(57) Abstract:

The drug antihistamine action is intended for use in medicine. The task of the invention is to reduce the side effects of diazoline in respect of the gastrointestinal tract with an option to increase to a single dose. The drug contains diasorin and sulfate or zinc aspartate at mass ratio diasorin: sulfate (aspartate) zinc 20-25:1. The preparation may further contain auxiliary substances and to provide a tablet containing, g: diasorin - 0,2-0,4, zinc sulfate - 0,01-0,02, auxiliary substances to the mass of 0.25-0.5. 1 C.p. f-crystals, 2 tab.

The present invention relates to antihistamine drugs, widely used in modern medical practice.

Known use as an antihistamine drug 3-methyl-9-benzyl-1,2,3,4-tetrahydrocarboline naphthalene-1,5-disulfonate: - international name mebhydrolin. /see VIDAL, 1996, drugs in Russia: a Handbook. M , LAST "Attraversare", 1996, G-18/. The drug was tested in Germany in the mid-50's, was in dermatology called omeril /bed, ed. 2, T. 9, M, 1959, S. 203/ and was approved for use in the USSR under the name diazole, So 1 - ed. 9-e, M, 1984, S. 315/: release powder and pills to 0.05 and 0.1 g with higher pay 0.3 and 0.6 g daily doses for adults.

Approved for use in the Russian Federation drug amaryl company Bayer /see VIDAL, 1995, drugs in Russia: a Handbook. M, JSC "Attraversare", 1995, S. S. 33, 695/ also comes in pills to 0.05 in the dose for adults is 2 to 6 pills a day.

Lack of diazoline is irritating effect on the mucous of the stomach and intestinal tract, therefore it is contraindicated in gastric ulcer and duodenal ulcer, inflammatory diseases of the gastrointestinal tract.

Diasorin recommended for use in capsules or in the form of index tablets after meals.

The present invention is to reduce the side effects of diazoline in respect of the gastrointestinal tract with increasing dose.

This goal is achieved by the fact that antihistamines drug of diazoline additionally contain used in medical practice salts of zinc sulfate, or zinc aspartate at mass ratio diasorin: sulfate or zinc aspartate 20-25:1.

Antihistamine drug preparation - 0,2-0,4, zinc sulfate - 0,01-0,02, auxiliary substances to the mass of 0.25-0.5.

As auxiliary substances can be used known pharmaceutical acceptable excipients, such as low-molecular polyvinylpyrrolidone, methylcellulose, apadravya agent - magnesium stearate, etc.

Getting a new drug is carried out in accordance with the normative and technical documentation for specific dosage forms.

Examples of the medicinal product.

Example 1.

In the pump-mixer download 987 ml of ethyl alcohol and 298 ml of distilled water and mix. Loaded into the mixer 4258,1 g diazoline, 212,9 g of zinc sulfate, 585,5 g of low-molecular polyvinylpyrrolidone, 212,9 g of methylcellulose. The mixture is stirred for 1 hour at 25 exchange rate/min Powder mixture from the mixer pour the second mixer, where the measuring device serves 1,285 l granulating fluid. The mixer was closed and the mixture is stirred at 50 rpm for 20 min, until a homogeneous pasty mass. Wet the mixture with a spatula transferred into the hopper pellet mill for wet granulation, with grid hole size 2.5 mm Include the granulator with skasowania layer of granules of 1-2 cm pallet mix. A pallet of pellets is placed in a pre-heated oven with forced air circulation and dried at 50oC 3 hours. Suspended granules pour into the mixer, add, or 50.8 g of magnesium stearate, include mixing at 25 rpm and stirred for 20 minutes Granules from the mixer is being poured into the hopper of rotary tablet machine with a press tool to get biconvex with a radius of curvature of 12 mm tablets with a diameter of 12 mm Tablets are collected in a container.

Example 2. The composition of the tablets, g:

Diasorin - 0, 2

Zinc sulfate 0.02

Excipients: low-molecular polyvinylpyrrolidone, methylcellulose, magnesium stearate to obtain tablets with a mass of 0.5 g

Example 3. The composition of the tablets, g:

Diasorin - 0,2

Zinc aspartate - 0,01

Low-molecular polyvinylpyrrolidone - 0,0225

Methylcellulose - 0,01

Magnesium stearate - 0,0025.

The average weight of the tablets of 0.25 g

Example 4. The test drug

On models ulcers of the gastric mucosa in rats investigated the ability of the claimed medicinal preparation to influence the effects of ulcerogenic substances /ethanol, indomet the cosy ethanol and indomethacin in combination with 0.6 n hydrochloric acid. Such models are used for the selection of compounds with antiulcer activity.

The studies were performed on male rats weighing 160-180 g, which prior experience were deprived of food for 24 hours, water was not limited. The claimed drug - 0.2 g of diazoline, 0.01 g of zinc sulfate /1:20 weight/, 0.25 g of auxiliary substances and control the official diasorin in terms of equal doses of 200 mg/kg) diazoline was introduced by the probe into the stomach 1 hour before damaging substances (ethanol - 1 ml per animal).

Experience with damaging action on mucous: indomethacin 20 mg/kg and 0.6 n hydrochloric acid and 5 ml/kg - stated the product had the composition: 0.2 g of diazoline and 0.008 g of zinc aspartate (1:25 by weight).

Control official diasorin in terms of equal doses of 200 mg/kg) diazoline.

