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US 12,758,504 B2Granted
Compositions comprising lipid-based nanoparticles for treating diabetes mellitus
AssigneeDiasome Pharmaceuticals, Inc.
InventorW. Blair Geho
Life of this patent
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Abstract
The invention provides methods of treating a subject having diabetes mellitus. The invention further provides methods of increasing distribution volume of insulin in a subject.
Claims33
A method of improving blood glucose control in a human subject suffering from diabetes mellitus, the method comprising:
- selecting a human subject suffering from diabetes mellitus with a baseline HbA1c value who had been administered a baseline diabetes treatment comprising a baseline free bolus insulin formulated in the absence of a hepatic delivery vehicle (HDV) and a baseline free basal insulin;
- administering to the human subject (a) instead of the baseline free bolus insulin, a HDV bolus insulin composition comprising insulin and a lipid-based nanoparticle, wherein the insulin is dispersed within the nanoparticle, and (b) a free basal insulin;
- wherein one of the following applies:
- (a) if the human subject has a baseline HbA1c value greater than 8.5%, then the human subject is administered a HDV bolus insulin composition with an insulin amount lower than the amount of baseline free bolus insulin and the human subject is administered a free basal insulin amount that is about the same as the baseline free basal insulin;
- (b) if the human subject has a baseline HbA1c value between 7% and 8.5%, then the human subject is administered a HDV bolus insulin composition with an insulin amount that is about equal to the baseline free bolus insulin and the human subject is administered a free basal insulin amount that is lower than the baseline free basal insulin;
- wherein the administering results in better blood glucose control as compared to the baseline diabetes treatment;
- wherein the administering further results in at least one of the following:
- (i) no significant hypoglycemia in the human subject;
- (ii) no significant iatrogenic hyperinsulinemia in the human subject;
- wherein the nanoparticle is enclosed by a bipolar lipid membrane comprising cholesterol, dicetyl phosphate, an amphipathic lipid, and a hepatocyte receptor binding molecule;
- wherein the amphipathic lipid comprises at least one selected from the group consisting of 1,2-distearoyl-sn-glycero-3-phosphocholine, 1,2-dipalmitoyl-sn-glycerol-[3-phospho-rac-(1-glycerol)], 1,2-distearoyl-sn-glycero-3-phosphoethanolamine, 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-(succinyl), 1,2-dimyristoyl-sn-glycero-3-phosphate, 1,2-dimyristoyl-sn-glycero-3-phosphocholine, 1,2-distearoyl-sn-glycero-3-phosphate, 1,2-dipalmitoyl-sn-glycero-3-phosphate, and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine;
- wherein the at least one hepatocyte receptor binding molecule extends outward from the nanoparticle;
- and
- wherein the size of the nanoparticle ranges from about 10 nm to about 150 nm.
11 more elements
A method of improving blood glucose control in a human subject suffering from diabetes mellitus, the method comprising:
- selecting a human subject suffering from diabetes mellitus with a baseline HbA1c value who had been administered a baseline treatment comprising a continuous administration of a baseline free insulin formulated in the absence of a hepatic delivery vehicle (HDV);
- administering to the human subject in a continuous manner, instead of the baseline free insulin, a HDV composition comprising insulin and a lipid-based nanoparticle, wherein the insulin is dispersed within the nanoparticle;
- wherein the amount of the insulin in the HDV composition is lower than the amount of the baseline free insulin;
- wherein the administering results in better blood glucose control as afforded by the baseline treatment;
- wherein the nanoparticle is enclosed by a bipolar lipid membrane comprising cholesterol, dicetyl phosphate, an amphipathic lipid, and a hepatocyte receptor binding molecule;
- wherein the amphipathic lipid comprises at least one selected from the group consisting of 1,2-distearoyl-sn-glycero-3-phosphocholine, 1,2-dipalmitoyl-sn-glycerol-[3-phospho-rac-(1-glycerol)], 1,2-distearoyl-sn-glycero-3-phosphoethanolamine, 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-(succinyl), 1,2-dimyristoyl-sn-glycero-3-phosphate, 1,2-dimyristoyl-sn-glycero-3-phosphocholine, 1,2-distearoyl-sn-glycero-3-phosphate, 1,2-dipalmitoyl-sn-glycero-3-phosphate, and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine;
- wherein the at least one hepatocyte receptor binding molecule extends outward from the nanoparticle;
- and
- wherein the size of the nanoparticle ranges from about 10 nm to about 150 nm.
6 more elements
Dependencies are inferred from the claim text.