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WO2008037037A2 - Anti-asthmatic medicine comprising i. a. caffeine, ergotamine, zinc, papaverine, atropine, aminophyyline, glaucine etc. - Google Patents

Anti-asthmatic medicine comprising i. a. caffeine, ergotamine, zinc, papaverine, atropine, aminophyyline, glaucine etc. Download PDF

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Publication number
WO2008037037A2
WO2008037037A2 PCT/BG2007/000021 BG2007000021W WO2008037037A2 WO 2008037037 A2 WO2008037037 A2 WO 2008037037A2 BG 2007000021 W BG2007000021 W BG 2007000021W WO 2008037037 A2 WO2008037037 A2 WO 2008037037A2
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Prior art keywords
hydrochloricum
asthmatic
medicine
sulfuricum
coffeinum
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PCT/BG2007/000021
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French (fr)
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WO2008037037A3 (en
Inventor
Ivan Hristov
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Ivan Hristov
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Publication of WO2008037037A2 publication Critical patent/WO2008037037A2/en
Publication of WO2008037037A3 publication Critical patent/WO2008037037A3/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/14—Alkali metal chlorides; Alkaline earth metal chlorides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4402—Non condensed pyridines; Hydrogenated derivatives thereof only substituted in position 2, e.g. pheniramine, bisacodyl
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/46—8-Azabicyclo [3.2.1] octane; Derivatives thereof, e.g. atropine, cocaine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/473—Quinolines; Isoquinolines ortho- or peri-condensed with carbocyclic ring systems, e.g. acridines, phenanthridines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/48—Ergoline derivatives, e.g. lysergic acid, ergotamine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
    • A61K31/515—Barbituric acids; Derivatives thereof, e.g. sodium pentobarbital
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A61K31/52—Purines, e.g. adenine
    • A61K31/522—Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • A61K33/30—Zinc; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics

Definitions

  • the invention relates to an anti-asthmatic medicine, which can be implemented in the field of the human medicine for a treatment of the bronchial asthma and the asthmatic bronchitis.
  • the ergotaminum is known as an syr ⁇ pathic ⁇ litic /Martinedale, 1989/. It improves the heart activities - enhances the systole contractions, improves the pulse. It has a specific effect with the lung congestion. This effect probably is due to the vasoconstrictive effect on the bronchial tubes.
  • the ergotamintartarat is a partial agonist and antagonist of the alpha- adrenergic system of the glabrous musculature of the blood vessels of the lung and other organs. It is mainly antagonist in the peripheral and the central nervous system.
  • the papaverinum hydrochloricum is known as an undisputed spasmolitic. It removes the bronchospasm and relieves the respiration center and the cough center /Martinedale, 1989/.
  • the atropinum sulfuricum is implemented for healing of the lung asthma /Paterson J.W. and Tara RA., Med. J.Aust. 1985, 143.390/.
  • the zincum sulfuricum is known. In the recent years a significant attention is paid to the zinc salts having in mind their effects influencing the immunity and the metabolic process in the organism.
  • the quantity of the microelement zinc in the organism is approximately 2g. Dependant on the zinc are important ferments as: corticotropinum, somatotropinum, gonadotropinum, insulin /Bjojovski, R., Tatalay, M. etc. "News in the pharmacology and the medicine", 1995, No 3, p.72-76/.
  • the zinc deficiency in the organism results in an immunity decrease.
  • the zinc is mainly accumulated around the centers regulating the respiration rhythm, the rhythm cheerfulness - sleep, the rhythm of the heart activity, intestinal tract etc.
  • zinc salts are used for treatment of the lung, heart-vessel etc. systems. The original moment in the lung asthma treatment is the adding of a zincum sulfuricum.
  • the aminophyllinum is a medicament for a treatment of the lung asthma. It removes the bronchospasm, reduces the resistance of the blood vessels, reduces the pressure in the lung artery system, expands the coronary vessels.
  • the glaucinum hydrochloricum is known - it has an anti-cough effect. Unlike the codeine, it does not suppress the respiration center, does not influence the motoricity of the intestinal tract and does not result in habitation and infatuation.
  • the sulfaguajacolas is known. It is used for treatment of the respiration organs, especially in childish age.
  • the chlorpyraminum is known. It is a competitive blockator of the histamine in term of Hl- receptors. It is used for treatment of the lung asthma in the intervals between the ebullitions.
  • corticosteroids preparations are known used for treatment of the lung asthma /Martindale, 1989/. They have the disadvantage that they may result in symptoms of medicamentous hypercorticismus - obesity, arterial hypertonia, osteoporosis, stomach and duodendal infections etc. After commencing the treatment the patient becomes completely dependant on exogenous corticosteroids and although an improvement to a certain extent of his condition is demonstrated, the appearance of new ebullitions are not prevented.
  • the invention seeks to provide an anti-asthmatic medicine, to be able to stop the attacks of the disease and to result in prolonged remission in the course of 10-20 years i.e. healing in practice and at the same time not to produce the acute side effects of the corticosteroids.
  • this object is accomplished in an antiasthmatic medicine, containing coffeinum purum, ergotamintartarat, zincum sulfuricum, papaverinum hydrochloricum, atropinum sulfuricum, aminophyllinum, glaucinum hydrochloricum, kalium sulfaguajacolicum and chlorpyraminum, having quantity proportions [in mg] as follows:
  • the anti-asthmatic medicine in accordance with the invention has a number of advantages, as follows: - even the acutest asthmatic ebullitions are being put under control in the course of 30-40 minutes;
  • the anti-asthmatic medicine has a good bearing and does not result in complications.
  • Example 1 The medicine contains, in mg:
  • Example 2 The medicine contains, in mg:
  • Example 3 The medicine contains, in mg:
  • Example 4 The medicine contains, in mg:
  • Example 5 Tests for the acute toxicology of the medicine combination. Tests representation:
  • the tests were used male white rats, breed Wistar, having average weight from 130 to 2QQg.
  • the animals were bred at standard conditions in terms of food and water supply. Taken as a whole 300 rats have been used for the tests.
  • the used substances have been supplied by the applicant and they include: coffeinum purum, ergotaminum, zincum sulfurieum, papaverihum hydrochloricum atropinum sulfurieum.
  • the substances were diluted in Tween 80 after good grind and were brought in by means of sound per orally in volume 1 ml/100g. corporal weight.
  • the tests results are generalized in Table 1.
  • Table 1 shows that the substances are classified, in term of their toxicity, as follows: most toxic is the ergotaminum, followed by coffeinum, papaverinum, atropinum and zincum sulfuricum.
  • the combined preparation shows a toxicity, which is in the range of the toxicity of the papaverinum and the atropinum.
  • 100 mg of the medicine are representing approximately 1/5 of LD50 of the combination (5iO mg/kg), which is the sum of the respective parts of the zincum sulfuricum, papaverinum and coffeinum.
  • the medicine in accordance with the invention is a combination having relatively low acute toxicity.
  • the medicine according to Example 1 is implemented orally in the form of dragees.
  • the anti-asthmatic medicine is tested on 2000 patients suffering from bronchial asthma and a chronic asthmatic bronchitis. The condition of all patients was improved after 30-40 minutes after the acceptance of the dragee. No side effects and complications characteristic of the corticosteroids were observed. The healing is lasting and no recidivations were observed.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Inorganic Chemistry (AREA)
  • Pulmonology (AREA)
  • Emergency Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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Abstract

