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US4424235A
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Hydrodynamically balanced controlled release compositions containing L-dopa and a decarboxylase inhibitor
Assignee: Hoffmann La Roche Inc
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Filing: 1982-11-01
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Granted: 1984-01-03
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Expires: 2002-11-01
Abstract
Abstract Hydrodynamically balanced controlled release compositions for the preparation of pharmaceutical capsules or tablets which contain L-Dopa and a decarboxylase inhibitor and which provide superior blood levels of L-Dopa are disclosed.
Inventors
- 👤 Prabhakar R. Sheth
- 👤 Jacques L. Tossounian
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-29 07:22
CPC Classifications
A; A61; A61K; A61K9/00; A61K9/0012; A61K9/0053; A61K9/0065; A61K31/00; A61K31/185; A61K31/19; A61K31/195
Claims Analysis
Total Claims: 22
Claim 1
Independent Claim
249 words
A hydrodynamically balanced controlled release composition comprising (a) as the active ingredient, an amount of L-Dopa which is effective in achieving desired levels of L-Dopa in the blood and an amount of a decarboxylase inhibitor selected from the group consisting of N 1 -dl-seryl-N 2 -(2,3,4-trihydroxybenzyl) hydrazine hydrochloride, β-(3,4-dihydroxyphenyl)-α-hydrazino-αmethyl propionic acid, m-hydroxybenzylhydrazine and β-methyldopa, which is effective for the amount of L-Dopa in the composition and wherein the ratio of L-Dopa to decarboxylase inhibitor ranges from about 4:1 to about 10:1 and, (b) in percents by weight based on the total weight of the composition, from about 5% to about 80% of a hydrocolloid or mixture of hydrocolloids selected from the group consisting of acacia, gum tragacanth, locust bean gum, guar gum, karaya gum, agar, pectin, carrageen, soluble and insoluble alginates, methylcellulose, hydroxy-propyl methylcellulose, hydroxypropylcellulose, sodium carboxymethylcellulose, carboxypolymethylene, gelatin, casein, zein and bentonite; up to about 60% of a fatty material or mixture of fatty materials selected from the group consisting of beeswax, cetyl alcohol, stearyl alcohol, glycerylmonosteareate, hydrogenated caster oil and hydrogenated cottonseed oil and up to about 80% of edible inert pharmaceutical adjunct materials whereby said composition, when used in capsule or tablet form, is hydrodynamically balanced so that, upon contact with gastric fluid, said capsule or tablet acquires and maintains a bulk density of less than one thereby being buoyant in the gastric fluid and remaining buoyant in the gastric fluid of the stomach until substantially all of the active ingredients contained therein have been released.
Claim 2
Dependent Claim
249 words
A hydrodynamically balanced controlled release composition comprising (a) as the active ingredient, an amount of L-Dopa which is effective in achieving desired levels of L-Dopa in the blood and an amount of a decarboxylase inhibitor selected from the group consisting of N 1 -dl-seryl-N 2 -(2,3,4-trihydroxybenzyl) hydrazine hydrochloride, β-(3,4-dihydroxyphenyl)-α-hydrazino-αmethyl propionic acid, m-hydroxybenzylhydrazine and β-methyldopa, which is effective for the amount of L-Dopa in the composition and wherein the ratio of L-Dopa to decarboxylase inhibitor ranges from about 4:1 to about 10:1 and, (b) in percents by weight based on the total weight of the composition, from about 5% to about 80% of a hydrocolloid or mixture of hydrocolloids selected from the group consisting of acacia, gum tragacanth, locust bean gum, guar gum, karaya gum, agar, pectin, carrageen, soluble and insoluble alginates, methylcellulose, hydroxy-propyl methylcellulose, hydroxypropylcellulose, sodium carboxymethylcellulose, carboxypolymethylene, gelatin, casein, zein and bentonite; up to about 60% of a fatty material or mixture of fatty materials selected from the group consisting of beeswax, cetyl alcohol, stearyl alcohol, glycerylmonosteareate, hydrogenated caster oil and hydrogenated cottonseed oil and up to about 80% of edible inert pharmaceutical adjunct materials whereby said composition, when used in capsule or tablet form, is hydrodynamically balanced so that, upon contact with gastric fluid, said capsule or tablet acquires and maintains a bulk density of less than one thereby being buoyant in the gastric fluid and remaining buoyant in the gastric fluid of the stomach until substantially all of the active ingredients contained therein have been released.
