EP0128831A2
Expired / Lapsed
EP
⏱️ 0.0 years remaining
Drug administration
Assignee: Individual
•
Filing: 1984-06-06
•
Granted: —
•
Expires: 2004-06-06
Abstract
Abstract Compositions and methods useful for the prevention or treatment of a human or animal disorder or for the regulation of a human or animal physiological condition are provided. The compositions used comprise, in admixture, a biologically-effective amount of a drug specific for the disorder or condition and a biocompatible, water-soluble, amphiphilic steroid, other than a natural bile salt, which is capable of increasing drug permeability of the human or animal body surface 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
EP
Data Source
google_patents
Last Synchronized
2026-10-25 19:06
CPC Classifications
A; A61; A61K; A61K9/00; A61K9/0012; A61K9/0048; A61K31/00; A61K31/13; A61K31/135; A61K31/137; A61K31/56; A61K31/575; A61K38/00; A61K38/16; A61K38/17; A61K38/22; A61K38/24; A61K38/26; A61K38/28; A61K45/00; A61K45/06; A61K47/00; A61K47/06; A61K47/28; A61K9/0014; A61K9/0043
Claims Analysis
Total Claims: 84
Claim 1
Independent Claim
96 words
A composition useful for the prevention or treatment of a human or animal disorder or for the regulation of a human or animal physiological condition comprising, in admixture: (a) as an active ingredient, a biologically-effective amount of a drug specific for the particular disorder or condition; and (b) as an adjuvant, a biocompatible, water-soluble, amphiphilic steroid, other than a natural bile salt, capable of increasing drug permeability of a human or animal body surface across which the drug is to be administered, in an amount effective to increase the permeability of said surface to said drug.
Claim 2
Dependent Claim
96 words
A composition useful for the prevention or treatment of a human or animal disorder or for the regulation of a human or animal physiological condition comprising, in admixture: (a) as an active ingredient, a biologically-effective amount of a drug specific for the particular disorder or condition; and (b) as an adjuvant, a biocompatible, water-soluble, amphiphilic steroid, other than a natural bile salt, capable of increasing drug permeability of a human or animal body surface across which the drug is to be administered, in an amount effective to increase the permeability of said surface to said drug.
Claim 3
Dependent Claim
102 words
The composition of claim 1 wherein said amphiphilic steroid has the formula: wherein a dashed line represents a single or a double bond; D represents a group having a molecular weight below about 600 daltons which renders an effective amount of said steroid water-soluble within a range of about pH 2 to about pH 12; E and G each represent OAc, OH, a lower alkyl group or a lower heteroalkyl group; W represents OAc or H; and Q, V and X each represent H or OH, said steroid containing from two to three polar functions, exclusive of the function represented by D.
Claim 4
Dependent Claim
139 words
The composition of claim 1 wherein said amphiphilic steroid has the formula: wherein a dashed line represents a single or a double bond; D represents a group having a molecular weight below about 600 daltons which renders an effective amount of said steroid water soluble within a range of about pH 2 to about pH 12; E represents 8 OAc, a OH, a lower alkyl group in a position, or a lower heteroalkyl group in 0 position; G represents a OAc, OH, a lower alkyl group, or a lower heteroalkyl group; W represents a OAc or H; Q represents H or OH, provided that, when W is a OAc and Q is a OH, Q is β-axial; V represents H or a OH; and X represents H or a OH, said steroid containing from two to three OH groups.
Claim 5
Dependent Claim
41 words
The composition of claim 2 wherein the steroid is in unconjugated form, with D being selected from the group consisting of O - Na + , O - R + , O - Rb + and O - Cs + .
Claim 6
Dependent Claim
20 words
The composition of claim 2 wherein D is a covalently linked organic group which contains at least one carbon atom.
Claim 7
Dependent Claim
33 words
The composition of claim 5 wherein the covalently linked organic group is an amino acid containing an ionic function which is dissociated within the range of about pH 2 to about pH 12.
Claim 8
Dependent Claim
21 words
The composition of claim 6 wherein the amino acid is selected from the group consisting of glycine, taurine, homoglycine and homotaurine.
Claim 9
Dependent Claim
19 words
The composition of claim 6 wherein the amino acid is selected from the group consisting of sulfobetaine and phosphobetaine.
