US4548922A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Drug administration
Assignee: The Brigham and Women's Hospital Inc
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Filing: 1983-06-06
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Granted: 1985-10-22
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Expires: 2003-06-06
Abstract
Abstract A composition useful for the treatment of an animal suffering from a predetermined medical disorder including, in admixture, a medically effective amount of a drug, other than an antibiotic, effective against the medical disorder, and a biocompatible, water-soluble, amphiphilic steroid, other than a bile salt, which is capable of increasing the permeability to the drug of a surface of the animal across which the drug is to be administered, in an amount effective to increase the permeability of the surface to the drug.
Inventors
- 👤 Martin C. Carey
- 👤 Alan C. Moses
- 👤 Jeffrey S. Flier
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-27 12:28
CPC Classifications
A; A61; A61K; A61K9/00; A61K9/0012; A61K9/0048; A61K38/00; A61K38/16; A61K38/17; A61K38/22; A61K38/28; A61K45/00; A61K45/06; A61K9/0043
Claims Analysis
Total Claims: 41
Claim 1
Independent Claim
173 words
A composition useful for the treatment of diabetes comprising, in admixture: (a) as an active ingredient, a medically-effective amount of insulin; and (b) as an adjuvant, a biocompatible, water-soluble, amphiphilic steroid of the following formula: ##STR3## wherein a dashed line represents a single or a double bond; D represents a group having a molecular weight below 600 daltons which renders an effective amount of said steroid water-soluble at pH 7.4; E represents OAc, a lower alkyl group or a lower heteroalkyl group; G represents OAc, OH, a lower alkyl group or a lower heteroalkyl group; W represents OAc or H; Q represents OH or H, provided that, when W is OAc and Q is OH, Q is β-equatorial; V represents H or α-axial OH; and X represents H or α-axial OH, said steroid (i) containing two OH groups; and (ii) being capable of increasing the permeability to insulin of a body surface across which insulin is to be administered, in an amount effective to increase the permeability of said body surface to insulin.
Claim 2
Dependent Claim
173 words
A composition useful for the treatment of diabetes comprising, in admixture: (a) as an active ingredient, a medically-effective amount of insulin; and (b) as an adjuvant, a biocompatible, water-soluble, amphiphilic steroid of the following formula: ##STR3## wherein a dashed line represents a single or a double bond; D represents a group having a molecular weight below 600 daltons which renders an effective amount of said steroid water-soluble at pH 7.4; E represents OAc, a lower alkyl group or a lower heteroalkyl group; G represents OAc, OH, a lower alkyl group or a lower heteroalkyl group; W represents OAc or H; Q represents OH or H, provided that, when W is OAc and Q is OH, Q is β-equatorial; V represents H or α-axial OH; and X represents H or α-axial OH, said steroid (i) containing two OH groups; and (ii) being capable of increasing the permeability to insulin of a body surface across which insulin is to be administered, in an amount effective to increase the permeability of said body surface to insulin.
Claim 3
Dependent Claim
41 words
The composition of claim 1 wherein the steroid is in unconjugated form, with D being selected from the group consisting of O - Na + , O - K + , O - Rb + and O - Cs + .
Claim 4
Dependent Claim
20 words
The composition of claim 1 wherein D is a covalently linked organic group which contains at least two carbon atoms.
Claim 5
Dependent Claim
25 words
The composition of claim 3 wherein the covalently linked organic group is an amino acid containing an ionic function which is dissociated at pH 7.4.
Claim 6
Dependent Claim
21 words
The composition of claim 4 wherein the amion acid is selected from the group consisting of glycine, taurine, homoglycine and homotaurine.
Claim 7
Dependent Claim
19 words
The composition of claim 4 wherein the amino acid is selected from the group consisting of sulfobetaine and phosphobetaine.
Claim 8
Dependent Claim
32 words
The composition of claim 3 wherein the covalently linked organic group is a peptide of two to three amino acids, said peptide containing an ionic function which is dissociated at pH 7.4.
Claim 9
Dependent Claim
18 words
The composition of claim 7 wherein the peptide is selected from the group consisting of diglycine and glutathione.
Claim 10
Dependent Claim
19 words
The composition of claim 7 wherein the peptide is selected from the group consisting of sarcosylcysteine, hydroxyprolinetaurine, and sarcosyltaurine.
Claim 11
Dependent Claim
33 words
The composition of claim 3 wherein the covalently linked organic group is a heteroalkyl group of three or fewer carbon atoms, said group containing an ionic function which is dissociated at pH 7.4.
Claim 12
Dependent Claim
34 words
The composition of claim 3 wherein the covalently linked organic group is a uronic acid of six or fewer carbon atoms, said uronic acid containing an ionic function which is dissolved at pH 7.4.
Claim 13
Dependent Claim
35 words
The composition of claim 3 wherein the covalently linked organic group is a polyether containing between six and fourteen carbon atoms, inclusive, said polyether terminating in an ionic function which is dissociated at pH 7.4.
