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WO1994008603A1 - Compositions - Google Patents

Compositions Download PDF

Info

Publication number
WO1994008603A1
WO1994008603A1 PCT/US1993/009915 US9309915W WO9408603A1 WO 1994008603 A1 WO1994008603 A1 WO 1994008603A1 US 9309915 W US9309915 W US 9309915W WO 9408603 A1 WO9408603 A1 WO 9408603A1
Authority
WO
WIPO (PCT)
Prior art keywords
fatty acyl
hlb surfactant
chain fatty
long
composition
Prior art date
Application number
PCT/US1993/009915
Other languages
English (en)
Inventor
Panayiotis Pericleous Constantinides
Original Assignee
Smithkline Beecham Corporation
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 Smithkline Beecham Corporation filed Critical Smithkline Beecham Corporation
Priority to EP93923917A priority Critical patent/EP0671929A4/fr
Priority to JP6510316A priority patent/JPH08502490A/ja
Publication of WO1994008603A1 publication Critical patent/WO1994008603A1/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/22—Hormones
    • A61K38/25—Growth hormone-releasing factor [GH-RF], i.e. somatoliberin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/39—Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin, cold insoluble globulin [CIG]
    • 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
    • A61K9/10—Dispersions; Emulsions
    • A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
    • A61K9/1075—Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers

Definitions

  • long-chain fatty acyl refers to a fatty acyl moiety which may be saturated, mono-unsaturated or poly-unsaturated, having from 14 to 22, preferably 14 to 18, carbon atoms which may be branched or unbranched, preferably unbranched, and which may be optionally substituted.
  • the blend of low and high HLB surfactants will have an HLB value in the range of from about 7 to about 15.
  • the present invention provides compositions in the form of microemulsions comprising a peptide which may be orally admimstered and which will retain biological activity, thereby overcoming the disadvantages of earlier formulations in which the bioavailability of the peptide has been less than satisfactory.
  • the present invention provides compositions which by their nature permit the preparation and administration of a peptide in sufficiently high concentration to allow not only convenient oral administration but also adequate bioavailability of the peptide.
  • compositions of the present invention may be avoided.
  • a mono- or polyhydroxyalcohol co-surfactant such as ethanol, butanol or propylene glycol
  • the hydrophilic phase of compositions of the present invention may be essentially aqueous and comprise less than 10%, preferrably less than 5% and more preferrably less than 2% by weight of the phase of an alcohol.
  • microemulsions were generally formulated by initially preparing die drug- containing hydrophilic phase, either by dissolving the appropriate amount of drug in the appropriate amount of saline solution or, more preferably, using a stock solution which was then further diluted if so required, with vortex stirring if necessary to obtain complete dissolution.
  • the hydrophilic phase containing the drug was then added to die appropriate amounts (by weight) of a mixture of the oil and die low HLB surfactant, to which was then added die high HLB surfactant, with gentle stirring (magnetic hot plate stirrer).
  • the hydrophilic phase containing d e drug was added to die high HLB surfactant and following upon complete mixing, this was added to the oil plus low HLB surfactant mixture.
  • the drug-containing microemulsion was then diluted witii die corresponding drug-free microemulsion to adjust the concentration of die drug.
  • Suitable rats for use in diis assement are male Sprague-Dawley (Caesarian Delivery - Virus Antibody Free; Charles River Laboratories). The rats are fasted overnight the day before the experiment. Dosing with the microemulsion at the desired dose is done by gavage at a volume not exceeding 10 ml/kg. Upon termination of die experiment animals are euthanized with asphyxiation using carbon dioxide and exsanguinated. Abdominal incisions are then performed and gross observations of the gastric and duodenal mucosa are made at naked eyes and under a microscope (Nikon model SMZ-10 binocular microscope).
  • a 0.2 ml blood sample is obtained via jugular catheter at the following intervals: -15, 0, 5, 10, 15, 30, 45, 60, 90, and 120 minutes. Blood samples are stored on ice and subsequently analyzed for Growth Hormone by an RIA method.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • Engineering & Computer Science (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Zoology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Immunology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Endocrinology (AREA)
  • Dispersion Chemistry (AREA)
  • Molecular Biology (AREA)
  • Biomedical Technology (AREA)
  • Biophysics (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

