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WO1992019237A1 - Utilisation d'un lipide pour l'elaboration d'une preparation pharmaceutique enterale destinee au traitement de la malabsorption des lipides. - Google Patents

Utilisation d'un lipide pour l'elaboration d'une preparation pharmaceutique enterale destinee au traitement de la malabsorption des lipides. Download PDF

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Publication number
WO1992019237A1
WO1992019237A1 PCT/DK1992/000150 DK9200150W WO9219237A1 WO 1992019237 A1 WO1992019237 A1 WO 1992019237A1 DK 9200150 W DK9200150 W DK 9200150W WO 9219237 A1 WO9219237 A1 WO 9219237A1
Authority
WO
WIPO (PCT)
Prior art keywords
lipid
mlm
lipids
type
malabsorption
Prior art date
Application number
PCT/DK1992/000150
Other languages
English (en)
Inventor
Tomas Tage Hansen
Anette MÜLLERTZ
Original Assignee
Novo Nordisk A/S
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 Novo Nordisk A/S filed Critical Novo Nordisk A/S
Priority to JP4509155A priority Critical patent/JPH06507161A/ja
Publication of WO1992019237A1 publication Critical patent/WO1992019237A1/fr

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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
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
    • A61K31/23—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics

Definitions

  • the invention comprises a new use of a lipid of a specified kind.
  • the lipid in question is of the type MLM and/or SLS.
  • L which represents a long chain acyl radical, is an acyl radical with 14-24 C atoms, e.g. palmitoyi (CH 3 (CH 2 ) 14 CO-)
  • M which represents a medium chain acyl radical, is an acyl radical with 6-13 C atoms, e.g. pelargoyl (CH 3 (CH 2 ) 7 CO-)
  • S which represents a short chain acyl radical, is an acyl radical with 2-5 C atoms, e.g. valeroyl (CH 3 (CH 2 ) 3 CO-). It is understood that a lipid of the type MLM can be represented as
  • enteral emulsions of lipids of the above indicated type are described, and likewise their use for nutritional purposes. Also, it is described that enteral emulsions of the above indicated type can be used as nutrition for seriously ill patients.
  • the purpose of the invention is to provide other uses for lipids of the above indicated type.
  • the lipids of the above indicated type can be used for treatment of patients with lipid malabsorption, e.g. patients suffering from pancreatic insufficiency, primary biliary cirrhosis or cystic fibrosis, i.e. that those lipids can be used for patients suffering from lipid malabsorption.
  • lipid malabsorption e.g. patients suffering from pancreatic insufficiency, primary biliary cirrhosis or cystic fibrosis, i.e. that those lipids can be used for patients suffering from lipid malabsorption.
  • One category of patients with lipid malabsorption has reduced capability in regard to secretion of pancreatic lipase, which is responsible for the major part of triglyceride hydrolysis in the gut.
  • pancreatic lipase which is responsible for the major part of triglyceride hydrolysis in the gut.
  • Structured lipids of the MLM type is easier hydrolyzed by pancreatic lipase (vide Example 1 ), meaning that even at a very low activity of pancreatic lipase, as in patients suffering from pancreatic insufficiency, the structured lipids of the MLM type will be hydrolyzed, and the formed 2- monoglycerides will be absorbed. It appears from Example 2 that feeding MLM to a pancreatic insufficient pig leads to as much lipid absorption as when feeding soy oil to a pancreatic sufficient pig. A study of pancreatic insufficient rats (vide E ⁇ xample 3) has shown that the total lipid absorption is greater when provided as structured MLM than as randomized MLM or a physical mixture of the corresponding lipids.
  • the content of the essential fatty acid linoleic acid in the lymph was higher in the MLM group, meaning that the total absorption of linoleic acid was higher.
  • the MLM also provides essential fatty acids for the functions of the cell, including formation of membrane lipids and intracellular mediators, e.g. eicosanoids.
  • these results indicate that MLM can be absorbed through the gut mucosa without prior hydrolysis.
  • the use according to the invention of a lipid of the type MLM and/or SLS is for production of a pharmaceutical preparation for treatment of lipid malabsorption.
  • the lipid related to the use according to the invention can be formulated as a part of a dressing or an oil incorporated in the diet or as a part of an emulsion. Typically the lipid should be administered in an amount of 0.5-4.5 g per kg of body weight per day.
  • the use according to the invention relates to lipid malabsorption in both humans and animals.
  • lipid of the type MLM and/or SLS is for patients suffering from lipid malabsorption.
  • the lipid contains more than 20% of lipids of the type MLM. This type of lipid is easily absorbed in the gut. In a preferred embodiment of the use according to the invention the lipid contains more than 10% of lipids of the type SLS. This type of lipid is easily absorbed in the gut.
  • the 5 preparation is formulated as an enteral formulation.
  • lipids of the type MLM or SLS are described, and so are their use as a nutritional agent, and also, use of lipids for treatment of lipid malabsorption are described, but not in relation to lipids of the type MLM or SLS; in particular WO-A-8,902,275 (New England Deaconess Hospital Corp.),
  • Lipids for enteral nutrition of the type LLL can only be absorbed with difficulty by patients suffering from lipid malabsorption. Lipids for enteral nutrition of the type LLL can only be absorbed with difficulty by patients suffering from lipid malabsorption. Lipids for enteral nutrition of
  • MMM cell membranes in the body.
  • the absorption of MMM might be due to a smaller molecular weight and a more compact structure and also a facilitated diffusion across the unstirred water layer of the gut, compared to long chain triglycerides.
  • the lipids of the above indicated type can be absorbed in individuals suffering from pancreatic insufficiency, thus providing essential fatty acids.
  • Lipid emulsions (50 ml) were prepared from 5 ml of lipid, 41 ml of gum arabic (10% w/v) and 4 ml of water and emulsified with Ultra Turrax 3 x 5 minutes at 4°C. The particle size distribution was measured microscopically before and after the titrations.
  • Fig. 2 shows the total lymphatic output.
  • the absorption peak is seen 5 hours after dosage, which is later than when pancreatic lipase and bile is present. After the peak the absorption of MLM continues at a higher level than the two other lipids. This leads to a higher total absorption of MLM.
  • the content of the essential fatty acid linoleic acid in the lymph fractions is shown in Fig. 3.
  • the content of linoleic acid is at a significantly higher level in the MLM group than in the two other groups.
  • the total absorption of linoleic acid is higher in the MLM group.

