CA2358505A1 - Novel hydrogel isolated cochleate formulations, process of preparation and their use for the delivery of biologically relevant molecules - Google Patents

Novel hydrogel isolated cochleate formulations, process of preparation and their use for the delivery of biologically relevant molecules Download PDF

Info

Publication number
CA2358505A1
CA2358505A1 CA002358505A CA2358505A CA2358505A1 CA 2358505 A1 CA2358505 A1 CA 2358505A1 CA 002358505 A CA002358505 A CA 002358505A CA 2358505 A CA2358505 A CA 2358505A CA 2358505 A1 CA2358505 A1 CA 2358505A1
Authority
CA
Canada
Prior art keywords
cochleates
polymer
lipid
biologically relevant
molecule
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.)
Granted
Application number
CA002358505A
Other languages
French (fr)
Other versions
CA2358505C (en
Inventor
Leila Zarif
Tuo Jin
Ignacio Segarra
Raphael Mannino
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 Medicine and Dentistry of New Jersey
Biodelivery Sciences Inc
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
Application filed by Individual filed Critical Individual
Publication of CA2358505A1 publication Critical patent/CA2358505A1/en
Application granted granted Critical
Publication of CA2358505C publication Critical patent/CA2358505C/en
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

Links

Classifications

    • 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
    • A61K9/127—Liposomes
    • A61K9/1274—Non-vesicle bilayer structures, e.g. liquid crystals, tubules, cubic phases, cochleates; Sponge phases
    • 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
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A61K31/07—Retinol compounds, e.g. vitamin A
    • 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
    • A61K31/11—Aldehydes
    • 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
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
    • 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
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/472—Non-condensed isoquinolines, e.g. papaverine
    • 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
    • A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene
    • 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
    • A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
    • A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
    • A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
    • 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
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
    • 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
    • A61K31/7088—Compounds having three or more nucleosides or nucleotides
    • A61K31/713—Double-stranded nucleic acids or oligonucleotides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/54—Lauraceae (Laurel family), e.g. cinnamon or sassafras
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/12—Cyclic peptides, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C
    • A61K38/13—Cyclosporins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P23/00—Anaesthetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/20—Hypnotics; Sedatives
    • 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
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/10—Antimycotics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • 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
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S436/00—Chemistry: analytical and immunological testing
    • Y10S436/829—Liposomes, e.g. encapsulation
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T428/00—Stock material or miscellaneous articles
    • Y10T428/29—Coated or structually defined flake, particle, cell, strand, strand portion, rod, filament, macroscopic fiber or mass thereof
    • Y10T428/2982—Particulate matter [e.g., sphere, flake, etc.]
    • Y10T428/2984—Microcapsule with fluid core [includes liposome]

Abstract

A process for producing a small-sized, lipid-based cochleate is described. Cochleates are derived from liposomes which are suspended in an aqueous two- phase polymer solution, enabling the differential partitioning of polar molecule based-structures by phase separation. The liposome-containing two- phase polymer solution, treated with positively charged molecules such as Ca 2+ or Zn2+, forms a cochleate precipitate of a particle size less than one micron. The process may be used to produce cochleates containing biologicall y relevant molecules. Small-sized cochleates may be administered orally or through the mucosa to obtain an effective method of treatment.

Claims (63)

