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CA2587883A1 - Use of polymer-lipid conjugates in the prevention and treatment of chronic pulmonary disease, allergic rhinitis and asthma - Google Patents

Use of polymer-lipid conjugates in the prevention and treatment of chronic pulmonary disease, allergic rhinitis and asthma Download PDF

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Publication number
CA2587883A1
CA2587883A1 CA002587883A CA2587883A CA2587883A1 CA 2587883 A1 CA2587883 A1 CA 2587883A1 CA 002587883 A CA002587883 A CA 002587883A CA 2587883 A CA2587883 A CA 2587883A CA 2587883 A1 CA2587883 A1 CA 2587883A1
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CA
Canada
Prior art keywords
use according
polysaccharide
glycosaminoglycan
phosphatidylethanolamine
nothing
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.)
Abandoned
Application number
CA002587883A
Other languages
French (fr)
Inventor
Saul Yedgar
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.)
Yissum Research Development Co of Hebrew University of Jerusalem
Original Assignee
Individual
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
Priority claimed from US10/989,606 external-priority patent/US7811999B2/en
Priority claimed from US10/989,607 external-priority patent/US7772196B2/en
Priority claimed from PCT/US2005/006591 external-priority patent/WO2005084307A2/en
Application filed by Individual filed Critical Individual
Publication of CA2587883A1 publication Critical patent/CA2587883A1/en
Abandoned legal-status Critical Current

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Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A61K31/726Glycosaminoglycans, i.e. mucopolysaccharides
    • A61K31/728Hyaluronic acid
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A61K31/737Sulfated polysaccharides, e.g. chondroitin sulfate, dermatan sulfate
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/54Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
    • A61K47/543Lipids, e.g. triglycerides; Polyamines, e.g. spermine or spermidine
    • A61K47/544Phospholipids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/56Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
    • A61K47/61Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule the organic macromolecular compound being a polysaccharide or a derivative thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00Drugs for disorders of the respiratory system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00Drugs for disorders of the respiratory system
    • A61P11/02Nasal agents, e.g. decongestants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00Drugs for disorders of the respiratory system
    • A61P11/06Antiasthmatics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00Drugs for disorders of the senses
    • A61P27/02Ophthalmic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04Antibacterial agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12Antivirals
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • A61P37/02Immunomodulators
    • A61P37/04Immunostimulants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • A61P37/08Antiallergic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00Drugs for disorders of the blood or the extracellular fluid

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pulmonology (AREA)
  • Epidemiology (AREA)
  • Molecular Biology (AREA)
  • Immunology (AREA)
  • Dermatology (AREA)
  • Oncology (AREA)
  • Communicable Diseases (AREA)
  • Neurosurgery (AREA)
  • Virology (AREA)
  • Diabetes (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Hematology (AREA)
  • Biophysics (AREA)
  • Otolaryngology (AREA)
  • Ophthalmology & Optometry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Polysaccharides And Polysaccharide Derivatives (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

This invention provides for the use of a compound comprising a lipid or phospholipid moiety bond to a physiologically acceptable monomer, dimer, oligomer, or polymer, and/or a pharmaceutically acceptable salt or a pharmaceutical product thereof, for the preparation of a composition for treating a subject suffering from asthma, allergic rhinitis, or chronic obstructive pulmonary disease. This invention also provides for the use of a compound comprising a lipid or phospholipid moiety bond to a physiologically acceptable monomer, dimer, oligomer, or polymer, and/or a pharmaceutically acceptable salt or a pharmaceutical product thereof, for the preparation of a composition for preventing asthma, allergic rhinitis, or chronic obstructive pulmonary disease in a subject.

