IL91343A - Combined pharmaceutical preparations containing a protein kinase C compound and an anti-neoplastic substance - Google Patents

Combined pharmaceutical preparations containing a protein kinase C compound and an anti-neoplastic substance

Info

Publication number: IL91343A
Authority: IL; Israel
Prior art keywords: pharmaceutical combination; protein kinase; active material; inhibitor; preparation according
Prior art date: 1988-08-18

Application number

IL9134389A

Other languages

English (en)

Hebrew (he)

Other versions

IL91343A0 (en

Original Assignee

Boehringer Mannheim Gmbh

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.)

1988-08-18

Filing date

1989-08-17

Publication date

1996-05-14

Family has litigation

First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=6361067&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=IL91343(A) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.

1989-08-17 Application filed by Boehringer Mannheim Gmbh filed Critical Boehringer Mannheim Gmbh

1990-03-19 Publication of IL91343A0 publication Critical patent/IL91343A0/xx

1996-05-14 Publication of IL91343A publication Critical patent/IL91343A/en

Links

238000002360 preparation method Methods 0.000 title claims description 29
229940034982 antineoplastic agent Drugs 0.000 title description 14
229940123924 Protein kinase C inhibitor Drugs 0.000 title description 9
239000003881 protein kinase C inhibitor Substances 0.000 title description 9
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239000002246 antineoplastic agent Substances 0.000 title description 2
102000003923 Protein Kinase C Human genes 0.000 claims abstract description 32
108090000315 Protein Kinase C Proteins 0.000 claims abstract description 32
150000001875 compounds Chemical class 0.000 claims abstract description 25
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239000000824 cytostatic agent Substances 0.000 claims abstract description 20
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230000000118 anti-neoplastic effect Effects 0.000 claims abstract description 18
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REFJWTPEDVJJIY-UHFFFAOYSA-N Quercetin Chemical compound C=1C(O)=CC(O)=C(C(C=2O)=O)C=1OC=2C1=CC=C(O)C(O)=C1 REFJWTPEDVJJIY-UHFFFAOYSA-N 0.000 claims description 41
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Classifications

- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/24—Heavy metals; Compounds thereof
- A61K33/243—Platinum; Compounds thereof
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
- A61K51/0489—Phosphates or phosphonates, e.g. bone-seeking phosphonates
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
- A61K51/08—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins

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Health & Medical Sciences (AREA)
Public Health (AREA)
Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Veterinary Medicine (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Epidemiology (AREA)
Inorganic Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Organic Chemistry (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Medicines Containing Plant Substances (AREA)

IL9134389A 1988-08-18 1989-08-17 Combined pharmaceutical preparations containing a protein kinase C compound and an anti-neoplastic substance IL91343A (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
DE3827974A DE3827974A1 (de)	1988-08-18	1988-08-18	Kombinationspraeparate von proteinkinase-c-inhibitoren mit lipiden, lipid-analoga, cytostatica oder inhibitoren von phospholipasen

Publications (2)

Publication Number	Publication Date
IL91343A0 IL91343A0 (en)	1990-03-19
IL91343A true IL91343A (en)	1996-05-14

Family

ID=6361067

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
IL9134389A IL91343A (en)	1988-08-18	1989-08-17	Combined pharmaceutical preparations containing a protein kinase C compound and an anti-neoplastic substance

Country Status (17)

Country	Link
US (2)	US5578590A (ja)
EP (1)	EP0359981B1 (ja)
JP (1)	JPH02108636A (ja)
KR (1)	KR900002784A (ja)
AT (1)	ATE91903T1 (ja)
AU (1)	AU627207B2 (ja)
CA (1)	CA1330035C (ja)
DD (1)	DD283938A5 (ja)
DE (2)	DE3827974A1 (ja)
DK (1)	DK401089A (ja)
ES (1)	ES2058420T3 (ja)
HU (1)	HUT52396A (ja)
IE (1)	IE64635B1 (ja)
IL (1)	IL91343A (ja)
NZ (1)	NZ230323A (ja)
PT (1)	PT91470A (ja)
ZA (1)	ZA896287B (ja)

