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US 5,444,041 AGranted
Convertible microemulsion formulations
AssigneeIbah, Inc.
InventorsAlbert J. Owen, Seang H. Yiv, Ani B. Sarkahian
Life of this patent
Estimating the term…
Abstract
There is provided a water-in-oil (w/o) microemulsion which readily converts to an oil-in-water (o/w) emulsion by the addition of aqueous fluid to the w/o microemulsion, whereby any water-soluble biologically-active material in the aqueous phase is released for absorption by the body. The w/o microemulsion is particularly useful for storing proteins and the like for long periods of time at room temperature and above until they are ready for use, at which time the addition of aqueous fluid converts the microemulsion to an o/w emulsion and releases the protein.
Claims137
A liquid biologically compatible water-in-oil microemulsion composition which converts to an oil-in-water emulsion by the addition of water, comprising:
- (a) up to about 20 volume percent of an internal dispersed aqueous phase comprising an effective amount of a biologically-active material, said biologically-active material consisting of therapeutic water-soluble materials,
- (b) from about 30 to 99 volume percent of a continuous oil phase comprising diesters of propylene glycol having from about 15 to 40 carbon atoms, and
- (c) from about 1 to 70 volume percent of a surfactant or mixture of surfactants, wherein the surfactant or surfactant mixture has a hydrophilic-lipophilic balance value of from 7 to 14.
A biologically compatible water-in-oil microemulsion composition which converts to an oil-in-water emulsion by the addition of water, comprising:
- (a) up to about 20 volume percent of an internal dispersed aqueous phase comprising an effective amount of a biologically-active material,
- (b) about 30 to 99 volume percent of a continuous oil phase comprising at least one pharmaceutically-acceptable oil comprising diesters of propylene glycol having from 7 to 55 carbon atoms, and
- (c) about 1 to about 70 volume percent of a mixture of surfactants comprising mono- and di-glycerides of capric and caprylic acid, wherein the surfactant mixture has a hydrophilic-lipophilic balance value of from 7 to 14;
- and
- wherein the biologically-active material is selected from the group consisting of calcitonin and insulin, and wherein the microemulsion is a liquid.
2 more elements
A biologically compatible water-in-oil microemulsion composition which is a solid at room temperature and which converts to an oil-in-water emulsion by the addition of water, comprising:
- (a) up to about 20 volume percent of an internal dispersed aqueous phase comprising an effective amount of a biologically-active material, wherein the biologically-active material is water-soluble and is a therapeutic and is a protein, peptide, or other pharmaceutically-active material;
- (b) from about 30 to 99 volume percent of a continuous oil phase comprising at least one pharmaceutically-acceptable oil which is a solid at room temperature, and wherein the oil phase comprises a diester of propylene glycol;
- and
- (c) from about 1 to 70 volume percent a surfactant or mixture of surfactants, wherein the surfactant or surfactant mixture has a hydrophilic-lipophilic balance value of from 7 to 14.
1 more element
A liquid water-in-oil microemulsion composition that converts to an oil-in-water emulsion by the addition of water, comprising:
- (a) up to about 60 volume percent, based upon the total volume of the microemulsion, of an internally dispersed aqueous phase comprising an effective amount of a biologically-active material;
- (b) from about 5 to 99 volume percent of a continuous oil phase comprising propylene glycol diesters having from 7 to 55 carbon atoms;
- and
- (c) from about 1 to 70 volume percent of a surfactant or mixture of surfactants comprising C.sub.9-13 monoglycerides, wherein the surfactant or surfactant mixture has a hydrophilic-lipophilic balance value of from 7 to 14,
- wherein the biologically-active material is selected from the group consisting of calcitonins, insulins, fibrinogen antagonists, growth hormone releasing peptides, interleukins, erythropoietins, colony stimulating factors, hematoregulatory peptides, vasopressin, collagenase inhibitors, angiotensin inhibitors, mammalian growth hormones, heparins, clotting factors, tissue plasminogen activators, atrial natriuretic peptides, and tumor necrosis factor, and wherein the water:oil partition coefficient of the active material is greater than 10:1.
