US4963367A
Expired / Lapsed
US
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Drug delivery compositions and methods
Assignee: Quixote Corp
•
Filing: 1987-12-15
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Granted: 1990-10-16
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Expires: 2007-12-15
Abstract
Abstract Drug delivery compositions yeild new and unexpected degrees of stabilization, solubilization and delivery of incorporated medicaments, drugs, or other physiologically-active compounds. The compositions enable administration of drugs and other medically useful compounds via a variety of routes. More particularly, a drug delivery system or composition including one or more monomeric or polymerized surface active agents allows for rapid dissolution and smooth liberation of any desired incorporated drug or combinations, and the method of preparing the drug composition. In one embodiment, the physiologically-active compound is encapsulated by a coacervate-derived film, and the finished product is suitable for transmucosal administration. Other formulations of this invention may be administered via inhalation, oral, parenteral and by transdermal and transmucosal routes.
Inventors
- 👤 Bernard Ecanow
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-29 08:28
CPC Classifications
A; A61; A61K; A61K9/00; A61K9/0012; A61K9/0019; A61K9/0026; A61K38/00; A61K38/16; A61K38/17; A61K38/38; A61K38/39; A61K9/10; A61K9/107; A61K9/1075; A61K9/48; A61K9/50; A61K9/5089; B; B82; B82Y; B82Y5/00; Y; Y10; Y10T; Y10T428/00; Y10T428/29; Y10T428/2982; Y10T428/2984
Claims Analysis
Total Claims: 55
Claim 1
Independent Claim
130 words
A method of preparing a composition useful as a system to introduce and transport medically useful compositions in the body of mammals; said composition comprising particles of a coacervate-based matrix having one or more physiologically-active compound incorporated therein and a coacervative-based encapsulating film surrounding each particle; said method comprising forming a mixture of one or more surface active agents, water and one or more physiologically-active compounds to produce a two phase aqueous coacervate composition containing said compound, and emulsifying the composition to produce an aqueous emulsion of coacervate-based matrix particles containing the physiologically-active compound, said coacervate-based matrix comprising water selected from the group consisting of coacervate phase water, equilibrium phase water, and mixtures thereof, and said physiologically-active compound solubilized therein, said particles having an encapsulating coacervate-based film surrounding the particles.
Claim 2
Independent Claim
130 words
A method of preparing a composition useful as a system to introduce and transport medically useful compositions in the body of mammals; said composition comprising particles of a coacervate-based matrix having one or more physiologically-active compound incorporated therein and a coacervative-based encapsulating film surrounding each particle; said method comprising forming a mixture of one or more surface active agents, water and one or more physiologically-active compounds to produce a two phase aqueous coacervate composition containing said compound, and emulsifying the composition to produce an aqueous emulsion of coacervate-based matrix particles containing the physiologically-active compound, said coacervate-based matrix comprising water selected from the group consisting of coacervate phase water, equilibrium phase water, and mixtures thereof, and said physiologically-active compound solubilized therein, said particles having an encapsulating coacervate-based film surrounding the particles.
Claim 3
Dependent Claim
21 words
The method of claim 1 further including adding an organic solvent to the mixture to form the two phase coacervate composition.
Claim 4
Dependent Claim
15 words
The method of claim 2 wherein the organic solvent comprises N-butyl alcohol or a glyceride.
Claim 5
Dependent Claim
23 words
The method of claim 1 wherein the surface active agents comprises a composition of a surface active protein and a surface active phospholipid.
Claim 6
Independent Claim
103 words
A method of preparing a composition containing one or more physiologically-active compounds for oral, inhalation, tissue absorptive or parenteral administration to a mammal comprising emulsifying an aqueous solution of water, a polymerized or polymerizable surface active agent, a coacervating agent and a physicologically-active compound to form an aqueous emulsion of coacervate-based matrix particles containing the physiologically-active compound solubilized therein, and bound in the coacervate matrix within a coacervate-based aqueous film containing the polymerized surface active agent wherein said coacervate matrix comprises water selected from the group consisting of coacervate phase water, equilibrium phase water, and mixtures thereof, and said physiologically-active compound solubilized therein.