Claim 10
Dependent Claim
40 words
The composition of claim 5 wherein the covalently linked organic group is a peptide of two to three amino acids, said peptide containing an ionic function which is dissociated within the range of about pH 2 to about pH 12.
Claim 11
Dependent Claim
18 words
The composition of claim 9 wherein the peptide is selected from the group consisting of diglycine and glutathione.
Claim 12
Dependent Claim
19 words
The composition of claim 9 wherein the peptide is selected from the group consisting of sarcosylcysteine, hydroxyprolinetaurine, and sarcosyltaurine.
Claim 13
Dependent Claim
42 words
The composition of claim 5 wherein the covalently linked organic group is a heteroalkyl group of about three or fewer carbon atoms, said group containing an ionic function which is dissociated within the range of about pH 2 to about pH 12.
Claim 14
Dependent Claim
43 words
The composition of claim 5 wherein the covalently linked organic group is a uronic acid of about six or fewer carbon atoms, said uronic acid containing an ionic function which is dissociated within the range of about pH 2 to about pH 12.
Claim 15
Dependent Claim
45 words
The composition of claim 5 wherein the covalently linked organic group is a polyether containing between about six and about fourteen carbon atoms, inclusive, said polyether terminating in an ionic function which is dissociated within the range of about pH 2 to about pH 12.
Claim 16
Dependent Claim
24 words
The composition of claim 5 wherein the covalently linked organic group is a polyether containing between about sixteen and about twenty-four carbon atoms, inclusive.
Claim 17
Dependent Claim
45 words
The composition of claim 5 wherein the covalently linked organic group is a polyether containing between about sixteen and about twenty-four carbon atoms, inclusive, said polyether terminating in an ionic function which is dissociated within the range of about pH 2 to about pH 12.
Claim 18
Dependent Claim
26 words
The composition of claim 5 wherein the covalently linked organic group is bonded to C 21 of the steroid by an amide or an ester linkage.
Claim 19
Dependent Claim
23 words
The composition of claim 5 wherein the covalently linked organic group contains an ionic function, said ionic function being , , or .
Claim 20
Dependent Claim
228 words
The composition of claim 3 wherein the steroid is further characterized in that (a) its unconjugated derivative is retained on a column for a length of time sufficient to produce a k' factor value of at least about 4, said k' factor value being obtained by subjecting a monomeric solution of 1 mg/mℓ of such unconjugated derivative to high-performance (3,000 psi) liquid column chromotography using a 250 x 4.6 nm column having octadecylsilane-coated 5 pm silica particles as the stationary phase and a mobile phase, delivered at 1.0 mℓ/min., consisting of 75% methanol in water, v/v, buffered with 0.005 M KH 2 PO 4 /H 3 PO 4 to give an apparent pH value, as measured using a glass electrode, of pH 5.0, said k' factor value being defined by where t 0 is the retention time in said column of the solvent front and t is the retention time in said column of said unconjugated derivative as measured by obtaining the elution profile of said steroid derivative by absorbance at 210 nm; (b) the critical micellar temperature of an aqueous 1% solution, w/v, of the steroid is below about 37°C within the range of about pH 2 to about pH 12; and (c) the critical micellar concentration of the steroid is less than about 8 mMolar in 0.15 M NaCl at 37°C, as measured by surface tension.
Claim 21
Dependent Claim
28 words
The composition of claim 19 wherein the critical micellar temperature of the steroid is below about 20°C and the critical micellar concentration is less than about 4 mMolar.
Claim 22
Dependent Claim
105 words
A composition useful for the prevention or treatment of a human or animal disorder or for the regulation of a human or animal physiological condition comprising, in admixture: (a) as an active ingredient, a biologically-effective amount of a drug specific for the disorder or condition: 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 drug permeability of a human or animal body surface across which the drug is to be administered, in an amount effective to increase the permeability of said surface to said drug.
Claim 23
Dependent Claim
105 words
A composition useful for the prevention or treatment of a human or animal disorder or for the regulation of a human or animal physiological condition comprising, in admixture: (a) as an active ingredient, a biologically-effective amount of a drug specific for the disorder or condition: 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 drug permeability of a human or animal body surface across which the drug is to be administered, in an amount effective to increase the permeability of said surface to said drug.
