PT3236943T - Composições para administração íleo-jejunal de drogas - Google Patents

Composições para administração íleo-jejunal de drogas

Info

Publication number
PT3236943T
PT3236943T PT158347740T PT15834774T PT3236943T PT 3236943 T PT3236943 T PT 3236943T PT 158347740 T PT158347740 T PT 158347740T PT 15834774 T PT15834774 T PT 15834774T PT 3236943 T PT3236943 T PT 3236943T
Authority
PT
Portugal
Prior art keywords
ileo
jejunal
compositions
drug delivery
drug
Prior art date
Application number
PT158347740T
Other languages
English (en)
Portuguese (pt)
Original Assignee
Principia Biopharma Inc
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 Principia Biopharma Inc filed Critical Principia Biopharma Inc
Publication of PT3236943T publication Critical patent/PT3236943T/pt

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0002Galenical forms characterised by the drug release technique; Application systems commanded by energy
    • A61K9/0004Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/20Pills, tablets, discs, rods
    • A61K9/28Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A61K9/2886Dragees; Coated pills or tablets, e.g. with film or compression coating having two or more different drug-free coatings; Tablets of the type inert core-drug layer-inactive layer
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic 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
    • A61K31/505Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/12Carboxylic acids; Salts or anhydrides thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/26Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/32Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A61K47/38Cellulose; Derivatives thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/20Pills, tablets, discs, rods
    • A61K9/28Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A61K9/2806Coating materials
    • A61K9/2813Inorganic compounds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/20Pills, tablets, discs, rods
    • A61K9/28Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A61K9/2806Coating materials
    • A61K9/282Organic compounds, e.g. fats
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/20Pills, tablets, discs, rods
    • A61K9/28Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A61K9/2806Coating materials
    • A61K9/2833Organic macromolecular compounds
    • A61K9/284Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone
    • A61K9/2846Poly(meth)acrylates
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/20Pills, tablets, discs, rods
    • A61K9/28Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A61K9/2806Coating materials
    • A61K9/2833Organic macromolecular compounds
    • A61K9/2853Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers, poly(lactide-co-glycolide)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/20Pills, tablets, discs, rods
    • A61K9/28Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A61K9/2806Coating materials
    • A61K9/2833Organic macromolecular compounds
    • A61K9/286Polysaccharides, e.g. gums; Cyclodextrin
    • A61K9/2866Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/48Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5005Wall or coating material
    • A61K9/5021Organic macromolecular compounds
    • A61K9/5026Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/48Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5073Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals having two or more different coatings optionally including drug-containing subcoatings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • A61P35/02Antineoplastic agents specific for leukemia

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Inorganic Chemistry (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Oncology (AREA)
  • Hematology (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pyridine Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
PT158347740T 2014-12-24 2015-12-23 Composições para administração íleo-jejunal de drogas PT3236943T (pt)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US201462096812P 2014-12-24 2014-12-24

Publications (1)

Publication Number Publication Date
PT3236943T true PT3236943T (pt) 2023-04-20

Family

ID=55361929

Family Applications (1)

Application Number Title Priority Date Filing Date
PT158347740T PT3236943T (pt) 2014-12-24 2015-12-23 Composições para administração íleo-jejunal de drogas

Country Status (15)

Country Link
US (1) US20180193274A1 (enExample)
EP (1) EP3236943B1 (enExample)
JP (1) JP6687248B2 (enExample)
DK (1) DK3236943T3 (enExample)
ES (1) ES2942642T3 (enExample)
FI (1) FI3236943T3 (enExample)
HR (1) HRP20230305T1 (enExample)
HU (1) HUE061809T2 (enExample)
LT (1) LT3236943T (enExample)
MA (1) MA41265B1 (enExample)
PL (1) PL3236943T3 (enExample)
PT (1) PT3236943T (enExample)
RS (1) RS64139B1 (enExample)
SI (1) SI3236943T1 (enExample)
WO (1) WO2016105582A1 (enExample)

