Use of rasagiline with or without riluzole

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The subject invention provides a method for treating amyotrophiclateral sclerosis (ALS) in a subject in need of such treatmentcomprising administering to the subjectR(+)-N-propargyl-1-aminoindan or a pharmaceutically acceptable saltthereof alone or in combination with 2-amino-6-trifluoromethoxybenzothiazole in amounts effective to treat ALS in the subject.
Description of the Invention
SUMMARY OF THE INVENTION

The subject invention provides a method for treating amyotrophiclateral sclerosis (ALS) in a subject in need of such treatmentcomprising administering to the subjectR(+)-N-propargyl-1-aminoindan or a pharmaceutically acceptable saltthereof in an amount effective to treat ALS in the subject.

The subject invention further provides a method for treatingamyotrophic lateral sclerosis (ALS) in a subject in need of suchtreatment comprising administering to the subject an amount ofR(+)-N-propargyl-1-aminoindan or a pharmaceutically acceptable saltthereof and an amount of 2-amino-6-trifluoromethoxy benzothiazole,wherein the total amount is effective to treat ALS in the subject.

The subject invention further provides a pharmaceutical compositioncomprising R(+)-N-propargyl-1-aminoindan or a pharmaceuticallyacceptable salt thereof, 2-amino-6-trifluoromethoxy benzothiazoleand a pharmaceutically acceptable carrier.

The subject invention further provides a package comprising apharmaceutically acceptable preparation ofR(+)-N-propargyl-1-aminoindan or a pharmaceutically acceptable saltthereof, a separate pharmaceutically acceptable preparation of2-amino-6-trifluoromethoxy benzothiazole, and instructions for useof the preparations in the treatment of amyotrophic lateralsclerosis (ALS).

DETAILED DESCRIPTION OF THE INVENTION

The subject invention provides a method for treating amyotrophiclateral sclerosis (ALS) in a subject in need of such treatmentcomprising administering to the subjectR(+)-N-propargyl-1-aminoindan or a pharmaceutically acceptable saltthereof in an amount effective to treat ALS in the subject.

In one embodiment of the above method, the pharmaceuticallyacceptable salt is the chloride, mesylate, maleate, fumarate,tartarate, hydrochloride, hydrobromide, esylate,p-toluenesulfonate, benzoate, acetate, phosphate or sulfate salt.

In a further embodiment, the pharmaceutically acceptable salt isthe mesylate salt.

In another embodiment, the effective amount ofR(+)-N-propargyl-1-aminoindan is from about 0.1 to about 20 mg.

In another embodiment, the method further comprises administering2-amino-6-trifluoromethoxy benzothiazole in an amount effective totreat ALS in the subject.

The subject invention also provides a method for treatingamyotrophic lateral sclerosis (ALS) in a subject in need of suchtreatment comprising administering to the subject an amount ofR(+)-N-propargyl-1-aminoindan or a pharmaceutically acceptable saltthereof and an amount of 2-amino-6-trifluoromethoxy benzothiazole,wherein the amounts when administered together are effective totreat ALS in the subject.

In one embodiment of the above method, the pharmaceuticallyacceptable salt is the chloride, mesylate, maleate, fumarate,tartarate, hydrochloride, hydrobromide, esylate,p-toluenesulfonate, benzoate, acetate, phosphate or sulfate salt.

In another embodiment of the method, the pharmaceuticallyacceptable salt is the mesylate salt.

In a further embodiment, the amount ofR(+)-N-propargyl-1-aminoindan or a pharmaceutically acceptable saltthereof is effective to treat ALS when administered alone, and theamount of 2-amino-6-trifluoromethoxy benzothiazole is effective totreat ALS when administered alone.

In a further embodiment, the administration ofR(+)-N-propargyl-1-aminoindan or a pharmaceutically acceptable saltthereof and 2-amino-6-trifluoromethoxy benzothiazole issubstantially concurrent.

In a further embodiment, R(+)-N-propargyl-1-aminoindan or apharmaceutically acceptable salt thereof is administered and then2-amino-6-trifluoromethoxy benzothiazole is administered.

In a further embodiment, the effective amount ofR(+)-N-propargyl-1-aminoindan or a pharmaceutically acceptable saltthereof is from about 0.1 to about 20 mg and the effective amountof 2-amino-6-trifluoromethoxy benzothiazole is from about 5 toabout 500 mg.

In one embodiment, the method comprises administering from about0.001 mg to about 20 mg of R(+)-N-propargyl-1-aminoindan, alone orin combination with 2-amino-6-trifluoromethoxy benzothiazole, fromabout 5 mg to about 500 mg.

In another embodiment, the method comprises administering fromabout 1.6 mg to about 2.4 mg of R(+)-N-propargyl-1-aminoindan or2.0 mg of R(+)-N-propargyl-1-aminoindan, from about 3 mg to about 5mg of R(+)-N-propargyl-1-aminoindan, 8.0 mg to about 16.0 mg ofR(+)-N-propargyl-1-aminoindan, 12.0 mg to about 16.0 mg ofR(+)-N-propargyl-1-aminoindan, 16.0 mg to about 20 mg ofR(+)-N-propargyl-1-aminoindan, 7.2 mg to about 8.8 mg ofR(+)-N-propargyl-1-aminoindan, or about 8.0 mg ofR(+)-N-propargyl-1-aminoindan, alone or in combination with about 5mg to about 500 mg of 2-amino-6-trifluoromethoxy benzothiazole.