On décrit des compositions qui comprennent un triglycéride interestérifié; un agent tensio-actif à équilibre hydrophile-lipophile bas qui est un mono- et/ou un diglycéride d'acyle gras à chaîne moyenne ou longue, un ester d'acide gras à longue chaîne de sorbitan ou certains de leurs mélanges; un agent tensio-acitf à équilibre hydrophile-lipophile élevé; une phase hydrophile aqueuse; et un agent thérapeutique hydrosoluble, qui forment lors de leur mélange une micro-émulsion huileuse auto-émulsifiante et stable.
PCT/US1993/009915 1992-10-16 1993-10-15 Compositions WO1994008603A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
EP93923917A EP0671929A4 (fr) 1992-10-16 1993-10-15 Compositions.
JP6510316A JPH08502490A (ja) 1992-10-16 1993-10-15 組成物

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US96295692A 1992-10-16 1992-10-16
US07/962,956 1992-10-16

Publications (1)

Publication Number Publication Date
WO1994008603A1 true WO1994008603A1 (fr) 1994-04-28

Family

ID=25506551

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1993/009915 WO1994008603A1 (fr) 1992-10-16 1993-10-15 Compositions

Country Status (3)

Country Link
EP (1) EP0671929A4 (fr)
JP (1) JPH08502490A (fr)
WO (1) WO1994008603A1 (fr)

Cited By (27)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5444041A (en) * 1991-04-19 1995-08-22 Ibah, Inc. Convertible microemulsion formulations
US5583105A (en) * 1994-11-21 1996-12-10 Biogal Gyogyszerguar Rt Oral pharmaceutical preparation
EP0753311A1 (fr) * 1993-04-19 1997-01-15 Institute For Advanced Skin Research Inc. Preparation en microemulsion contenant une substance difficilement absorbable
EP0799620A1 (fr) * 1996-04-03 1997-10-08 Research Triangle Pharmaceuticals Ltd. Emulsions à base de cyclosporine
US5688761A (en) * 1991-04-19 1997-11-18 Lds Technologies, Inc. Convertible microemulsion formulations
WO1998000169A1 (fr) * 1996-07-02 1998-01-08 Cortecs (Uk) Limited) Preparations hydrophobes contenant des monoglycerides de chaine moyenne
WO1999053941A1 (fr) * 1998-04-15 1999-10-28 Shionogi & Co., Ltd. Preparations orales contenant des derives de trh
US6008228A (en) * 1995-06-06 1999-12-28 Hoffman-La Roche Inc. Pharmaceutical compositions containing proteinase inhibitors
US6187993B1 (en) 1995-02-25 2001-02-13 Imperial Cancer Research Technology Limited Transgenic animals as model of psoriasis
WO2001034111A1 (fr) * 1999-11-08 2001-05-17 The Procter & Gamble Company Compositions cosmetiques
US6284268B1 (en) 1997-12-10 2001-09-04 Cyclosporine Therapeutics Limited Pharmaceutical compositions containing an omega-3 fatty acid oil
US6531139B1 (en) * 1997-07-29 2003-03-11 Pharmacia & Upjohn Company Self-emulsifying formulation for lipophilic compounds
WO2003051385A1 (fr) * 2001-12-14 2003-06-26 Jagotec Ag Formulation pharmaceutique contenant de la ciclosporine et son utilisation
US6720001B2 (en) * 1999-10-18 2004-04-13 Lipocine, Inc. Emulsion compositions for polyfunctional active ingredients
KR100508695B1 (ko) * 2001-02-13 2005-08-17 한국과학기술연구원 인슐린의 경구투여용 제형과 그의 제조방법
US6979456B1 (en) 1998-04-01 2005-12-27 Jagotec Ag Anticancer compositions
WO2006024095A1 (fr) 2004-08-31 2006-03-09 Connetics Australia Pty Ltd Procede et compositions a base de microemulsion & émulsion submicronique
US7060672B2 (en) 2001-10-19 2006-06-13 Isotechnika, Inc. Cyclosporin analog formulations
US8802087B2 (en) 2004-03-22 2014-08-12 Abbott Products Gmbh Pharmaceutical compositions of lipase-containing products, in particular of pancreation
US9198871B2 (en) 2005-08-15 2015-12-01 Abbott Products Gmbh Delayed release pancreatin compositions
EP3104841A4 (fr) * 2014-02-14 2017-09-06 Jingjun Huang Compositions de systèmes de distribution de nano-émulsion
EP3177262A4 (fr) * 2014-08-08 2018-04-18 Novan Inc. Émulsions topiques
US10072256B2 (en) 2006-05-22 2018-09-11 Abbott Products Gmbh Process for separating and determining the viral load in a pancreatin sample
US10226483B2 (en) 2013-08-08 2019-03-12 Novan, Inc. Topical compositions and methods of using the same
US10704037B2 (en) 2005-07-29 2020-07-07 Abbott Products Gmbh Processes for the manufacture and use of pancreatin
US10912743B2 (en) 2016-03-02 2021-02-09 Novan, Inc. Compositions for treating inflammation and methods of treating the same
US11266607B2 (en) 2005-08-15 2022-03-08 AbbVie Pharmaceuticals GmbH Process for the manufacture and use of pancreatin micropellet cores

