MA27855A1 - Composition contenant un inhibiteur de pde4 et un inhibiteur de pde5 - Google Patents

Composition contenant un inhibiteur de pde4 et un inhibiteur de pde5

Info

Publication number
MA27855A1
MA27855A1 MA28653A MA28653A MA27855A1 MA 27855 A1 MA27855 A1 MA 27855A1 MA 28653 A MA28653 A MA 28653A MA 28653 A MA28653 A MA 28653A MA 27855 A1 MA27855 A1 MA 27855A1
Authority
MA
Morocco
Prior art keywords
inhibitor
pde5
composition containing
containing pde4
pde4
Prior art date
Application number
MA28653A
Other languages
English (en)
French (fr)
Inventor
Thorsten Dunkern
Armin Hatzelmann
Christian Schudt
Friedrich Grimminger
Hossein Ardeschir Ghofrani
Original Assignee
Altana Pharma Ag
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 Altana Pharma Ag filed Critical Altana Pharma Ag
Publication of MA27855A1 publication Critical patent/MA27855A1/fr

Links

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
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/205—Amine addition salts of organic acids; Inner quaternary ammonium salts, e.g. betaine, carnitine
    • 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
    • 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
    • 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
    • A61K31/52—Purines, e.g. adenine
    • A61K31/522—Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
    • 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
    • A61K31/53—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • 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]
    • 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
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure

Landscapes

  • Health & Medical 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)
  • Life Sciences & Earth Sciences (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Immunology (AREA)
  • Pulmonology (AREA)
  • Cardiology (AREA)
  • Rheumatology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Hospice & Palliative Care (AREA)
  • Pain & Pain Management (AREA)
  • Transplantation (AREA)
  • Urology & Nephrology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
MA28653A 2003-05-22 2005-12-12 Composition contenant un inhibiteur de pde4 et un inhibiteur de pde5 MA27855A1 (fr)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
EP03011609 2003-05-22

Publications (1)

Publication Number Publication Date
MA27855A1 true MA27855A1 (fr) 2006-04-03

Family

ID=33462087

Family Applications (1)

Application Number Title Priority Date Filing Date
MA28653A MA27855A1 (fr) 2003-05-22 2005-12-12 Composition contenant un inhibiteur de pde4 et un inhibiteur de pde5

Country Status (23)

Country Link
US (3) US20060094723A1 (enExample)
EP (1) EP1628682B1 (enExample)
JP (1) JP2006528229A (enExample)
KR (1) KR20060012004A (enExample)
CN (1) CN1791429A (enExample)
AU (1) AU2004241749B2 (enExample)
BR (1) BRPI0410326A (enExample)
CA (1) CA2525946C (enExample)
CO (1) CO5660275A2 (enExample)
EA (1) EA012279B1 (enExample)
EC (1) ECSP056173A (enExample)
GE (1) GEP20084342B (enExample)
IL (1) IL171306A (enExample)
IS (1) IS8181A (enExample)
MA (1) MA27855A1 (enExample)
MX (1) MXPA05012302A (enExample)
NO (1) NO333501B1 (enExample)
NZ (1) NZ544040A (enExample)
RS (1) RS52730B (enExample)
TN (1) TNSN05265A1 (enExample)
UA (1) UA83041C2 (enExample)
WO (1) WO2004103407A2 (enExample)
ZA (1) ZA200508116B (enExample)