1. A method for producing lipid-based cochleates comprising the steps of:
a) providing an aqueous suspension of liposomes;
b) mixing the liposome suspension with polymer A;
c) adding the liposome/polymer A suspension into a solution comprising polymer B, wherein polymer A and polymer B are immiscible, thereby creating a two-phase polymer system;
d) adding a solution of a cationic moiety to the two-phase polymer system; and e) washing the two-phase polymer system to remove the polymers.
2. A method of claim 1 wherein the addition of liposome/polymer A suspension is done by injection.
3. A method of claim 1 or claim 2 wherein the liposomes are formed of lipid comprising negatively charged lipid.
4. A method of claim 3 wherein the negatively charged lipid is phosphatidylserine0.
5. A method of claim 3 or claim 4 wherein the lipid comprises a minor amount of other lipids.
6. A method of claim 5 wherein the other lipid is selected from the group of zwitterionic lipids.
7. A method of claim 5 wherein the other lipid is selected from the group of cationic lipids.
8. A method of claim 5 wherein the other lipids are selected from the group of lipids capable of forming hydrogen bands to a biologically active molecule.
9. A method of claim 8 wherein the neutral lipid is a PFGylated lipid.
10. A method of any preceding claim wherein polymer A is at least one member selected from the group consisting of dextran and polyethylene glycol.
11. A method of any preceding claim wherein the concentration of polymer A in the two-phase polymer system ranges in concentration from 2 to 20% w/w.
12. A method of any preceding claim wherein polymer B is at least one member selected from the group consisting of polyvinylpyrrolidone, polyvinylalochol, Ficoll, polyvinyl methyl ether, and polyethylene glycol.
13. A method of any preceding claim wherein the concentration of polymer B in the two-phase polymer system is the range of 2 to 20% w/w.
14. A method of any preceding claim wherein the two-phase polymer solution is at least one member selected from the group consisting of dextran/polyethylene glycol, dextran/polyvinylpyrrolidone, dextran/polyvinylalcohol, dextran/Ficoll and polyethylene glycol/polyvinyl methyl ether.
15. A method of any preceding claim wherein the cationic moiety comprises a di-or higher- valent ion.
16. A method of any preceding claim wherein the cationic moiety comprises a di-or higher- valent metal ion.
17. A method of claim 16 wherein the metal ion is added as a salt of an inorganic acid, preferably wherein the salt is calcium chloride, zinc chloride or cobalt chloride.
18. A method of any preceding claim wherein the lipid cochleates are small-sized cochleates.
19. A method according to claim 18 wherein the size of the cochleates is less than 1 micron.
20. A method according to claim 18 wherein the cochleates are formed using small unilamellar liposomes.
21. A method according to any preceding claim wherein the aqueous suspension of liposomes comprises a biologically relevant molecule, whereby the cochleates also comprise the biologically relevant molecule.
22. A method according to claim 21 which comprises the preliminary step of forming the liposome suspension by forming a film comprising a mixture of the biologically relevant molecule and lipid and contacting the film with an aqueous phase to form the aqueous suspension of small unilamellar liposomes.
23. A method according to claim 21 in which the biologically relevant molecule is present in the aqueous phase.
24. A method according to claim 23 comprising the preliminary step of forming liposomes in which a film of lipid is contacted with aqueous phase containing the biologically relevant molecule to form the aqueous suspension of liposomes.
25. A method according to claim 21 including a preliminary step in which a suspension of empty liposomes is mixed with the biologically relevant molecule to form the said liposome suspension.
26. A method according to claim 23 wherein the biologically relevant molecule bears a charge.
27. A method according to claim 26 wherein the biologically relevant molecule is positively charged.
28. A method according to claim 26 wherein the biologically relevant molecule is negatively charged.
29. A method according to claim 23 wherein the negatively charged molecule is a polynucleotide.
30. A method according to claim 29 wherein the polynucleotide is DNA.
31. A method for producing lipid-based cochleates comprising the steps of:
a) providing an aqueous suspension containing a detergent-lipid mixture;
b) mixing the detergent-lipid suspension with polymer A;
c) adding the detergent-lipid/polymer A suspension into a solution comprising polymer B, wherein polymer A and polymer B are immiscible, thereby creating a two-phase polymer system;
d) adding a solution of a cationic moiety to the two-phase polymer system; and e) washing the two-phase polymer system to remove the polymer.
32. A method for producing lipid-based cochleates according to claim 31 wherein the detergent is octyl glucoside.
33. A method for producing lipid-based cochleates according to claim 31 wherein the cochleate comprises a biologically active molecule.
34. A method according to claim 33 wherein the biologically active molecule bear a charge.
35. A method according to claim 33 wherein the biologically active molecule is positively charged.
36. A method according to claim 33 wherein the biologically active molecule is negatively charged.
