Therapy for neurological diseases

• US 6,036,973 A
• Filed: 07/15/1997
• Issued: 03/14/2000
• Est. Priority Date: 06/27/1994
• Status: Expired due to Term

• Current Assignee: Encinal Pharmaceutical Investments, LLC
• Original Assignee: ALZA Corporation (Johnson & Johnson)
• Inventors: Childers, Jerry D., Wong, Patrick S.-L., Kidney, David J., Guittard, George V., Gumucio, Fernando E.
• Primary Examiner(s): Mullis, Jeffrey C.
• Application Number:
  US08/892,995
• Time in Patent Office: 973 Days
• Field of Search: 424/468, 424/471, 424/472, 424/480, 424/439, 424/451, 424/452, 424/457, 424/463, 424/486, 424/488, 424/473, 424/479, 424/482
• US Class Current: 424/457
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0004 Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas
• CPC Class Codes: A61K 9/2018 Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
• CPC Class Codes: A61K 9/2027 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose

Abstract

A dosage form is disclosed for administering 10 ng to 1200 mg tacrine to a patient in need of tacrine therapy.

Claims

1. A method for treating Alzheimer'"'"'s disease, wherein the method comprises administering orally to a patient having Alzheimer'"'"'s disease a pulsed-release dose of tacrine for treating the disease and an extended-release dose of tacrine administered with a therapeutic member selected from the group consisting of aniracetam, bifemelane, phosphatidylserine, pramiracetam, physostigmine, fampridine, linopirdine, selegiline, nimodipine, propentofylline, alpha-tocopherol, estrogen, aminopyridine, cytisine, 1-hydroxy-tacrine, and donepezil, for treating the Alzheimer'"'"'s disease.

2. A method for treating Alzheimer'"'"'s disease wherein the method comprises administering orally to a patient having Alzheimer'"'"'s disease a pulsed-release dose of tacrine for treating the disease administered with a therapeutic member selected from the group consisting of selegiline, alpha-tocopherol, 1-hydroxy-tacrine, and donepezil, and an extended-release dosage of tacrine, for treating the Alzheimer'"'"'s disease, wherein the tacrine and said therapeutic member are present in combination in a dosage form.

3. A method for treating Alzheimer'"'"'s disease wherein the method comprises administering orally to a patient having Alzheimer'"'"'s disease a dose of tacrine administered with a dose of a member selected from the group consisting of selegiline, alpha-tocopherol, 1-hydroxy-tacrine, and donepezil for treating the disease, and an extended release dose of a therapeutic member selected from the group consisting of aniracetam, tacrine, bifemelane, phosphatidylserine, pramiracetam, physostigmine, fampridine, linopirdine, selegiline, nimodipine, propentofylline, alpha-tocopherol, estrogen, aminopyridine, cytisine, 1-hydroxy-tacrine, and donepezil, for treating the Alzheimer'"'"'s disease.

4. A method for treating a neurological disease wherein the method comprises administering orally to a patient having a neurological disease a dose of tacrine for treating the disease administered at a dose corresponding to the following therapeutic program:

from 20 to 50 mg of tacrine in 0 to 2 hours, from 60 to 120 mg in 0 to 8 hours, from 110 to 170 mg in 0 to 14 hours, and from 170 to 200 mg in 0 to 24 hours, accompanied by a therapeutic member selected from the group consisting of aniracetam, bifemelane, phosphatidylserine, pramiracetam, physostigmine, fampridine, linopirdine, selegiline, nimodipine, estrogen, propentofylline, alpha-tocopherol, aminopyridine, cytisine, 1-hydroxy-tacrine, and donepezil, for treating the neurological disease.

5. A method for treating a neurological disease wherein the method comprises administering orally to a patient having a neurological disease a pulsed-release dose of tacrine for treating the disease accompanied by the administration of a therapeutically effective dose of a member selected from the group consisting of selegiline, alpha-tocopherol, 1-hydroxy-tacrine, and donepazil, and an extended-release dose of tacrine administered according to the following therapeutic pattern:

from 0 to 2 hours the administered dose is 10 to 25%, from 0 to 8 hours the administered dose is 30 to 60%, from 0 to 14 hours the administered dose is 55 to 85%, and from 0 to 24 hours the administered dose is greater than 85% of the tacrine, accompanied by a dose of a member selected from the group consisting of aniracetam, bifemelane, phosphatidylserine, pramiracetam, physostigmine, fampridine, linopirdine, selegiline, nimodipine, estrogen, propentofylline, alpha-tocopherol, aminopyridine, cytisine, 1-hydroxy-tacrine, and donepezil, for the treatment of the neurological disease.