Families Citing this family (52)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
ZA908852B (en) *	1989-11-13	1991-09-25	Merrell Dow Pharma	Treatment of multi-drug resistant tumors with pyridyloxazole-2-ones
ZA908936B (en) *	1989-11-13	1991-09-25	Merrell Dow Pharma	Treatment of multi-drug resistant tumors with quinolyloxazole-2-ones
US5141957A (en) *	1990-11-02	1992-08-25	Sphinx Pharmaceuticals Corporation	1,4-bis-(amino-hydroxyalkylamino)-anthraquinones for inhibiting protein kinase c
US5204370A (en) *	1990-11-05	1993-04-20	Sphinx Pharmaceuticals Corporation	Bis-(hydroxyalkylamino)-anthraquinone inhibitors of protein kinase C
CA2072889A1 (en) *	1990-11-02	1992-05-03	Jack B. Jiang	Bis-(hydroxyalkylamino)-anthraquinone inhibitors of protein kinase c
CA2087334A1 (en) *	1991-05-14	1992-11-15	Alan J. Bitonti	Inhibition of metastasis in patients having cancer with pyridyloxazole-2-ones
WO1993002209A1 (en) *	1991-07-22	1993-02-04	The Regents Of The University Of California	Methods of designing specific affectors using three-dimensional conformation of enzyme/affector complex
US5216014A (en) *	1991-09-10	1993-06-01	Sphinx Pharmaceuticals Corporation	Furo-coumarinsulfonamides as protein kinase C inhibitors
GB9126209D0 (en) *	1991-12-10	1992-02-12	Orion Yhtymae Oy	Drug formulations for parenteral use
US5270310A (en) *	1991-12-13	1993-12-14	Sphinx Pharmaceuticals Corporation	N-aminoalkyl amide inhibitors of protein kinase C
US5292737A (en) *	1992-10-23	1994-03-08	Sphinx Pharmaceuticals Corporation	N,N'-bis(sulfonamido)-2-amino-4-iminonaphthalen-1-ones and N,N'-bis(amido)-2-amino-4-iminonaphthalen-1-ones
ZA941290B (en) *	1993-02-26	1995-08-25	Res Dev Foundation	Combination cisplatin/tamoxifen therapy for human cancers
US5844001A (en) *	1993-02-26	1998-12-01	Research Development Foundation	Combination platinum chemotherapeutic/antiestrogen therapy for human cancers
WO1994020106A1 (fr) *	1993-03-03	1994-09-15	Kyowa Hakko Kogyo Co., Ltd.	Renforceur de sensibilite pour agent antineoplasique
GB9509572D0 (en) *	1995-05-11	1995-07-05	Cancer Res Campaign Tech	Cancer therapy
CA2225682A1 (en) *	1995-06-27	1997-01-16	Henry M. Jackson Foundation For The Advancement Of Military Medicine	Method of dynamic retardation of cell cycle kinetics to potentiate cell damage
US6274576B1 (en)	1995-06-27	2001-08-14	The Henry Jackson Foundation For The Advancement Of Military Medicine	Method of dynamic retardation of cell cycle kinetics to potentiate cell damage
US5744460A (en) *	1996-03-07	1998-04-28	Novartis Corporation	Combination for treatment of proliferative diseases
US6232299B1 (en)	1996-05-01	2001-05-15	Eli Lilly And Company	Use of protein kinase C inhibitors to enhance the clinical efficacy of oncolytic agents and radiation therapy
US6063814A (en) *	1997-04-14	2000-05-16	Chang; Richard L.	Phorbol esters as anti-neoplastic and white blood cell elevating agents
CA2320117A1 (en) *	1998-02-12	1999-08-19	Emory University	Sphingolipid derivatives and their methods of use
JP3565003B2 (ja) *	1998-04-02	2004-09-15	日産自動車株式会社	自動車の排水構造
ATE226843T1 (de) *	1998-12-04	2002-11-15	Max Delbrueck Centrum	Mittel zur tumortherapie auf liposomenbasis, die tamoxifen enthalten
CA2385528C (en)	1999-10-01	2013-12-10	Immunogen, Inc.	Compositions and methods for treating cancer using immunoconjugates and chemotherapeutic agents
AUPQ641100A0 (en) *	2000-03-23	2000-04-15	Australia Nuclear Science & Technology Organisation	Methods of synthesis and use of radiolabelled platinum chemotherapeutic ag ents
AU2001271257A1 (en) *	2000-06-29	2002-01-14	Eli Lilly And Company	Use of a protein kinase c inhibitor to enhance the clinical efficacy of anti-neoplastic chemotherapeutic agents and radiation therapy
