DE69207847D1 - Verwendung von Rapamycin zur Herstellung eines Arzneimittels zur Behandlung von Augenentzündungen - Google Patents

Verwendung von Rapamycin zur Herstellung eines Arzneimittels zur Behandlung von Augenentzündungen

Info

Publication number
DE69207847D1
DE69207847D1 DE69207847T DE69207847T DE69207847D1 DE 69207847 D1 DE69207847 D1 DE 69207847D1 DE 69207847 T DE69207847 T DE 69207847T DE 69207847 T DE69207847 T DE 69207847T DE 69207847 D1 DE69207847 D1 DE 69207847D1
Authority
DE
Germany
Prior art keywords
rapamycin
treatment
medicament
manufacture
eye inflammation
Prior art date
Legal status (The legal status 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 status listed.)
Expired - Lifetime
Application number
DE69207847T
Other languages
English (en)
Other versions
DE69207847T2 (de
Inventor
Prasad Shrikrishna Kulkarni
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
University of Louisville Research Foundation ULRF
Original Assignee
University of Louisville Research Foundation ULRF
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 University of Louisville Research Foundation ULRF filed Critical University of Louisville Research Foundation ULRF
Application granted granted Critical
Publication of DE69207847D1 publication Critical patent/DE69207847D1/de
Publication of DE69207847T2 publication Critical patent/DE69207847T2/de
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • 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
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365—Lactones
    • 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
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
DE69207847T 1991-07-25 1992-07-24 Verwendung von Rapamycin zur Herstellung eines Arzneimittels zur Behandlung von Augenentzündungen Expired - Lifetime DE69207847T2 (de)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US73560491A 1991-07-25 1991-07-25

Publications (2)

Publication Number Publication Date
DE69207847D1 true DE69207847D1 (de) 1996-03-07
DE69207847T2 DE69207847T2 (de) 1996-05-30

Family

ID=24956475

Family Applications (1)

Application Number Title Priority Date Filing Date
DE69207847T Expired - Lifetime DE69207847T2 (de) 1991-07-25 1992-07-24 Verwendung von Rapamycin zur Herstellung eines Arzneimittels zur Behandlung von Augenentzündungen

Country Status (20)

Country Link
US (1) US5387589A (de)
EP (1) EP0532862B1 (de)
JP (1) JP2568962B2 (de)
KR (1) KR100216768B1 (de)
AT (1) ATE133336T1 (de)
AU (1) AU653415B2 (de)
CA (1) CA2074641C (de)
CZ (1) CZ285660B6 (de)
DE (1) DE69207847T2 (de)
DK (1) DK0532862T3 (de)
ES (1) ES2083030T3 (de)
HK (1) HK1005705A1 (de)
HU (1) HU211218B (de)
IE (1) IE922430A1 (de)
IL (1) IL102414A (de)
MX (1) MX9204381A (de)
NZ (1) NZ243679A (de)
RU (1) RU2048812C1 (de)
SK (1) SK280511B6 (de)
ZA (1) ZA924953B (de)