Claim 3
Dependent Claim
239 words
A hydrodynamically balanced controlled release composition comprising (a) as the active ingredient, an amount of L-Dopa which is effective in achieving desired levels of L-Dopa in the blood and an amount of N 1 -dl-seryl-N 2 -(2,3,4-trihydroxybenzyl)-hydrazine hydrochloride which is effective as a decarboxylase inhibitor for the L-Dopa in the composition and wherein the ratio of L-Dopa to N 1 -dl-seryl-N 2 -(2,3,4-trihydroxybenzyl-hydrazine ranges from about 5:1 to about 3:1 and, (b) in percents by weight based on the total weight of the composition from about 5% to about 80% of a hydrocolloid or mixture of hydrocolloids selected from the group consisting of acacia, gum tragacanth, locust bean gum, guar gum, karaya gum, agar, pectin, carrageen, soluble and insoluble alginates, methylcellulose, hydroxy-propyl methylcellulose, hydroxypropylcellulose, sodium carboxymethylcellulose, carboxypolymethylene, gelatin, casein, zein and bentonite; up to about 60% of a fatty material or mixture of fatty materials, selected from the group consisting of beeswax, cetyl alcohol, stearyl alcohol, glyceryl monosteareate, hydrogenated caster oil and hydrogenated cottonseed oil and up to about 80% of edible inert pharmaceutical adjunct materials whereby said composition, when used in capsule or tablet form, is hydrodynamically balanced so that, upon contact with gastric fluid, said capsule or tablet acquires and maintains a bulk density of less than one thereby being buoyant in the gastric fluid and remaining buoyant in the gastric fluid of the stomach until substantially all of the active ingredients contained therein have been released.
Claim 4
Dependent Claim
239 words
A hydrodynamically balanced controlled release composition comprising (a) as the active ingredient, an amount of L-Dopa which is effective in achieving desired levels of L-Dopa in the blood and an amount of N 1 -dl-seryl-N 2 -(2,3,4-trihydroxybenzyl)-hydrazine hydrochloride which is effective as a decarboxylase inhibitor for the L-Dopa in the composition and wherein the ratio of L-Dopa to N 1 -dl-seryl-N 2 -(2,3,4-trihydroxybenzyl-hydrazine ranges from about 5:1 to about 3:1 and, (b) in percents by weight based on the total weight of the composition from about 5% to about 80% of a hydrocolloid or mixture of hydrocolloids selected from the group consisting of acacia, gum tragacanth, locust bean gum, guar gum, karaya gum, agar, pectin, carrageen, soluble and insoluble alginates, methylcellulose, hydroxy-propyl methylcellulose, hydroxypropylcellulose, sodium carboxymethylcellulose, carboxypolymethylene, gelatin, casein, zein and bentonite; up to about 60% of a fatty material or mixture of fatty materials, selected from the group consisting of beeswax, cetyl alcohol, stearyl alcohol, glyceryl monosteareate, hydrogenated caster oil and hydrogenated cottonseed oil and up to about 80% of edible inert pharmaceutical adjunct materials whereby said composition, when used in capsule or tablet form, is hydrodynamically balanced so that, upon contact with gastric fluid, said capsule or tablet acquires and maintains a bulk density of less than one thereby being buoyant in the gastric fluid and remaining buoyant in the gastric fluid of the stomach until substantially all of the active ingredients contained therein have been released.
Claim 5
Dependent Claim
96 words
The hydrodynamically balanced controlled release composition of claim 1 which comprises, in percents by weight based on the total weight of the composition, (a) from about 20% to about 50% of L-Dopa; (b) from about 2% to about 20% of a decarboxylase inhibitor; (c) from about 15% to about 60% of hydrocolloid; (d) up to about 30% of a fatty material or mixture of fatty materials and (e) from about 5% to about 60% of edible inert pharmaceutical adjunct materials and wherein the ratio of L-Dopa to decarboxylase inhibitor is from about 4:1 to about 10:1.