37. A method according to claim 36 wherein the negatively charged molecule is a polynucleotide.
38. A method according to claim 37 wherein the polynucleotide is DNA.
39. A method according to claim 31 wherein the biologically active molecule is added in step a.
40. A method according to claim 21 or claim 33 in which the biologically relevant molecule is selected from the group consisting of drugs, polynucleotides, polypeptides and antigens.
41. A method of claim 40 wherein the biologically relevant molecule is a drug selected from the group consisting of antiviral agents, anesthetics, antibacterial agents, antifungal agents, anticancer agents, immunosuppressants, steroidal anti-inflammatory agents, non-steroidal anti-inflammatory agents, tranquilisers and vasodilators.
42. A method of claim 41 in which the drug is at least one member selected from the group consisting of Amphotericin B, acyclovir, adriamycin, cabamazepine, melphalan, nifedipine, indomethacin, naproxen, estrogens, testosterones, steroids, phenytoin, ergotamines, cannabinoids rapamycin, propanidid, propocol, alphadione, echinomycin, miconazole nitrate, teniposide, taxol and taxotere.
43. A method according to any preceding claim in which the washing step involved centrifuging the two-phase polymer system to separate the cochleate precipitate, removing the supernatant containing the polymer, resuspending the precipitate in a washing buffer, centrifuging the washed precipitate , and optionally repeating the resuspension and centrifugation steps one or more times.
44. A method according to claim 43 in which the washing buffer contairus dissolved cationic moiety.
45. A method according to claim 44 in which the cationic moiety comprises di-or higher- valent ions.
46. A method according to claim 45 in which the di- or higher- valent ions are metal ions.
47. A method according to claim 46 in which the metal ions are selected from calcium and zinc.
48. A method according to any of claims 43 to 47 in which the cationic moiety is present in the washing buffer at a concentration of at least 1mM.
49. Cochleates containing a biologically relevant molecule prepared ac;cording to claims 1 to 48.
50. Cochleates containing a biologically relevant molecule according to claim 49 having a mean particle size less than 1 micron.
51. Cochleates according to claim 49 wherein the biologically relevant molecules are selected from the group consisting of drugs, polynucleotides, polypeptides and antigens.
52. Cochleates according to claim 51 wherein the biologically relevant molecule is a drug selected from the group consisting of antiviral agents, anesthetics, antibacterial agents, antifungal agents, anticancer agents, immunosuppressants, steroidal anti-inflammatory agents, non-steriodal anti-inflammatory agents, tranquilisers and vasodilators.
53. Cochleatcs according to claim 52 wherein the drug is at least one member selected from the group consisting of Amphotericin B, acyclovir, adriamycin, cabamazepine, melphalan, nifcdipine, indomethacin, naproxen, estrogens, testosterones, steroids, phenytoin, ergotamines, cannabinoids rapamycin, propanidid, propofol, atphadione, echinomycin, miconazole nitrate, teniposide, taxol and taxotere.
54. Cochleates according to any of claims 49 to 53, or the product of a method of any of claims 1 to 48, for use in a method of delivering a biologically relevant molecule to a host.
55. Use of cochleates according to any of claims 49 to 54, or of the product of a method according to claims 1 to 48, in the manufacture of a composition for use in the method of treatment of the human or animal body or to deliver a biologically relevant molecule to a host.
56. A method of treatment comprising administering to a human or animal cochleates according to any of claims 49 to 54, or the product of any of claims 1 to 48.
57. Use according to claim 55 or method according to claim 56 in which the administration is by a mucosal or a systemic route.
58. Use or method of claim 57 wherein the administration is a mucosal route selected from oral, intranasal, intraocular, intraanal, intravaginal, parenteral or intrapulmonary.
59. Use or method according to claim 57 in which the route is oral.
60. Use or method according to claim 58 in which the administration is proceeded by aerosol.
61. Use or method according to claim 57 wherein the administration is systemic and is by a route selected from intravenous, intramuscular, subcutaneous, transdermal or intradermal.
62. A composition comprising cochleates according to any of claims 49 to 54 of the product of the process according to any of claims 1 to 48, and a carrier.
63. A pharmaceutical composition comprising cochleates according to any of claims 49 to 54 or the product of a process according to any of claims 1 to 48, and a pharmaceutically acceptable carrier.
CA2358505A 1999-01-22 2000-01-24 Novel hydrogel isolated cochleate formulations, process of preparation and their use for the delivery of biologically relevant molecules Expired - Fee Related CA2358505C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US09/235,400 1999-01-22
US09/235,400 US6153217A (en) 1999-01-22 1999-01-22 Nanocochleate formulations, process of preparation and method of delivery of pharmaceutical agents
PCT/US2000/001684 WO2000042989A2 (en) 1999-01-22 2000-01-24 Novel hydrogel isolated cochleate formulations, process of preparation and their use for the delivery of biologically relevant molecules