The drugs were injected probe into the stomach 1 hour before damaging substances (ethanol - 1 ml per animal). One hour after injection of ethanol and 4 hours after administration of indomethacin in conjunction with the acid of animals scored, drew the stomachs and determined the length of the stripe-shaped hemorrhagic lesions of the gastric mucosa.

The results of the study are presented in table. 1 and 2.

As can be seen from tables 1 and 2 stated p is the influence of ethanol on gastric mucosa in rats.

It is important to note that the claimed drug weakened the damaging effect of ulcerogenic substances at a dose of 200 mg/kg, i.e. the dose at which the drug has a strong and long-lasting anti-histamine action.

Our data indicate possible to assign claimed the drug in higher doses compared with the official bean diazoline, which distinguishes the claimed drug, is not conducive to the development of inflammatory or ulcerative lesions of the gastric mucosa.

Example 5.

In experiments on mice conducted by the definition of toxicity after a single dose of a medicinal product on the basis of diazoline with the addition of zinc sulfate in a ratio by weight of 1:20 and officinal bean diazoline.

Tablet mass of the test preparations in the form of aqueous suspensions were administered orally in doses up to 2000 mg/kg Each dose was tested on 6 - 8 mice given within 5 days of the General condition, behavior, and death of animals in groups.

It was found that the claimed product and the official diasorin when introduced orally in doses of 2000 mg/kg did not cause mortality and the change in their behavior. In accordance with S="ptx2">

Example 6.

Defined clinical benefit and tolerability of the tablets of the claimed preparation containing each 0.4 g diazoline 0.02 g of zinc sulfate daily intake of 2 times a day in 30 patients, of which 17 patients with seasonal allergic rhinitis (group 1) and 13 - chronic recurrent urticaria during clinical manifestations (group 2). The patients ' age from 18 to 59 years, mean age 36 years, 14 women and 16 men. Disease duration from 2 to 13 years, mean duration of 6.2 years. Of comorbidities 6 patients suffered from chronic hypoacid gastritis, 5 - a dysbacteriosis, 3 - hypertension.

All patients voluntarily implemented the claimed preparation in the specified composition of the tablets during the course of 21 days.

Results: in 9 patients of the 1st group treated with the claimed preparation in the period of the season, dusting, on the third day of admission clinical symptoms disappeared completely, and 8 decreased. In addition to the requested drug to patients enjoyed intranasal vasoconstrictor drops, the need for which has disappeared or decreased from 8 doses up to 1 to 2 doses per day. Sick of working. Showed a significant reduction of eosinophilia in the blood and in mask (47%), satisfactory - 3 (17,7%). All patients were symptomatic of soplivosti, diarrhoea or any other side effects.

The 2nd group of patients on a 4-5 day reception in 7 (54%) noted a significant reduction of pruritus, reduction in the prevalence and intensity urticarnae rash. In 6 patients itchy skin is preserved, but the additional lesions not appeared. None of the groups were observed growth or occurrence of dyspepsia.

All patients of the 1-St and 2-nd group had previously officinal drug diasorin and they all said (100%) higher efficacy and better tolerability claimed the drug.

Example 7.

Clinical trials of alleged drug (diasorin 0.4 g of zinc sulfate 0.02 g, excipients up to 0.5 g) were performed on 30 patients (17 women and 13 men) aged from 17 to 72 years. 13 - chronic eczema, 7 with atopic dermatitis, 6 - exudative form of psoriasis, 3 - with allergic dermatitis and 1 with lichen planus.

Patients received the drug for 3 to 4 weeks 1 tablet per day. At the same time spent outside symptomatic therapy (lotions, creams, masnadieri of treatment in 8 of 13 patients itching stopped completely, the remaining 10 - 14 days. The resolution of rash elements 4 patients were observed to the end of the first week, the 7 - by the end of the second, and two in three weeks.

For atopic dermatitis in 3 cases, the effect was obtained for 3 - 4 days: reducing itching, blanching rash. 4 patients remission by the end of the 3rd week.

At the exudative form of psoriasis itching decreased by 3-day and 7 - 9 days - completely stopped. Allergic dermatitis pruritus was reduced by 2 - 3 days with stabilization process of the skin. Full stop itching for 2 weeks. In a patient with lichen planus itching disappeared for 7 days, the full resolution of rash elements with residual pigmentation - by the end of the 3rd week.

The obtained results were compared with the results in the control group (28 patients) with similar diseases treated officinal drug diasorin dose of 0.1 to 3 tablets 3 times a day after meals. There was marked a stronger therapeutic effect in the claimed product in the first 10 days, the following days have also seen the advantage antipruritic and anti-inflammatory action. No side effects were.

An advantage of the claimed drug identified in the convenience premenstrually nervous system.

Thus, adding to diazoline zinc salts in amounts of from 1:20 to 1:25 essentially changes the tolerability of the drug, allowing you to use tablets containing more diazoline and reduce the amount of medication to once per day, i.e. to get a surprise for specialists in clinical pharmacology effect. As is well known, zinc sulfate irritating to the mucous membrane of the stomach and is even used in medicine as a means of causing vomiting, but adding to diazoline in the specified proportions, he not only enhances the irritant diazoline on mucous, but gives unexpected and opposite result, thereby giving a significant differences of the claimed medicinal preparation from previously known drugs diazoline.

1. Antihistamine drug containing diasorin, characterized in that it further comprises a sulfate or zinc aspartate at mass ratio diasorin : sulfate or zinc aspartate 20 - 25 : 1.

2. The drug under item 1, characterized in that it further comprises an excipient and made in the form of tablets containing, g:

Diasorin - 0,2 - 0,4

Zinc sulfate - 0


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