Claim 6
Dependent Claim
100 words
The hydrodynamically balanced controlled release composition of claim 2 which comprises, in percents by weight based on the total weight of the composition, (a) from about 20% to about 50% of L-Dopa; (b) from about 4% to about 10% of N 1 -dl-seryl-N 2 -(2,3,4-trihydroxybenzyl)-hydrazine hydrochloride; (c) from about 15% to about 60% of a hydrocolloid; (d) up to about 30% of a fatty material or mixture of fatty materials and (e) from about 5% to about 60% of edible inert pharmaceutical adjunct materials and wherein the ratio of L-Dopa to N 1 -dl-seryl-N 2 -(2,3,4-trihydroxybenzyl)-hydrazine hydrochlorine is about 4:1.
Claim 7
Dependent Claim
31 words
The hydrodynamically balanced controlled release composition of claim 1 wherein the hydrocolloid or mixture of hydrocolloids is selected from the group consisting of methylcellulose, hydroxypropylcellulose, hydroxypropyl methylcellulose, sodium carboxymethylcellulose and carboxypolymethylene.
Claim 8
Dependent Claim
31 words
The hydrodynamically balanced controlled release composition of claim 2 wherein the hydrocolloid or mixture of hydrocolloids is selected from the group consisting of methylcellulose, hydroxypropylcellulose, hydroxypropyl methylcellulose, sodium carboxymethylcellulose and carboxypolymethylene.
Claim 9
Dependent Claim
15 words
The hydrodynamically balanced controlled release composition of claim 3 wherein the hydrocolloid is hydroxypropyl methylcellulose.
Claim 10
Dependent Claim
15 words
The hydrodynamically balanced controlled release composition of claim 4 wherein the hydrocolloid is hydroxypropyl methylcellulose.
Claim 11
Dependent Claim
15 words
A hydrodynamically balanced controlled release capsule dosage form prepared from the composition of claim 1.
Claim 12
Dependent Claim
15 words
A hydrodynamically balanced controlled release capsule dosage form prepared from the composition of claim 2.
Claim 13
Dependent Claim
15 words
A hydrodynamically balanced controlled release tablet dosage form prepared from the composition of claim 1.
Claim 14
Dependent Claim
15 words
A hydrodynamically balanced controlled release tablet dosage form prepared from the composition of claim 2.
Claim 15
Dependent Claim
15 words
A hydrodynamically balanced controlled release capsule dosage form prepared from the composition of claim 3.
Claim 16
Dependent Claim
15 words
A hydrodynamically balanced controlled release capsule dosage form prepared from the composition of claim 4.
Claim 17
Dependent Claim
15 words
A hydrodynamically balanced controlled release tablet dosage form prepared from the composition of claim 3.
Claim 18
Dependent Claim
15 words
A hydrodynamically balanced controlled release tablet dosage form prepared from the composition of claim 4.
Claim 19
Dependent Claim
41 words
A method for achieving desired high levels of L-Dopa in the blood of a subject which comprises orally administering to the subject the hydrodynamically balanced controlled release capsule of claim 9 containing the required amounts of L-Dopa and of decarboxylase inhibitor.
Claim 20
Dependent Claim
51 words
A method for achieving desired high levels of l-Dopa in the blood of a subject without undesirable side effects which comprises orally administering to the subject the hydrodynamically balanced controlled release capsule of claim 10 containing the required amounts of L-Dopa and of N 1 -dl-seryl-N 2 -(2,3,4-trihydroxybenzyl)hydrazine hydrochloride decarboxylase inhibitor.
Claim 21
Dependent Claim
39 words
A method for achieving desired levels of L-Dopa in the blood of a subject which comprises orally administering to the subject the hydrodynamically balanced controlled release tablet of claim 11 containing the required amounts of L-Dopa and decarboxylase inhibitor.
Claim 22
Dependent Claim
45 words
A method for achieving desired levels of l-Dopa in the blood of a subject which comprises orally administering to the subject the hydrodynamically balanced controlled release tablet of claim 12 containing the required amounts of L-Dopa and N 1 -dl-seryl-N 2 (2,3,4-trihydroxybenzyl)-hydrazine hydrochloride decarboxylase inhibitor.
References Cited (Backward Citations)
US3557292A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1987-01-02 | 1987-07-04 | 1988-01-03 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1991-01-02 | 1991-07-04 | 1992-01-03 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1995-01-02 | 1995-07-04 | 1996-01-03 | $7700.00 | Window Closed / Lapsed |