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US 2015/0031608 A1Published application
Lipid construct for delivery of insulin to a mammal
AssigneeSDG, Inc.
InventorsJOHN R. LAU, W. BLAIR GEHO
Life of this patent
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Abstract
The instant invention is drawn to a hepatocyte targeted composition comprising insulin associated with a lipid construct comprising an amphipathic lipid and an extended amphipathic lipid that targets the construct to a receptor displayed by an hepatocyte. The composition can comprise a mixture of free insulin and insulin associated with the complex. The composition can be modified to protect insulin and the complex from degradation. The invention also includes methods for the manufacture of the composition and loading insulin into the composition and recycling various components of the composition. Methods of treating individuals inflicted with diabetes.
Claims29
1-75. (canceled)
A lipid construct comprising an amphipathic lipid and an extended amphipathic lipid,
- wherein the amphipathic lipid comprises at least one lipid selected from the group consisting of 1,2-distearoyl-sn-glycero-3-phosphocholine, cholesterol, dicetyl phosphate, 1,2-dipalmitoyl-sn-glycerol-[3-phospho-rac-(1-glycero)], 1,2-distearoyl-sn-glycero-3-phosphoethanolamine, 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-(succinyl);
- and,
- wherein the extended amphipathic lipid is selected from the group consisting of N-hydroxysuccinimide (NHS) biotin;
- sulfo-NHS-biotin;
- N-hydroxysuccinimide long chain biotin;
- sulfo-N-hydroxysuccinimide long chain biotin;
- D-biotin;
- biocytin;
- sulfo-N-hydroxysuccinimide-S—S-biotin;
- biotin-BMCC;
- biotin-HPDP;
- iodoacetyl-LC-biotin;
- biotin-hydrazide;
- biotin-LC-hydrazide;
- biocytin hydrazide;
- biotin cadaverine;
- carboxybiotin;
- photobiotin;
- ρ-aminobenzoyl biocytin trifluoroacetate;
- ρ-diazobenzoyl biocytin;
- biotin DHPE;
- biotin-X-DHPE;
- 12-((biotinyl)amino)dodecanoic acid;
- 12-((biotinyl)amino)dodecanoic acid succinimidyl ester;
- S-biotinyl homocysteine;
- biocytin-X;
- biocytin x-hydrazide;
- biotinethylenediamine;
- biotin-XL;
- biotin-X-ethylenediamine;
- biotin-XX hydrazide;
- biotin-XX-SE;
- biotin-XX, SSE;
- biotin-X-cadaverine;
- α-(t-BOC)biocytin;
- N-(biotinyl)-N′-(iodoacetyl)ethylenediamine;
- DNP-X-biocytin-X-SE;
- biotin-X-hydrazide;
- norbiotinamine hydrochloride;
- 3-(N-maleimidylpropionyl)biocytin;
- ARP;
- biotin-l-sulfoxide;
- biotin methyl ester, biotin-maleimide;
- biotin-poly(ethyleneglycol)amine;
- (+) biotin 4-amidobenzoic acid sodium salt;
- Biotin 2-N-acetylamino-2-deoxy-β-D-glucopyranoside;
- Biotin-α-D-N-acetylneuraminide;
- Biotin-α-L-fucoside;
- Biotin lacto-N-bioside;
- Biotin-Lewis-A trisaccharide;
- Biotin-Lewis-Y tetrasaccharide;
- and Biotin-α-D-mannopyranoside;
- biotin 6-O-phospho-α-D-mannopyranoside.
