물질을 포함하는 고형 제약학적 조성물
CN107998097B (zh) 一种含奥美沙坦酯的片剂及其制备方法
JPWO2020004630A1 (ja) 難溶性の塩基性薬剤を含有する医薬組成物
CN102871977A (zh) 醋酸优力司特分散片及其制备方法
CN103142525A (zh) 奥氮平胃溶型片剂及其制备方法
TWI794214B (zh) 包含5-氯-n4-[2-(二甲基磷醯基)苯基]-n2-{2-甲氧基-4-[4-(4-甲基哌嗪-1-基)哌啶-1-基]苯基}嘧啶-2,4-二胺之醫藥調配物
KR20200024165A (ko) 의약 조성물
TWI808217B (zh) 稠合三環γ-胺基酸衍生物之組合物及其製備方法
AU2013347264B2 (en) Dispersible tablet
CN103989643B (zh) 含有雷美替胺和共聚维酮的片剂
JP5843986B2 (ja) 粒状医薬組成物
CN111973567A (zh) 一种辅料组合物及其制备方法与应用
JPH05229936A (ja) 内服用顆粒製剤
JP2022112698A (ja) アピキサバン含有医薬組成物
KR102065090B1 (ko) 레베티라세탐 또는 이의 약제학적으로 허용되는 염을 함유하는 서방성 제제 및 이의 제조방법

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: 22762576

Country of ref document: EP

Kind code of ref document: A1

WWE Wipo information: entry into national phase

Ref document number: 202280018385.7

Country of ref document: CN

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 22762576

Country of ref document: EP

Kind code of ref document: A1