Families Citing this family (24)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
MY140561A (en) 2002-02-20 2009-12-31 Nycomed Gmbh Dosage form containing pde 4 inhibitor as active ingredient
MXPA04008070A (es) 2003-03-10 2004-11-26 Altana Pharma Ag Novedoso proceso para la preparacion de roflumilasto.
WO2005023253A1 (en) 2003-09-05 2005-03-17 Altana Pharma Ag Use of pde4 inhibitors for the treatment of diabetes mellitus
WO2005107749A1 (en) * 2004-05-10 2005-11-17 Altana Pharma Ag Use of roflumilast for the prophylaxis or treatment of emphysema
MX2007010560A (es) * 2005-03-08 2008-02-21 Nycomed Gmbh Roflumilast para el tratamiento de diabetes mellitus.
WO2006094942A1 (en) * 2005-03-08 2006-09-14 Nycomed Gmbh Roflumilast for the treatment of diabetes mellitus
US8663694B2 (en) 2005-03-16 2014-03-04 Takeda Gmbh Taste masked dosage form containing roflumilast
DE102005016345A1 (de) * 2005-04-09 2006-10-12 Bayer Healthcare Ag Neue Verwendung von 2-Phenyl-substituierten Imidazotriazinon-Derivaten
CA2604295C (en) * 2005-04-19 2014-10-07 Nycomed Gmbh Roflumilast for the treatment of pulmonary hypertension
NL2000291C2 (nl) 2005-11-10 2009-02-17 Pfizer Prod Inc 1-(1-(2-ethoxyethyl)-3-ethyl-7-(4-methylpyridin-2-ylamino)-1H- pyrazool(4,3-d)pyrimidine-5-yl)piperidine-4-carbonzuur en zouten daarvan.
UA106422C2 (uk) * 2006-07-05 2014-08-26 Такеда Гмбх КОМБІНОВАНЕ ЗАСТОСУВАННЯ ІНГІБІТОРА PDE4 ТА ІНГІБІТОРА HMG-CоA-РЕДУКТАЗИ ДЛЯ ПРОФІЛАКТИКИ АБО ЗЦІЛЮВАЛЬНОГО ЛІКУВАННЯ ЗАПАЛЬНОГО ЗАХВОРЮВАННЯ ЛЕГЕНІВ
CN101547922B (zh) * 2006-10-04 2012-06-20 辉瑞产品公司 作为钙受体拮抗剂的吡啶并[4,3-d]嘧啶-4(3H)-酮衍生物
WO2010013925A2 (en) * 2008-07-31 2010-02-04 Dong-A Pharmaceutical. Co., Ltd. Pharmacological composition for prevention and treatment of respiratory disease containing pyrazolopyrimidinone compound or pharmaceutically acceptable salts thereof
JP2014526461A (ja) * 2011-09-09 2014-10-06 エスケー ケミカルズ カンパニー，リミテッド Ｐｄｅ５抑制剤を含む皮膚しわ改善用組成物
JP6225178B2 (ja) * 2012-05-31 2017-11-01 フェネックス ファーマシューティカルス アーゲー オーファン核内受容体ＲＯＲγの調整剤としてのカルボキサミドまたはスルホンアミド置換されたチアゾールおよび関連する誘導体
WO2015089105A1 (en) 2013-12-09 2015-06-18 Respira Therapeutics, Inc. Pde5 inhibitor powder formulations and methods relating thereto
EP3165224A1 (en) 2015-11-09 2017-05-10 Albert-Ludwigs-Universität Freiburg Use of pde4 inhibitors for the prophylaxis and/or therapy of dyslipoproteinaemia and related disorders
US10058545B2 (en) * 2016-08-09 2018-08-28 Cipla Limited Method of treating pulmonary arterial hypertension
CN107648224A (zh) * 2017-10-31 2018-02-02 泰州中国医药城中医药研究院 一种治疗和预防心力衰竭药物及其在制药中的应用
US20210031012A1 (en) 2018-01-26 2021-02-04 Progenity, Inc. Treatment of a disease of the gastrointestinal tract with a pde4 inhibitor
CN108976107B (zh) * 2018-08-23 2021-03-23 南方医科大学 3-芳基-4-烷氧基苄胺衍生物及其制备方法和应用
WO2020106704A2 (en) 2018-11-19 2020-05-28 Progenity, Inc. Ingestible device for delivery of therapeutic agent to the gastrointestinal tract
CN121197633A (zh) 2019-12-13 2025-12-26 比特比德科有限责任公司 用于将治疗剂递送至胃肠道的可摄取装置
US20230124467A1 (en) * 2020-03-03 2023-04-20 Mios Pharmaceuticals Limited Compounds and methods for treating diseases and/or conditions caused by coronavirus