Description

USE OF LIPID

Claims (48)

1. Use of a compound represented by the structure of the general formula (A):
wherein L is a lipid or a phospholipid;
Z is either nothing, ethanolamine, serine, inositol, choline, or glycerol;
Y is either nothing or a spacer group ranging in length from 2 to 30 atoms;
X is a physiologically acceptable monomer, dimer, oligomer, or polymer; and n is a number from 1 to 1000 for the preparation of a composition to treat asthma.
2. The use according to claim 1, wherein X is a polysaccharide.
3. The use according to claim 2, wherein said polysaccharide is carboxymethylcellulose.
4. The use according to claim 2, wherein said polysaccharide is a glycosaminoglycan.
5. The use according to claim 4, wherein said glycosaminoglycan is hyaluronic acid.
6. The use according to claim 4, wherein said glycosaminoglycan is heparin.
7. The use according to claim 1, wherein L is phosphatidylethanolamine.
8. The use according to claim 7, wherein said phosphatidylethanolamine is dipalmitoyl phosphatidylethanolamine.
9. Use of a compound represented by the structure of the general formula (A):

wherein L is a lipid or a phospholipid;
Z is either nothing, ethanolamine, serine, inositol, choline, or glycerol;
Y is either nothing or a spacer group ranging in length from 2 to 30 atoms;
X is a physiologically acceptable monomer, dimer, oligomer, or polymer; and n is a number from 1 to 1000 for the preparation of a composition to prevent asthma.
10. The use according to claim 9, wherein X is a polysaccharide.
11. The use according to claim 10, wherein said polysaccharide is carboxymethylcellulose.
12. The use according to claim 10, wherein said polysaccharide is a glycosaminoglycan.
13. The use according to claim 12, wherein said glycosaminoglycan is hyaluronic acid.
14. The use according to claim 12, wherein said glycosaminoglycan is heparin.
15. The use according to claim 9, wherein L is phosphatidylethanolamine.
16. The use according to claim 15, wherein said phosphatidylethanolamine is dipalmitoyl phosphatidylethanolamine.
17. Use of a compound represented by the structure of the general formula (A):

wherein L is a lipid or a phospholipid;
Z is either nothing, ethanolamine, serine, inositol, choline, or glycerol;
Y is either nothing or a spacer group ranging in length from 2 to 30 atoms;
X is a physiologically acceptable monomer, dimer, oligomer, or polymer; and n is a number from 1 to 1000 for the preparation of a composition to treat allergic rhinitis.
18. The use according to claim 17, wherein X is a polysaccharide.
19. The use according to claim 18, wherein said polysaccharide is carboxymethylcellulose.
20. The use according to claim 18, wherein said polysaccharide is a glycosaminoglycan.
21. The use according to claim 20, wherein said glycosaminoglycan is hyaluronic acid.
22. The use according to claim 20, wherein said glycosarninoglycan is heparin.
23. The use according to claim 17, wherein L is phosphatidylethanolamine.
24. The use according to claim 23, wherein said phosphatidylethanolamine is dipalmitoyl pho sphatidylethanolamine.
25. Use of a compound represented by the structure of the general formula (A):

wherein L is a lipid or a phospholipid;
Z is either nothing, ethanolamine, serine, inositol, choline, or glycerol;
Y is either nothing or a spacer group ranging in length from 2 to 30 atoms;
X is a physiologically acceptable monomer, dimer, oligomer, or polymer; and n is a number from 1 to 1000 for the preparation of a composition to prevent allergic rhinitis.
26. The use according to claim 25, wherein X is a polysaccharide.
27. The use according to claim 26, wherein said polysaccharide is carboxymethylcellulose.
28. The use according to claim 26, wherein said polysaccharide is a glycosaminoglycan.
29. The use according to claim 28, wherein said glycosaminoglycan is hyaluronic acid.
30. The use according to claim 28, wherein said glycosaminoglycan is heparin.
31. The use according to claim 25, wherein L is phosphatidylethanolamine.
32. The use according to claim 31, wherein said phosphatidylethanolamine is dipalmitoyl phosphatidylethanolamine.
33. Use of a compound represented by the structure of the general formula (A):

