BG109687A - Antiasthmatic drug - Google Patents

Abstract

The antiasthmatic drug finds application in human medicine for the treatment of bronchial asthma and asthmatic bronchitis. It helps to overcome even the most serious asthma attacks within 30 or 40 minutes, as well as to avoid any further cases of hard asthmatic breathing and asthma attacks for a period of 10 - 20 years or even longer, i.e. in actual fact asthma gets fully cured. Besides, the side effects and complications of corticosteroids are avoided. The drug is characterized by good tolerability and does not cause any complications. Its ingredients in mg are: pure caffeine 30,00 to 250,00; ergotamintartarat 0,25 to 2,00; zinc sulphate 10,00 to 400,00; papaverine hydrochloride 30,00 to 200,00; atropine sulphate 0,25 to 1,00; aminophylline 40,00 to 250,00; glaucine hydrochloride 30,00 to 200,00; calcium sulphaguaiacolas 100,00 to 600,00; and chloropyramine 30,00 to 200,00.

Description

TECHNICAL FIELD

The invention relates to an anti-asthmatic drug for use in human medicine for the treatment of bronchial asthma and asthmatic bronchitis.

BACKGROUND OF THE INVENTION

There are a number of medicines known to treat bronchial asthma and asthmatic bronchitis. Xanthines are known for their stimulating effect on breathing and for the relief of bronchoslasms (Martindale, 1989). There are also known combinations thereof with other medicaments. In the concepts of Pavlovskaya doctrine, caffeine enhances excitatory processes in the cerebral cortex and processes of internal retention. It excites vasomotor centers and causes relocation of blood supply to the various internal organs. Within classical pharmacology, caffeine is considered to be a weak protoplasmic poison that inhibits the development of germs. As a xanthine derivative (weaker than theophylline), it removes spasms of the bronchi and is used to treat asthmaticus status (BE 903065).

The ergotamine is known to be a sympatholigic (Martindale 1989). It improves heart activity - increases heart rate, improves heart rate. Has a specific effect on congestive conditions of the lung. This effect is probably due to vasoconstrictive action on the bronchial vessels. Ergotamintartarate is a partial agonist and antagonist of the alpha-adrenergic system of the smooth muscle of the blood vessels of the lungs and other organs. He is mainly an antagonist in the peripheral and central nervous systems.

Co-administration of caffeine with ergotamine increases both the absorption and peak plasma concentrations of caffeine about 2-fold, which allows for a reduction in its dose (ergotintartartar) in combination.

Papaverine hydrochloride is known as an indisputable antispasmodic. It eliminates bronchial spasms and soothes the center of breathing and coughing, / Martindale 1989 /

Atropinsulfate is known to be an antimuscarinic agent and its use for the treatment of pulmonary asthma. / Paterson J.W.h Tarala R.A., Med. JAust.1985,143,390 /.

Zinc sulphate is known. In recent years, much attention has been paid to zinc salts in connection with their systemic action, affecting the immune and metabolic processes in the body. The amount of trace element zinc in the body is about 2 g. Zinc-dependent enzymes are vital, such as: corticotropin, somatotropin, gonadotropin, insulin / Brzozowski, R., Tatalai, M. et al.,. the body leads to a weakening of immunity. In the central nervous system, zinc accumulates most around the centers that regulate the rhythm of breathing, the circadian rhythm of wakefulness - sleep, the rhythm of cardiac activity, the motility of the gastrointestinal tract, etc. Zinc salts are now used to treat the lung, digestive, cardiovascular and other systems. The addition of zinc sulphate to the anti-asthmatic drug combination is the original moment in the treatment of pulmonary asthma.

Aminophylline is known as a medicament for the treatment of pulmonary asthma. It eliminates bronchial spasms, reduces blood vessel resistance, lowers the pressure in the pulmonary artery system, widens the coronary vessels.

Glaucinhydrochloride is known - has a cough action. Unlike codeine, it does not suppress the center of respiration, does not affect the motility of the gastrointestinal tract, does not lead to accustoming and addiction.

The sulphaguayacol is known. It is a mixture of the potassium salts of m-and p-guaiacolsulfonic acids. It has broncho-antiseptic and expectorant action. It is used in respiratory diseases, especially in childhood.

Chlorpyramine is known. It is a competitive histamine blocker with respect to H1 receptors. It is used for the treatment of pulmonary asthma in the intracranial period.