Families Citing this family (36)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
PL2892900T3 (pl) 2012-09-10 2018-02-28 Principia Biopharma Inc. Związki pyrazolopirymidonowe jako inhibitory kinazy
SMT201700160T1 (it) 2013-04-25 2017-05-08 Beigene Ltd Composti eterociclici fusi come inibitori di protein chinasi
ES2792183T3 (es) 2013-09-13 2020-11-10 Beigene Switzerland Gmbh Anticuerpos anti-PD1 y su uso como productos terapéuticos y de diagnóstico
CA2939186C (en) 2014-02-21 2023-03-07 Principia Biopharma Inc. Salts and solid form of a btk inhibitor
CN106604742B (zh) 2014-07-03 2019-01-11 百济神州有限公司 抗pd-l1抗体及其作为治疗剂及诊断剂的用途
US10485797B2 (en) 2014-12-18 2019-11-26 Principia Biopharma Inc. Treatment of pemphigus
MA42242A (fr) 2015-06-24 2018-05-02 Principia Biopharma Inc Inhibiteurs de la tyrosine kinase
SG11201809751XA (en) 2016-05-26 2018-12-28 Zeno Royalties & Milestones Llc Egfr inhibitor compounds
MX390619B (es) 2016-06-29 2025-03-21 Principia Biopharma Inc Formulaciones de liberacion modificada de 2-[3-[4-amino-3-(2-fluoro-4-fenoxi-fenil)pirazolo[3,4-d]pirimidin-1-il]piperidina-1-carbonil]-4-metil-4-[4-(oxetan-3-il)piperazin-1-il]pent-2-enenitrilo
CN109475536B (zh) 2016-07-05 2022-05-27 百济神州有限公司 用于治疗癌症的PD-l拮抗剂和RAF抑制剂的组合
WO2018033853A2 (en) 2016-08-16 2018-02-22 Beigene, Ltd. Crystalline form of (s)-7-(1-acryloylpiperidin-4-yl)-2-(4-phenoxyphenyl)-4,5,6,7-tetra-hydropyrazolo[1,5-a]pyrimidine-3-carboxamide, preparation, and uses thereof
PT3500299T (pt) 2016-08-19 2024-02-21 Beigene Switzerland Gmbh Combinação de zanubrutinib com um anticorpo anti-cd20 ou anti-pd-1 para utilização no tratamento do cancro
CN106588937B (zh) * 2017-01-16 2018-09-21 东莞市真兴贝特医药技术有限公司 咪唑并吡嗪类化合物及其制备方法和应用
CN110461847B (zh) 2017-01-25 2022-06-07 百济神州有限公司 (S)-7-(1-(丁-2-炔酰基)哌啶-4-基)-2-(4-苯氧基苯基)-4,5,6,7-四氢吡唑并[1,5-a]嘧啶-3-甲酰胺的结晶形式、其制备及用途
TW202515616A (zh) 2017-06-26 2025-04-16 英屬開曼群島商百濟神州有限公司 抗pd-1抗體或其抗原結合片段在製備治療用於患有肝細胞癌(hcc)之藥物的用途
CN110997677A (zh) 2017-08-12 2020-04-10 百济神州有限公司 具有改进的双重选择性的Btk抑制剂
CN114478544B (zh) * 2017-09-28 2023-06-16 上海海雁医药科技有限公司 4,6,7-三取代1,2-二氢吡咯并[3,4-c]吡啶/嘧啶-3-酮衍生物及用途
WO2019108795A1 (en) 2017-11-29 2019-06-06 Beigene Switzerland Gmbh Treatment of indolent or aggressive b-cell lymphomas using a combination comprising btk inhibitors
US11576917B2 (en) 2018-01-20 2023-02-14 Natco Pharma Limited Pharmaceutical compositions comprising Ibrutinib
KR102328682B1 (ko) 2018-08-27 2021-11-18 주식회사 대웅제약 신규한 헤테로사이클릭아민 유도체 및 이를 포함하는 약학 조성물
MX2021003064A (es) * 2018-09-18 2021-05-27 Beijing Innocare Pharma Tech Co Ltd Formas cristalinas de 6-(1-acriloilpiperidin-4-il)-2-(4-fenoxifeni l)nicotinamida.
MX2021004965A (es) * 2018-11-06 2021-06-15 Beijing Innocare Pharma Tech Co Ltd Dispersion solida amorfa que comprende 6-(1-acriloilpiperidin-4-il )-2-(4-fenoxifenil)nicotinamida.
WO2020102304A1 (en) * 2018-11-13 2020-05-22 Rain Therapeutics Inc. Combination of a kinase inhibitor and an electrolyte, compositions and methods comprising the same
PL3666262T3 (pl) * 2018-12-10 2022-02-28 Aphaia Ip Ag Farmaceutyczne doustne postaci dawkowania do leczenia zaburzeń metabolicznych i powiązanych chorób poprzez zorganizowane uwalnianie enterokin
CN109851725A (zh) * 2018-12-29 2019-06-07 华南理工大学 纳米纤维素-聚丙烯酰胺-明胶复合水凝胶、其制备方法及应用
WO2020249001A1 (zh) 2019-06-10 2020-12-17 百济神州瑞士有限责任公司 一种含有布鲁顿氏酪氨酸激酶抑制剂的口服固体片剂及其制备方法
CN114787150A (zh) 2019-08-15 2022-07-22 黑钻治疗公司 炔基喹唑啉化合物
MX2022004427A (es) 2019-10-14 2022-07-12 Principia Biopharma Inc Metodos para el tratamiento de la trombocitopenia inmunitaria mediante la administracion de (r)-2-[3-[4-amino-3-(2-fluoro-4-feno xi-fenil)pirazolo[3,4-d]pirimidin-1-il]piperidino-1-carbonil]-4-m etil-4-[4-(oxetan-3-il)piperazin-1-il]pent-2-enonitrilo.
WO2021080375A1 (en) * 2019-10-24 2021-04-29 Hanmi Pharm. Co., Ltd. A pharmaceutical preparation comprising an amide derivative inhibiting the growth of cancer cell and a pharmaceutical product containing the same
KR20220130184A (ko) 2020-01-22 2022-09-26 프린시피아 바이오파마, 인코퍼레이티드 2-[3-[4-아미노-3-(2-플루오로-4-페녹시-페닐)-1H-피라졸로[3,4-d]피리미딘-1-일]피페리딘-1-카르보닐]-4-메틸-4-[4-(옥세탄-3-일)피페라진-1-일]펜트-2-엔니트릴의 결정질 형태
TW202235083A (zh) * 2020-11-02 2022-09-16 美商黑鑽醫療公司 使用經炔取代之喹唑啉衍生物類以治療癌症之方法
WO2022260667A1 (en) * 2021-06-10 2022-12-15 Hikma Pharmaceuticals Usa Inc. Oral dosage forms of ibrutinib
CN113855695B (zh) * 2021-11-01 2023-06-06 上海理工大学 一种结肠释药口服复方药物组合物及其制备方法
CN114181159B (zh) * 2021-12-28 2024-02-20 南通大学 含2,4,5-三取代嘧啶酰肼衍生物及其制备方法与应用
US11786531B1 (en) 2022-06-08 2023-10-17 Beigene Switzerland Gmbh Methods of treating B-cell proliferative disorder
CN116473923B (zh) * 2023-05-29 2024-05-14 杭州剂泰医药科技有限责任公司 一种奈拉替尼固体分散体组合物及其制备方法和应用