Claim 7
Independent Claim
103 words
A method of preparing a composition containing one or more physiologically-active compounds for oral, inhalation, tissue absorptive or parenteral administration to a mammal comprising emulsifying an aqueous solution of water, a polymerized or polymerizable surface active agent, a coacervating agent and a physicologically-active compound to form an aqueous emulsion of coacervate-based matrix particles containing the physiologically-active compound solubilized therein, and bound in the coacervate matrix within a coacervate-based aqueous film containing the polymerized surface active agent wherein said coacervate matrix comprises water selected from the group consisting of coacervate phase water, equilibrium phase water, and mixtures thereof, and said physiologically-active compound solubilized therein.
Claim 8
Dependent Claim
29 words
The method of claim 5 further including emulsifying and microemulsifying the composition to form coacervate particles useful for oral administration having a particle size less than about 800 microns.
Claim 9
Dependent Claim
17 words
The method of claim 5 wherein the coacervate particles are microemulsified to less than about 1 micron.
Claim 10
Dependent Claim
14 words
The method of claim 5 wherein the surface active agent is a polymerized phospholipid.
Claim 11
Dependent Claim
12 words
The method of claim 8 wherein the polymerized phospholipid is polymerized lecithin.
Claim 12
Dependent Claim
30 words
The method of claim 8 wherein the phospholipid is selected from the group consisting of lecithin, cephalin, isolecithin, sphingomyelin, phosphalidyl serine, phosphatidic acid, phosphatidyl inositol, phosphatidyl choline, and mixtures thereof.
Claim 13
Dependent Claim
30 words
The method of claim 5 wherein the coacervate system includes two surface active agents, at least one of which is a polymer having a molecular weight of 300,000 or less.
Claim 14
Dependent Claim
19 words
The method of claim 11 wherein the two surface active agents comprise a phospholipid and a surface active protein.
Claim 15
Dependent Claim
16 words
The method of claim 12 wherein the two surface active agents comprise lecithin and polymerized albumin.
Claim 16
Dependent Claim
25 words
The method of claim 5 further including drying the composition to form a powder capable of being reconstituted by the addition of a physiologically-acceptable liquid.
Claim 17
Dependent Claim
46 words
The method of claim 5 wherein the surface active agent is added in monometric form and further including adding a polymerization initiator to said composition, said polymerization initiator capable of and in an amount sufficient to polymerize the surface active agent during processing of said composition.
Claim 18
Dependent Claim
11 words
The method of claim 15 wherein the polymerization initiator is 1-ethyl-3-dimethyl-aminopropylcarbodiimide.
Claim 19
Dependent Claim
12 words
The method of claim 5 wherein the physiologically-active compound is a peptide.
Claim 20
Dependent Claim
12 words
The method of claim 17 wherein the physiologically-active compound is a polypeptide.
Claim 21
Dependent Claim
94 words
The method of claim 5 including admixing with the coacervate composition a glyceride selected from the group consisting of a monoglyceride, a diglyceride, a triglyceride, and mixtures thereof; said physiologically-active compound being dissolved or dispersed in the glyceride; said aqueous coacervate-based matrix particles encapsulated in a coacervate-based film encapsulating the glyceride and the physiologically-active compound within the coacervate-based matrix particles, said coacervate-based matrix particles comprising water selected form the group consisting of coacervate phase water, equilibrium phase water, and mixtures thereof, the glyceride, and the physiologically-active compound dissolved or dispersed within the matrix particles.
Claim 22
Dependent Claim
22 words
The method of claim 19 wherein the glyceride is a triglyceride having 8 to 18 carbon atoms per each substituted acid chain.