Publications (2)

Publication Number Publication Date
CA2358505A1 true CA2358505A1 (en) 2000-07-27
CA2358505C CA2358505C (en) 2010-04-06

Family

ID=22885334

Family Applications (1)

Application Number Title Priority Date Filing Date
CA2358505A Expired - Fee Related CA2358505C (en) 1999-01-22 2000-01-24 Novel hydrogel isolated cochleate formulations, process of preparation and their use for the delivery of biologically relevant molecules

Country Status (12)

Country Link
US (7) US6153217A (en)
EP (1) EP1143933B1 (en)
JP (1) JP2002535267A (en)
AT (1) ATE367800T1 (en)
AU (1) AU3213300A (en)
CA (1) CA2358505C (en)
CY (1) CY1106916T1 (en)
DE (1) DE60035669T2 (en)
DK (1) DK1143933T3 (en)
ES (1) ES2290019T3 (en)
PT (1) PT1143933E (en)
WO (1) WO2000042989A2 (en)

Families Citing this family (62)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6153217A (en) 1999-01-22 2000-11-28 Biodelivery Sciences, Inc. Nanocochleate formulations, process of preparation and method of delivery of pharmaceutical agents
AU3111401A (en) * 2000-01-24 2001-07-31 Biodelivery Sciences, Inc. New cochleate formulations, process of preparation and their use for the delivery of biologically relevant molecules
DE10154464B4 (en) * 2001-11-08 2005-10-20 Max Delbrueck Centrum Orally administrable pharmaceutical preparation comprising liposomally encapsulated taxol
US20030219473A1 (en) * 2002-03-26 2003-11-27 Leila Zarif Cochleates made with purified soy phosphatidylserine
US20040092727A1 (en) * 2002-11-13 2004-05-13 Biopharm Solutions Inc. Cochleates without metal cations as bridging agents
WO2004012709A1 (en) * 2002-08-06 2004-02-12 Tuo Jin Cochleates without metal cations as the bridging agents
JP3927887B2 (en) * 2002-08-09 2007-06-13 本田技研工業株式会社 Stator blade of axial compressor
US8685428B2 (en) * 2002-12-10 2014-04-01 Advanced Cardiovascular Systems, Inc. Therapeutic composition and a method of coating implantable medical devices
US8980310B2 (en) * 2002-12-31 2015-03-17 Bharat Serums and Vaccines, Ltd. Non-pegylated long-circulating liposomes
WO2004064805A1 (en) * 2003-01-15 2004-08-05 Biodelivery Sciences International, Inc. Cochleate preparations of fragile nutrients
JP4789208B2 (en) 2003-04-09 2011-10-12 バイオデリバリー サイエンシーズ インターナショナル インコーポレイティッド Swirl composition for protein expression
WO2004091578A2 (en) 2003-04-09 2004-10-28 Biodelivery Sciences International, Inc. Novel encochleation methods, cochleates and methods of use
DE10322439A1 (en) * 2003-05-19 2004-12-09 Bayer Ag Method and device for determining the isomer composition in isocyanate production processes
SE527505C2 (en) * 2003-06-10 2006-03-28 Anna Imberg Composite materials and particles
US20060188573A1 (en) * 2003-06-10 2006-08-24 Anna Imberg Composite materials and particles
US20070258926A1 (en) * 2003-10-15 2007-11-08 Ltt Bio-Pharma Co., Ltd. Composition containing retinoic acid nanoparticles coated with inorganic salt of polyvalent metal
WO2005037267A1 (en) * 2003-10-15 2005-04-28 Ltt Bio-Pharma Co., Ltd. Method of controlling paticle size of retinoic acid nanoparticles coated with polyvalent metal inorganic salt and nanoparticles obtained by the controlling method
WO2005063213A1 (en) * 2003-12-19 2005-07-14 Biodelivery Sciences International, Inc. Rigid liposomal cochleate and methods of use and manufacture
US20050244522A1 (en) * 2004-04-30 2005-11-03 Carrara Dario Norberto R Permeation enhancer comprising genus Curcuma or germacrone for transdermal and topical administration of active agents
US7494526B2 (en) * 2004-07-14 2009-02-24 Yavitz Edward Q Plant protection and growth stimulation by nanoscalar particle folial delivery
US20060040896A1 (en) * 2004-08-18 2006-02-23 Paringenix, Inc. Method and medicament for anticoagulation using a sulfated polysaccharide with enhanced anti-inflammatory activity
US20070082107A1 (en) * 2005-10-07 2007-04-12 Aimutis William R Jr Compositions and methods for reducing food intake and controlling weight
US20070082030A1 (en) * 2005-10-07 2007-04-12 Aimutis William R Fiber satiety compositions
US20070082115A1 (en) * 2005-10-07 2007-04-12 Aimutis William Ronald Jr Methods for inducing satiety, reducing food intake and reducing weight
US20070082029A1 (en) * 2005-10-07 2007-04-12 Aimutis William R Fiber satiety compositions
WO2008024389A2 (en) * 2006-08-23 2008-02-28 Biodelivery Sciences International, Inc. Amphiphilic nucleotide cochleate compositions and methods of using the same
US20080085354A1 (en) * 2006-10-06 2008-04-10 Teresa Marie Paeschke Controlled hydration of hydrocolloids