Claim 14
Dependent Claim
22 words
The composition of claim 3 wherein the covalently linked organic group is a polyether containing between sixteen and twenty-four carbon atoms, inclusive.
Claim 15
Dependent Claim
35 words
The composition of claim 3 wherein the covalently linked organic group is a polyether containing between sixteen and twenty-four carbon atoms, inclusive, said polyether terminating in an ionic function which is dissociated at pH 7.4.
Claim 16
Dependent Claim
26 words
The composition of claim 3 wherein the covalently linked organic group is bonded to C 21 of the steroid by an amide or an ester linkage.
Claim 17
Dependent Claim
31 words
The composition of claim 3 wherein the covalently linked organic group contains an ionic function, said ionic function being SO 3 - , SO 4 - , or COO - .
Claim 18
Dependent Claim
26 words
The composition of claim 1 wherein the critical micellar temperature of an aqueous 1% solution, w/v, of said steroid is below 4° C. at pH 7.4.
Claim 19
Dependent Claim
30 words
The composition of claim 1 wherein the critical micellar concentration of said steroid is less than 4 mM in 0.15 M NaCl at 37° C., as measured by surface tension.
Claim 20
Dependent Claim
79 words
A composition useful for the treatment of diabetes comprising, in admixture: (a) as an active ingredient, a medically-effective amount of insulin; and (b) as an adjuvant, an ionized or partially ionized, water-soluble alkali salt of fusidic acid or a derivative thereof, said fusidic acid or derivative being capable of increasing the permeability to insulin of a body surface across which insulin is to be administered, in an amount effective to increase the permeability of said body surface to insulin.
Claim 21
Dependent Claim
79 words
A composition useful for the treatment of diabetes comprising, in admixture: (a) as an active ingredient, a medically-effective amount of insulin; and (b) as an adjuvant, an ionized or partially ionized, water-soluble alkali salt of fusidic acid or a derivative thereof, said fusidic acid or derivative being capable of increasing the permeability to insulin of a body surface across which insulin is to be administered, in an amount effective to increase the permeability of said body surface to insulin.
Claim 22
Dependent Claim
79 words
A composition useful for the treatment of diabetes comprising, in admixture: (a) as an active ingredient, a medically-effective amount of insulin; and (b) as an adjuvant, an ionized or partially ionized, water-soluble alkali salt of cephalosporin P 1 or a derivative thereof, said cephalosporin or derivative being capable of increasing the permeability to insulin of a body surface across which insulin is to be administered, in an amount effective to increase the permeability of said body surface to insulin.
Claim 23
Dependent Claim
79 words
A composition useful for the treatment of diabetes comprising, in admixture: (a) as an active ingredient, a medically-effective amount of insulin; and (b) as an adjuvant, an ionized or partially ionized, water-soluble alkali salt of cephalosporin P 1 or a derivative thereof, said cephalosporin or derivative being capable of increasing the permeability to insulin of a body surface across which insulin is to be administered, in an amount effective to increase the permeability of said body surface to insulin.
Claim 24
Dependent Claim
14 words
The composition of claim 19 wherein the derivative of fusidic acid is 24,25-dihydrofusidic acid.
Claim 25
Dependent Claim
14 words
The composition of claim 19 wherein the derivative of fusidic acid is 17,20-24,25-tetrahydrofusidic acid.
Claim 26
Dependent Claim
14 words
The composition of claim 19 wherein the derivative of fusidic acid is 3-acetoxyl-fusidic acid.
Claim 27
Dependent Claim
22 words
The composition of claim 19, 21, 22 or 23 wherein the fusidic acid or derivative thereof is conjugated at C 21 .
Claim 28
Dependent Claim
16 words
The composition of claim 20 wherein the cephalosporin or derivative is conjugated at C 21 .
Claim 29
Dependent Claim
14 words
The composition of claim 19 wherein the derivative of fusidic acid is tauro-24,25-dihydrofusidic acid.
Claim 30
Dependent Claim
14 words
The composition of claim 19 wherein the derivative of fusidic acid is tauro-17,20-24,25-tetrahydrofusidic acid.
Claim 31
Dependent Claim
29 words
A composition useful for the treatment of diabetes comprising, in admixture: (a) as an active ingredient, a medically-effective amount of insulin; and (b) as an adjuvant, sodium tauro-24,25-dihydrofusidic acid.
Claim 32
Dependent Claim
29 words
A composition useful for the treatment of diabetes comprising, in admixture: (a) as an active ingredient, a medically-effective amount of insulin; and (b) as an adjuvant, sodium tauro-24,25-dihydrofusidic acid.