Claim 24
Dependent Claim
115 words
A composition useful for the prevention or treatment of a human or animal disorder or for the regulation of a human or animal physiological condition comprising, in admixture: (a) as an active ingredient, a biologically-effective amount of a drug specific for the disorder or condition; and (b) as an adjuvant, an ionized or partially ionized, water-soluble alkali salt of cephalosporin P 1 . p 2' p 3' P 4 or p 5 or a derivative thereof, said cephalosporin or derivative being capable of increasing drug permeability of a human or animal body surface across which the drug is to be administered, in an amount effective to increase the permeability of said surface to said drug.
Claim 25
Dependent Claim
115 words
A composition useful for the prevention or treatment of a human or animal disorder or for the regulation of a human or animal physiological condition comprising, in admixture: (a) as an active ingredient, a biologically-effective amount of a drug specific for the disorder or condition; and (b) as an adjuvant, an ionized or partially ionized, water-soluble alkali salt of cephalosporin P 1 . p 2' p 3' P 4 or p 5 or a derivative thereof, said cephalosporin or derivative being capable of increasing drug permeability of a human or animal body surface across which the drug is to be administered, in an amount effective to increase the permeability of said surface to said drug.
Claim 26
Dependent Claim
14 words
The composition of claim 21 wherein the derivative of fusidic acid is 24,25-dihydrofusidic acid.
Claim 27
Dependent Claim
14 words
The composition of claim 21 wherein the derivative of fusidic acid is 17,20-24,25-tetrahydrofusidic acid.
Claim 28
Dependent Claim
14 words
The composition of claim 21 wherein the derivative of fusidic acid is 3-acetoxyl-fusidic acid.
Claim 29
Dependent Claim
22 words
The composition of claim 21, 23, 24 or 25 wherein the fusidic acid or derivative thereof is conjugated at C 21 *
Claim 30
Dependent Claim
16 words
The composition of claim 22 wherein the cephalosporin or derivative is conjugated at C 21 .
Claim 31
Dependent Claim
13 words
The composition of claim 21 wherein the derivative of fusidic acid is tauro-24,25-dihydrofusidate.
Claim 32
Dependent Claim
13 words
The composition of claim 21 wherein the derivative of fusidic acid is tauro-16a-OH-17,20-24,25-tetrahydrofusidate.
Claim 33
Dependent Claim
13 words
The composition of claim 21 wherein the derivative of fusidic acid is tauro-16a-OH-24,25-dihydrofusidate.
Claim 34
Dependent Claim
13 words
The composition of claim 21 wherein the derivative of fusidic acid is tauro-17,20-24,25-tetrahydrofusidate.
Claim 35
Dependent Claim
13 words
The composition of claim 21 wherein the derivative of fusidic acid is glyco-24,25-dihydrofusidate.
Claim 36
Dependent Claim
13 words
The composition of claim 21 wherein the derivative of fusidic acid is tauro-16-O-methyl-ether-24,25-dihydrofusidate.
Claim 37
Dependent Claim
13 words
The composition of claim 21 wherein the derivative of fusidic acid is tauro-16-O-methyl-ether-17,20-24,25-tetrahydrofusidate.
Claim 38
Dependent Claim
14 words
The composition of claim 1, 21 or 22 wherein said drug is a peptide.
Claim 39
Dependent Claim
25 words
The composition of claim 1, 21 or 22 wherein said drug is a peptide having a molecular weight between about 100 and about 300,000 daltons.
Claim 40
Dependent Claim
17 words
The composition of claim 35 wherein said peptide is a hormone or a precursor or inhibitor thereof.
Claim 41
Dependent Claim
18 words
The composition of claim 35 wherein said peptide is an enzyme or a precursor or an inhibitor thereof.
Claim 42
Dependent Claim
14 words
The composition of claim 1, 21 or 22 wherein said drug is a glycoprotein.