US6569853B1 (en) *	2000-11-06	2003-05-27	Combinatorx, Incorporated	Combinations of chlorpromazine and pentamidine for the treatment of neoplastic disorders
US6693125B2 (en) *	2001-01-24	2004-02-17	Combinatorx Incorporated	Combinations of drugs (e.g., a benzimidazole and pentamidine) for the treatment of neoplastic disorders
US20050065205A1 (en)	2002-03-07	2005-03-24	Daniel Alkon	Methods for Alzheimer's disease treatment and cognitive enhance
US6825229B2 (en)	2002-03-07	2004-11-30	Blanchette Rockefeller Neurosciences Institute	Methods for Alzheimer's Disease treatment and cognitive enhancement
US20080004332A1 (en) *	2002-03-07	2008-01-03	Alkon Daniel L	Methods for alzheimer's disease treatment and cognitive enhancement
JP2005536509A (ja) *	2002-07-11	2005-12-02	コンビナトアールエックスインコーポレーティッド	新生物の治療のための薬物の組み合わせ
US20040096436A1 (en) *	2002-08-02	2004-05-20	Regents Of The University Of California	Methods for inhibiting protein kinases in cancer cells
US20040175384A1 (en) *	2003-12-12	2004-09-09	Mohapatra Shyam S.	Protein kinase C as a target for the treatment of respiratory syncytial virus
US20050080075A1 (en) *	2003-08-25	2005-04-14	Nichols M. James	Formulations, conjugates, and combinations of drugs for the treatment of neoplasms
US20050158320A1 (en) *	2003-11-12	2005-07-21	Nichols M. J.	Combinations for the treatment of proliferative diseases
US20050100508A1 (en) *	2003-11-12	2005-05-12	Nichols M. J.	Methods for identifying drug combinations for the treatment of proliferative diseases
US8592368B2 (en)	2003-12-19	2013-11-26	University Of South Florida	JAK/STAT inhibitors and MAPK/ERK inhibitors for RSV infection
TW201206425A (en)	2004-05-18	2012-02-16	Brni Neurosciences Inst	Treatment of depressive disorders
AU2005247943A1 (en)	2004-05-23	2005-12-08	Gerard M. Housey	Theramutein modulators
ES2246165B1 (es) *	2004-07-20	2006-12-01	Universitat De Valencia	Uso combinado del pteroestilbeno y la quercetina para la fabricacion de medicamentos utiles en el tratamiento del cancer.
US8431110B2 (en)	2005-05-23	2013-04-30	Hmi Medical Innovations, Llc.	Compounds and method of identifying, synthesizing, optimizing and profiling protein modulators
US20070054890A1 (en)	2005-07-29	2007-03-08	Alkon Daniel L	Protein synthesis required for long-term memory is induced by PKC activation on days preceding associative learning
AR056517A1 (es)	2005-09-16	2007-10-10	Schering Corp	Composiciones y metodos farmaceuticos utilizando temozolomida y un inhibidor de la proteina quinasa
CA2631182C (en) *	2005-11-23	2019-08-06	Hmi, Inc.	Compounds and methods of identifying, synthesizing, optimizing and profiling protein modulators
CA2668923C (en) *	2006-11-10	2015-01-13	Alphaptose Gmbh	Use of tri-substituted glycerol compounds for the treatment of radiation injuries
ES2382756T3 (es) *	2006-11-10	2012-06-13	Alphaptose Gmbh	Forma de dosificación oral que comprende compuestos de glicerol trisustituido
KR20140049054A (ko)	2007-02-09	2014-04-24	블랜체트 록펠러 뉴로사이언시즈 인스티튜트	두부 외상으로 유발된 기억 장애 및 뇌 손상에 대한 브리오스타틴, 브리오로그 및 기타 관련 물질의 치료학적 효과
CA3226825A1 (en) *	2014-06-19	2015-12-23	Quercis Pharma AG	Method for treating cancer with a combination of quercetin and a chemotherapy agent
WO2019169389A1 (en) *	2018-03-02	2019-09-06	Epicentrx, Inc.	Methods and compositions for treating cancer and sensitizing tumor cells to kinase inhibitors
EP3886838A4 (en)	2018-11-30	2022-08-10	Beth Israel Deaconess Medical Center, Inc.	COMPOSITIONS AND METHODS FOR REDUCING MAJOR THROMBOTIC EVENTS IN CANCER PATIENTS
GB202014831D0 (en)	2020-09-21	2020-11-04	Dc Europa Ltd	Disconnection agents