Family Cites Families (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB9013750D0 (en) 1990-06-20 1990-08-08 Pfizer Ltd Therapeutic agents
HU220041B (hu) 1993-07-02 2001-10-28 Byk Gulden Lomberg Chemische Fabrik Gmbh. Fluor-alkoxi-helyettesített benzamidszármazékok, eljárás előállításukra és ezeket a vegyületeket tartalmazó gyógyászati készítmények
GB9401090D0 (en) 1994-01-21 1994-03-16 Glaxo Lab Sa Chemical compounds
EP0779292A4 (en) * 1994-08-29 1997-09-24 Yamanouchi Pharma Co Ltd NEW NAPHTHYRIDE DERIVATIVES AND MEDICAL COMPOSITIONS CONTAINING THEM
US6127363A (en) * 1997-10-28 2000-10-03 Vivus, Inc. Local administration of Type IV phosphodiesterase inhibitors for the treatment of erectile dysfunction
US6362178B1 (en) 1997-11-12 2002-03-26 Bayer Aktiengesellschaft 2-phenyl substituted imidazotriazinones as phosphodiesterase inhibitors
US6417190B1 (en) * 1998-12-17 2002-07-09 Boehringer Ingelheim Pharma Kg Tricyclic nitrogen heterocycles as PDE IV inhibitors
TWI224966B (en) * 1999-11-02 2004-12-11 Pfizer Pharmaceutical composition (I) useful for treating or preventing pulmonary hypertension in a patient
EA200300836A1 (ru) * 2001-02-15 2004-02-26 Алтана Фарма Аг Производные фталазинон-пиперидина в качестве ингибиторов pde4
AU2002314102A1 (en) * 2001-05-25 2002-12-09 Boehringer Ingelheim Pharma Gmbh & Co. Kg Combination of a pde4 inhibitor and tiotropium or derivate thereof for treating obstructive airways
US20030114469A1 (en) * 2001-09-27 2003-06-19 Cohen David Saul Combinations
GB0202254D0 (en) * 2002-01-31 2002-03-20 Pfizer Ltd Prevention of scarring
US20030216407A1 (en) * 2002-01-31 2003-11-20 Pfizer Inc. Use of PDE5 inhibitors in the treatment of scarring
MY140561A (en) 2002-02-20 2009-12-31 Nycomed Gmbh Dosage form containing pde 4 inhibitor as active ingredient

Also Published As

Publication number Publication date
EP1628682A2 (en) 2006-03-01
NO20055941L (no) 2005-12-14
RS20050858A (sr) 2007-12-31
AU2004241749A1 (en) 2004-12-02
RS52730B (sr) 2013-08-30
MXPA05012302A (es) 2006-01-30
UA83041C2 (ru) 2008-06-10
CA2525946C (en) 2013-01-29
ECSP056173A (es) 2006-04-19
EP1628682B1 (en) 2013-09-25
TNSN05265A1 (en) 2007-07-10
US20100234382A1 (en) 2010-09-16
NZ544040A (en) 2009-03-31
BRPI0410326A (pt) 2006-05-23
IL171306A (en) 2013-08-29
JP2006528229A (ja) 2006-12-14
CN1791429A (zh) 2006-06-21
US20120196867A1 (en) 2012-08-02
AU2004241749B2 (en) 2010-03-25
KR20060012004A (ko) 2006-02-06
WO2004103407A3 (en) 2005-02-17
CO5660275A2 (es) 2006-07-31
EA200501690A1 (ru) 2006-06-30
WO2004103407A2 (en) 2004-12-02
ZA200508116B (en) 2007-01-31
CA2525946A1 (en) 2004-12-02
GEP20084342B (en) 2008-03-25
EA012279B1 (ru) 2009-08-28
NO333501B1 (no) 2013-06-24
US20060094723A1 (en) 2006-05-04
IS8181A (is) 2005-12-14