Families Citing this family (91)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1992019278A1 (en) * 1991-04-26 1992-11-12 Kurume University Use of macrolide compounds for eye diseases
CH686761A5 (de) * 1993-05-27 1996-06-28 Sandoz Ag Galenische Formulierungen.
AT408520B (de) * 1993-05-27 2001-12-27 Novartis Erfind Verwalt Gmbh Galenische formulierungen
US5362718A (en) 1994-04-18 1994-11-08 American Home Products Corporation Rapamycin hydroxyesters
US5561138A (en) * 1994-12-13 1996-10-01 American Home Products Corporation Method of treating anemia
US5496832A (en) * 1995-03-09 1996-03-05 American Home Products Corporation Method of treating cardiac inflammatory disease
BE1009856A5 (fr) 1995-07-14 1997-10-07 Sandoz Sa Composition pharmaceutique sous la forme d'une dispersion solide comprenant un macrolide et un vehicule.
TW427904B (en) * 1995-12-07 2001-04-01 American Home Prod Neuroprotective agents
US5780462A (en) * 1995-12-27 1998-07-14 American Home Products Corporation Water soluble rapamycin esters
GB9601120D0 (en) 1996-01-19 1996-03-20 Sandoz Ltd Organic compounds
WO1997031020A1 (en) * 1996-02-22 1997-08-28 The General Hospital Corporation METHODS AND COMPOSITIONS FOR ENHANCING CELLULAR RESPONSE TO TGF-β LIGANDS
JPH09278653A (ja) * 1996-04-05 1997-10-28 Santen Pharmaceut Co Ltd 網膜疾患治療剤
US5922730A (en) * 1996-09-09 1999-07-13 American Home Products Corporation Alkylated rapamycin derivatives
KR19990048077A (ko) * 1997-12-08 1999-07-05 전원중 인조대리석 성형품의 제조방법
JP2002503692A (ja) * 1998-02-23 2002-02-05 藤沢薬品工業株式会社 マクロライド系化合物の緑内障治療用途
CN1114401C (zh) * 1998-07-14 2003-07-16 阿尔康实验室公司 11－(3－二甲氨基亚丙基)－6,11－二氢二苯并[b,e]噁庚英－2－乙酸用于制药的新用途
US6384056B1 (en) 1998-08-14 2002-05-07 Gpi Nil Holdings, Inc. Heterocyclic thioesters or ketones for vision and memory disorders
US6399648B1 (en) 1998-08-14 2002-06-04 Gpi Nil Holdings, Inc. N-oxides of heterocyclic ester, amide, thioester, or ketone for vision and memory disorders
US6335348B1 (en) 1998-08-14 2002-01-01 Gpi Nil Holdings, Inc. Nitrogen-containing linear and azepinyl/ compositions and uses for vision and memory disorders
US7410995B1 (en) 1998-08-14 2008-08-12 Gpi Nil Holdings Inc. N-linked sulfonamide of heterocyclic thioesters for vision and memory disorders
US6339101B1 (en) 1998-08-14 2002-01-15 Gpi Nil Holdings, Inc. N-linked sulfonamides of N-heterocyclic carboxylic acids or isosteres for vision and memory disorders
US6333340B1 (en) 1998-08-14 2001-12-25 Gpi Nil Holdings, Inc. Small molecule sulfonamides for vision and memory disorders
US6337340B1 (en) 1998-08-14 2002-01-08 Gpi Nil Holdings, Inc. Carboxylic acids and isosteres of heterocyclic ring compounds having multiple heteroatoms for vision and memory disorders
US6376517B1 (en) * 1998-08-14 2002-04-23 Gpi Nil Holdings, Inc. Pipecolic acid derivatives for vision and memory disorders
US6218423B1 (en) 1998-08-14 2001-04-17 Gpi Nil Holdings, Inc. Pyrrolidine derivatives for vision and memory disorders
US7338976B1 (en) 1998-08-14 2008-03-04 Gpi Nil Holdings, Inc. Heterocyclic esters or amides for vision and memory disorders
US7265150B1 (en) 1998-08-14 2007-09-04 Gpi Nil Holdings Inc. Carboxylic acids and carboxylic acid isosteres of N-heterocyclic compounds for vision and memory disorders
US6506788B1 (en) 1998-08-14 2003-01-14 Gpi Nil Holdings, Inc. N-linked urea or carbamate of heterocyclic thioesters for vision and memory disorders
US6015809A (en) * 1998-08-17 2000-01-18 American Home Products Corporation Photocyclized rapamycin
US6864232B1 (en) 1998-12-24 2005-03-08 Sucampo Ag Agent for treating visual cell function disorder
CN1224420C (zh) * 1998-12-24 2005-10-26 苏坎波公司 视细胞功能紊乱治疗剂
US7063857B1 (en) 1999-04-30 2006-06-20 Sucampo Ag Use of macrolide compounds for the treatment of dry eye
IL146162A0 (en) * 1999-04-30 2002-07-25 R Tech Ueno Ltd Macrolide compounds for the treatment of dry eye
US6331547B1 (en) 1999-08-18 2001-12-18 American Home Products Corporation Water soluble SDZ RAD esters
US6670355B2 (en) * 2000-06-16 2003-12-30 Wyeth Method of treating cardiovascular disease
ATE411321T1 (de) 2000-09-19 2008-10-15 Wyeth Corp Wasserlösliche rapamycin-ester
US6399625B1 (en) 2000-09-27 2002-06-04 Wyeth 1-oxorapamycins
US6399626B1 (en) 2000-10-02 2002-06-04 Wyeth Hydroxyesters of 7-desmethylrapamycin
US6440991B1 (en) 2000-10-02 2002-08-27 Wyeth Ethers of 7-desmethlrapamycin
US20040018228A1 (en) * 2000-11-06 2004-01-29 Afmedica, Inc. Compositions and methods for reducing scar tissue formation
US20040241211A9 (en) * 2000-11-06 2004-12-02 Fischell Robert E. Devices and methods for reducing scar tissue formation
US6534693B2 (en) * 2000-11-06 2003-03-18 Afmedica, Inc. Surgically implanted devices having reduced scar tissue formation
TWI286074B (en) 2000-11-15 2007-09-01 Wyeth Corp Pharmaceutical composition containing CCI-779 as an antineoplastic agent
TWI233359B (en) * 2001-04-06 2005-06-01 Wyeth Corp Pharmaceutical composition for treating neoplasm
ZA200603888B (en) * 2001-06-01 2007-05-30 Wyeth Corp Antineoplastic combinations
UA77200C2 (en) 2001-08-07 2006-11-15 Wyeth Corp Antineoplastic combination of cci-779 and bkb-569
BR0211905A (pt) 2001-08-22 2004-09-21 Wyeth Corp Dialdeìdos de rapamicina
CN1310908C (zh) 2001-08-22 2007-04-18 惠氏公司 雷帕霉素29－烯醇
IL161849A0 (en) * 2001-11-19 2005-11-20 Novartis Ag Use of an ascomycin for the treatment of blepharitis
CN101717410B (zh) 2002-02-01 2015-04-29 阿里亚德医药股份有限公司 含磷化合物及其应用
JP4265888B2 (ja) * 2002-06-12 2009-05-20 株式会社リコー 画像形成装置
AU2003254168A1 (en) 2002-07-30 2004-02-16 Wyeth Parenteral formulations containing a rapamycin hydroxyester
DK1635830T3 (da) * 2002-09-17 2009-02-23 Wyeth Corp Granulatformulering af rapamycinesteren CCI-779
WO2004027027A2 (en) * 2002-09-18 2004-04-01 Trustees Of The University Of Pennsylvania Method of inhibiting choroidal neovascularization
US7354574B2 (en) 2002-11-07 2008-04-08 Advanced Ocular Systems Limited Treatment of ocular disease
AR042938A1 (es) * 2003-02-06 2005-07-06 Wyeth Corp Uso del cci-779 en el tratamiento de la fibrosis hepatica
UA83484C2 (uk) * 2003-03-05 2008-07-25 Уайт Спосіб лікування раку грудей комбінацією похідного рапаміцину і інгібітора ароматази - летрозолу, фармацевтична композиція
BRPI0409632A (pt) * 2003-04-22 2006-04-25 Wyeth Corp combinações antineoplásticas
US7083802B2 (en) * 2003-07-31 2006-08-01 Advanced Ocular Systems Limited Treatment of ocular disease
AU2004274026A1 (en) * 2003-09-18 2005-03-31 Macusight, Inc. Transscleral delivery
US7083803B2 (en) 2003-09-19 2006-08-01 Advanced Ocular Systems Limited Ocular solutions
US7087237B2 (en) * 2003-09-19 2006-08-08 Advanced Ocular Systems Limited Ocular solutions
CA2571710A1 (en) 2004-06-24 2006-11-02 Nicholas Valiante Small molecule immunopotentiators and assays for their detection
US8313763B2 (en) * 2004-10-04 2012-11-20 Tolmar Therapeutics, Inc. Sustained delivery formulations of rapamycin compounds
CA2582374A1 (en) * 2004-10-04 2006-04-20 Qlt Usa, Inc. Ocular delivery of polymeric delivery formulations
ES2564194T3 (es) * 2005-02-09 2016-03-18 Santen Pharmaceutical Co., Ltd. Formulaciones líquidas para el tratamiento de enfermedades o dolencias
US8663639B2 (en) * 2005-02-09 2014-03-04 Santen Pharmaceutical Co., Ltd. Formulations for treating ocular diseases and conditions
EP1871366A2 (de) * 2005-03-21 2008-01-02 Macusight, Inc. Arzneimittelabgabesysteme zur behandlung von krankheiten oder zuständen
EP1890652B1 (de) 2005-05-13 2017-08-02 Akkolens International B.V. Künstliche intraokularlinse für durch die iris bewirkte akkomodation
WO2007011880A2 (en) 2005-07-18 2007-01-25 Minu, L.L.C. Enhanced ocular neuroprotection/neurostimulation
US20070014760A1 (en) * 2005-07-18 2007-01-18 Peyman Gholam A Enhanced recovery following ocular surgery
US20070071754A1 (en) * 2005-09-26 2007-03-29 Peyman Gholam A Method to ameliorate inflammation
CN102579467A (zh) 2005-11-14 2012-07-18 阿里亚德医药股份有限公司 雷帕霉素衍生物在治疗癌症中的用途
KR20140093764A (ko) * 2006-02-09 2014-07-28 산텐 세이야꾸 가부시키가이샤 안정한 제제와 그 제조 및 사용 방법
DK2001466T3 (en) * 2006-03-23 2016-02-29 Santen Pharmaceutical Co Ltd LOW-DOSAGE RAPAMYCINE FOR TREATMENT OF VASCULAR PERMEABILITY-RELATED DISEASES
US20100081681A1 (en) * 2006-08-16 2010-04-01 Blagosklonny Mikhail V Methods and compositions for preventing or treating age-related diseases
EP2083834B1 (de) 2006-09-13 2017-06-21 Elixir Medical Corporation Makrozyklische lactonverbindungen und verfahren zu ihrer verwendung
CN101918019B (zh) * 2007-10-08 2014-11-26 奥里尼亚制药有限公司 包含钙调神经磷酸酶抑制剂或mTOR抑制剂的眼科组合物
AU2008329876A1 (en) * 2007-11-27 2009-06-04 Alcon Research, Ltd. Topical ophthalmic or otic solution formulations containing moxifloxacin hydrochloride and dexamethasone phosphate
WO2010040064A1 (en) * 2008-10-03 2010-04-08 Elixir Medical Corporation Macrocyclic lactone compounds and methods for their use
WO2010118419A2 (en) * 2009-04-10 2010-10-14 Haiyan Qi Novel anti-aging agents and methods to identify them
MX338355B (es) 2009-06-09 2016-04-13 Aurinia Pharmaceuticals Inc Sistemas de suministro de farmaco topico para uso oftalmico.
US8912215B2 (en) 2011-12-13 2014-12-16 Everon Biosciences, Inc. Rapamycin composition
US20140255355A1 (en) * 2013-03-07 2014-09-11 Stemnion, Inc. Methods for treating blepharitis
CA3025258A1 (en) 2016-05-25 2017-11-30 Santen Pharmaceutical Co., Ltd. Use of sirolimus to treat exudative age-related macular degeneration with persistent edema
CN115645399A (zh) 2016-06-30 2023-01-31 度瑞公司 长效配制物
US10682340B2 (en) 2016-06-30 2020-06-16 Durect Corporation Depot formulations
JP2020507632A (ja) 2017-02-10 2020-03-12 マウント タム セラピューティクス, インコーポレイテッドMount Tam Therapeutics, Inc. ラパマイシン類似体
US20190224275A1 (en) 2017-05-12 2019-07-25 Aurinia Pharmaceuticals Inc. Protocol for treatment of lupus nephritis
EP3639854A4 (de) 2017-06-16 2021-03-03 The Doshisha Mtor-hemmendes arzneimittel zur behandlung oder prävention von ophthalmischen symptomen, störungen oder erkrankungen und anwendung davon
JPWO2021132565A1 (de) 2019-12-26 2021-07-01