Landscapes

  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Emergency Medicine (AREA)
  • Epidemiology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

Le lipide a la/les formules (I) et/ou (II) où L est un radical acyle à chaîne longue, M est un radical acyle à chaîne moyenne et S est un radical acide à chaîne courte. Ce lipide peut être employé avec succès pour l'élaboration d'une préparation pharmaceutique destinée au traitement de l'insuffisance pancréatique, de la cirrhose biliaire primaire ou de la fibrose cystique.
PCT/DK1992/000150 1991-05-08 1992-05-08 Utilisation d'un lipide pour l'elaboration d'une preparation pharmaceutique enterale destinee au traitement de la malabsorption des lipides. WO1992019237A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP4509155A JPH06507161A (ja) 1991-05-08 1992-05-08 脂質吸収不良の治療用経腸医薬製剤の製造のための脂質の使用

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP91610043 1991-05-08
BE91610043.1 1991-05-08

Publications (1)

Publication Number Publication Date
WO1992019237A1 true WO1992019237A1 (fr) 1992-11-12

Family

ID=8208778

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/DK1992/000150 WO1992019237A1 (fr) 1991-05-08 1992-05-08 Utilisation d'un lipide pour l'elaboration d'une preparation pharmaceutique enterale destinee au traitement de la malabsorption des lipides.

Country Status (3)

Country Link
EP (1) EP0583337A1 (fr)
JP (1) JPH06507161A (fr)
WO (1) WO1992019237A1 (fr)

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0577371A2 (fr) * 1992-06-29 1994-01-05 Fuji Oil Company, Limited Matière première contenant de l'huile de la graisse et résistant au gel, procédé de fabrication de cette matière première et aliments congelés la renfermant
WO1994024889A1 (fr) * 1993-04-23 1994-11-10 Loders Croklaan B.V. Matieres grasses alimentaires a digestibilite amelioree
WO1994026855A1 (fr) * 1993-05-13 1994-11-24 Loders-Croklaan Succedanes de matieres grasses de lait obtenus a partir de melanges interesterifies de triglycerides
US5503855A (en) * 1992-06-29 1996-04-02 Fuji Oil Company, Limited Freezing-resistant oil-and-fat feedstock, method for producing said feedstock and frozen food containing said feedstock
US6013665A (en) * 1997-12-16 2000-01-11 Abbott Laboratories Method for enhancing the absorption and transport of lipid soluble compounds using structured glycerides
US6827963B2 (en) 2001-12-28 2004-12-07 The Nisshin Oillio, Ltd. Fats and oils composition for reducing lipids in blood
WO2010149170A1 (fr) * 2009-06-24 2010-12-29 Københavns Universitet Traitement de l'insulinorésistance et de l'obésité par la stimulation de la libération de glp-1