AR064359A1 (en) 2006-12-15 2009-04-01 Ca Nat Research Council AGGREGATES OF POLAR LIPIDS OF ARCHES FOR ADMINISTRATION TO ANIMALS
US20090054374A1 (en) * 2007-02-28 2009-02-26 Paringenix, Inc. Methods of treating acute exacerbations of chronic obstructive pulmonary disease
US8591225B2 (en) * 2008-12-12 2013-11-26 Align Technology, Inc. Tooth movement measurement by automatic impression matching
US20090036405A1 (en) * 2007-07-23 2009-02-05 University Of Utah Method for blocking ligation of the receptor for advanced glycation end-products (rage)
US20090047336A1 (en) * 2007-08-17 2009-02-19 Hong Kong Baptist University novel formulation of dehydrated lipid vesicles for controlled release of active pharmaceutical ingredient via inhalation
WO2009036368A2 (en) 2007-09-14 2009-03-19 Nitto Denko Corporation Drug carriers
ES2630805T3 (en) 2008-07-14 2017-08-24 Polypid Ltd. Sustained release drug vehicle composition
US20100113352A1 (en) 2008-11-06 2010-05-06 Elliott Millstein Retinol formulations and methods for their use
WO2011007353A1 (en) 2009-07-14 2011-01-20 Polypid Ltd. Sustained-release drug carrier composition
WO2011016043A2 (en) 2009-08-06 2011-02-10 Technion Research & Development Foundation Ltd. Antibiotic drug delivery and potentiation
WO2011031018A2 (en) * 2009-09-14 2011-03-17 한남대학교 산학협력단 Water-soluble drug delivery system allowing slow release
US8795726B2 (en) 2010-01-19 2014-08-05 Polypid Ltd. Sustained-release nucleic acid matrix compositions
WO2011099964A1 (en) * 2010-02-10 2011-08-18 Biopelle, Inc. Retinol formulations and methods for their use
WO2012149393A2 (en) 2011-04-29 2012-11-01 Selecta Biosciences, Inc. Tolerogenic synthetic nanocarriers for antigen-specific deletion of t effector cells
EP2704688B1 (en) * 2011-05-05 2019-07-10 Matinas BioPharma Nanotechnologies, Inc. Cochleate compositions and methods of making and using same
US20140186436A1 (en) 2011-07-06 2014-07-03 The Regents Of The University Of California Oral delivery of enzymes by nanocapsules for targeted metabolism of alcohol or toxic metabolites
US9993440B2 (en) 2011-09-02 2018-06-12 The Regents Of The University Of California Enzyme responsive nanocapsules for protein delivery
AU2013260101B2 (en) 2012-05-09 2016-10-27 Cantex Pharmaceuticals, Inc. Treatment of myelosuppression
US10973266B2 (en) * 2013-03-15 2021-04-13 Robert Bosch Tool Corporation Heated garment and battery holster
EA201592103A3 (en) * 2013-05-03 2016-08-31 Селекта Байосайенсиз, Инк. METHODS AND COMPOSITIONS FOR STRENGTHENING CD4 + REGULATORY T-CELLS
US9937223B2 (en) 2015-01-30 2018-04-10 Par Pharmaceutical, Inc. Vasopressin formulations for use in treatment of hypotension
US9750785B2 (en) 2015-01-30 2017-09-05 Par Pharmaceutical, Inc. Vasopressin formulations for use in treatment of hypotension
US9687526B2 (en) 2015-01-30 2017-06-27 Par Pharmaceutical, Inc. Vasopressin formulations for use in treatment of hypotension
US9744209B2 (en) 2015-01-30 2017-08-29 Par Pharmaceutical, Inc. Vasopressin formulations for use in treatment of hypotension
US9925233B2 (en) 2015-01-30 2018-03-27 Par Pharmaceutical, Inc. Vasopressin formulations for use in treatment of hypotension
US9375478B1 (en) 2015-01-30 2016-06-28 Par Pharmaceutical, Inc. Vasopressin formulations for use in treatment of hypotension
EP3258941A4 (en) 2015-02-17 2018-09-26 Cantex Pharmaceuticals, Inc. Treatment of cancers and hematopoietic stem cell disorders privileged by cxcl12-cxcr4 interaction
CA2978308C (en) 2015-03-03 2024-02-13 Matinas Biopharma Nanotechnologies, Inc. Cochleates and methods of using the same to enhance tissue penetration of pharmacologically active agent
US11116726B2 (en) 2015-11-10 2021-09-14 Childrens Research Institute, Childrens National Medical Center Echinomycin formulation, method of making and method of use thereof
EP3484447A4 (en) * 2016-07-12 2020-07-22 Matinas BioPharma Nanotechnologies, Inc. Encochleated antifungal compounds for central nervous system delivery and treatment ofcryptococcus
KR101989789B1 (en) 2017-11-30 2019-06-18 (주) 에이치엔에이파마켐 Cochleates using phosphatidylserine/anionic surfactant/calcium chloride
KR20210016403A (en) * 2018-09-28 2021-02-15 가부시키가이샤 만다무 Cosmetic
US20220226465A1 (en) 2021-01-18 2022-07-21 ConserV Bioscience Coronavirus Immunogenic Compositions, Methods and Uses Thereof
WO2024039733A1 (en) 2022-08-16 2024-02-22 Matinas Biopharma Nanotechnologies, Inc. Methods of controlling lipid nanocrystal particle size and lipid nanocrystals produced by such methods
WO2024039729A1 (en) 2022-08-16 2024-02-22 Matinas Biopharma Nanotechnologies, Inc. Antifungal agent encapsulated in a lipid nanocrystal for treating mucormycosis

