BG65658B1 - Galantamin-based combined medicamentous product - Google Patents

Abstract

The invention relates to a combined medicamentous product comprising galantamin and vitamins of group B, including B1, B2, B5, B6 and vitamin PP. The combined preparation shall find application in the treatment and prevention of the central and the peripheral nervous systems.

Description

Technical field

The invention relates to a combination drug based on galantamine, which will find application for the treatment and prevention of the central and peripheral nervous system.

BACKGROUND OF THE INVENTION

Galantamine is a tertiary alkaloid isolated from various plant sources such as marshmallow (Leocojum aestivum), narcissus (Narcissus spp.) And others. Galantamine is a well-known reversible cholinesterase inhibitor that interacts competitively with the acetylcholinesterase enzyme. Galantamine has been used to treat many ailments. The use of galantamine or its pharmaceutically acceptable salts has been shown to be effective in treating Alzheimer's disease [US 4,663,318]; in the treatment of alcoholism [EP 0449247]; in the treatment of nicotine dependence [WO 1994/016708]; in the treatment of mania [US 5,336,675] and the like.

Galantamine has been well studied, has participated in numerous pharmacological and clinical studies, and has shown good effect in improving neuromuscular transmission and inter-neuronal impulse transmission in the central and peripheral nervous systems.

Group B vitamins play an important role in the direct and indirect mechanism for the proper functioning of the nervous system [Pharmaceutical Catalog for Medicinal Products authorized for use in Bulgaria, 1998].

Known daily dietary supplement for increasing the efficiency of the muscular activity of athletes, containing galanthamine in the form of complete plant extract of Leucojum aestivum, Co-QlO, vitamins B, substitutable amino acids and antioxidants, as well as herbal composition for increasing the efficiency of the athlete's muscular activity containing complete plant extract of Leucojum aestivum, inositol hexanicotinate, thiamine, vitamin B complex, green tea, Gandoderma, N-acetylcysteine, L carnitine, Co-Q10 and calcium patenotenate [BG 105796 / W02000 / 041540].

A nutritional supplement is also known to improve estrogen deficiency associated with neurodegeneration and cognitive impairment in women, comprising plant extract of Leucojum aestivum, Co-QlO, vitamins B, substitutable amino acids and antioxidants, optionally, and Spagic bil extract, Gunko bil extract, bare cola, acetyl L-carnitine and zinc. Also known from the same source and herbal composition for improving estrogen deficiency associated with neurodegeneration and cognitive impairment in women, containing complete plant extract of Leucojum aestivum, Vitamin B complex, acetyl L-carnitine, Co-QlO, zinc, Gunko extract biloba, Vasora moniera and Convolulus pluricaulise [US 2001/0046522].

The creation of many new drugs for the treatment and prophylaxis of the central and peripheral nervous systems has been dictated by the high growth of these diseases in recent years.

The problem to be solved is the creation of a combined medicinal product based on galantamine, which has a potent anticholinesterase effect, exerts a prophylactic effect on the proper functioning of the central and peripheral nervous system and has a curative effect in diseases related to functional disorders of the nervous system.

SUMMARY OF THE INVENTION

The problem is solved with a combination preparation containing galantamine and B vitamins, including thiamine (vitamin B), riboflavin-5-phosphate sodium / vitamin B ₂ /, calcium pantothenate / vitamin B ₅ /, pyridoxine hydrochloride / vitamin ₆ (and nicotinamide (vitamin PP) and pharmaceutically acceptable excipients in solid and liquid form. The amounts of the active substances per unit dose are: galantamine from 1 to 10 mg, vitamin Bj from 2 to 20 mg, B ₂ from 1 to 10 mg, vitamin B ₅ from 10 to 40 mg, vitamin B ₆ from 5 to 50 mg and vitamin PP from 20 to 40 mg.

In one embodiment of the invention, the combined product is in liquid form and represents 2

65658 Bl syrup, which in one unit dose contains the active substances in the above amounts and the following excipients: sorbitol, citric acid, sodium monohydrogen phosphate dodecahydrate, benzoic acid, sodium salt of 2,3 dimercapto-1-propanesulfonic acid / DMPS / , glycerol, ethanol, essence and purified water up to 5 ml.

In a further embodiment of the invention, the combined product is in solid form and is a film tablet containing the active ingredients in a unit dose in the above amounts and the following excipients: copolyvidone, wheat starch, microcrystalline cellulose, colloidal silica, talc and composition for film coverage.

The medicinal product of the present invention has potent anticholinesterase action along with essential B vitamins and has a potent effect on the proper functioning of the peripheral and central nervous systems.

The drug product is pharmaceutically stable in said dosage forms.

The dosage forms can be used as a therapeutic and prophylactic agent in the following diseases: paresis and paralysis of peripheral nerves, neuritis, neuralgia, toxic drug neuropathies, myopathies, progressive muscular dystrophy, in disorders of muscular tone / mucous atonia of smoothie 10 bladder and gastrointestinal tract /, postoperative and postpartum paresis, cerebral palsy, in violation of cognitive and memory functions due to atherosclerosis, cerebrovascular disease and degenerative disorders diseases of the central nervous system.

Embodiments of the invention

The exemplary embodiments and variations described are for illustration only and do not limit the inventive idea, the scope of which is determined by the scope of the claims.

Example 1.