In a further embodiment, the method comprises administering any ofthe above dosages of R(+)-N-propargyl-1-aminoindan in combinationwith from about 25 mg to about 65 mg of 2-amino-6-trifluoromethoxybenzothiazole, from about 65 mg to about 150 mg of2-amino-6-trifluoromethoxy benzothiazole, from about 150 mg toabout 300 mg of 2-amino-6-trifluoromethoxy benzothiazole, fromabout 300 mg to about 500 mg of 2-amino-6-trifluoromethoxybenzothiazole, from about 25 mg to about 35 mg of2-amino-6-trifluoromethoxy benzothiazole, from about 45 mg to about55 mg of 2-amino-6-trifluoromethoxy benzothiazole, or from about 35mg to about 65 mg of 2-amino-6-trifluoromethoxy benzothiazole.

The subject invention also provides a pharmaceutical compositioncomprising R(+)--N-propargyl-1-aminoindan or a pharmaceuticallyacceptable salt thereof, 2-amino-6-trifluoromethoxy benzothiazoleand a pharmaceutically acceptable carrier.

In one embodiment, the pharmaceutical composition is formulated fororal, topical, parenteral or nasal administration.

The subject invention further provides a package comprising thepharmaceutical composition and instructions for use of thepharmaceutical composition in the treatment of amyotrophic lateralsclerosis (ALS).

The subject invention further provides a package comprising apharmaceutically acceptable preparation ofR(+)-N-propargyl-1-aminoindan or a pharmaceutically acceptable saltthereof, a separate pharmaceutically acceptable preparation of2-amino-6-trifluoromethoxy benzothiazole, and instructions for useof the preparations in the treatment of amyotrophic lateralsclerosis (ALS).

The subject invention further provides the use ofR(+)-N-propargyl-1-aminoindan or a pharmaceutically acceptable saltthereof for manufacturing a medicament useful for treatingamyotrophic lateral sclerosis (ALS) in a subject.

In one embodiment of the above use, the pharmaceutically acceptablesalt is the chloride, mesylate, maleate, fumarate, tartarate,hydrochloride, hydrobromide, esylate, p-toluenesulfonate, benzoate,acetate, phosphate or sulfate salt.

In another embodiment, the pharmaceutically acceptable salt is themesylate salt.

In another embodiment of the above use, the medicament furthercomprises 2-amino-6-trifluoromethoxy benzothiazole.

The subject invention further provides the use ofR(+)-N-propargyl-1-aminoindan or a pharmaceutically acceptable saltthereof for manufacturing a first medicament in a package havinginstructions for administration of the first medicament to treatamyotrophic lateral sclerosis (ALS) in a subject.

In one embodiment of the above use, the pharmaceutically acceptablesalt is the chloride, mesylate, maleate, fumarate, tartarate,hydrochloride, hydrobromide, esylate, p-toluenesulfonate, benzoate,acetate, phosphate or sulfate salt.

In another embodiment, the pharmaceutically acceptable salt is themesylate salt.

In another embodiment of the above use, the package separatelycomprises a second medicament which comprises2-amino-6-trifluoromethoxy benzothiazole and instructions foradministration of the second medicament to treat ALS in thesubject.

The subject invention further providesR(+)-N-propargyl-1-aminoindan or a pharmaceutically acceptable saltthereof for use in treating amyotrophic lateral sclerosis (ALS).

In one embodiment, the pharmaceutically acceptable salt is thechloride, mesylate, maleate, fumarate, tartarate, hydrochloride,hydrobromide, esylate, p-toluenesulfonate, benzoate, acetate,phosphate or sulfate salt for use in treating amyotrophic lateralsclerosis (ALS).

In another embodiment, the pharmaceutically acceptable salt is themesylate salt, for use in treating amyotrophic lateral sclerosis(ALS).

The subject invention further providesR(+)--N-propargyl-1-aminoindan or a pharmaceutically acceptablesalt thereof for use in treating amyotrophic lateral sclerosis(ALS) in combination with 2-amino-6-trifluoromethoxy benzothiazole.

In one embodiment, the pharmaceutically acceptable salt is thechloride, mesylate, maleate, fumarate, tartarate, hydrochloride,hydrobromide, esylate, p-toluenesulfonate, benzoate, acetate,phosphate or sulfate salt for use in treating amyotrophic lateralsclerosis (ALS) in combination with 2-amino-6-trifluoromethoxybenzothiazole.

In another embodiment, the pharmaceutically acceptable salt is themesylate salt, for use in treating amyotrophic lateral sclerosis(ALS) in combination with 2-amino-6-trifluoromethoxy benzothiazole.

Pharmaceutically acceptable salts include, but are not limited to,mesylate, maleate, fumarate, tartarate, hydrochloride,hydrobromide, esylate, p-toluenesulfonate, benzoate, acetate,phosphate and sulfate salts.