Claim 23
Independent Claim
77 words
A method of introducing a physiologically-active compound into the circulatory system of a mammal comprising having the mammal orally ingest a composition comprising an aqueous coacervate system including water and a surface active agent, said coacervate system including an aqueous emulsion of coacervate-based matrix particles containing the compound solubilized therein; said aqueous coacervate-based matrix comprising water selected from the group consisting of coacervate phase water, equilibrium phase water, and mixtures thereof, and said physiologically-active compound solubilized therein.
Claim 24
Independent Claim
77 words
A method of introducing a physiologically-active compound into the circulatory system of a mammal comprising having the mammal orally ingest a composition comprising an aqueous coacervate system including water and a surface active agent, said coacervate system including an aqueous emulsion of coacervate-based matrix particles containing the compound solubilized therein; said aqueous coacervate-based matrix comprising water selected from the group consisting of coacervate phase water, equilibrium phase water, and mixtures thereof, and said physiologically-active compound solubilized therein.
Claim 25
Dependent Claim
21 words
The method of claim 21 wherein the surface active agent comprises a protein, polymerized protein, phospholipid, polymerized phospholipid, or mixtures thereof.
Claim 26
Dependent Claim
12 words
The method of claim 22 wherein the polymerized protein is polymerized albumin.
Claim 27
Dependent Claim
36 words
The method of claim 22 wherein the polymerized phospholipid is a polymer of a compound selected from the group consisting of lecithin, cephalin, isolecithin, sphingomyelin, phosphatidyl serine, phosphatidic acid, phosphatidyl inositol, phosphatidyl choline, and mixtures thereof.
Claim 28
Dependent Claim
12 words
The method of claim 24 wherein the polymerized phospholipid is polymerized lecithin.
Claim 29
Dependent Claim
28 words
The method of claim 21 further including the step of drying the coacervate to form a powder capable of being reconstituted by the addition of a physiologically-acceptable fluid.
Claim 30
Independent Claim
86 words
A method of introduction a drug into the circulatory system of a mammal comprising having the mammal orally ingest a composition comprising an aqueous emulsion of coacervate-based matrix particles containing water, a surface active agent, and a drug solubilized therein; said coacervate system including a coacervate-based matrix containing the drug in aqueous solution; and a coacervate-based film encapsulating the matrix particles, said aqueous coacervate-based matrix particles comprising water selected from the group consisting of coacervate phase water, equilibrium phase water, and mixtures thereof and the drug.
Claim 31
Independent Claim
86 words
A method of introduction a drug into the circulatory system of a mammal comprising having the mammal orally ingest a composition comprising an aqueous emulsion of coacervate-based matrix particles containing water, a surface active agent, and a drug solubilized therein; said coacervate system including a coacervate-based matrix containing the drug in aqueous solution; and a coacervate-based film encapsulating the matrix particles, said aqueous coacervate-based matrix particles comprising water selected from the group consisting of coacervate phase water, equilibrium phase water, and mixtures thereof and the drug.
Claim 32
Dependent Claim
10 words
The method of claim 27 wherein the drug comprises insulin.
Claim 33
Dependent Claim
12 words
The method of claim 27 wherein the drug comprises an atrial peptide.
Claim 34
Independent Claim
88 words
A method of introducing a drug into the circulatory system of a mammal comprising injecting the body of the mammal with a composition comprising an aqueous coacervate composition including water, a surface active agent, and a drug; said coacervate composition including a coacervate-based matrix containing the drug in aqueous solution or aqueous suspension and a film encapsulating the matrix particles; said aqueous matrix particles containing water selected from the group consisting of coacervate phase water, equilibrium phase water, and mixtures thereof, and the drug solubilized or dispersed therein.
Claim 35
Independent Claim
88 words
A method of introducing a drug into the circulatory system of a mammal comprising injecting the body of the mammal with a composition comprising an aqueous coacervate composition including water, a surface active agent, and a drug; said coacervate composition including a coacervate-based matrix containing the drug in aqueous solution or aqueous suspension and a film encapsulating the matrix particles; said aqueous matrix particles containing water selected from the group consisting of coacervate phase water, equilibrium phase water, and mixtures thereof, and the drug solubilized or dispersed therein.