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20110144010A1 (en) * 2007-06-01 2011-06-16 Novo Nordisk A/S Spontaneously Dispersible Preconcentrates Including a Peptide Drug in a Solid or Semisolid Carrier
BRPI0910348B1 (pt) 2008-03-18 2021-06-29 Novo Nordisk A/S Insulina estabilizada em protease acilada, composição farmacêutica compreendendo a mesma e seus usos
KR20150002777A (ko) 2012-04-11 2015-01-07 노보 노르디스크 에이/에스 인슐린 제제
US20180169190A1 (en) 2016-12-16 2018-06-21 Novo Nordisk A/S Insulin containing pharmaceutical compositions

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3876765A (en) * 1968-05-03 1975-04-08 Choay Sa Pharmaceutical composition containing vitamin b' 12', process of making the same and method of treatment therewith

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4146499A (en) * 1976-09-18 1979-03-27 Rosano Henri L Method for preparing microemulsions
IE60024B1 (en) * 1987-02-03 1994-05-18 Stiefel Laboratories Ltd Microemulsions
DE3908047A1 (de) * 1989-03-13 1990-09-20 Desitin Arzneimittel Gmbh Hochdisperse pharmazeutische zusammensetzung
JPH06511419A (ja) * 1990-06-08 1994-12-22 アフィニティー　バイオテック，インコーポレイテッド ミクロエマルジョンを製造する方法
DE69229779T2 (de) * 1991-04-19 1999-12-23 Lds Technologies, Inc. Konvertierbare mikroemulsionsverbindungen
ATE144137T1 (de) * 1991-07-26 1996-11-15 Smithkline Beecham Corp W/o mikroemulsionen
JPH06509577A (ja) * 1991-07-26 1994-10-27 スミスクライン・ビーチャム・コーポレイション Ｗ／ｏミクロエマルジョン

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3876765A (en) * 1968-05-03 1975-04-08 Choay Sa Pharmaceutical composition containing vitamin b' 12', process of making the same and method of treatment therewith

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See also references of EP0671929A4 *

