Pharmaceutical formulations that have a biologically active hydrophilic phase and a chylomicra-containing hydrophobic phase
AssigneePatralan Limited
InventorsYoung W. Cho, Michael John Flynn
Life of this patent
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Abstract
Orally or rectally administrable formulations of biologically active material comprise a water-in-oil microemulsion, wherein the hydrophilic phase of the microemulsion comprises the biologically active material and the hydrophobic phase comprises chylomicra or material capable of forming chylomicra in the intestinal mucosa after administration. The biologically active material may be any of a wide range of substances including insulin, calcitonin and somatotrophin or growth hormone. Formulations of the invention are particularly suitable for the oral administration of insulin in the treatment of diabetes.
Claims60
A pharmaceutical formulation consisting essentially of an emulsion having a hydrophilic phase and a continuous hydrophobic phase, wherein (A) the hydrophilic phase has a proteinaceous pharmaceutically active material and (B) the continuous hydrophobic phase consists essentially of the following components:
- ______________________________________ % (v/v) ______________________________________ cholesterol 0.1-20 phospholipid 0.1-40 lipophilic surfactant 0.1-70 unesterified fatty acid 1-75 cholesterol ester 0-10 apoprotein 0-10, ______________________________________
- wherein said lipophilic surfactant is selected from the group consisting of:
- glycerol esters;
- polyoxyethylated glycol monoethers;
- polyoxyethylated fatty acids;
- sorbitan fatty acid esters;
- polyoxyethylated sorbitan fatty esters;
- polyoxyethylated castor oils;
- poloxamers;
- and mixtures thereof.
A pharmaceutical formulation consisting essentially of an emulsion having a hydrophilic phase and a continuous hydrophobic phase, wherein (A) the hydrophilic phase has a proteinaceous pharmaceutically active material and (B) the continuous hydrophobic phase consists essentially of the following components:
- ______________________________________ % (v/v) ______________________________________ cholesterol 0.1-20 phospholipid 0.1-40 lipophilic surfactant 0.1-70 unesterified fatty acid 1-75 cholesterol ester 0-10 apoprotein 0-10, ______________________________________
- wherein said lipophilic surfactant is selected from the group consisting of:
- glycerol esters;
- polyoxyethylated glycol monoethers;
- polyoxyethylated fatty acids;
- sorbitan fatty acid esters;
- polyoxyethylated sorbitan fatty esters;
- polyoxyethylated castor oils;
- poloxamers;
- and mixtures thereof;
- and wherein chylomicra comprising said components of the continuous hydrophobic phase are formed upon enteral administration of the formulation.
A pharmaceutical formulation consisting essentially of an emulsion having a hydrophilic phase and a continuous hydrophobic phase, wherein (A) the hydrophilic phase has a proteinaceous pharmaceutically active material and (B) the continuous hydrophobic phase consists essentially of the following components:
- ______________________________________ % (v/v) ______________________________________ cholesterol 0.1-5 phospholipid 0.1-40 lipophilic surfactant 0.1-70 unesterified fatty acid 1-75 cholesterol ester 0-10 apoprotein 0-10, ______________________________________
- wherein said lipophilic surfactant is selected from the group consisting of:
- glycerol esters;
- polyoxyethylated glycol monoethers;
- polyoxyethylated fatty acids;
- sorbitan fatty acid esters;
- polyoxyethylated sorbitan fatty esters;
- polyoxyethylated castor oils;
- poloxamers;
- and mixtures thereof.
A pharmaceutical formulation consisting essentially of an emulsion having a hydrophilic phase and a continuous hydrophobic phase, wherein (A) the hydrophilic phase has a proteinaceous pharmaceutically active material and (B) the continuous hydrophobic phase consists essentially of the following components:
- ______________________________________ % (v/v) ______________________________________ cholesterol 0.1-5 phospholipid 0.1-40 lipophilic surfactant 0.1-70 unesterified fatty acid 1-75 cholesterol ester 0-10 apoprotein 0-10, ______________________________________
- wherein said lipophilic surfactant is selected from the group consisting of:
- glycerol esters;
- polyoxyethylated glycol monoethers;
- polyoxyethylated fatty acids;
- sorbitan fatty acid esters;
- polyoxyethylated sorbitan fatty esters;
- polyoxyethylated castor oils;
- poloxamers;
- and mixtures thereof;
- and wherein chylomicra comprising said components of the continuous hydrophobic phase are formed upon enteral administration of the formulation.
A formulation as claimed in 1, wherein said phospholipid is lecithin.
A pharmaceutical formulation consisting essentially of
- (1) an emulsion having a hydrophilic phase and a continuous hydrophobic phase, wherein
- (A) the hydrophilic phase has a proteinaceous pharmaceutically active material and
- (B) the continuous hydrophobic phase consists essentially of the following components:
- ______________________________________ % (v/v) ______________________________________ cholesterol 0.1-20 phospholipid 0.1-40 lipophilic surfactant 0.1-70 unesterified fatty acid 1-75 cholesterol ester 0-10 apoprotein 0-10, ______________________________________
- wherein said lipophilic surfactant is selected from the group consisting of glycerol esters, polyoxyethylated glycol monoethers, polyoxyethylated fatty acids, sorbitan fatty acid esters, polyoxyethylated sorbitan fatty esters, polyoxyethylated castor oils, poloxamers, and mixtures thereof, and
- (2) an ingredient selected from the group consisting of (a) up to 0.5% w/v of a protease inhibitor;
- (b) up to 10% w/v of an emulsification aid;
- (c) up to 10% w/v of a compound selected from the group consisting of dextrin, acacia, carboxypolymethylene and colloidal aluminum hydroxide;
- (d) up to 0.3% w/v of an antioxidant, and (e) up to about 3% of an antimicrobial agent.
A formulation as claimed in 3, wherein said phospholipid is lecithin.
A pharmaceutical formulation consisting essentially of
- (1) an emulsion having a hydrophilic phase and a continuous hydrophobic phase, wherein
- (A) the hydrophilic phase has a proteinaceous pharmaceutically active material and
- (B) the continuous hydrophobic phase consists essentially of the following components:
- ______________________________________ % (v/v) ______________________________________ cholesterol 0.1-5 phospholipid 0.1-40 lipophilic surfactant 0.1-70 unesterified fatty acid 1-75 cholesterol ester 0-10 apoprotein 0-10, ______________________________________
- wherein said lipophilic surfactant is selected from the group consisting of glycerol esters, polyoxyethylated glycol monoethers, polyoxyethylated fatty acids, sorbitan fatty acid esters, polyoxyethylated sorbitan fatty esters, polyoxyethylated castor oils, poloxamers, and mixtures thereof, and
- (2) an ingredient selected from the group consisting of (a) up to 0.5% w/v of a protease inhibitor, (b) up to 10% w/v of an emulsification aid, (c) up to 10% w/v of a compound selected from the group consisting of dextrin, acacia, carboxypolymethylene and colloidal aluminum hydroxide, (d) up to 0.3% w/v of an antioxidant, and (e) up to about 3% of an antimicrobial agent.
Dependencies are inferred from the claim text.