50 more elements
A method of manufacturing a construct comprising an amphipathic lipid and an extended amphipathic lipid, the method comprising forming in aqueous media a suspension of a mixture comprising the amphipathic lipid and an extended amphipathic lipid,
- wherein the amphipathic lipid comprises at least one lipid selected from the group consisting of 1,2-distearoyl-sn-glycero-3-phosphocholine, cholesterol, dicetyl phosphate, 1,2-dipalmitoyl-sn-glycerol-[3-phospho-rac-(1-glycero)], 1,2-distearoyl-sn-glycero-3-phosphoethanolamine, 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-(succinyl);
- and,
- wherein the extended amphipathic lipid is selected from the group consisting of N-hydroxysuccinimide (NHS) biotin;
- sulfo-NHS-biotin;
- N-hydroxysuccinimide long chain biotin;
- sulfo-N-hydroxysuccinimide long chain biotin;
- D-biotin;
- biocytin;
- sulfo-N-hydroxysuccinimide-S—S-biotin;
- biotin-BMCC;
- biotin-HPDP;
- iodoacetyl-LC-biotin;
- biotin-hydrazide;
- biotin-LC-hydrazide;
- biocytin hydrazide;
- biotin cadaverine;
- carboxybiotin;
- photobiotin;
- ρ-aminobenzoyl biocytin trifluoroacetate;
- ρ-diazobenzoyl biocytin;
- biotin DHPE;
- biotin-X-DHPE;
- 12-((biotinyl)amino)dodecanoic acid;
- 12-((biotinyl)amino)dodecanoic acid succinimidyl ester;
- S-biotinyl homocysteine;
- biocytin-X;
- biocytin x-hydrazide;
- biotinethylenediamine;
- biotin-XL;
- biotin-X-ethylenediamine;
- biotin-XX hydrazide;
- biotin-XX-SE;
- biotin-XX, SSE;
- biotin-X-cadaverine;
- α-(t-BOC)biocytin;
- N-(biotinyl)-N′-(iodoacetyl)ethylenediamine;
- DNP-X-biocytin-X-SE;
- biotin-X-hydrazide;
- norbiotinamine hydrochloride;
- 3-(N-maleimidylpropionyl)biocytin;
- ARP;
- biotin-l-sulfoxide;
- biotin methyl ester;
- biotin-maleimide;
- biotin-poly(ethyleneglycol)amine;
- (+) biotin 4-amidobenzoic acid sodium salt;
- Biotin 2-N-acetylamino-2-deoxy-β-D-glucopyranoside;
- Biotin-α-D-N-acetylneuraminide;
- Biotin-α-L-fucoside;
- Biotin lacto-N-bioside;
- Biotin-Lewis-A trisaccharide;
- Biotin-Lewis-Y tetrasaccharide;
- and Biotin-α-D-mannopyranoside;
- biotin 6-O-phospho-α-D-mannopyranoside.
51 more elements
A method of treating a subject afflicted with diabetes,
- the method comprising administering to the subject in need thereof a therapeutically effective amount of a construct comprising an insulin, an amphipathic lipid and an extended amphipathic lipid;
- wherein the amphipathic lipid comprises at least one lipid selected from the group consisting of 1,2-distearoyl-sn-glycero-3-phosphocholine, cholesterol, dicetyl phosphate, 1,2-dipalmitoyl-sn-glycerol-[3-phospho-rac-(1-glycero)], 1,2-distearoyl-sn-glycero-3-phosphoethanolamine, 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-(succinyl);
- wherein the extended amphipathic lipid is selected from the group consisting of N-hydroxysuccinimide (NHS) biotin;
- sulfo-NHS-biotin;
- N-hydroxysuccinimide long chain biotin;
- sulfo-N-hydroxysuccinimide long chain biotin;
- D-biotin;
- biocytin;
- sulfo-N-hydroxysuccinimide-S—S-biotin;
- biotin-BMCC;
- biotin-HPDP;
- iodoacetyl-LC-biotin;
- biotin-hydrazide;
- biotin-LC-hydrazide;
- biocytin hydrazide;
- biotin cadaverine;
- carboxybiotin;
- photobiotin;
- ρ-aminobenzoyl biocytin trifluoroacetate;
- ρ-diazobenzoyl biocytin;
- biotin DHPE;
- biotin-X-DHPE;
- 12-((biotinyl)amino)dodecanoic acid;
- 12-((biotinyl)amino)dodecanoic acid succinimidyl ester;
- S-biotinyl homocysteine;
- biocytin-X;
- biocytin x-hydrazide;
- biotinethylenediamine;
- biotin-XL;
- biotin-X-ethylenediamine;
- biotin-XX hydrazide;
- biotin-XX-SE;
- biotin-XX, SSE;
- biotin-X-cadaverine;
- α-(t-BOC)biocytin;
- N-(biotinyl)-N′-(iodoacetyl)ethylenediamine;
- DNP-X-biocytin-X-SE;
- biotin-X-hydrazide;
- norbiotinamine hydrochloride;
- 3-(N-maleimidylpropionyl)biocytin;
- ARP;
- biotin-l-sulfoxide;
- biotin methyl ester;
- biotin-maleimide;
- biotin-poly(ethyleneglycol)amine;
- (+) biotin 4-amidobenzoic acid sodium salt;
- Biotin 2-N-acetylamino-2-deoxy-β-D-glucopyranoside;
- Biotin-α-D-N-acetylneuraminide;
- Biotin-α-L-fucoside;
- Biotin lacto-N-bioside;
- Biotin-Lewis-A trisaccharide;
- Biotin-Lewis-Y tetrasaccharide;
- and Biotin-α-D-mannopyranoside;
- biotin 6-O-phospho-α-D-mannopyranoside;
- and,
- wherein the insulin comprises at least one free insulin molecule and at least one insulin molecule associated with a water insoluble target molecule complex.