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ZA737247B (en) * 1972-09-29 1975-04-30 Ayerst Mckenna & Harrison Rapamycin and process of preparation
US3993749A (en) * 1974-04-12 1976-11-23 Ayerst Mckenna And Harrison Ltd. Rapamycin and process of preparation
US4885171A (en) * 1978-11-03 1989-12-05 American Home Products Corporation Use of rapamycin in treatment of certain tumors
US5066493A (en) * 1978-11-03 1991-11-19 American Home Products Corporation Rapamycin in treatment of tumors
BE877700A (fr) * 1978-11-03 1980-01-14 Ayerst Mckenna & Harrison Compositions pharmaceutiques a base de rapamycine pour le traitement de tumeurs carcinogenes
US4316885A (en) * 1980-08-25 1982-02-23 Ayerst, Mckenna And Harrison, Inc. Acyl derivatives of rapamycin
US4650803A (en) * 1985-12-06 1987-03-17 University Of Kansas Prodrugs of rapamycin
US5100899A (en) * 1989-06-06 1992-03-31 Roy Calne Methods of inhibiting transplant rejection in mammals using rapamycin and derivatives and prodrugs thereof
DE69016515T2 (de) * 1989-07-05 1995-06-08 Fujisawa Pharmaceutical Co Wässriges flüssiges Mittel zur äusserlichen Anwendung.

