WO2014032735A1

WO2014032735A1 - Use of 3-(2,2,2-trimethylhydrazinium)-ethylpropionate or a pharmaceutically acceptable salt for treating high tension glaucoma

Info

Publication number: WO2014032735A1
Application number: PCT/EP2012/067081
Authority: WO
Inventors: Ilmars Stonans; Ivars Kalvins; Maija Dambrova; Baiba SVALBE; Helena CIRULE; Reinis Vilskersts; Indra JONANE-OSA
Original assignee: Grindeks
Priority date: 2012-09-03
Filing date: 2012-09-03
Publication date: 2014-03-06

Abstract

The invention provides the use of 3-(2,2,2-trimethylhydrazinium)-ethylpropionate or a pharmaceutically acceptable salt in the treatment of increased intraocular pressure.

Description

Use of 3-(2,2,2-trimethylhydraziniunn)-ethylpropionate or a pharmaceutically acceptable salt for treating high tension glaucoma

Technical Field

The present invention relates to treatment of high tension glaucoma by lowering of intraocular pressure by administrating 3-(2,2,2-trimethylhydrazinium)- ethylpropionate or a pharmaceutically acceptable salt.

Background Art

The elevated intraocular pressure is one of the major risk factors for occurrence of high tension glaucoma which increases with age DIELEMANS , I., et al. Primary open-angle glaucoma, intraocular pressure, and systemic blood pressure in the general elderly population. The Rotterdam Study.. Ophthalmology. 1995, vol.102, no.1 , p.54-60.

3-(2,2,2-Trimethylhydrazinium)-ethylpropionate chloride as compound is known from US 4481218 A (INST ORGANICHESKOGO SINTEZA AK ) 06.1 1.1984 where it was used as starting material for synthesis of 3-(2,2,2- trimethylhydrazinium)propionate, pharmacological properties of 3-(2,2,2- trimethylhydrazinium)-ethylpropionate chloride were not described.

3-(2,2,2-Trimethylhydrazinium)propionate dihydrate was disclosed as effective substance in the treatment of acute disorders of blood circulation in the fibrous tunic of the eyeball in SU 1703108 A (INST ORGANICHESKOGO SINTEZA AK )

07.01.1992 , where it was introduced as 10% 3-(2,2,2- trimethylhydrazinium)propionate dihydrate solution.

In GOLOVACHOVA, M., et al. Neuroprotective treatment of patients with normal tension glaucoma. Georgian medical news. 2006, vol.2, no.131 , p.37-40.

experiments were described, where 35 patients received 3-(2,2,2- trimethylhydrazinium)propionate dihydrate during 2,5-3 months, in the result positive dynamics were noticed in 34 patients, negative dynamics 1 patient. It was recommended to use 3-(2,2,2-trimethylhydrazinium) propionate dihydrate in patients with primary open angle glaucoma with normalised intraocular pressure and in patients with normal tension glaucoma. Also in BOTABEKOVA, TK., et al. Mildronate in the treatment of the optic neuropathy in glaucoma. Meditsina. 2004, p.289-291. it was disclosed, that 3-(2,2,2-trimethylhydrazinium) propionate dihydrate is effective in treatment of optic neuropathy.

An object of the present invention is to provide a compound, which would possess a pronounced effect in the treatment of high tension glaucoma.

Disclosure of Invention

The above-mentioned object is attained by providing 3-(2,2,2- trimethylhydrazinium)-ethylpropionate or a pharmaceutically acceptable salt , particularly 3-(2,2,2-trimethylhydrazinium)-ethylpropionate chloride. The 3-(2,2,2- trimethylhydrazinium)-ethylpropionate chloride possesses the pronounced effect of decreasing the intraocular pressure and may be used in medicine for treatment of high tension glaucoma. The 3-(2,2,2-trimethylhydrazinium)-ethylpropionate chloride can be used as a solution for eye drop, or a preparation for intraocular implant comprising 3-(2,2,2-trimethylhydrazinium)-ethylpropionate chloride for use in the treatment or prevention of glaucoma by lowering of intraocular pressure. Unlike 3-(2,2,2-trimethylhydrazinium)propionate dihydrate, the 3-(2,2,2- trimethylhydrazinium)-ethylpropionate chloride pronouncedly reduces the intraocular pressure.

Best Mode for Carrying Out the Invention

The present invention will be described in more detail by referring to the following non-limiting examples.

Animals

Experiments were conducted on 13-14 weeks old adult male Wistar rats with initial weight of 300-350g. The feed was a standardized diet. The room temperature was kept at 21 -23°C, relative humidity at 65±10%, 12 hour light/darkness cycle.

Measurement of intraocular pressure

Animals were randomly assigned to three different groups for treatment with the following test solutions:

group 1 : isotonic NaCI solution (0.9% NaCI in water)

group 2: 5% 3-(2,2,2-trimethylhydrazinium)propionate dihydrate solution in isotonic NaCI solution;

group 3: 5% 3-(2,2,2-trimethylhydrazinium)-ethylpropionate chloride solution in isotonic NaCI solution. One drop (50 μΙ) of appropriate test solution was applied to the right eye. The same amount of isotonic NaCI solution was applied to the left eye. In all groups the left eye served as control.

Before application of test solutions intraocular pressure was measured in both eyes with a tonometer TonoVet (Paragon Medical, USA) as described previously WANG, W.-H., et al.: Noninvasive Measurement of Rodent Intraocular Pressure with a Rebound Tonometer. Investigative Ophthalmology & Visual Science. 2005, vol.46, no.12, p.4617.

Before application of the test solutions, intraocular pressure in both eyes was equal (6,1 ± 0,1 mmHg).

Influence of isotonic NaCI solution, 5% 3-(2,2,2-trimethylhydrazinium)propionate dihydrate solution and 5% 3-(2,2,2-trimethylhydrazinium)-ethylpropionate chloride solution on intraocular pressure in rats 3 hours after treatment is summarized in Table 1.

Table 1

^*p<0.05 between intraocular pressure values in right and left eyes 3 hours after the treatment.

To our surprise, the intraocular pressure 3 hours after the application of 3-(2,2,2- trimethylhydrazinium)-ethylpropionate chloride decreased by 16%.

Claims

1. 3-(2,2,2-Trimethylhydrazinium)-ethylpropionate chloride for use as a medicament.

2. 3-(2,2,2-Trimethylhydrazinium)-ethylpropionate chloride for use in the treatment of increased intraocular pressure.

3. 3-(2,2,2-Trimethylhydrazinium)-ethylpropionate chloride for use in the treatment according to claim 2, wherein increased intraocular pressure is associated with glaucoma.