wherein L is a lipid or a phospholipid;
Z is either nothing, ethanolamine, serine, inositol, choline, or glycerol;
Y is either nothing or a spacer group ranging in length from 2 to 30 atoms;
X is a physiologically acceptable monomer, dimer, oligomer, or polymer; and n is a number from 1 to 1000 for the preparation of a composition to treat chronic obstructive pulmonary disease.
34. The use according to claim 33, wherein X is a polysaccharide.
35. The use according to claim 34, wherein said polysaccharide is carboxymethylcellulose.
36. The use according to claim 34, wherein said polysaccharide is a glycosaminoglycan.
37. The use according to claim 36, wherein said glycosaminoglycan is hyaluronic acid.
38. The use according to claim 36, wherein said glycosaminoglycan is heparin.
39. The use according to claim 33, wherein L is phosphatidylethanolamine.
40. The use according to claim 39, wherein said phosphatidylethanolamine is dipalmitoyl phosphatidylethanolamine.
41. Use of a compound represented by the structure of the general formula (A):

wherein L is a lipid or a phospholipid;
Z is either nothing, ethanolamine, serine, inositol, choline, or glycerol;
Y is either nothing or a spacer group ranging in length from 2 to 30 atoms;
X is a physiologically acceptable monomer, dimer, oligomer, or polymer; and n is a number from 1 to 1000 for the preparation of a composition to prevent chronic obstructive pulmonary disease.
42. The use according to claim 41, wherein X is a polysaccharide.
43. The use according to claim 42, wherein said polysaccharide is carboxymethylcellulose.
44. The use according to claim 42, wherein said polysaccharide is a glycosaminoglycan.
45. The use according to claim 44, wherein said glycosaminoglycan is hyaluronic acid.
46. The use according to claim 44, wherein said glycosaminoglycan is heparin.
47. The use according to claim 41, wherein L is phosphatidylethanolamine.
48. The use according to claim 47, wherein said phosphatidylethanolamine is dipalmitoyl phosphatidylethanolamine.
CA002587883A 2004-11-17 2005-11-17 Use of polymer-lipid conjugates in the prevention and treatment of chronic pulmonary disease, allergic rhinitis and asthma Abandoned CA2587883A1 (en)

Applications Claiming Priority (7)

Application Number Priority Date Filing Date Title
US10/989,606 2004-11-17
US10/989,606 US7811999B2 (en) 2000-01-10 2004-11-17 Use of lipid conjugates in the treatment of diseases
US10/989,607 2004-11-17
US10/989,607 US7772196B2 (en) 2000-01-10 2004-11-17 Use of lipid conjugates in the treatment of diseases
USPCT/US2005/006591 2005-03-02
PCT/US2005/006591 WO2005084307A2 (en) 2004-03-02 2005-03-02 Use of lipid conjugates in the treatment of disease
PCT/IL2005/001225 WO2006054304A2 (en) 2004-11-17 2005-11-17 Use of lipid conjugates in the treatment of disease

Publications (1)

Publication Number Publication Date
CA2587883A1 true CA2587883A1 (en) 2006-05-26

Family

ID=39619055

Family Applications (1)

Application Number Title Priority Date Filing Date
CA002587883A Abandoned CA2587883A1 (en) 2004-11-17 2005-11-17 Use of polymer-lipid conjugates in the prevention and treatment of chronic pulmonary disease, allergic rhinitis and asthma

Country Status (10)

Country Link
EP (1) EP1819345A4 (en)
JP (2) JP2008520650A (en)
CN (1) CN101175499B (en)
AU (1) AU2005305456B2 (en)
BR (1) BRPI0516810A (en)
CA (1) CA2587883A1 (en)
EA (1) EA012138B1 (en)
IL (3) IL183227A0 (en)
MX (1) MX2007005975A (en)
WO (1) WO2006054304A2 (en)