Claim 33
Independent Claim
190 words
A method of administrating insulin for the treatment of diabetes which comprises applying to an animal body surface for absorption across said body surface a composition comprising, in admixture; (a) as an active ingredient, a medically-effective amount of insulin; (b) as an adjuvant, a biocompatible, water-soluble, amphiphilic steroid of the following formula: ##STR4## wherein a dashed line represents a single or a double bond; D represents a group having a molecular weight below 600 daltons which renders an effective amount of said steroid water-soluble at pH 7.4; E represents OAc, a lower alkyl group or a lower heteroalkyl group; G represents OAc, OH, a lower alkyl group or a lower heteroalkyl group; W represents OAc or H; Q represents OH or H, provided that, when W is OAc and Q is OH, Q is β-equatorial; V represents H or α-axial OH; and X represents H or α-axial OH, said steroid (i) containing two OH groups; and (ii) being capable of increasing the permeability to insulin of a body surface across which insulin is to be administered, in an amount effective to increase the permeability of said body surface to insulin.
Claim 34
Independent Claim
190 words
A method of administrating insulin for the treatment of diabetes which comprises applying to an animal body surface for absorption across said body surface a composition comprising, in admixture; (a) as an active ingredient, a medically-effective amount of insulin; (b) as an adjuvant, a biocompatible, water-soluble, amphiphilic steroid of the following formula: ##STR4## wherein a dashed line represents a single or a double bond; D represents a group having a molecular weight below 600 daltons which renders an effective amount of said steroid water-soluble at pH 7.4; E represents OAc, a lower alkyl group or a lower heteroalkyl group; G represents OAc, OH, a lower alkyl group or a lower heteroalkyl group; W represents OAc or H; Q represents OH or H, provided that, when W is OAc and Q is OH, Q is β-equatorial; V represents H or α-axial OH; and X represents H or α-axial OH, said steroid (i) containing two OH groups; and (ii) being capable of increasing the permeability to insulin of a body surface across which insulin is to be administered, in an amount effective to increase the permeability of said body surface to insulin.
Claim 35
Independent Claim
96 words
A method of administering insulin for the treatment of diabetes which comprises applying to an animal body surface for absorption across said body surface a composition comprising, in admixture: (a) as an active ingredient, a medically-effective amount of insulin; (b) as an adjuvant, an ionized or partially ionized, water-soluble alkali salt of fusidic acid or a derivative thereof, said fusidic acid or derivative being capable of increasing the permeability to insulin of a body surface across which insulin is to be administered, in an amount effective to increase the permeability of said body surface to insulin.
Claim 36
Independent Claim
96 words
A method of administering insulin for the treatment of diabetes which comprises applying to an animal body surface for absorption across said body surface a composition comprising, in admixture: (a) as an active ingredient, a medically-effective amount of insulin; (b) as an adjuvant, an ionized or partially ionized, water-soluble alkali salt of fusidic acid or a derivative thereof, said fusidic acid or derivative being capable of increasing the permeability to insulin of a body surface across which insulin is to be administered, in an amount effective to increase the permeability of said body surface to insulin.
Claim 37
Independent Claim
100 words
A method for administering insulin for the treatment of diabetes which comprises applying to an animal body surface for absorption across said body surface a composition comprising, in admixture: (a) as an acitve ingredient, a medically-effective amount of insulin; and (b) as an adjuvant, an ionized or partially ionized, water-soluble alkali salt of cephalosporin P 1 or a derivative thereof, said cephalosporin P 1 or derivative thereof being capable of increasing the permeability to insulin of a body surface across which insulin is to be administered, in an amount effective to increase the permeability of said body surface to insulin.
Claim 38
Independent Claim
100 words
A method for administering insulin for the treatment of diabetes which comprises applying to an animal body surface for absorption across said body surface a composition comprising, in admixture: (a) as an acitve ingredient, a medically-effective amount of insulin; and (b) as an adjuvant, an ionized or partially ionized, water-soluble alkali salt of cephalosporin P 1 or a derivative thereof, said cephalosporin P 1 or derivative thereof being capable of increasing the permeability to insulin of a body surface across which insulin is to be administered, in an amount effective to increase the permeability of said body surface to insulin.
Claim 39
Dependent Claim
18 words
The method of claim 29, 30 or 31 wherein the animal body surface is a nasal mucosal surface.
Claim 40
Independent Claim
42 words
A method of administering insulin for the treatment of diabetes which comprises applying to a nasal mucosal surface for absorption across said surface a composition comprising, in admixture: (a) a medically-effective amount of insulin; and (b) as an adjuvant, sodium tauro-24,25-dihydrofusidic acid.
Claim 41
Independent Claim
42 words
A method of administering insulin for the treatment of diabetes which comprises applying to a nasal mucosal surface for absorption across said surface a composition comprising, in admixture: (a) a medically-effective amount of insulin; and (b) as an adjuvant, sodium tauro-24,25-dihydrofusidic acid.
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1988-10-21 | 1989-04-22 | 1989-10-22 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1992-10-21 | 1993-04-22 | 1993-10-22 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1996-10-21 | 1997-04-22 | 1997-10-22 | $7700.00 | Window Closed / Lapsed |