US5141674A
Expired / Lapsed
US
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Methods of preparing pro-liposome dispersions and aerosols
Assignee: Westernbank Puerto Rico
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Filing: 1991-06-24
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Granted: 1992-08-25
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Expires: 2011-06-24
Abstract
Abstract Compositions that are sprayable or that are in the form of discrete particles and that contain a lipid and a biologically active compound in the form of a micronized powder combine a high initial entrapment of the active compound in the membrane lipid with sustained release at the site of application as indicated by in-vitro and in-vivo tests. In a first form pro-liposomes are prepared by spraying under pressure through a nozzle a single composition comprising at least one volatile liquid propellant, at least one membrane lipid that is at least partly dissolved or dispersed in the propellant and at least one biologically active compound that is present in dispersion in the propellant and/or the lipid, the composition being free from other solvent for the lipid. In a second form the membrane lipid and the biologically active compound are minor components of micronized solid particles whose major component is a physiologically acceptable solid carrier.
Inventors
- 👤 Steven Leigh
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-29 09:06
CPC Classifications
A; A61; A61K; A61K9/00; A61K9/14; A61K9/16; A61K9/167; A61K9/1676; A61K9/10; A61K9/127; A61K9/1277
Claims Analysis
Total Claims: 34
Claim 1
Independent Claim
70 words
A method for the preparation of a pro-liposome composition, which method comprises: providing a membrane lipid that on contact with water forms vesicles comprising lipid bilayers surrounding an aqueous space; and uniformly dispersing discrete micronised particles of a biologically active compound in the membrane lipid, said dispersing being performed in the presence of a solvent for the lipid bi-layer, said solvent not being a solvent for the biologically active compound.
Claim 2
Independent Claim
70 words
A method for the preparation of a pro-liposome composition, which method comprises: providing a membrane lipid that on contact with water forms vesicles comprising lipid bilayers surrounding an aqueous space; and uniformly dispersing discrete micronised particles of a biologically active compound in the membrane lipid, said dispersing being performed in the presence of a solvent for the lipid bi-layer, said solvent not being a solvent for the biologically active compound.
Claim 3
Dependent Claim
43 words
A method according to claim 1, wherein the membrane lipid is selected from the group consisting of natural or hydrogenated lecithin, a glycolipid, a long chain dialkyl ammonium compound and a mixture of any of the aforesaid compounds with a compatible lipophilic material.
Claim 4
Dependent Claim
26 words
A method according to claim 1, wherein the biologically active compound is selected from the group consisting of bronchodilators, steroids, antibiotics, antihistamines, vasoconstrictors and anti-inflammatory compounds.
Claim 5
Dependent Claim
36 words
A method according to claim 1, wherein the biologically active compound is selected from the group consisting of salbutamol, terbutaline, orciprenaline, isoprenaline, reproterol, pirbuterol, butenoside, beclamethasone dipropionate, sodium chromoglycate, fenoterol, ipratropium, betamethasone valerate, rimiterol and ketotifen.
Claim 6
Dependent Claim
29 words
A method according to claim 1, wherein the biologically active compound is dispersed in the lipid in the form of particles of average size from 0.5 to 8 micrometers.
Claim 7
Dependent Claim
16 words
A method of making vesicles which comprises contacting the pro-liposome composition of claim 1 with water.
Claim 8
Dependent Claim
12 words
A method according to claim 6, wherein the contact is in vivo.
Claim 9
Dependent Claim
12 words
A method according to claim 6, wherein the contact is in vitro.
Claim 10
Independent Claim
67 words
A method for the preparation of a pro-liposome composition in the form of a powder, which method comprises: providing a membrane lipid that on contact with water forms vesicles comprising lipid bilayers surrounding an aqueous space, and providing a biologically active compound; and dispersing the biologically active compound in the membrane lipid while forming discrete micronised solid particles of the biologically active compound suspended in the lipid.
Claim 11
Independent Claim
67 words
A method for the preparation of a pro-liposome composition in the form of a powder, which method comprises: providing a membrane lipid that on contact with water forms vesicles comprising lipid bilayers surrounding an aqueous space, and providing a biologically active compound; and dispersing the biologically active compound in the membrane lipid while forming discrete micronised solid particles of the biologically active compound suspended in the lipid.
Claim 12
Dependent Claim
57 words
A method according to claim 9, wherein while forming the discrete micronized solid particles, there is further provided a carrier in an amount such that in the micronised solid particles formed the lipid and the biologically active compound together are a minor component of said particles and the solid carrier is the major component of said particles.
Claim 13
Dependent Claim
15 words
A method according to claim 10, wherein the carrier is selected from glucose and lactose.
