Fatty acid formulations for oral delivery of proteins and peptides, and uses thereof
First Claim
1. A water soluble solid pharmaceutical composition formulated for oral administration by ingestion, comprising:
- (a) from about 5 to about 65% w/w of a salt of a fatty acid component, where the salt of a fatty acid component comprises saturated or unsaturated C4, C5, C6, C7, C8, C9, C10, C11, or C12 fatty acids; and
(b) an insulin compound conjugate comprising an insulin protein coupled to a modifying moiety having a formula;
—
X—
R1—
Y-PAG-Z-R2
(Formula VI)where,X, Y and Z are independently selected linking groups and each is optionally present, and X, when present, is coupled to the insulin compound by a covalent bond, wherein the linking group is selected from —
C(O)—
, —
O—
, —
S—
, —
C— and
—
N—
,R1, if present, is a lower alkyl and may optionally include a carbonyl group;
R2 is selected from the group consisting of a lower alkyl, optionally including a carbonyl group, and a capping group selected from the group consisting of —
CH3, —
H, tosylate, branched or linear C1-6 and an activating group, wherein when R1 present, R2 is a member of the capping group; and
PAG is a linear or branched carbon chain incorporating one or more polyethylene glycol moieties, and optionally incorporating one or more additional moieties selected from the group consisting of —
S—
, —
O—
, —
N—
, and —
C(O)—
; and
an enteric coating material for coating of the water soluble solid composition fabricated into a solid form to survive passage through the stomach without substantial loss of the insulin protein.
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Accused Products
Abstract
Fatty acid compositions for administration of of pharmaceutical agents, such as proteins and peptides, protein and peptide conjugates, and/or cation-polypeptide conjugate complexes. In particular, the invention provides a solid pharmaceutical composition formulated for oral administration by ingestion, having from about 0.1 to about 75% w/w fatty acid component, where the fatty acid component comprises saturated or unsaturated C4, C5, C6, C7, C8, C9, C10, C11, or C12 fatty acids and/or salts of such fatty acids; and a therapeutic agent. Further, the invention provides a liquid pharmaceutical composition formulated for oral administration by ingestion, comprising: from about 0.1 to about 10% w/v fatty acid component, where the fatty acid component comprises saturated or unsaturated C4, C5, C6, C7, C8, C9, C10, C11, or C12 fatty acids and/or salts of such fatty acids; and a therapeutic agent.
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Citations
15 Claims
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1. A water soluble solid pharmaceutical composition formulated for oral administration by ingestion, comprising:
-
(a) from about 5 to about 65% w/w of a salt of a fatty acid component, where the salt of a fatty acid component comprises saturated or unsaturated C4, C5, C6, C7, C8, C9, C10, C11, or C12 fatty acids; and (b) an insulin compound conjugate comprising an insulin protein coupled to a modifying moiety having a formula;
—
X—
R1—
Y-PAG-Z-R2
(Formula VI)where, X, Y and Z are independently selected linking groups and each is optionally present, and X, when present, is coupled to the insulin compound by a covalent bond, wherein the linking group is selected from —
C(O)—
, —
O—
, —
S—
, —
C— and
—
N—
,R1, if present, is a lower alkyl and may optionally include a carbonyl group;
R2 is selected from the group consisting of a lower alkyl, optionally including a carbonyl group, and a capping group selected from the group consisting of —
CH3, —
H, tosylate, branched or linear C1-6 and an activating group, wherein when R1 present, R2 is a member of the capping group; andPAG is a linear or branched carbon chain incorporating one or more polyethylene glycol moieties, and optionally incorporating one or more additional moieties selected from the group consisting of —
S—
, —
O—
, —
N—
, and —
C(O)—
; andan enteric coating material for coating of the water soluble solid composition fabricated into a solid form to survive passage through the stomach without substantial loss of the insulin protein. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15)
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10. The pharmaceutical composition of claim 1 where the insulin compound conjugate consists of human insulin coupled at B29 to a modifying moiety having a structure:
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11. The pharmaceutical composition of claim 1 where the insulin compound conjugate consists of human insulin coupled at A1, B1 and/or B29 to a modifying moiety having a structure:
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12. The pharmaceutical composition of claim 1 where the modifying moiety has a structure:
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13. The pharmaceutical composition of claim 1 where the insulin compound conjugate is coupled at A1, B1 and/or B29 to a linear or branched PEG moiety having from 2 to 15 PEG or from 2 to 10 PEG subunits.
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14. The pharmaceutical composition of claim 1 wherein the insulin compound conjugate is complexed with zinc.
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15. The pharmaceutical composition of claim 14 wherein the water solubility of the insulin compound conjugate is decreased by addition of the zinc.
Specification