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
WO1984001506A1 (en) *	1982-10-13	1984-04-26	Univ Birmingham	Pharmaceutical preparations for use in antitumour therapy
EP0409845A4 (en) *	1988-02-23	1991-07-03	U.S. Bioscience	Method for protection from chemotherapeutic side effects
GB8813682D0 (en) *	1988-06-09	1988-07-13	Reckitt & Colmann Prod Ltd	Pharmaceutical compositions

1988
- 1988-08-18 DE DE3827974A patent/DE3827974A1/de not_active Ceased
1989
- 1989-08-10 ES ES89114818T patent/ES2058420T3/es not_active Expired - Lifetime
- 1989-08-10 AT AT89114818T patent/ATE91903T1/de not_active IP Right Cessation
- 1989-08-10 DE DE8989114818T patent/DE58905028D1/de not_active Revoked
- 1989-08-10 EP EP89114818A patent/EP0359981B1/de not_active Revoked
- 1989-08-11 AU AU39550/89A patent/AU627207B2/en not_active Ceased
- 1989-08-15 DK DK401089A patent/DK401089A/da not_active Application Discontinuation
- 1989-08-15 DD DD89331796A patent/DD283938A5/de not_active IP Right Cessation
- 1989-08-16 NZ NZ230323A patent/NZ230323A/en unknown
- 1989-08-17 PT PT91470A patent/PT91470A/pt not_active Application Discontinuation
- 1989-08-17 HU HU894234A patent/HUT52396A/hu unknown
- 1989-08-17 IE IE264689A patent/IE64635B1/en not_active IP Right Cessation
- 1989-08-17 IL IL9134389A patent/IL91343A/en not_active IP Right Cessation
- 1989-08-17 ZA ZA896287A patent/ZA896287B/xx unknown
- 1989-08-18 CA CA000608760A patent/CA1330035C/en not_active Expired - Fee Related
- 1989-08-18 JP JP1211525A patent/JPH02108636A/ja active Pending
- 1989-08-18 KR KR1019890011848A patent/KR900002784A/ko not_active Ceased
1994
- 1994-10-07 US US08/319,478 patent/US5578590A/en not_active Expired - Fee Related
1995
- 1995-06-05 US US08/464,343 patent/US5770593A/en not_active Expired - Fee Related