Cited By (41)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5633226A (en) * 1991-04-19 1997-05-27 Lds Technologies, Inc. Convertible microemulsion formulations
US5646109A (en) * 1991-04-19 1997-07-08 Lds Technologies, Inc. Convertible microemulsion formulations
US5444041A (en) * 1991-04-19 1995-08-22 Ibah, Inc. Convertible microemulsion formulations
US5688761A (en) * 1991-04-19 1997-11-18 Lds Technologies, Inc. Convertible microemulsion formulations
US5948825A (en) * 1993-04-19 1999-09-07 Institute For Advanced Skin Research Inc. Microemulsion preparation containing a slightly absorbable substance
EP0753311A1 (fr) * 1993-04-19 1997-01-15 Institute For Advanced Skin Research Inc. Preparation en microemulsion contenant une substance difficilement absorbable
EP0753311A4 (fr) * 1993-04-19 1997-05-21 Inst Advanced Skin Res Inc Preparation en microemulsion contenant une substance difficilement absorbable
US5583105A (en) * 1994-11-21 1996-12-10 Biogal Gyogyszerguar Rt Oral pharmaceutical preparation
US6187993B1 (en) 1995-02-25 2001-02-13 Imperial Cancer Research Technology Limited Transgenic animals as model of psoriasis
US6008228A (en) * 1995-06-06 1999-12-28 Hoffman-La Roche Inc. Pharmaceutical compositions containing proteinase inhibitors
EP0799620A1 (fr) * 1996-04-03 1997-10-08 Research Triangle Pharmaceuticals Ltd. Emulsions à base de cyclosporine
WO1998000169A1 (fr) * 1996-07-02 1998-01-08 Cortecs (Uk) Limited) Preparations hydrophobes contenant des monoglycerides de chaine moyenne
US6258377B1 (en) 1996-07-02 2001-07-10 Provalis Uk Limited Hydrophobic preparations containing medium chain monoglycerides
US6531139B1 (en) * 1997-07-29 2003-03-11 Pharmacia & Upjohn Company Self-emulsifying formulation for lipophilic compounds
US6284268B1 (en) 1997-12-10 2001-09-04 Cyclosporine Therapeutics Limited Pharmaceutical compositions containing an omega-3 fatty acid oil
US6979456B1 (en) 1998-04-01 2005-12-27 Jagotec Ag Anticancer compositions
WO1999053941A1 (fr) * 1998-04-15 1999-10-28 Shionogi & Co., Ltd. Preparations orales contenant des derives de trh
US6720001B2 (en) * 1999-10-18 2004-04-13 Lipocine, Inc. Emulsion compositions for polyfunctional active ingredients
WO2001034111A1 (fr) * 1999-11-08 2001-05-17 The Procter & Gamble Company Compositions cosmetiques
KR100508695B1 (ko) * 2001-02-13 2005-08-17 한국과학기술연구원 인슐린의 경구투여용 제형과 그의 제조방법
US7060672B2 (en) 2001-10-19 2006-06-13 Isotechnika, Inc. Cyclosporin analog formulations
US7429562B2 (en) 2001-10-19 2008-09-30 Isotechnika Inc. Cyclosporin analog formulations
US8568748B2 (en) 2001-12-14 2013-10-29 Jagotec Ag Pharmaceutical formulation comprising cyclosporin and use thereof
WO2003051385A1 (fr) * 2001-12-14 2003-06-26 Jagotec Ag Formulation pharmaceutique contenant de la ciclosporine et son utilisation
AU2002231703B2 (en) * 2001-12-14 2007-03-29 Jagotec Ag Pharmaceutical formulation comprising cyclosporin and use thereof
CN100360175C (zh) * 2001-12-14 2008-01-09 杰格特克公司 包含环孢菌素的药物制剂及其用途
CZ302649B6 (cs) * 2001-12-14 2011-08-17 Jagotec Ag Farmaceutická formulace zahrnující cyklosporin a její použití
US8802087B2 (en) 2004-03-22 2014-08-12 Abbott Products Gmbh Pharmaceutical compositions of lipase-containing products, in particular of pancreation
WO2006024095A1 (fr) 2004-08-31 2006-03-09 Connetics Australia Pty Ltd Procede et compositions a base de microemulsion & émulsion submicronique
EP2438910A1 (fr) 2004-08-31 2012-04-11 Stiefel Research Australia Pty Ltd Procédé et compositions de micro-émulsion et d'émulsion submicronique
US10704037B2 (en) 2005-07-29 2020-07-07 Abbott Products Gmbh Processes for the manufacture and use of pancreatin
US9198871B2 (en) 2005-08-15 2015-12-01 Abbott Products Gmbh Delayed release pancreatin compositions
US11266607B2 (en) 2005-08-15 2022-03-08 AbbVie Pharmaceuticals GmbH Process for the manufacture and use of pancreatin micropellet cores
US10072256B2 (en) 2006-05-22 2018-09-11 Abbott Products Gmbh Process for separating and determining the viral load in a pancreatin sample
US10828323B2 (en) 2013-08-08 2020-11-10 Novan, Inc. Topical compositions and methods of using the same
US10226483B2 (en) 2013-08-08 2019-03-12 Novan, Inc. Topical compositions and methods of using the same
US10206947B2 (en) 2013-08-08 2019-02-19 Novan, Inc. Topical compositions and methods of using the same
US11813284B2 (en) 2013-08-08 2023-11-14 Novan, Inc. Topical compositions and methods of using the same
EP3104841A4 (fr) * 2014-02-14 2017-09-06 Jingjun Huang Compositions de systèmes de distribution de nano-émulsion
EP3177262A4 (fr) * 2014-08-08 2018-04-18 Novan Inc. Émulsions topiques
US10912743B2 (en) 2016-03-02 2021-02-09 Novan, Inc. Compositions for treating inflammation and methods of treating the same

Also Published As

Publication number Publication date
EP0671929A1 (fr) 1995-09-20
JPH08502490A (ja) 1996-03-19
EP0671929A4 (fr) 1996-09-25

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