Claim 43
Dependent Claim
63 words
The composition of claim 1, 21 or 22 wherein said drug is selected from the group consisting of insulin, glucagon, parathyroid hormone, parathyroid hormone antagonist, calcitonin, vasopressin, renin, prolactin, growth hormone, thyroid stimulating hormone, corticotropin, corticotropin-releasing factor, follicle stimulating hormone, luteinizing hormone, chorionic gonadotropin, atrial peptides, interferon, tissue plasminogen activator, gammaglobulin, Factor VIII, growth hormone releasing hormone, luteinizing hormone releasing hormone and somatostatin.
Claim 44
Dependent Claim
14 words
The composition of claim l, 21 or 22 wherein said drug is an antihistamine.
Claim 45
Dependent Claim
15 words
The composition of claim 1, 21 or 22 wherein said drug is a sympathomimetic drug.
Claim 46
Dependent Claim
15 words
The composition of claim 1, 21 or 22 wherein said drug is an anti-infective agent.
Claim 47
Dependent Claim
23 words
The composition of claim 43 wherein said anti-infective agent is selected from the group consisting of antibacterial agents, antiviral agents and antifungal agents.
Claim 48
Dependent Claim
15 words
The composition of claim 1, 21 or 22 wherein said drug is an anti-arthritic agent.
Claim 49
Dependent Claim
15 words
The composition of claim 1, 21 or 22 wherein said drug is an anti-inflammatory agent.
Claim 50
Dependent Claim
15 words
The composition of claim 1, 21 or 22 wherein said drug is an anti-tumor agent.
Claim 51
Dependent Claim
14 words
The composition of claim 1, 21 or 22 wherein said drug is a tranquilizer.
Claim 52
Dependent Claim
15 words
The composition of claim 1, 21 or 22 wherein said drug is a cardiovascular agent.
Claim 53
Dependent Claim
17 words
The composition of claim 1, 21 or 22 wherein said drug is a water-insoluble, fat-soluble hydrophobic drug.
Claim 54
Dependent Claim
35 words
The composition of claim 50 wherein the hydrophobic drug is selected from the group consisting of progesterone, an estrogen, ethinyl estradiol, an androgen, an androgen analog, vitamin A, vitamin D, vitamin E and vitamin K.
Claim 55
Dependent Claim
15 words
The composition of claim 1, 21 or 22 wherein said drug is a vaccinating agent.
Claim 56
Dependent Claim
22 words
The composition of claim l, 21 or 22 wherein said drug is selected from the group consisting of renal and hepatic agents.
Claim 57
Dependent Claim
10 words
The composition of claim 37 wherein the hormone is insulin.
Claim 58
Dependent Claim
10 words
The composition of claim 37 wherein the hormone is glucagon.
Claim 59
Dependent Claim
12 words
The composition of claim 37 wherein the hormone is human chorionic gonadotropin.
Claim 60
Dependent Claim
11 words
The composition of claim 37 wherein the hormone is corticotropin-releasing factor.
Claim 61
Dependent Claim
11 words
The composition of claim 42 wherein the sympathomimetic drug is epinephrine.
Claim 62
Dependent Claim
81 words
A composition useful for the treatment of diabetes comprising, in admixture: (a) as an active ingredient, a medically-effective amount of insulin or precursor thereof; 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 insulin permeability of a body surface across which the drug is to be administered, in an amount effective to increase the permeability of said surface to said drug.
Claim 63
Dependent Claim
81 words
A composition useful for the treatment of diabetes comprising, in admixture: (a) as an active ingredient, a medically-effective amount of insulin or precursor thereof; 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 insulin permeability of a body surface across which the drug is to be administered, in an amount effective to increase the permeability of said surface to said drug.
Claim 64
Dependent Claim
16 words
The composition of claim 59 wherein the derivative of fusidic acid is a salt of tauro-24,25-dihydrofusidate.
Claim 65
Dependent Claim
14 words
The composition of claim 59 wherein the adjuvant is a salt of fusidic acid.
Claim 66
Dependent Claim
15 words
The composition of claim 59 wherein the derivative of fusidic acid is glyc Q -24,25-dihydrofusidate.
Claim 67
Dependent Claim
16 words
The composition of claim 59 wherein the derivative of fusidic acid is a salt of 24,25-dihydrofusidate.
Claim 68
Dependent Claim
15 words
The composition of claim 60, 61 or 63 wherein the salt is a sodium salt.