Claim 36
Dependent Claim
12 words
The method of claim 30 wherein the drug comprises an atrial peptide.
Claim 37
Independent Claim
138 words
A method of preparing a composition containing one or more physiologically-active compounds for oral, tissue absorptive, inhalation, or parenteral administration to a mammal comprising mixing an aqueous solution of water, a surface active agent, a coacervating agent and a physiologically-active compound to form a two phase aqueous coacervate composition containing the physiologically-active compound in one or both of the two-phase bound as particles in a coacervate matrix and within a coacervate-based aqueous film containing the surface active agent, said coacervate-based matrix comprising water selected from the group consisting of coacervate phase water, equilibrium phase water, and mixtures thereof and the physiologically-active compound in solution within the matrix water; separating the particles; and adding a hydrocolloid to the particles in an amount of 2-20% w/v to form a gel-like surface film surrounding the matrix particles containing the physiologically-active compound.
Claim 38
Independent Claim
138 words
A method of preparing a composition containing one or more physiologically-active compounds for oral, tissue absorptive, inhalation, or parenteral administration to a mammal comprising mixing an aqueous solution of water, a surface active agent, a coacervating agent and a physiologically-active compound to form a two phase aqueous coacervate composition containing the physiologically-active compound in one or both of the two-phase bound as particles in a coacervate matrix and within a coacervate-based aqueous film containing the surface active agent, said coacervate-based matrix comprising water selected from the group consisting of coacervate phase water, equilibrium phase water, and mixtures thereof and the physiologically-active compound in solution within the matrix water; separating the particles; and adding a hydrocolloid to the particles in an amount of 2-20% w/v to form a gel-like surface film surrounding the matrix particles containing the physiologically-active compound.
Claim 39
Dependent Claim
20 words
The method of claim 32 further including emulsifying and microemulsifying the composition to form coacervate particles useful for oral administration.
Claim 40
Dependent Claim
29 words
The method of claim 32 further including emulsifying and microemulsifying the composition to form coacervate particles useful for oral administration having a particle size less than about 10 microns.
Claim 41
Dependent Claim
17 words
The method of claim 32 wherein the coacervate particles are microemulsified to less than about 2 microns.
Claim 42
Dependent Claim
17 words
The method of claim 32 wherein the coacervate particles are microemulsified to less than about 1 micron.
Claim 43
Dependent Claim
14 words
The method of claim 32 wherein the surface active agent is a polymerized phospholipid.
Claim 44
Dependent Claim
14 words
The method of claim 32 further including adding an anti-oxidant to the separated particles.
Claim 45
Independent Claim
111 words
A method of introducing a drug into the circulatory system of a mammal comprising having the mammal orally ingest a composition comprising an aqueous coacervate system including water, a surface active agent, and a drug; said coacervate system including a coacervate-based matrix containing the drug and a film encapsulating the matrix particles; said aqueous coacervate-based matrix comprising water selected from the group consisting of coacervate phase water, equilibrium phase water, and mixtures thereof, and the drug in solution within the matrix water; separating the particles; and adding a hydrocolloid to the particles in an amount of 2-20% w/v to form a gel-like surface film surrounding the matrix particles containing the drug.
Claim 46
Independent Claim
111 words
A method of introducing a drug into the circulatory system of a mammal comprising having the mammal orally ingest a composition comprising an aqueous coacervate system including water, a surface active agent, and a drug; said coacervate system including a coacervate-based matrix containing the drug and a film encapsulating the matrix particles; said aqueous coacervate-based matrix comprising water selected from the group consisting of coacervate phase water, equilibrium phase water, and mixtures thereof, and the drug in solution within the matrix water; separating the particles; and adding a hydrocolloid to the particles in an amount of 2-20% w/v to form a gel-like surface film surrounding the matrix particles containing the drug.
Claim 47
Dependent Claim
21 words
The method of claim 39 wherein the surface active agent comprises a protein, polymerized protein, phospholipid, polymerized phospholipid, or mixtures thereof.