The disadvantage of any of the above medicines is that they influence individual moments of the symptoms of pulmonary asthma without interrupting the development of the disease.

Corticosteroid preparations are also known as medicaments for the treatment of pulmonary asthma. / Martindale 1989 / Their disadvantages are that they can lead to manifestations of drug hypercorticism - obesity, arterial hypertension, osteoporosis, gastric and duodenal ulcers, infections, etc. In addition, after initiation of treatment, the patient becomes completely dependent on exogenous corticosteroids and, although improving his condition to some extent, does not prevent the onset of new attacks.

SUMMARY OF THE INVENTION

It is an object of the invention to provide an anti-asthmatic drug that will stop the onset of the disease and lead to prolonged remission for 10-20 years or more, i. to a practical cure, while not showing the severe side effects of corticosteroids.

The object of the invention is achieved by the creation of an anti-asthmatic drug containing pure caffeine, ergotamintartarate, zinc sulfate, papaverine hydrochloride, atropinsulfate, aminophylline, gpautsinhydrochloride, kaliisulfagvayaklass and cholirpiramine, the following:

Pure Caffeine Ergotamintartrate Zinc Sulphate Papaverine Hydrochloride Atropinsulfate Aminophylline Gpautsinhydrochloride from 30.00 to 250.00 from 0.25 to 2.00 from 10.00 to 400.00 from 30.00 to 200.00 from 0.25 to 1.00 from 40.00 to 250.00 from 30.00 to 200.00

Chloropyramine from 100.00 to 600.00 from 30.00 to 200.00

The combination of active substances is suitable for the preparation of pharmaceutical forms using conventional pharmaceutical auxiliaries and carriers.

The benefits of an anti-asthmatic drug are the following:

- The most severe asthmatic attacks in 30-40 minutes are mastered;

- A new onset of agonizing asthmatic breathing and subsequent asthmatic attacks for a period of 10-20 years or more is prevented, ie, a practical cure is undertaken;

- Avoid severe side effects and complications of cortacosteroids.

- The anti-asthmatic drug is well tolerated and does not lead to complications.

EXAMPLES FOR THE IMPLEMENTATION OF THE INVENTION

The following examples further illustrate the invention:

Example 1. The agent contains in mg:

Pure caffeine 50.00 Ergotamintartrate 0.25 Zinc sulphate 40,00 Papaverium hydrochloride 40,00 Atropinsulfate 0.25 Aminophylline 50.00 Glaucinhydrochloride 40,00 Potassium sulfagzayakayle 50.00 Chloropyramine 50.00

Example 2. The agent contains in mg:

Pure caffeine 100.00 Ergotamintartrate 1.00 Zinc sulphate 200,00 Papaverine hydrochloride 100.00 Atropinsulfate 1.00 Aminophylline 100.00 Glaucinhydrochloride 80,00 Potassium sulphaguayacolos 250,00

Chloropyramine

100.00

Example 3. The agent contains in mg: Pure caffeine 100.00 Ergototingartartate 0.25 Zinc sulphate 400,00 Papaverine hydrochloride 40,00 Atropinsulfate 0.25 Aminophylline 50.00 Glaucinhydrochloride 40,00 Potassium sulphaguayacolos 50.00 Chloropyramine 50.00

Example 4. The agent contains in mg :. Pure caffeine 100.00 Ergototingartartate 1.00 Zinc sulphate 200,00 Papaverine hydrochloride 100.00 Atropinsulfate 1.00 Aminophylline 100.00 Glaupinhydrochloride 80,00 Potassium sulphaguayacolos 250,00 Chloropyramine 100.00

Example 5: Acute toxicity studies of a combination drug.

Experimental production:

Male white rats, of the Wistar breed, with an average weight of 130 to 200g were used for the studies. Animals were reared under standard food and water conditions. A total of 300 rats were used for the experiments. The substances used were provided by the applicant and include: ergotamine, atropinsulfate, papaverine hydrochloride, zinc sulfate and pure

Substances were dissolved in Tween 80 after a good grinding and injected orally in a volume of 1 ml / 100 g mp. (body weight).

For the preparation of the combination according to the invention, 1 part ergotamine, 1/4 part atropinsulfate, 40 parts zinc sulfate, 40 parts papaverine hydrochloride and 50 parts pure caffeine are mixed accordingly. The combination is introduced in the same way as the individual substances.