Family Cites Families (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4871488A (en) * 1985-04-22 1989-10-03 Albany Medical College Of Union University Reconstituting viral glycoproteins into large phospholipid vesicles
US4663161A (en) * 1985-04-22 1987-05-05 Mannino Raphael J Liposome methods and compositions
US4990291A (en) * 1986-04-15 1991-02-05 The United States Of America As Represented By The Secretary Of The Navy Method of making lipid tubules by a cooling process
US5269979A (en) * 1988-06-08 1993-12-14 Fountain Pharmaceuticals, Inc. Method for making solvent dilution microcarriers
DE69014885T2 (en) * 1989-06-22 1995-04-27 Vestar Inc CAPSULE PROCEDURE.
US5840707A (en) * 1993-10-04 1998-11-24 Albany Medical College Stabilizing and delivery means of biological molecules
US5994318A (en) * 1993-10-04 1999-11-30 Albany Medical College Cochleate delivery vehicles
US5643574A (en) * 1993-10-04 1997-07-01 Albany Medical College Protein- or peptide-cochleate vaccines and methods of immunizing using the same
WO1997030725A1 (en) 1996-02-22 1997-08-28 Raphael James Mannino Cochleat delivery vehicles
US6120751A (en) * 1997-03-21 2000-09-19 Imarx Pharmaceutical Corp. Charged lipids and uses for the same
US6153217A (en) 1999-01-22 2000-11-28 Biodelivery Sciences, Inc. Nanocochleate formulations, process of preparation and method of delivery of pharmaceutical agents