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2771010A4 (en) * 2011-10-19 2015-04-01 Pharmacyclics Inc USE OF BRUTON TYROSINE KINASE (BTK) INHIBITORS
US20160045503A1 (en) * 2012-06-18 2016-02-18 Principia Biopharma Inc. Formulations containing reversible covalent compounds
WO2014004707A1 (en) 2012-06-29 2014-01-03 Principia Biopharma Inc. Formulations comprising ibrutinib
PL2892900T3 (pl) * 2012-09-10 2018-02-28 Principia Biopharma Inc. Związki pyrazolopirymidonowe jako inhibitory kinazy
SG10201705437SA (en) * 2013-01-05 2017-07-28 Elcelyx Therapeutics Inc Delayed-release composition comprising biguanide

Also Published As

Publication number Publication date
HRP20230305T1 (hr) 2023-05-26
JP2018500353A (ja) 2018-01-11
HUE061809T2 (hu) 2023-08-28
US20180193274A1 (en) 2018-07-12
JP6687248B2 (ja) 2020-04-22
EP3236943B1 (en) 2023-01-25
MA41265A (fr) 2017-10-31
ES2942642T3 (es) 2023-06-05
SI3236943T1 (sl) 2023-06-30
LT3236943T (lt) 2023-04-11
RS64139B1 (sr) 2023-05-31
WO2016105582A1 (en) 2016-06-30
MA41265B1 (fr) 2023-05-31
FI3236943T3 (fi) 2023-04-27
DK3236943T3 (da) 2023-04-11
PL3236943T3 (pl) 2023-05-29
EP3236943A1 (en) 2017-11-01
HK1245071A1 (en) 2018-08-24

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