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4528197A (en) * 1983-01-26 1985-07-09 Kabivitrum Ab Controlled triglyceride nutrition for hypercatabolic mammals
US4607052A (en) * 1983-04-15 1986-08-19 Roussel-Uclaf Triglycerides, dietetic and therapeutical applications and compositions containing them
US4847296A (en) * 1984-09-13 1989-07-11 Babayan Vigen K Triglyceride preparations for the prevention of catabolism
WO1990012080A1 (fr) * 1989-04-07 1990-10-18 New England Deaconess Hospital Corporation Triglycerides a chaîne courte

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4528197A (en) * 1983-01-26 1985-07-09 Kabivitrum Ab Controlled triglyceride nutrition for hypercatabolic mammals
US4607052A (en) * 1983-04-15 1986-08-19 Roussel-Uclaf Triglycerides, dietetic and therapeutical applications and compositions containing them
US4847296A (en) * 1984-09-13 1989-07-11 Babayan Vigen K Triglyceride preparations for the prevention of catabolism
WO1990012080A1 (fr) * 1989-04-07 1990-10-18 New England Deaconess Hospital Corporation Triglycerides a chaîne courte

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
Dialog Information Services, File 155, Medline 66-90/May, Accession No. 06312169, Medline Accession No. 87286169, RAHAYAN V.K.: "Medium chain triglycerides and structured lipids", & Lipids Jun 1987, 22 (6) p417-20. *
Dialog Information Services, File 155, Medline 66-90/May, Accession No. 07856234, Medline Accession No. 91375234, TAKEDA I. et al.: "Lymphatic absorption of structured glycerolipids containing medium-chain fatty acids and linoleic acid, and their effect on cholesterol absorption in rats", & Lipids May 1991; 26 (5) p369-73. *

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0577371A2 (fr) * 1992-06-29 1994-01-05 Fuji Oil Company, Limited Matière première contenant de l'huile de la graisse et résistant au gel, procédé de fabrication de cette matière première et aliments congelés la renfermant
EP0577371A3 (fr) * 1992-06-29 1994-12-07 Fuji Oil Co Ltd Matière première contenant de l'huile de la graisse et résistant au gel, procédé de fabrication de cette matière première et aliments congelés la renfermant.
US5503855A (en) * 1992-06-29 1996-04-02 Fuji Oil Company, Limited Freezing-resistant oil-and-fat feedstock, method for producing said feedstock and frozen food containing said feedstock
WO1994024889A1 (fr) * 1993-04-23 1994-11-10 Loders Croklaan B.V. Matieres grasses alimentaires a digestibilite amelioree
US5681608A (en) * 1993-04-23 1997-10-28 Loders Croklaan B.V. Nutrient fats having improved digestibility
WO1994026855A1 (fr) * 1993-05-13 1994-11-24 Loders-Croklaan Succedanes de matieres grasses de lait obtenus a partir de melanges interesterifies de triglycerides
US6013665A (en) * 1997-12-16 2000-01-11 Abbott Laboratories Method for enhancing the absorption and transport of lipid soluble compounds using structured glycerides
US6160007A (en) * 1997-12-16 2000-12-12 Abbott Laboratories Method for enhancing the absorption and transport of lipid soluble compounds using structured glycerides
US6827963B2 (en) 2001-12-28 2004-12-07 The Nisshin Oillio, Ltd. Fats and oils composition for reducing lipids in blood
WO2010149170A1 (fr) * 2009-06-24 2010-12-29 Københavns Universitet Traitement de l'insulinorésistance et de l'obésité par la stimulation de la libération de glp-1

Also Published As

Publication number Publication date
EP0583337A1 (fr) 1994-02-23
JPH06507161A (ja) 1994-08-11

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