2 more elements
A liquid water-in-oil microemulsion composition that converts to an oil-in-water emulsion by the addition of water, comprising:
- (a) up to about 60 volume percent, based upon the total volume of the microemulsion, of an internally dispersed aqueous phase comprising an effective amount of a biologically-active material wherein the biologically-active material consists of therapeutic materials which have a water:oil partition coefficient greater than 10:1;
- (b) from about 5 to 99 volume percent of a continuous oil phase comprising diesters of propylene glycol having from about 7 to 55 carbon atoms;
- (c) from about 1 to 70 volume percent of a surfactant or mixture of surfactants, wherein the surfactant or surfactant mixture has a hydrophilic-lipophilic balance value of from 7 to 14.
A water-in-oil microemulsion composition which is a solid at room temperature and that converts to an oil-in-water emulsion by the addition of water, comprising:
- (a) up to about 60 volume percent, based upon the total volume of the microemulsion, of an internally dispersed aqueous phase comprising an effective amount of a biologically-active material, wherein the biologically-active material consists of water-soluble therapeutics which are either proteins, peptides, immunogens, or other pharmaceutically-active materials;
- (b) from about 5 to 99 volume percent of a continuous oil phase comprising at least one pharmaceutically-acceptable oil comprising a diester of propylene glycol;
- and
- (c) from about 1 to 70 volume percent of a surfactant or mixture of surfactants, wherein the surfactant or surfactant mixture has a hydrophilic-lipophilic balance value of from 7 to 14,
- wherein the water:oil partition coefficient of the biologically-active material is greater than 10:1, and
- wherein the oil phase, surfactant or surfactant mixture, or both, comprise a component that has a melting point above about 23.degree. C.
3 more elements
A water-in-oil microemulsion composition, comprising:
- (a) up to about 60 volume percent, based upon the total volume of the microemulsion, of an internally dispersed aqueous phase comprising an effective amount of a biologically-active material wherein the biologically-active material consists of therapeutic water-soluble materials having a water:oil partition coefficient greater than 10:1, and a modifier comprising sorbitol, polyethylene glycol, propylene glycol, mannitol, monosaccharides, or disaccharides, present in an amount of from 10-50% by weight of the aqueous phase and sufficient to cause the water-in-oil microemulsion to convert to an oil-in-water microemulsion upon the addition of aqueous medium;
- (b) a continuous oil phase comprising at least one pharmaceutically acceptable oil;
- and
- (c) a surfactant or mixture of surfactants, wherein the surfactant or mixture of surfactants comprises monoglycerides or diglycerides of capric or caprylic acid and has a hydrophilic-lipophilic balance value of greater than 7,
- wherein the amounts of the aqueous phase, oil phase, and surfactant or surfactant mixture are such that the water-in-oil microemulsion converts to an oil-in-water microemulsion upon the addition of water.
2 more elements
A method of administering to animals by controlled release a biologically-active material which comprises:
- (a) providing a phase-reversible water-in-oil microemulsion composition that converts to an oil-in-water emulsion by the addition of water, comprising:
- (1) up to about 20 volume percent of an internal, dispersed aqueous phase comprising an effective amount of a biologically-active material wherein said biologically-active material is a therapeutic and is water-soluble,
- (2) from about 30 to 99 volume percent of a continuous oil phase comprising at least one pharmaceutically-acceptable oil, and
- (3) from about 1 to 70 volume percent of a surfactant mixture having a hydrophilic-lipophilic balance value of from 7 to 14 and comprising a mixture of mono-and di-glycerides of captic and caprylic acid, and
- (b) administering an effective amount of the microemulsion to the body of an animal, wherein the water-in-oil microemulsion is administered orally.