Claim 14
Dependent Claim
20 words
A method according to claim 10, wherein the weight ratio of membrane lipid to carrier is from 1:1 to 1:25.
Claim 15
Dependent Claim
20 words
A method according to claim 12, wherein the weight ratio biologically active compound to lipid is from 1:0.5 to 1:25.
Claim 16
Dependent Claim
21 words
A method according to claim 12, wherein the weight ratio of biologically active compound to lipid is from 1:6 to 1:20.
Claim 17
Dependent Claim
49 words
A method according to claim 9, wherein the biologically active compound is dispersed in the membrane lipid before the micronised particles are formed by adding the biologically active compound in micronised form to a solution of the membrane lipid in a solvent therefor and allowing the solvent to evaporate.
Claim 18
Dependent Claim
27 words
A method according to claim 9, wherein the biologically active compound is dispersed in the membrane lipid by milling simultaneously with formation of the micronised solid particles.
Claim 19
Dependent Claim
43 words
A method according to claim 9, wherein the membrane lipid is selected from the group consisting of natural or hydrogenated lecithin, a glycolipid, a long chain dialkyl ammonium compound and a mixture of any of the aforesaid compounds with a compatible lipophilic material.
Claim 20
Dependent Claim
26 words
A method according to claim 9, wherein the biologically active compound is selected from the group consisting of bronchodilators, steroids, antibiotics, antihistamines, vasoconstrictors and anti-inflammatory compounds.
Claim 21
Dependent Claim
36 words
A method according to claim 9, wherein the biologically active compound is selected from the group consisting of salbutamol, terbutaline, orciprenaline, isoprenaline, reproterol, pirbuterol, butenoside, beclamethasone dipropionate, sodium chromoglycate, fenoterol, ipratropium, betamethasone valerate, rimiterol and ketotifen.
Claim 22
Dependent Claim
16 words
A method of making vesicles which comprises contacting the pro-liposome composition of claim 9 with water.
Claim 23
Dependent Claim
12 words
A method according to claim 20, wherein the contact is in vivo.
Claim 24
Dependent Claim
12 words
A method according to claim 20, wherein the contact is in vitro.
Claim 25
Independent Claim
79 words
A method for forming an aerosol of particles that have the property of spontaneously forming vesicles on contact with an excess of water, said method comprising the step of introducing into a moving air stream solid particles which are the result of micronising together a lipid, a biologically active compound insoluble in said lipid, and a physiologically acceptable carrier in the absence of liquid so that the biologically active compound is present in the aerosol as discrete micronised particles.
Claim 26
Independent Claim
79 words
A method for forming an aerosol of particles that have the property of spontaneously forming vesicles on contact with an excess of water, said method comprising the step of introducing into a moving air stream solid particles which are the result of micronising together a lipid, a biologically active compound insoluble in said lipid, and a physiologically acceptable carrier in the absence of liquid so that the biologically active compound is present in the aerosol as discrete micronised particles.
Claim 27
Dependent Claim
41 words
A method according to claim 23, wherein the lipid is selected from the group consisting of a natural or hydrogenated lecithin, a glycolipid, a long chain dialkyl ammonium compound, and a mixture of the aforesaid compounds with a compatible lipophilic material.
Claim 28
Dependent Claim
26 words
A method according to claim 23, wherein the biologically active compound is selected from the group consisting of bronchodilators, steroids, antibiotics, antihistamines, vascoconstrictors and anti-inflammatory compounds.
Claim 29
Dependent Claim
36 words
A method according to claim 23, wherein the biologically active compound is selected from the group consisting of salbutamol, terbutaline, orciprenaline, isopronaline, reproterol, pirbuterol, butenoside, beclamethasone dipropionate, sodium chromoglycate, fenoterol, ipratropium, betamethasone valerate, rimiterol and ketotifen.
Claim 30
Dependent Claim
29 words
A method according to claim 23, wherein the biologically active compound is dispersed in the lipid in the form of particles of average size from 0.5 to 8 micrometers.
Claim 31
Dependent Claim
25 words
A method according to claim 23, wherein the carrier is a member selected from the group consisting of glucose, lactose, a dextran and a starch.
Claim 32
Dependent Claim
20 words
A method according to claim 23, wherein the weight ratio of membrane lipid to carrier is from 1:1 to 1:25.
Claim 33
Dependent Claim
21 words
A method according to claim 23, wherein the weight ratio of biologically active compound to lipid is from 1:0.5 to 1:25.
Claim 34
Dependent Claim
21 words
A method according to claim 30, wherein the weight ratio of biologically active compound to lipid is from 1:6 to 1:20.
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