Method and composition for treating alzheimer-type dementia

a technology of acetylcholinesterase and alzheimer's type, applied in the field of method and composition for treating alzheimer's type dementia, can solve the problems of merely employing the concomitant use of antiemetics such as propantheline and domperidone, and merely achieving the full therapeutic potential of this acetylcholinesterase approach to the treatment of alzheimer's type dementia. achieve the effect of improving

Inactive Publication Date: 2011-08-18
CHASE PHARMA CORP
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0030]In summary, the literature neither discloses nor suggests the possibility of taking advantage of the side effect mitigation discovered by Faber 1999, achieved with propantheline, or of the nausea/vomiting side effect mitigations achieved with antiemetics, to improve the magnitude and/or duration of the otherwise marginal therapeutic response to AChEIs, by allowing an increase in the doses of said AChEIs beyond the recommended maximal dose levels and concurrently improving neurobehavioral function and quality of life. No attempt was made in this direction heretofore.
[0031]Considering the results of the above-cited previously published studies in animal models of human cognitive function indicating a dose-response relation between the amount of AChEIs and the degree of cognitive improvement achieved in the clinically relevan...

Problems solved by technology

Nevertheless, the aforementioned application of the general concept for improving the treatment of dementias of the Alzheimer type provides only limited benefit to patients suffering from these disorders.
While potentially lessening side effects, merely employing the concomitant use of a...

Method used

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  • Method and composition for treating alzheimer-type dementia

Examples

Experimental program
Comparison scheme
Effect test

example 1

Orally Disintegrating Tablets Containing 15 Mg of Donepezil Hydrochloride and 4 Mg of Ondansetron

[0176]One and a half kilogram of donepezil hydrochloride and 1.8 kg of corn starch are mixed thoroughly until complete homogenizing of the mixture which, after a passage through a 35 mesh sieve, is added with a previously prepared mixture of 400 g of ondansetron base, thoroughly stirred together with 2.4 kg of corn starch and sieved at 35 mesh. The mixture thus obtained is added with 0.6 kg of strawberry flavor powder, 0.2 kg of sodium saccharin, 13.08 kg of lactose, 4.4 kg of microcrystalline cellulose, and 2.9 kg of sorbitol. The mixture is mixed until complete homogenization, then it is added with 0.1 kg of magnesium stearate, mixed again and compressed with punches of 7 mm to obtain 100,000 orally disintegrating tablets having the following composition

Donepezil hydrochloride15.00mgOndansetron4.00mgCorn starch42.00mgStrawberry flavor powder6.00mgSodium saccharin2.00mgLactose130.00mgMi...

example 2

[0177]Capsules for IR oral administration are prepared by mixing the following ingredients:

IngredientsParts by weightRivastigmine (as hydrogen tartrate)900Domperidone (as maleate)1,000Lactose USP7,350Colloidal silicon dioxide50

[0178]After mixing, the mixture is screened through a 40 mesh screen and introduced in two-piece hard gelatin capsules No. 3, each containing 9 mg of rivastigmine and 10 mg of domperidone.

example 3

[0179]Tablets for IR oral administration containing 5 mg of donepezil hydrochloride formulated with a pharmaceutical carrier, tablets containing 10 mg of donepezil hydrochloride formulated with a pharmaceutical carrier and tablets containing 10 mg of metoclopramide formulated with a pharmaceutical carrier are distributed in capsules as described in GB 1,254,580, such that unit dosage forms containing 15 mg of donepezil hydrochloride and 10 mg of metoclopramide are prepared.

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Abstract

There is described a method for increasing the maximal tolerated dose and thus the efficacy of an acetylcholinesterase inhibitor (AChEI) in a patient suffering from an Alzheimer type dementia by decreasing concomitant adverse effects by administration of said AChEI in combination with a non-anticholinergic antiemetic agent, whereby an enhanced acetylcholinesterase inhibition in the CNS of said patient is achieved and alleviation of the symptoms of Alzheimer type dementia in said patient is thereby improved to a greater extent. The use of a non-anticholinergic antiemetic agent for the preparation of a pharmaceutical composition for the treatment of Alzheimer type dementia in combination with an acetylcholinesterase inhibitor (AChEI) and pharmaceutical compositions comprising (a) a 5HT3 receptor antagonist, a dopamine antagonist, a H1-receptor antagonist, a cannabinoid agonist, aprepitant or casopitant as an antiemetic agent and (b) an acetylcholinesterase inhibitor are also described.

Description

CROSS REFERENCE TO RELATED APPLICATIONS[0001]This application is a continuation-in-part of U.S. application Ser. No. 12 / 880,395, filed on Sep. 13, 2010, taking benefit from U.S. Provisional Application No. 61 / 272,382, filed on Sep. 18, 2009, which are incorporated herein in their entirety. This application also is a continuation-in-part of the PCT / US2010 / 002475 Application filed on 13 Sep. 2010, taking benefit from U.S. Provisional Application No. 61 / 272,382 filed on Sep. 18, 2009. This application also is a continuation-in-part of U.S. application Ser. No. 12 / 934,140 which is the US national phase of PCT / US09 / 01662 filed on 13 Mar. 2009, taking benefit from EP Application No. 08005750.8 filed on Mar. 27, 2008.FIELD OF THE INVENTION[0002]This invention concerns a method for enhancing the maximal efficacy and maximal tolerated dose of an acetylcholinesterase inhibitor in a patient suffering from dementia of the Alzheimer type by combining said acetylcholinsterase inhibitor with an an...

Claims

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Application Information

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IPC IPC(8): A61K31/55A61K31/445A61P25/28
CPCA61K31/445A61K31/454A61K31/55A61K45/06A61K31/27A61K31/166A61K31/4178A61K2300/00A61P25/28
Inventor CHASE, THOMAS N.CLARENCE-SMITH, KATHLEEN E.
Owner CHASE PHARMA CORP
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