2 more elements
A method of administering to animals a biologically-active material which method comprises:
- (a) providing a water-in-oil microemulsion composition that converts to an oil-in-water emulsion by the addition of water, comprising:
- (1) up to about 60 volume percent, based upon the total volume of the microemulsion, of an internally dispersed aqueous phase comprising an effective amount of a biologically-active material that is water-soluble;
- (2) from about 5 to 99 volume percent of a continuous oil phase comprising diesters of propylene glycol having from about 7 to 55 carbon atoms;
- and
- (3) from about 1 to 70 volume percent of a surfactant or mixture of surfactants, wherein the surfactant or surfactant mixture has a hydrophilic-lipophilic balance value from 7 to 14, and
- (b) administering an effective amount of the microemulsion to the body of an animal, wherein the water-in-oil microemulsion is administered orally, rectally or via any other mucous membrane.
3 more elements
A method of administering to animals a biologically-active material which method comprises:
- (a) providing a water-in-oil microemulsion composition that converts to an oil-in-water emulsion by the addition of water, comprising:
- (1) up to about 60 volume percent, based upon the total volume of the microemulsion, of an internally dispersed aqueous phase comprising an effective amount of a biologically-active material wherein the biologically-active material has a water:oil partition coefficient of greater than 10:1;
- (2) from about 5 to 99 volume percent of a continuous oil phase comprising at least one pharmaceutically-acceptable oil;
- and
- (3) from 1 to 70 volume percent of a surfactant or mixture of surfactants comprising monoglycerides or diglycerides of capric or caprylic acid and having a hydrophilic-lipophilic balance value of from 7 to 14, and
- (b) administering an effective amount of the microemulsion to the body of an animal, wherein the water-in-oil microemulsion is administered orally.
3 more elements
A method of administering to animals a biologically-active material which method comprises:
- (a) providing a water-in-oil microemulsion comprising:
- (1) up to about 60 volume percent, based upon the total volume of the microemulsion, of an internally dispersed aqueous phase comprising an effective amount of a biologically-active material which consists of therapeutic water-soluble materials having a water:oil partition coefficient of greater than 10:1, and a modifier, present in an amount of from 10-50% by weight of the aqueous phase and sufficient to cause the water-in-oil microemulsion to convert to an oil-in-water microemulsion upon the addition of aqueous medium;
- (2) from about 5 to 99 volume percent of a continuous oil phase comprising at least one pharmaceutically-acceptable oil;
- and
- (3) a surfactant or mixture of surfactants comprising monoglycerides or diglycerides of capric or caprylic acid, wherein the surfactant or surfactant mixture has a hydrophilic-lipophilic balance value of at least 7;
- (b) administering an effective amount of the water-in-oil microemulsion to the body of an animal, wherein the water-in-oil microemulsion is administered parenterally, enterally, or via any other mucous membrane;
- and
- (c) converting the water-in-oil microemulsion into an oil-in-water microemulsion.
5 more elements
A water-in-oil microemulsion composition which is a solid at room temperature and that converts to an oil-in-water emulsion by the addition of water, comprising:
- (a) up to about 60 volume percent, based upon the total volume of the microemulsion, of an internally dispersed aqueous phase comprising an effective amount of a biologically-active material, wherein the biologically-active material is a therapeutic and is a protein, peptide, immunogen, or other pharmaceutically-active material;
- (b) from about 5 to 99 volume percent of a continuous oil phase comprising at least one pharmaceutically-acceptable oil comprising diesters of propylene glycol having from about 7 to 55 carbon atoms;
- and
- (c) from about 1 to 70 volume percent of a surfactant or mixture of surfactants comprising C.sub.9-13 monoglycerides, C.sub.15-23 diglycerides, or mixtures thereof, and wherein the surfactant or surfactant mixture has a hydrophilic-lipophilic balance value of from 7 to 14,
- wherein the water:oil partition coefficient of the active material is greater than 10:1, and
- wherein the oil phase, surfactant or surfactant mixture, or both, comprise a component that has a melting point above about 23.degree. C.