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20090325876A1 (en) * 2004-09-29 2009-12-31 Saul Yedgar Use of lipid conjugates in the treatment of diseases associated with vasculature
WO2010132402A1 (en) * 2009-05-11 2010-11-18 Morria Biopharmaceuticals, Inc Lipid-polymer conjugates, their preparation and uses thereof
US20100035843A1 (en) * 2007-02-12 2010-02-11 The General Hospital Corporation Methods for attenuating allergen-induced airway hyperreactivity using cd1d dependent antagonists
WO2014070769A1 (en) 2012-10-29 2014-05-08 The University Of North Carolina At Chapel Hill Methods and compositions for treating mucosal tissue disorders
WO2015005459A1 (en) * 2013-07-10 2015-01-15 生化学工業株式会社 Pharmaceutical composition for respiratory administration
EP4292651A3 (en) * 2016-06-27 2024-03-13 Ohio State Innovation Foundation Liponucleotide-based therapy for ards
NZ753749A (en) 2016-11-17 2025-10-31 Renovion Inc Treatment of respiratory tract diseases and infections with glutathione compositions
PT3710036T (en) 2017-11-17 2025-01-22 Renovion Inc Stable ascorbic acid compositions and methods of using the same
AU2023205178B2 (en) 2022-01-04 2025-09-25 Renovion, Inc. Aqueous solution comprising a glutathione salt

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IL84252A (en) * 1987-10-23 1994-02-27 Yissum Res Dev Co Phospholipase inhibiting compositions
JPH0232013A (en) * 1988-07-20 1990-02-01 Denki Kagaku Kogyo Kk Nasal drop
US6022866A (en) * 1991-07-03 2000-02-08 Hyal Pharmaceutical Corporation Use of hyaluronic acid and forms to prevent arterial restenosis
ES2044781B1 (en) * 1992-04-14 1994-10-01 Menarini Lab PROCEDURE FOR THE PREPARATION OF NEW AMIDES WITH PHOSPHOLIPASE A2 INHIBITING ACTION
JP3714683B2 (en) * 1992-07-30 2005-11-09 生化学工業株式会社 Anti-rheumatic agent
EP0785773B1 (en) * 1994-10-14 2001-01-03 The Liposome Company, Inc. Ether lipid liposomes and their therapeutic use
US6180596B1 (en) * 1995-05-18 2001-01-30 Wisconsin Alumni Research Foundation Methods of inhibiting phospholipase A2 and phospholipase A2 stimulator activities
US6071532A (en) * 1996-10-15 2000-06-06 Emory University Synthesis of glycophospholipid and peptide-phospholipid conjugates and uses thereof
JPH11147901A (en) * 1997-11-19 1999-06-02 Maruho Co Ltd Kallikrein-kinin system inhibitor
US6162787A (en) * 1999-04-02 2000-12-19 Immudyne, Inc. Methods for treating arthritis using collagen type II, glucosamine chondroitin sulfate, and compositions
US7141552B2 (en) * 2000-01-10 2006-11-28 Yissum Research Development Company Of The Hebrew University Of Jerusalem Use of lipid conjugates in the treatment of diseases
US7101859B2 (en) * 2000-01-10 2006-09-05 Yissum Research Development Company Of The Hebrew University Of Jerusalem Use of lipid conjugates in the treatment of diseases
EP2845596A3 (en) * 2000-01-10 2015-07-15 Yissum Research Development Company of the Hebrew University of Jerusalem Ltd. Use of lipid conjugates in the treatment of disease

Also Published As

Publication number Publication date
JP2008520650A (en) 2008-06-19
WO2006054304A3 (en) 2007-01-25
EA012138B1 (en) 2009-08-28
EP1819345A4 (en) 2012-04-18
WO2006054304A2 (en) 2006-05-26
JP2012001559A (en) 2012-01-05
BRPI0516810A (en) 2008-09-23
CN101175499A (en) 2008-05-07
IL212214A0 (en) 2011-06-30
MX2007005975A (en) 2007-10-08
AU2005305456B2 (en) 2011-05-19
IL212215A0 (en) 2011-06-30
EA200701077A1 (en) 2008-04-28
CN101175499B (en) 2010-12-22
AU2005305456A1 (en) 2006-05-26
EP1819345A2 (en) 2007-08-22
IL183227A0 (en) 2007-08-19

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Effective date: 20140604