6. A dosage form comprising a therapeutically effective dose of a member selected from the group consisting of tacrine and a pharmaceutically acceptable salt that is administered in from instantly to thirty minutes accompanied by a therapeutically effective dose of a member selected from the group consisting of selegiline, alpha-tocopherol, 1-hydroxy-tacrine, and donepezil for treating a neurological disease, and an extended-release therapeutically effective dose of a member selected from the group consisting of tacrine and a pharmaceutically acceptable salt that is administered from thirty minutes to 24 hours accompanied by a therapeutically effective dose of a member selected from the group consisting of aniracetam, bifemelane, phosphatidylserine, pramiracetam, physostigmine, fampridine, linopirdine, selegiline, nimodipine, propentofylline, alpha-tocopherol, estrogen, aminopyridine, cytisine, 1-hydroxy-tacrine, and donepezil for treating the neurological disease.

7. A caplet for delivering a therapeutically effective composition orally to an Alzheimer'"'"'s patient, wherein the caplet comprises:

(a) a therapeutic composition comprising 100 ng to 500 mg of tacrine and a therapeutic member selected from the group consisting of aniracetam, bifemelane, phosphatidylserine, pramiracetam, physostigmine, fampridine, linopirdine, selegiline, nimodipine, propentofylline, alpha-tocopherol, estrogen, aminopyridine, cytisine, 1-hydroxy-tacrine, and donepezil for treating the Alzheimer'"'"'s patient;

(b) an expandable composition that imbides fluid and increases in volume for displacing the therapeutic composition from the caplet;

(c) a wall comprising a composition permeable to fluid and impermeable to the therapeutic composition that surrounds the therapeutic composition;

(d) an overcoat on the surface of the caplet comprising a therapeutically effective dose of a member selected from the group consisting of selegiline, tacrine alpha-tocopherol, 1-hydroxy-tacrine, and donepezil for treating the Alzheimer'"'"'s patient; and

,

(e) a passageway in the wall for delivering the therapeutic composition from the caplet to the patient.

8. A dosage form for delivering a therapeutically effective composition orally to the gastrointestinal environment of an Alzheimer'"'"'s patient, wherein the dosage form comprises:

(a) a therapeutic composition comprising 100 ng to 500 mg of a member selected from the group consisting of tacrine and tacrine pharmaceutically acceptable salt, and a therapeutically effective dose of a therapeutic member selected from the group consisting of aniracetam, bifemelane, phosphatidylserine, pramiracetam, physostigmine, fampridine, linopirdine, selegiline, nimodipine, propentofylline, alpha-tocopherol, estrogen, aminopyridine, cytisine, 1-hydroxy-tacrine, and donepezil for treating Alzheimer'"'"'s disease,

(b) a wall comprising a semipermeable composition permeable to gastrointestinal fluid and impermeable to the therapeutic composition that surrounds the therapeutic composition;

(c) an overcoat on the wall comprising a therapeutically effective dose of a member selected from the group consisting of selegiline, tacrine, alpha-tocopherol, 1-hydroxy-tacrine, and donepezil;

(d) an exit in the dosage form wall for delivering therapeutic composition to the patient; and

,

(e) wherein when the dosage form is administered to an Alzheimer'"'"'s patient, the dosage form delivers the therapeutic composition over a 24 hour period at a therapeutic rate to slow the progression of Alzheimer'"'"'s disease in the patient.

9. An osmotic dosage form for delivering tacrine to an Alzheimer'"'"'s patient'"'"'s gastrointestinal tract, wherein the dosage form comprises:

(a) a tacrine composition comprising 108 mg of tacrine hydrochloride, 154.80 mg of sodium carboxymethylcellulose, 79.20 mg of sorbitol, 14.40 mg of poly(vinylpyrrolidone), and 3.60 mg of magnesium stearate;

(b) a displacement composition comprising 84.60 mg of sodium carboxymethylcellulose, 43.20 mg of sodium chloride, 7.20 mg of hydroxypropylcellulose, 7.20 mg of hydroxypropylmethylcellulose, and 0.36 mg of magnesium stearate, that develops an osmotic pressure greater than the gastrointestinal tract;

(c) a wall that surrounds the tacrine composition and the displacement composition, said wall comprising an 88;

12 (wt;

wt) mixture of cellulose acetate and polyethylene glycol; and

,

(d) an exit passageway in the wall that connects the tacrine composition with the exterior of the dosage form for delivering tacrine over 24 hours.

