US4086334A
Expired / Lapsed
US
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Composition and method for the treatment of disorders of calcium metabolism
Assignee: Henkel AG and Co KGaA
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Filing: 1976-11-29
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Granted: 1978-04-25
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Expires: 1996-11-29
Abstract
Abstract The water-soluble calcitonins and the water-soluble pharmaceutically-acceptable compounds of acidic nature which are effective against Paget's disease and which contain at least two acidic groups separated by not more than two carbon atoms act synergistically in inhibiting a pathological increased calcium metabolism rate (including the solubilization of bone calcium which occurs in Paget's disease). The components in combination, when administered in respectively preferred amounts, inhibit or arrest loss of calcium by the bones of the body with less severe side effects than those caused by equivalent therapeutic doses of the calcitonin alone or by equivalent therapeutic doses of the compounds of acidic nature alone.
Inventors
- 👤 Manfred Schmidt-Dunker
- 👤 Matthias Potokar
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-25 20:54
CPC Classifications
A; A61; A61K; A61K38/00; A61K38/16; A61K38/17; A61K38/22; A61K38/23
Claims Analysis
Total Claims: 32
Claim 1
Independent Claim
98 words
A composition for inhibiting pathological solubilization of bone calcium in mammals, comprising (A) a water-soluble calcitonin and (B) a water-soluble pharmaceutically acceptable organic adjuvant compound effective against Paget's disease, said compound containing at least two acidic groups separated by not more than two carbon atoms, and being selected from the group consisting of cyclohexanehexacarboxylic acid, azacycloheptane-2,2-diphosphonic acid,2,7-dioxo-2-hydroxy-3-amino-3-phosphono-1,2-azaphosphacycloheptane, 3-amino-1-hydroxypropane-1,1-diphosphonic acid, phosphono-1,2-ethanedicarboxylic acid, 2-phosphono-2,3-propanedicarboxylic acid, 2-phosphonobutane-1,2,4-tricarboxylic acid, and the water-soluble salts thereof, the ratio of (A) to (B) being between 1:10 and 10:1, if the amount of (A) is expressed in MRC units and the amount of (B) in mg.
Claim 2
Dependent Claim
98 words
A composition for inhibiting pathological solubilization of bone calcium in mammals, comprising (A) a water-soluble calcitonin and (B) a water-soluble pharmaceutically acceptable organic adjuvant compound effective against Paget's disease, said compound containing at least two acidic groups separated by not more than two carbon atoms, and being selected from the group consisting of cyclohexanehexacarboxylic acid, azacycloheptane-2,2-diphosphonic acid,2,7-dioxo-2-hydroxy-3-amino-3-phosphono-1,2-azaphosphacycloheptane, 3-amino-1-hydroxypropane-1,1-diphosphonic acid, phosphono-1,2-ethanedicarboxylic acid, 2-phosphono-2,3-propanedicarboxylic acid, 2-phosphonobutane-1,2,4-tricarboxylic acid, and the water-soluble salts thereof, the ratio of (A) to (B) being between 1:10 and 10:1, if the amount of (A) is expressed in MRC units and the amount of (B) in mg.
Claim 3
Dependent Claim
12 words
A composition according to claim 1 wherein the calcitonin is human calcitonin.
Claim 4
Dependent Claim
12 words
A composition according to claim 1 wherein the calcitonin is salmon calcitonin.
Claim 5
Dependent Claim
12 words
A composition according to claim 1 wherein the calcitonin is pig calcitonin.
Claim 6
Dependent Claim
19 words
A composition according to claim 1 wherein the adjuvant compound is cyclohexanehexacarboxylic acid or a pharmaceutically-acceptable water-soluble salt thereof.
Claim 7
Dependent Claim
18 words
A composition according to claim 1 wherein the adjuvant compound is 2,7-dioxo-2-hydroxy-3-amino-3-phosphono-1,2-azaphosphacycloheptane or a pharmaceutically-acceptable water-soluble salt thereof.
Claim 8
Dependent Claim
19 words
A composition according to claim 1 wherein the adjuvant compound is 3-amino-1-hydroxypropane-1,1-disphosphonic acid or a pharmaceutically-acceptable water-soluble salt thereof.
Claim 9
Dependent Claim
19 words
A composition according to claim 1 wherein the adjuvant compound is phosphono-1,2-ethanedicarboxylic acid or a pharmaceutically-acceptable water-soluble salt thereof.