Also Published As

Publication number	Publication date
DK401089A (da)	1990-02-19
IL91343A0 (en)	1990-03-19
IE892646L (en)	1990-02-18
DD283938A5 (de)	1990-10-31
CA1330035C (en)	1994-06-07
AU3955089A (en)	1990-02-22
EP0359981A1 (de)	1990-03-28
KR900002784A (ko)	1990-03-23
US5578590A (en)	1996-11-26
ATE91903T1 (de)	1993-08-15
DE3827974A1 (de)	1990-02-22
AU627207B2 (en)	1992-08-20
NZ230323A (en)	1992-05-26
DE58905028D1 (de)	1993-09-02
JPH02108636A (ja)	1990-04-20
IE64635B1 (en)	1995-08-09
DK401089D0 (da)	1989-08-15
EP0359981B1 (de)	1993-07-28
ZA896287B (en)	1990-05-30
ES2058420T3 (es)	1994-11-01
PT91470A (pt)	1990-03-08
HUT52396A (en)	1990-07-28
US5770593A (en)	1998-06-23

Legal Events

Date	Code	Title
1996-10-16	FF	Patent granted
1997-01-10	KB	Patent renewed
1999-12-31	KB	Patent renewed
2004-05-12	RH1	Patent not in force

Publication	Publication Date	Title
US5770593A (en)	1998-06-23	Method of determining a pharmaceutical combination preparations for use in anti-neoplastic therapy
Gaynon et al.	1990	Carboplatin in childhood brain tumors: a Children's Cancer Study Group phase II trial
JP2528115B2 (ja)	1996-08-28	イノシト−ルトリホスフエ−トを含有する医薬組成物
PT1385498E (pt)	2007-12-14	Ácidos gordos como factores de sobrevivência e activação de neutrófilos
JP2001527541A (ja)	2001-12-25	ヒト免疫不全ウイルスおよびその他感染性疾患の抗菌予防と治療
MD	1966	The effect of CNS depressants on mitosis
JPH11506766A (ja)	1999-06-15	炎症反応を抑制するためのジ−ベータ−ｄ−グルコピラノシルアミン化合物の使用、及び合成方法
US6248905B1 (en)	2001-06-19	Acyl derivatives of glycosyl-L-ascorbic acid
GB2052976A (en)	1981-02-04	Pharmaceutical preparation containing carnitine for lowering the lipid level in the body
DeVita et al.	1966	Preliminary clinical studies with ibenzmethyzin
JPH02191221A (ja)	1990-07-27	イノシトールトリホスフェートを含有する移植に関する障害に対する医薬
IL143751A (en)	2006-07-05	Phospholipid complexes of proanthocyanidin A2 that act as anti-atherosclerotic substances
JPS63145279A (ja)	1988-06-17	医薬品生成物
PT738147E (pt)	2000-08-31	Aplicacao do riluzolo no tratamento das doencas mitocondriais
US5116600A (en)	1992-05-26	Composition and method for inhibiting inflammation caused by non-parenteral administration of 5-fluorouracil type compounds
US3144387A (en)	1964-08-11	Anti-inflammatory compositions
EP0215956A1 (en)	1987-04-01	Composition for treating skin disease
US4439450A (en)	1984-03-27	Treatment of the blood-brain barrier with ibuprofen
Pruitt et al.	1970	Possible basis for the cariostatic effect of inorganic phosphates
JPH02502096A (ja)	1990-07-12	抗ウイルス化合物、そのような化合物を含む組成物及び治療方法
Thayer et al.	1939	Vitamin K potencies of synthetic compounds
JPH01313433A (ja)	1989-12-18	抗ｈｉｖ剤
US3772433A (en)	1973-11-13	Treatment of hepatopathias with saccharides
RO134937A1 (ro)	2021-05-28	Supliment ali- mentar cu proprietăţi antioxidante şi anti- inflamatoare
EP0260606A2 (en)	1988-03-23	Medicament for curing neurotic disturbance or disorder comprising sialocylglycerolipid