After pre-determining the minimum and maximum lethal dose for each substance, rats, divided into groups of 6, were randomized to different doses of the substance and combination. Mortality rates are monitored up to the 24th hour and the 7th day (the results only present data from the 24th hour, since they do not show differences with those from the 7th day).

The results are calculated by sample analysis in the REGRESS PC nonlinear regression program, determining the LD50 and the corresponding confidence interval.

The results of the studies are summarized in Table 1. It shows that by their toxicity the substances are classified as follows: the most toxic is ergotamine, followed by caffeine, papaverine, atropine and zinc sulfate. The combination preparation showed toxicity between that of papaverine and atropine.

If the quantity of the individual components in the combination and

V · what part of the calculated values for LD50 is it can make the following calculations:

100 mg of the combination contains mg: 0.762 ergotamine (which is 1/105 part of the corresponding LD50}; 30.470 zinc sulfate {1/50 part); 30,470 papaverine hydrochloride (1/14 part); 0.190 atropinsulfate (1/3158 part) 30 and 38.090 caffeine (1/5 part).

From the obtained values for LD50 it can be seen that the amounts of ergotamine, atropine, zinc sulfate and to some extent papaverine in the combined preparation are far from the values obtained for the corresponding LD50. From this it can be concluded that the toxicity of the combination is unlikely to be determined by them.

100 mg of the agent represent approximately 1/5 of the LD50 of the combination (510 mg / kg), which is the sum of the respective parts of zinc sulfate, papaverine and caffeine. This demonstrates the simple synergistic action of the individual constituents with respect to the acute oral toxicity of the agent of the invention. From the determined value for acute oral toxicity of white rats of the drug combination according to the invention, as well as its individual constituents, it can be concluded that the latter are in such a quantitative ratio in the combination that they neither exacerbate nor suppress their own toxic effects. The agent is a drug combination with relatively low acute toxicity.

ORAL ACUTE TOXICITY OF MALE WHITE RATS

Table 1

Substance Dose mg / kg t Mortality (died / attempted) ... LD50 mg / kg Ergotamine 50 65 75 50 100 125 1/6 2/6 3/6 ^! 4/6 ¹ 5/6 6/6 80 (63-97) Zinc sulphate 1000 1250 1500 1750 2000 2250 0/6 1/6 3/6 4/6 5 <6 6/0 1500 (1250-1750) Papaverine 200 250 300 350 400 500 0/6 1/6 213 3/6 3/6 5/6 440 (390-490) Atropine 200 300 450 500 650 750 0/6 '/ 6 2> 6 2/6 3/6 5/6 600 (485-725) Caffeine 100 125 150 200 250 300 0/6 1/6 2/6 4/6 5/6 6/6 192 (155-229) Combination according to the invention 200 350 500 500 700 300 0.6 1/6 3/6 4/6 5/8 8/6 5Y (385-635)

The drug according to Example 1 was administered orally in the form of dragees.

The first 40 days are given 4 times a day, at least every 4 hours for 1 dragee. The next 50 days - 3 times a day, every 8 hours 1 dragee, Another 60 days - twice / morning and evening / 1 dragee,

Another 90 days on 1 dragee just the night before bed.

The agent was tested on 2000 patients with bronchial asthma and chronic asthmatic bronchitis. In all patients there was an improvement in the condition after the first 30-40 minutes after taking the dragee. In the observed patients, it was found that there were no side effects, complications inherent in corticosteroids. The treatment is permanent and they are not

The results support the conclusion that the individual components of the combination, in addition to having additive effects, mutually reinforce their effect on the bronchi, as evidenced by numerous clinical trials.

Claims (1)

Patent Claims An anti-asthmatic drug, characterized in that it contains pure caffeine, ergotamintartrate, zinc sulfate, papaverine hydrochloride, atropinsulfate, aminophylline, glaucinhydrochloride, potassium sulfagvaicol and chloropyramine, having the following collagen components: 250.00; ergototintartrate from 0.25 to 2.00; zinc sulphate from 10.00 to 400.00; papaverine hydrochloride from 30.00 to 200.00; atropinsulfate from 0.25 to 1.00; aminophylline from 40.00 to 250.00; glaucinhydrochloride from 30.00 to 200.00; potassium sulfagvayakol from 100,00 to 600,00; chlorpyramine from 30.00 to 200.00. or ».