Claim 10
Dependent Claim
19 words
A composition according to claim 1 wherein the adjuvant compound is 2-phosphono-2,3-propanedicarboxylic acid or a pharmaceutically-acceptable water-soluble salt thereof.
Claim 11
Dependent Claim
19 words
A composition according to claim 1 wherein the adjuvant compound is 2-phosphono-1,2,4-tricarboxylic acid or a pharmaceutically-acceptable water-soluble salt thereof.
Claim 12
Dependent Claim
16 words
A solution of a composition according to claim 1 in a physiologically acceptable injectable aqueous solvent.
Claim 13
Dependent Claim
132 words
A hermetically sealed, sterile daily dose package for dosing a mammal suffering from pathological increased calcium metabolism, which comprises at least one sterile ampoule containing a calcitonin in an amount sufficient to supply from 0.01 to 20 MRC units per kilogram of body weight and at least one tablet containing between 25 mg. and 400 mg. of a water-soluble organic adjuvant compound for inhibiting pathological solubilization of bone calcium in mammals, comprising (A) a water-soluble calcitonin and (B) a water-soluble pharmaceutically acceptable organic adjuvant compound effective against Paget's disease, said compound containing at least two acidic groups separated by not more than two carbon atoms and being selected from the group consisting of cyclohexanehexacarboxylic acid, azacycloheptane-2,2-diphosphonic acid, 2-7-dioxo-2hydroxy-3-amino-3-phosphono-1,2-azaphosphacycloheptane, 3-amino-1-hydroxypropane-1,1-diphosphonic acid, phosphono-1,2-ethanedicarboxylic acid, 2-phosphono-2,3-propanedicarboxylic acid, 2-phosphonobutane, 1,2,4-tricarboxylic acid, and the water-soluble salts thereof.
Claim 14
Dependent Claim
132 words
A hermetically sealed, sterile daily dose package for dosing a mammal suffering from pathological increased calcium metabolism, which comprises at least one sterile ampoule containing a calcitonin in an amount sufficient to supply from 0.01 to 20 MRC units per kilogram of body weight and at least one tablet containing between 25 mg. and 400 mg. of a water-soluble organic adjuvant compound for inhibiting pathological solubilization of bone calcium in mammals, comprising (A) a water-soluble calcitonin and (B) a water-soluble pharmaceutically acceptable organic adjuvant compound effective against Paget's disease, said compound containing at least two acidic groups separated by not more than two carbon atoms and being selected from the group consisting of cyclohexanehexacarboxylic acid, azacycloheptane-2,2-diphosphonic acid, 2-7-dioxo-2hydroxy-3-amino-3-phosphono-1,2-azaphosphacycloheptane, 3-amino-1-hydroxypropane-1,1-diphosphonic acid, phosphono-1,2-ethanedicarboxylic acid, 2-phosphono-2,3-propanedicarboxylic acid, 2-phosphonobutane, 1,2,4-tricarboxylic acid, and the water-soluble salts thereof.
Claim 15
Dependent Claim
13 words
A daily dose package according to claim 12 containing four of said tablets.
Claim 16
Dependent Claim
65 words
A pharmaceutically acceptable injectable aqueous solution of (A) a water-soluble calcitonin and (B) a water-soluble pharmaceutically-acceptable adjuvant compound effective against Paget's disease, said adjuvant compound containing at least two acidic groups separated by not more than two carbon atoms and being selected from the group consisting of cyclohexanehexacarboxylic acid, azacycloheptane-2,2-diphosphonic acid, 2,7-dioxo-2-hydroxy-3-amino-3-phosphono-1,2-azaphosphacycloheptane, 3-amino-1-hydroxypropane-1,1-diphosphonic acid, phosphono-1,2-ethanedicarboxylic acid, 2-phosphono-2,3-propanedicarboxylic acid, 2-phosphonobutane-1,2,4-tricarboxylic acid, and the water-soluble salts thereof.
Claim 17
Dependent Claim
65 words
A pharmaceutically acceptable injectable aqueous solution of (A) a water-soluble calcitonin and (B) a water-soluble pharmaceutically-acceptable adjuvant compound effective against Paget's disease, said adjuvant compound containing at least two acidic groups separated by not more than two carbon atoms and being selected from the group consisting of cyclohexanehexacarboxylic acid, azacycloheptane-2,2-diphosphonic acid, 2,7-dioxo-2-hydroxy-3-amino-3-phosphono-1,2-azaphosphacycloheptane, 3-amino-1-hydroxypropane-1,1-diphosphonic acid, phosphono-1,2-ethanedicarboxylic acid, 2-phosphono-2,3-propanedicarboxylic acid, 2-phosphonobutane-1,2,4-tricarboxylic acid, and the water-soluble salts thereof.