Similar Documents

Publication Publication Date Title
MA27855A1 (fr) Composition contenant un inhibiteur de pde4 et un inhibiteur de pde5
EP1554256A4 (en) PIPERIDINOPYRIMIDINEIPEPTIDYLPEPTIDASEINHIBITORS FOR THE TREATMENT OF DIABETES
TNSN02022A1 (fr) Triazolopyridines anti-inflammatoires nouvelles, et compositions les contenant
EP1673078A4 (en) BENZYL ETHER AND BENZYLAMINO BETA SEKRETASE INHIBITORS FOR THE TREATMENT OF ALZHEIMER DISEASE
LU91470I2 (fr) Beta-amino-tétrahydroimidazo (1,2-A) pyrazines et betaamino-tétrahydrotrioazolo (4,3-A) pyrazines utilisées en tant qu'inhibiteurs de la dipeptidyl peptibase dans le traitement ou la prévention du diabète
TNSN99073A1 (fr) Pyrazolopyrimidinones nouvelles, procede pour leur preparation et compositions pharmaceutiques les contenant
EP1651623A4 (en) HEXAHYDRODIAZEPINONE AS INHIBITORS OF DIPEPTIDYLPEPTIDASE-IV FOR TREATMENT OR PREVENTION OF DIABETES
EP1385508A4 (en) DIPEPTIDYLPEPTIDASE INHIBITORS FOR THE TREATMENT OR PREVENTION OF DIABETES
EP1490335A4 (en) HETEROCYCLIC BETA-AMINO COMPOUNDS AS INHIBITORS OF DIPEPTIDYLPEPTIDASE FOR TREATMENT OR PREVENTION OF DIABETES
ATE245648T1 (de) 1h-pyrazolo(3,4-d)pyrimidine-4,6-dione als inhibitoren für die vermehrung von t-zellen
TNSN99155A1 (fr) 1-aryl-3-arylmethyl-1,8-naphtyridine-4(1h)-ones nouvelles, procede pour leur preparation et compositions pharmaceutiques les contenant
MA27556A1 (fr) Derives de phenylalanine comme inhibiteurs de la dipeptidyl peptidase pour le traitement ou la prevention du diabete
ATE447574T1 (de) 3-amino-4-phenylbutansäurederivate als dipeptidylpeptidase-hemmer zur behandlung oder vorbeugung von diabetes
TNSN00169A1 (fr) Pyrimidine-2,4,6-triones inhibitrices de metalloproteinases, et compositions pharmaceutiques les contenant
TNSN99095A1 (fr) 4 - phenylpiperidines nouvelles, procede pour leur preparation et compositions pharmaceutiques les contenant
CY1108098T1 (el) Διαγνωστικη μεθοδος για την προβλεψη της απορριψης μεταμοσχευσεων νεφρου
TNSN98017A1 (fr) Derives de sulfonyluree, procede pour leur preparation et compositions pharmaceutiques les contenant.
MA27334A1 (fr) Utilisation d'inhibiteurs de l'ikb kinase dans le traitement de la douleur
MA30333B1 (fr) Aminotetrahydropyranes utiles en tant qu'inhibiteurs de la dipeptidyle peptidase-iv pour le traitement ou la prevention du diabete.
MA29169B1 (fr) Formulations intraveineuses d'inhibiteurs de la pde-5
EP1784188A4 (en) CONDENSED TRIAZOLE DERIVATIVES AS DIPEPTIDYLPEPTIDASE IV HEMMER FOR TREATMENT OR PREVENTION OF DIABETES
WO2004062625A3 (en) Macrocyclic beta-secretase inhibitors for treatment of alzheimer's disease
ATE517861T1 (de) Benzylether und benzylaminoverbindungen als inhibitoren von beta-secretase zur behandlung von alzheimer-krankheit
MA27305A1 (fr) Derives de 7-aryl-3,9-diazabicyclo(3.3.1)non-6-ene et leur utilisation en tant qu'inhibiteurs de renine dans le traitement de l'hypertension, de maladies cardiovasculaires ou renales
MA28680B1 (fr) 3-aminocyclopentanecarboxamides utiles comme modulateurs de récepteurs de chimiokines