Also Published As

Publication number Publication date
MX9204381A (es) 1993-02-01
HU9202448D0 (en) 1992-10-28
IL102414A0 (en) 1993-01-14
JPH05194212A (ja) 1993-08-03
CZ285660B6 (cs) 1999-10-13
AU653415B2 (en) 1994-09-29
HU211218B (en) 1995-11-28
RU2048812C1 (ru) 1995-11-27
CZ230792A3 (en) 1993-02-17
DK0532862T3 (da) 1996-02-19
CA2074641A1 (en) 1993-01-26
EP0532862B1 (de) 1996-01-24
SK280511B6 (sk) 2000-03-13
SK230792A3 (en) 1996-05-08
HK1005705A1 (en) 1999-01-22
US5387589A (en) 1995-02-07
ATE133336T1 (de) 1996-02-15
DE69207847T2 (de) 1996-05-30
EP0532862A1 (de) 1993-03-24
KR100216768B1 (ko) 1999-09-01
KR930001913A (ko) 1993-02-22
JP2568962B2 (ja) 1997-01-08
NZ243679A (en) 1997-06-24
ZA924953B (en) 1993-04-28
IL102414A (en) 1996-08-04
ES2083030T3 (es) 1996-04-01
IE922430A1 (en) 1993-01-27
HUT63763A (en) 1993-10-28
CA2074641C (en) 1999-05-04
AU2035092A (en) 1993-01-28

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