Claim 69
Dependent Claim
34 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 effective amount of cephalosporin P 1 .
Claim 70
Dependent Claim
34 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 effective amount of cephalosporin P 1 .
Claim 71
Dependent Claim
38 words
A composition useful for regulating blood glucose and free fatty acid levels comprising, in admixture: (a) as an active ingredient, a medically-effective amount of glucagon; and (b) as an adjuvant, an effective amount of a salt of tauro-24,25-dihydrofusidate.
Claim 72
Dependent Claim
38 words
A composition useful for regulating blood glucose and free fatty acid levels comprising, in admixture: (a) as an active ingredient, a medically-effective amount of glucagon; and (b) as an adjuvant, an effective amount of a salt of tauro-24,25-dihydrofusidate.
Claim 73
Dependent Claim
35 words
A composition useful for affecting human pregnancy comprising, in admixture: (a) as an active ingredient, a medically-effective amount of human chorionic gonadotropin; and (b) as an adjuvant, an effective amount of a salt of tauro-24,25-dihydrofusidate.
Claim 74
Dependent Claim
35 words
A composition useful for affecting human pregnancy comprising, in admixture: (a) as an active ingredient, a medically-effective amount of human chorionic gonadotropin; and (b) as an adjuvant, an effective amount of a salt of tauro-24,25-dihydrofusidate.
Claim 75
Dependent Claim
36 words
A composition useful for regulating adrenocorticotropin synthesis and release comprising, in admixture: (a) as an active ingredient, a medically-effective amount of corticotropin-releasing hormone; and (b) as an adjuvant, an effective amount of a salt of tauro-24,25-dihydrofusidate.
Claim 76
Dependent Claim
36 words
A composition useful for regulating adrenocorticotropin synthesis and release comprising, in admixture: (a) as an active ingredient, a medically-effective amount of corticotropin-releasing hormone; and (b) as an adjuvant, an effective amount of a salt of tauro-24,25-dihydrofusidate.
Claim 77
Dependent Claim
43 words
A composition useful for the treatment of disorders or regulation of physiological conditions responsive to sympathomimetic drugs comprising, in admixture: (a) as an active ingredient, a medically-effective amount of epinephrine; and (b) as an adjuvant, an effective amount of a salt of tauro-24,25-dihydrofusidate.
Claim 78
Dependent Claim
43 words
A composition useful for the treatment of disorders or regulation of physiological conditions responsive to sympathomimetic drugs comprising, in admixture: (a) as an active ingredient, a medically-effective amount of epinephrine; and (b) as an adjuvant, an effective amount of a salt of tauro-24,25-dihydrofusidate.
Claim 79
Dependent Claim
16 words
The composition of claim 66, 67, 68 or 69 wherein the salt is a sodium salt.
Claim 80
Dependent Claim
41 words
A pharmaceutical preparation suitable for use as a nasal spray or nose drops comprising a solution or suspension of the composition of claim 1, 21, 22, 60, 61, 62, 63, 65, 66, 67, 68 or 69 in a physiologically acceptable carrier.
Claim 81
Dependent Claim
28 words
The pharmaceutical preparation of claim 71 wherein the physiologically acceptable carrier is a sodium phosphate buffer, a sodium phosphate buffered sodium chloride solution, or a sodium chloride solution.
Claim 82
Dependent Claim
30 words
A pharmaceutical preparation suitable for use as eye drops comprising a solution or suspension of the composition of claim 1, 21, 22, 60 or 66 in a physiologically acceptable carrier.
Claim 83
Dependent Claim
52 words
A pharmaceutical preparation in the form of a nasal spray or nose drops useful for the treatment of diabetes comprising a solution or suspension in a physiologically buffered sodium chloride solution of an admixture of a medically-effective amount of insulin as active ingredient and an effective amount of sodium tauro-24,25-dihydrofusidate as adjuvant.
Claim 84
Dependent Claim
52 words
A pharmaceutical preparation in the form of a nasal spray or nose drops useful for the treatment of diabetes comprising a solution or suspension in a physiologically buffered sodium chloride solution of an admixture of a medically-effective amount of insulin as active ingredient and an effective amount of sodium tauro-24,25-dihydrofusidate as adjuvant.
References Cited (Backward Citations)
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