EP0361894B1
Expired / Lapsed
EP
⏱️ 0.0 years remaining
Loading and controlled release of amphiphatic molecules to and from liposomes
Assignee: Yissum Research Development Co of Hebrew University of Jerusalem
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Filing: 1989-09-27
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Granted: 1994-11-09
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Expires: 2009-09-27
Abstract
Abstract The present invention relates to an improved transmembrane loading procedure for efficient loading of amphiphatic drugs into liposomes using the transmembrane gradient of ammonium and of pH. The resulting liposomes loaded with the drug are stable and safe. The procedure is equally applicable for sustained release of liposome-encapsulated drugs. The liposomes may be used in ultrasound imaging to release CO2.
Inventors
- 👤 Yechezkel Barenholz
- 👤 Gilad Haran
Bibliographic Details
Application Number
—
Jurisdiction
EP
Data Source
google_patents
Last Synchronized
2026-10-23 02:13
CPC Classifications
A; A61; A61K; A61K49/00; A61K49/22; A61K49/222; A61K49/227; A61K9/00; A61K9/10; A61K9/127; A61K9/1277; A61K9/1278; Y; Y10; Y10S; Y10S436/00; Y10S436/829; Y10T; Y10T428/00; Y10T428/29; Y10T428/2982; Y10T428/2984
Claims Analysis
Total Claims: 10
Claim 1
Independent Claim
66 words
A system for loading an amphiphatic molecule into liposomes comprising a formation of liposome suspension in the presence of ammonium compound or ammonium salt wherein said suspension is diluted with buffer or salt to provide an inside to outside ammonium gradient between internal aqueous and external aqueous phases and a pH gradient wherein the inside pH of the liposomes is more acidic than the outside pH.
Claim 2
Dependent Claim
19 words
The system of Claim 1 wherein the ammonium compound is ammonium sulfate, ammonium hydroxide, ammonium bicarbonate or ammonium carbonate.
Claim 3
Dependent Claim
85 words
The system of Claim 2 wherein the amphiphatic molecule is selected from the group consisting of doxorubicin, daunorubicin, chloroquinone, propranolol, pentamidine, epirubicin, carcinomycin, N-acetyladriamycin, rubidazole, 5-imidodaunomycin, N-acetyldauno-mycine, all anthracyline drugs, daunoryline, dibucaine, tetracaine, procaine, chlorpromazine, vinblastine, vincristine, mitomycin C, pilocarpine, physostigmine, neostigmine, chloroquine, amodiaquine, chloroguanide, primaquine, mefloquine, quinine, pridinol, prodipine, benztropine, mesylate, trihexyphenidyl hydrochloride, timolol, pindolol, quinacrine, benadryl, promethazine, dopamine, serotonin, epinephrine, codeine, meperidine, methadone, morphine, atropine, decyclomine, methixene, propantheline, imipramine, amitriptyline, doxepin, desipramine, quinidine, lidocaine, chlorpromazine, promethazine, perphenazine, acridine orange, prostaglandin, fluorescein and carboxyfluorescein.
Claim 4
Dependent Claim
52 words
The system of Claim 3 wherein the amphiphatic molecule is loaded into the liposomes in exchange for the ammonium effluxing the liposomes due to its concentration and the extent of the drug loading is dependent on the ratio of outside to inside ammonium sulfate and on pH in the internal aqueous phase.
Claim 5
Independent Claim
72 words
A method for efficient loading of amphiphatic molecules into liposomes comprising: (a) formation of liposomal suspension in the presence of ammonium sulfate; (b) creating inside to outside ammonium gradient and outside to inside pH gradient by diluting the external aqueous phase of suspension of step (a) with a suitable salt or buffer or by removing ammonia; and c) loading the deprotonated amphiphatic drug from the outside to the inside of the liposomes.
Claim 6
Dependent Claim
25 words
The method of Claim 5 wherein the amphiphatic drug is loaded into liposomes by influx in exchange for the ammonium efflux according to ammonium gradient.
Claim 7
Dependent Claim
65 words
A suspension of liposomes and ammonium salt suitable for loading of amphiphatic drug into liposomes by providing an ammonium gradient from an internal aqueous phase to external aqueous phase of the liposomes by diluting or removing ammonium from the external aqueous phase, wherein said inside to outside ammonium gradient creates an outside to inside pH gradient allowing an amphiphatic drug to be loaded into liposomes.
Claim 8
Dependent Claim
29 words
Ammonium liposomes for loading of amphiphatic drug having an inside to outside ammonium gradient created by dilution or removal of ammonium in the liposomes suspension by salt or buffer.
Claim 9
Dependent Claim
33 words
A suspension of liposomes and ammonium salt suitable for release of an amphiphatic drug from liposomes by creating a reverse pH from an internal aqueous phase to external aqueous phase of the liposomes.
Claim 10
Dependent Claim
21 words
Ammonium liposomes suitable for generating carbon dioxide and releasing said carbon dioxide to the tissue to enhance hyperechogenicity of ultrasound imaging.
References Cited (Backward Citations)
No citation records indexed.
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