Liquid formulation of the combined medicinal product, related to 1500 kg of syrup

No Name of the constituents medicinal substances Quantity in kg 1. Galantamine hydrobromide 0.625 2. Thiamine hydrochloride / Vitamin B / 1,875 th most common 3. Riboflafin-5-phosphatrium / vitamin B2 / 0.75 4. Pyridoxine hydrochloride / vitamin B ₆ / 1,250 th most common 5. Nicotinamide / vitamin PP / 6,250 th most common 6. Calcium Pantothenate / Vitamin B ₅ / Excipients 6,250 th most common 7. Sorbitol 500,000 8. Citric acid 6,250 th most common 9. Glycerol 250,000 10. Sodium monohydrogen phosphate dodecahydrate 8,750 th most common 11. Benzoic acid 1,875 th most common 12. 2,3-Dimercapto-1-propanesulfonic acid sodium salt (DMPS) 0,125 th most common 13. Ethanol 96% 75,000 14. Raspberry essence 3,125 th most common 15. Purified water 612,875

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Example 2.

Solid formulation in mg attributed to one combination tablet

No Name of the constituents medicinal substances Amount in mg 1. Galantamine hydrobromide 2.5 2. Thiamine mononitrate / Vitamin B / 7.5 3. Riboflavin-5-phosphate sodium / vitamin B ₂ / 3.0 4. Pyridoxine hydrochloride / vitamin B ₆ / 5.0 5. Nicotinamide / vitamin PP / 25,0 6. Calcium Pantothenate / Vitamin B ₅ / Excipients 25,0 Ί. Copolyvidone 5.0 8. Wheat starch 58.5 9. Microcrystalline cellulose 34.0 10. Colloidal silica 1.5 11. Talc 3.0 12. Composition for film coating 5.0

The present combination composition with the particular pharmaceutical forms is in accordance with the physicochemical properties of the active ingredients. The stability of the product is ensured by the created qualitative and quantitative composition of the excipients. The stability of the pharmaceutical forms of the combined medicinal product is presented in Tables 1 and 2.

Table 1

Stability of the liquid form of the combined medicinal product at a temperature below 25 ° C, 60% relative humidity and protected from light

Indicators and standards Storage time Appearance: clear syrupy liquid Initial analysis 3 '™ month 6 '™ month 9 '™ month Color - yellow He responds He responds He responds He responds Solution reaction (pH) - from 3.60 to 4.40 4.10 4.10 4.15 4.15 Content in mg per 100 ml in the range: Galantamine hydrobromide: 45.0-55.0 Thiamine hydrochloride: 135-165 Riboflavin sodium phosphate: 54.0-66.0 Pyridoxine hydrochloride: 90.0-110.0 Nicotine amide: 0.45-0.55 Calcium Pantothenate: 0.45-0.55 Ethanol: 5.40- 6.60 Glycerol: 18.00-22.00 Benzoic acid: 0.135-0.165 48.8 140 59.4 109.8 0.55 0.47 6.07 20.35 0.147 48.5 140 59.0 109.2 0.55 0.47 6.05 20.20 0.146 48.0 143 58.5 108.8 0.54 0.48 6.01 20.02 0.146 47.6 143 58.0 108.1 0.55 0.47 6.00 8 pm 0.145 Microbial content • Total number of microorganisms in units / g: not more than 10 ³ Molds and yeast-like mushrooms in units / g: not more than 10 ² • Ps. Aeruginosa, S.aureus, Enterobacteriaceae: not allowed He responds He responds He responds He responds

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TABLE # 2 θ

Solid form stability of the combined medicinal product at a temperature below 25 ° C ± 2, 60% relative humidity and protected from light

Times stored Appearance Color The min bridge falls apart, no more than 30 Degree of dissolution and hydrobromide detergent after 45 pitches per cent »not less than 75,0 Content in 1 movie Microbial content Galactamine bromide 1375 * 2.625 Tiamnes nitrate 6,937 + 8,063 Riboflavn 2,775 + 3,225 Pnloxnone chloride 4 ^ 25 + 5.375 Nicotine amide 23.125 + 26.875 Calcium Pantothenic 23,125 * 26,875 010503A Initial analysis Film, flat round tablet, double convex (bomb type), diameter 8,0 mm White 113 93,3 235 7.44 3.03 5.12 26.03 24,92 He responds 3 months He responds He responds 14,0 90,8 234 7.38 3.11 5.03 25.88 24.92 He responds 6 months He responds He responds 16.5 87,1 23 « 7D6 3.07 ' 4.99 25.92 24.77 He responds 0J5OZB Initial analysis Movie. tab. is a regular circular shape, double-convex (bomb type), with a diameter of 8.0 mm White 11,0 89,2 2.48 7.11 3.03 5.02 25.11 25.01 He responds 3 months He responds He responds 13L 87,7 2 ^ 1 7.02 3.06 4.98 25.11 24,89 He responds 6 months He responds He responds 15.0 84,9 2L0 7,00 3.02 4.88 25.05 24.66 He responds

Claims

Claims (3)

Claims 1. A galanthamine-based and B-group combination medicinal product comprising vitamin PP and pharmaceutically acceptable excipients, wherein the content of the active substances per unit dose is in the following amounts: galantamine (as salt) from 1 to 10 mg, vitamin B j from 2 to 20 mg, vitamin B ₂ from 1 to 10 mg, vitamin B ₅ from 10 to 40 mg, vitamin B ₆ from 5 to 50 mg and vitamin PP from 20 to 40 mg. A combination medicament according to claim 1, characterized in that it is in liquid and solid form. Use of the combination product according to claims 1 and 2 for the treatment and prophylaxis of the central and peripheral nervous systems.