Claim 18
Dependent Claim
11 words
A solution according to claim 14 having a pH about 7.4.
Claim 19
Dependent Claim
21 words
A solution according to claim 14 containing dissolved sodium chloride in amount sufficient to adjust said solution to plasma ionic strength.
Claim 20
Independent Claim
109 words
A method of inhibiting the pathological increased calcium metabolism in mammals, which comprises administering daily thereto, (A) a water-soluble calcitonin and (B) a water-soluble pharmaceutically-acceptable organic adjuvant compound effective against Paget's disease, said adjuvant compound containing at least two carbon atoms and being selected from the group consisting of cyclohexane-hexacarboxylic acid, azacycloheptane-2,2-diphosphonic acid, 2,7-dioxo-2-hydroxy-3-amino-3-phosphono-1,2-azaphosphacycloheptane, 3-amino-1-hydroxypropane-1,1-diphosphonic acid, phosphono-1,2-ethanedicarboxylic acid, 2-phosphono-2,3-propanedicarboxylic acid, 2-phosphonobutane-1,2,4-tricarboxylic acid, and the water-soluble salts thereof, the amount of said calcitonin being sufficient to supply between 0.01 and 20 Medical Research Council units thereof per kilogram of body weight per day and the amount of said adjuvant being from 0.05 to 30 mg./kg. of body weight per day.
Claim 21
Independent Claim
109 words
A method of inhibiting the pathological increased calcium metabolism in mammals, which comprises administering daily thereto, (A) a water-soluble calcitonin and (B) a water-soluble pharmaceutically-acceptable organic adjuvant compound effective against Paget's disease, said adjuvant compound containing at least two carbon atoms and being selected from the group consisting of cyclohexane-hexacarboxylic acid, azacycloheptane-2,2-diphosphonic acid, 2,7-dioxo-2-hydroxy-3-amino-3-phosphono-1,2-azaphosphacycloheptane, 3-amino-1-hydroxypropane-1,1-diphosphonic acid, phosphono-1,2-ethanedicarboxylic acid, 2-phosphono-2,3-propanedicarboxylic acid, 2-phosphonobutane-1,2,4-tricarboxylic acid, and the water-soluble salts thereof, the amount of said calcitonin being sufficient to supply between 0.01 and 20 Medical Research Council units thereof per kilogram of body weight per day and the amount of said adjuvant being from 0.05 to 30 mg./kg. of body weight per day.
Claim 22
Dependent Claim
16 words
A method according to claim 17 wherein the calcitonin is administered by injection into the body.
Claim 23
Dependent Claim
19 words
A method according to claim 17 wherein the adjuvant compound is administered orally at least 4 times a day.
Claim 24
Dependent Claim
22 words
A method according to claim 17 wherein compounds (A) and (B) are administered by injection as a single pharmaceutically acceptable aqueous solution.
Claim 25
Dependent Claim
14 words
A method according to claim 17 wherein the solution is administered once per day.
Claim 26
Dependent Claim
15 words
A method according to claim 17 wherein the solution has a pH of about 7.4.
Claim 27
Dependent Claim
23 words
A method according to claim 17 wherein the solution contains dissolved sodium chloride in amount to adjust said solution to plasma ionic strength.
Claim 28
Dependent Claim
14 words
A method according to claim 17 wherein the pathological increased metabolism is Paget's disease.
Claim 29
Dependent Claim
13 words
A method according to claim 17 wherein the pathological increased metabolism is hypercalcemia.
Claim 30
Dependent Claim
13 words
A method according to claim 17 wherein the pathological increased metabolism is osteoporosis.
Claim 31
Dependent Claim
25 words
The method of claim 17 wherein the organic adjuvant compound is administered per os in a dosage of 0.5 to 20 mg./kg. of body weight.
Claim 32
Dependent Claim
24 words
The method of claim 17 wherein the organic adjuvant compound is administered parenterally in a dosage of 0.05 to 10 mg./kg. of body weight.
References Cited (Backward Citations)
No citation records indexed.
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1981-04-24 | 1981-10-24 | 1982-04-25 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1985-04-24 | 1985-10-24 | 1986-04-25 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1989-04-24 | 1989-10-24 | 1990-04-25 | $7700.00 | Window Closed / Lapsed |