53 more elements
A kit for use in treating a mammal inflicted with diabetes, the kit comprising a lipid construct, a physiological buffer solution, an applicator, and an instructional material for the use thereof;
- wherein the construct comprises an amphipathic lipid and an extended amphipathic lipid;
- wherein the amphipathic lipid comprises at least one lipid selected from the group consisting of 1,2-distearoyl-sn-glycero-3-phosphocholine, cholesterol, dicetyl phosphate, 1,2-dipalmitoyl-sn-glycerol-[3-phospho-rac-(1-glycero)], 1,2-distearoyl-sn-glycero-3-phosphoethanolamine, and 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-(succinyl);
- and,
- wherein the extended amphipathic lipid is selected from the group consisting of N-hydroxysuccinimide (NHS) biotin;
- sulfo-NHS-biotin;
- N-hydroxysuccinimide long chain biotin;
- sulfo-N-hydroxysuccinimide long chain biotin;
- D-biotin;
- biocytin;
- sulfo-N-hydroxysuccinimide-S—S-biotin;
- biotin-BMCC;
- biotin-HPDP;
- iodoacetyl-LC-biotin;
- biotin-hydrazide;
- biotin-LC-hydrazide;
- biocytin hydrazide;
- biotin cadaverine;
- carboxybiotin;
- photobiotin;
- ρ-aminobenzoyl biocytin trifluoroacetate;
- ρ-diazobenzoyl biocytin;
- biotin DHPE;
- biotin-X-DHPE;
- 12-((biotinyl)amino)dodecanoic acid;
- 12-((biotinyl)amino)dodecanoic acid succinimidyl ester;
- S-biotinyl homocysteine;
- biocytin-X;
- biocytin x-hydrazide;
- biotinethylenediamine;
- biotin-XL;
- biotin-X-ethylenediamine;
- biotin-XX hydrazide;
- biotin-XX-SE;
- biotin-XX, SSE;
- biotin-X-cadaverine;
- α-(t-BOC)biocytin;
- N-(biotinyl)-N′-(iodoacetyl)ethylenediamine;
- DNP-X-biocytin-X-SE;
- biotin-X-hydrazide;
- norbiotinamine hydrochloride;
- 3-(N-maleimidylpropionyl)biocytin;
- ARP;
- biotin-l-sulfoxide;
- biotin methyl ester;
- biotin-maleimide;
- biotin-poly(ethyleneglycol)amine;
- (+) biotin 4-amidobenzoic acid sodium salt;
- Biotin 2-N-acetylamino-2-deoxy-β-D-glucopyranoside;
- Biotin-α-D-N-acetylneuraminide;
- Biotin-α-L-fucoside;
- Biotin lacto-N-bioside;
- Biotin-Lewis-A trisaccharide;
- Biotin-Lewis-Y tetrasaccharide;
- and Biotin-α-D-mannopyranoside;
- biotin 6-O-phospho-α-D-mannopyranoside.
52 more elements
Dependencies are inferred from the claim text.