Claim 48
Dependent Claim
10 words
The method of claim 39 wherein the drug comprises insulin.
Claim 49
Dependent Claim
12 words
The method of claim 39 wherein the drug comprises an atrial peptide.
Claim 50
Independent Claim
125 words
A method of preparing a composition useful as a system to introduce and transport medically useful composition in the body of mammals; said composition comprising an aqueous emulsion of particles of a coacervate-based matrix having one or more physiologically-active compounds incorporated therein; said coacervate-based matrix comprising water selected from the group consisting of coacervate phase water, equilibrium phase water, and mixtures thereof, said matrix particles including the physiologically-active compound solubilized in the matrix water; said method comprising forming a mixture of one or more surface active agents, water and one or more physiologically-active compounds to produce a two phase aqueous coacervate composition containing said compounds, and emulsifying the composition under conditions to produce an aqueous emulsion of the coacervate-based matrix particles containing the physiologically-active compound.
Claim 51
Independent Claim
125 words
A method of preparing a composition useful as a system to introduce and transport medically useful composition in the body of mammals; said composition comprising an aqueous emulsion of particles of a coacervate-based matrix having one or more physiologically-active compounds incorporated therein; said coacervate-based matrix comprising water selected from the group consisting of coacervate phase water, equilibrium phase water, and mixtures thereof, said matrix particles including the physiologically-active compound solubilized in the matrix water; said method comprising forming a mixture of one or more surface active agents, water and one or more physiologically-active compounds to produce a two phase aqueous coacervate composition containing said compounds, and emulsifying the composition under conditions to produce an aqueous emulsion of the coacervate-based matrix particles containing the physiologically-active compound.
Claim 52
Independent Claim
87 words
A method of administering a physiologically-active compound to a mammal comprising topically applying a coacervate composition containing a physiologically-active compound on the skin of a mammal; said coacervate composition comprising an aqueous emulsion of coacervate-based matrix particles, said matrix particles comprising water, selected from the group consisting of coacervate phase water, equilibrium phase water, and mixtures thereof, said matrix particles including the physiologically-active compound solubilized in the matrix water; and applying sound waves to the topically applied coacervate composition to drive the coacervate composition into the skin.
Claim 53
Independent Claim
87 words
A method of administering a physiologically-active compound to a mammal comprising topically applying a coacervate composition containing a physiologically-active compound on the skin of a mammal; said coacervate composition comprising an aqueous emulsion of coacervate-based matrix particles, said matrix particles comprising water, selected from the group consisting of coacervate phase water, equilibrium phase water, and mixtures thereof, said matrix particles including the physiologically-active compound solubilized in the matrix water; and applying sound waves to the topically applied coacervate composition to drive the coacervate composition into the skin.
Claim 54
Independent Claim
124 words
A method of maintaining tissue or an organ of a mammal viable, outside of the mammal's body comprising forming a mixture of one or more surface active agents and water to form a two phase aqueous coacervate composition, and emulsifying the composition to form an aqueous emulsion of coacervate-based matrix particles comprising water selected from the group consisting of coacervate phase water, equilibrium phase water, and mixtures thereof, said matrix particles having solubilized within the matrix water, a compound capable of extending the life of the organ when in contact therewith, and contacting the tissue or organ, outside of the mammal's body, with said aqueous emulsion to maintain the visibility of the tissue or organ until said tissue organ is attached to a mammal.
Claim 55
Independent Claim
124 words
A method of maintaining tissue or an organ of a mammal viable, outside of the mammal's body comprising forming a mixture of one or more surface active agents and water to form a two phase aqueous coacervate composition, and emulsifying the composition to form an aqueous emulsion of coacervate-based matrix particles comprising water selected from the group consisting of coacervate phase water, equilibrium phase water, and mixtures thereof, said matrix particles having solubilized within the matrix water, a compound capable of extending the life of the organ when in contact therewith, and contacting the tissue or organ, outside of the mammal's body, with said aqueous emulsion to maintain the visibility of the tissue or organ until said tissue organ is attached to a mammal.
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