10. A dosage form for delivering tacrine to an Alzheimer'"'"'s patient, wherein the dosage form comprises:

(a) a tacrine composition comprising 34% tacrine, 57% mannitol, 3% hydroxypropylmethylcellulose, 1% noncrossed-linked poly(vinylpyrrolidone), 3% crosslinked poly(vinylpyrrolidone), and 1% magnesium stearate,

(b) a wall comprising 95% cellulose acetate and 5% polyethylene glycol that surrounds the tacrine composition; and

,

(c) an exit through the wall for delivering tacrine from the dosage form.

11. A dosage form for delivering tacrine according to claim 10, wherein an overcoat is coated onto the wall, which overcoat comprises 80% tacrine, 18% hydroxypropylmethylcellulose and 2% polyethylene glycol.

12. A dosage form for delivering tacrine according to claim 10, wherein the tacrine is a member selected from the group consisting of tacrine base, tacrine salt, tacrine hydrochloride, tacrine hydrobromide, tacrine sulfate, tacrine phosphate, tacrine lactate, tacrine citrate, tacrine tartrate, tacrine malate, tacrine maleate, tacrine fumarate, tacrine ascorbate, tacrine gluconate, tacrine asparate, tacrine salicylate, tacrine edisylate, tacrine laurate, tacrine palmitate, tacrine nitrate, tacrine borate, tacrine acetate and tacrine oleate.

13. A dosage form for delivering a therapeutic composition to an Alzheimer'"'"'s patient, wherein the dosage form comprises:

(a) a therapeutic composition comprising 100 ng to 500 mg of a member selected from the group consisting of tacrine and its pharmaceutically acceptable salt, and a therapeutically effective dose comprising member selected from the group consisting of aniracetam, bifemelane, phosphatidylserine, pramiracetam, physostigmine, fampridine, linopirdine, selegiline, nimodipine, estrogen, propentofylline, alpha-tocopherol, aminopyridine, cytisine, 1-hydroxy-tacrine, and donepezil;

2 to 60 wt % of an osmotically active agent, 0.25 to 15 wt % of a poly(vinylpyrrolidone), 0 to 20 wt % of a cellulose ether, and 0.01 to 10 wt % of a lubricant, with the weight of all components in the composition equal to 100 wt %;

(b) a wall that surrounds the composition, said wall permeable to fluid;

(c) an overcoat on the wall comprising a therapeutically effective dose of a member selected from the group consisting of selegiline, tacrine, alpha-tocopherol, 1-hydroxy-tacrine, and donepezil indicated for the management of Alzheimer'"'"'s disease; and

,

(d) an exit passageway in the wall that connects the therapeutic composition with the exterior of the dosage form for delivering the therapeutic composition over 24 hours to the patient for the management of Alzheimer'"'"'s disease.

14. A caplet for delivering a therapeutic composition orally to an Alzheimer'"'"'s patient, for the management of Alzheimer'"'"'s disease, wherein the caplet comprises:

(a) a therapeutic composition comprising 10 ng to 500 mg of a member selected from the group consisting of tacrine and its pharmaceutically acceptable salt, and a therapeutically effective dose of a member selected from the group consisting of aniracetam, bifemelane, phosphatidylserine, pramiracetam physostigmine, fampridine, linopirdine, selegiline, nimodipine, estrogen, propentofylline, alpha-tocopherol, aminopyridine, cytisine, 1-hydroxy-tacrine, and donepezil;

(b) a subcoat comprising a hydrophilic composition that surrounds the therapeutic composition;

(c) a wall comprising a semipermeable composition that surrounds the subcoat;

(d) a passageway in the caplet for delivering the therapeutic composition; and

(e) an overcoat that surrounds the wall comprising 1 to 125 mg of a member selected from the group consisting of tacrine and its pharmaceutically acceptable salt, accompanied by a therapeutically effective dose of a member selected from the group consisting of selegiline, alpha-tocopherol, 1-hydroxy-tacrine, and donepazil, indicated for the management of Alzheimer'"'"'s disease.