Also Published As

Publication number Publication date
US20030228355A1 (en) 2003-12-11
CA2358505C (en) 2010-04-06
US20050186265A1 (en) 2005-08-25
WO2000042989A3 (en) 2000-11-30
JP2002535267A (en) 2002-10-22
DK1143933T3 (en) 2007-11-26
US20090028904A1 (en) 2009-01-29
US6592894B1 (en) 2003-07-15
US20120294901A1 (en) 2012-11-22
EP1143933B1 (en) 2007-07-25
ATE367800T1 (en) 2007-08-15
DE60035669D1 (en) 2007-09-06
AU3213300A (en) 2000-08-07
WO2000042989A2 (en) 2000-07-27
PT1143933E (en) 2007-09-03
US20140220109A1 (en) 2014-08-07
US6153217A (en) 2000-11-28
EP1143933A2 (en) 2001-10-17
CY1106916T1 (en) 2012-09-26
DE60035669T2 (en) 2008-02-07
ES2290019T3 (en) 2008-02-16

Similar Documents

Publication Publication Date Title
CA2358505A1 (en) Novel hydrogel isolated cochleate formulations, process of preparation and their use for the delivery of biologically relevant molecules
Guevara et al. Advances in lipid nanoparticles for mRNA-based cancer immunotherapy
Jadhav et al. Novel vesicular system: an overview
Sankhyan et al. Recent Trends in Niosome as Vesicular DrugDelivery System
JP2002535267A5 (en)
Pardakhty et al. Nano-niosomes in drug, vaccine and gene delivery: a rapid overview
AU2012302422B2 (en) Sustained-release lipid pre-concentrate of pharmacologically active substance and pharmaceutical composition comprising the same
JP5674831B2 (en) Transpulmonary administration liposome for drug delivery control
Apolinario et al. Lipid nanovesicles for biomedical applications:‘What is in a name’?
JP2002521423A (en) Lipid emulsions and solid lipid microparticles as gene or drug carriers
Shanmugam et al. Nanostructured self assembled lipid materials for drug delivery and tissue engineering
CA2748520A1 (en) Pharmaceutical composition containing an anionic drug, and a production method therefor
WO2010009186A1 (en) Liposome formulation having hydrophilic and hydrophobic pharmaceutical compounds co-encapsulated therein
CN108366964A (en) The method for preparing the polymer micelle containing anionic drugs
WO2019212288A1 (en) Polymer nanoparticle composition for delivering messenger rna, and preparation method therefor
Sudhakar et al. Ethosomes as non-invasive loom for transdermal drug delivery system
Swami et al. Liposome: An art for drug delivery
Patel Liposome: a novel carrier for targeting drug delivery system
CN113825497A (en) Method for producing liposomes
Bally et al. Lipid/DNA complexes as an intermediate in the preparation of particles for gene transfer: an alternative to cationic liposome/DNA aggregates
Vijeta et al. Nanocochleate: as drug delivery vehicle
JP2005529086A (en) A spiral made of purified soy phosphatidylserine
US20050037200A1 (en) New non-phospholipid lipid vesicles (nplv) and their use in cosmetic, therapeutic and prophylactic applications
Gol et al. Nanocochleates: A novel approach for drug delivery
Wasankar et al. Nanocochleate: a review

Legal Events

Date Code Title Description
EEER Examination request
MKLA Lapsed

Effective date: 20130124