3 more elements
A method of administering to animals a biologically-active material which method comprises:
- (a) providing a water-in-oil microemulsion composition comprising:
- (1) up to about 60 volume percent, based upon the total volume of the microemulsion, of an internally dispersed aqueous phase comprising an effective amount of a biologically-active material that is water-soluble and is a therapeutic and is a protein or peptide;
- (2) from about 5 to 99 volume percent of a continuous oil phase comprising diesters of propylene glycol having from about 7 to 55 carbon atoms;
- (3) from about 1 to 70 volume percent of a surfactant or mixture of surfactants, wherein the surfactant or surfactant mixture has a hydrophilic-lipophilic balance value from 7 to 14;
- (b) administering an effective amount of the microemulsion to the body of an animal, wherein the water-in-oil microemulsion is administered parenterally, enterally, or via any other mucous membrane;
- and
- (c) converting the water-in-oil microemulsion to an oil-in-water emulsion after the administration step by the addition of aqueous body fluid.
4 more elements
A method of administering to animals a biologically-active material which method comprises:
- (a) providing a water-in-oil microemulsion composition that converts to an oil-in-water emulsion by the addition of water, comprising:
- (1) up to about 60 volume percent, based upon the total volume of the microemulsion, of an internally dispersed aqueous phase comprising an effective amount of a biologically-active, water-soluble material, said biologically-active material having a water:oil partition coefficient of greater than 10:1 and being selected from the group consisting of calcitonin, insulin, growth hormone releasing peptide and human growth hormone;
- (2) from about 5 to 99 volume percent of a continuous oil phase comprising at least one pharmaceutically-acceptable oil;
- and
- (3) from 1 to 70 volume percent of a surfactant or mixture of surfactants, said surfactant or surfactant mixture having a hydrophilic-lipophilic balance value of from 7 to 14, and
- (b) administering an effective amount of the microemulsion to the body of an animal, said administration being oral;
- and
- (c) achieving a therapeutically effective increase in the blood system of said animal of said biologically-active material.
5 more elements
A method of administering to animals by controlled release a biologically-active material which comprises:
- (a) providing a solid phase-reversible water-in-oil microemulsion composition that converts to an oil-in-water emulsion by the addition of water, comprising:
- (1) up to about 20 volume percent of an internal, dispersed aqueous phase comprising an effective amount of a biologically-active material consisting of therapeutic water soluble materials,
- (2) from about 30 to 99 volume percent of a continuous oil phase comprising at least one pharmaceutically-acceptable oil, and
- (3) from about 1 to 70 volume percent of a surfactant or surfactant mixture having a hydrophilic-lipophilic balance value of from 7 to 14;
- and
- (b) administering an effective amount of the microemulsion to the body of an animal, wherein the water-in-oil microemulsion is administered rectally.
3 more elements
A water-in-oil microemulsion composition which is a solid at room temperature, comprising:
- (a) a liquid water-in-oil microemulsion composition that converts to an oil-in-water emulsion by the addition of water, comprising
- (1) up to about 60 volume percent, based upon the total volume of the microemulsion, of an internally dispersed aqueous phase comprising an effective amount of a biologically-active material, wherein the biologically-active material is a therapeutic and is a protein, peptide, or immunogen;
- (2) from about 5 to 99 volume percent of a continuous oil phase comprising at least one pharmaceutically-acceptable oil comprising diesters of propylene glycol having from about 7 to 55 carbon atoms;
- and
- (3) from about 1 to 70 volume percent of a surfactant or mixture of surfactants comprising C.sub.9-13 monoglycerides, C.sub.15-23 diglycerides, or mixtures thereof, and wherein the surfactant or surfactant mixture has a hydrophilic-lipophilic balance value of from 7 to 14,
- wherein the water:oil partition coefficient of the active material is greater than 10:1, and
- (b) a solid matrix for said liquid water-in-oil microemulsion, said matrix consisting of a high melting point oil which melts at a temperature of about 25.degree.-60.degree. C., wherein the volume ratio of the high melting point oil to the liquid water-in-oil microemulsion is from about 0.5:1 to about 2:1,
- wherein said liquid water-in-oil microemulsion is dispersed within said solid matrix to form a solid composition.
5 more elements
Dependencies are inferred from the claim text.