The anti-asthmatic medicine can be implemented in the field o the human medicine for a treatment of the bronchial asthma and the asthmatic bronchitis. The medicine contains coffeinum purum, ergotamintartarat, zincum sulfuricum papaverinum hydrochloricum, atropinum sulfuricum, aminophyllinum, glaucinum hydrochloricum, kalium sulfaguajacolicum and chlorpyraminum, having quantity proportions [in mgj: coffeinum paru 30,00 to 250,00;' ergotamintartarat 0,25 to 2,00; zincum sulfuricum10,00 to 400,00; papaverinum hydrochloricum 30,00 to 200,00; atropinum sulfuricum 0,25 to 1,00; aminophyllinum 40,00 to 250,00;glaucinum hydrochloricum 30,00 to 250,00; kalium sulfaguajacolicum 100,00 to 600,00; chlorpyraminum 30,00 to 200,00. The medicine has a number of advangates, as follows: even the acutest asthmatic ebullitions are being put under control in the course of 30-40 minutes; prevented is a new appearance of a painful asthmatic respiration and of consequent asthmatic ebullitions for periods of 10-20 and more vears i.e. in practice a treatment of the disease is achieved; prevented are the acute side effects and complications of the corticosteroids; the medicinbe has a good bearing and does not result in complications.

Description

Ivan Hristov - s. Kolartsi, obst.Tervel, Bulgaria
ANTI-ASTHMATIC MEDICINE
TECHNICAL FIELD
The invention relates to an anti-asthmatic medicine, which can be implemented in the field of the human medicine for a treatment of the bronchial asthma and the asthmatic bronchitis.
BACKGROUND ART
Medicines are known for a treatment of the bronchial asthma and the asthmatic bronchitis. The xantins are known having stimulating effect to the breathing and the relieve of the bronchospasms /Martinedale, 1989/. Their combinations with other medicines are also known. In the Pavlov's doctrine the coffeinum enhances the dithery processes in the cerebral cortex and the processes of the internal detention. It excites the vasomotorial centers. In the frames of the classic pharmacology it is believed mat the coffeinum is an weak protoplasmatic poison, restricting the microbes development. As a xantin emanation /weaker than the theophilinum/ it removes the bronchospasm and is implemented for a treatment of a status asthmaticus /BE 903065/.
The ergotaminum is known as an syrøpathicølitic /Martinedale, 1989/. It improves the heart activities - enhances the systole contractions, improves the pulse. It has a specific effect with the lung congestion. This effect probably is due to the vasoconstrictive effect on the bronchial tubes. The ergotamintartarat is a partial agonist and antagonist of the alpha- adrenergic system of the glabrous musculature of the blood vessels of the lung and other organs. It is mainly antagonist in the peripheral and the central nervous system.
The joint implementation of a coffeinum with an ergotaminum enhances double the pick plasma concentration of the latter. Thus the dose of the ergotamintartrat in the combination can be reduced.
The papaverinum hydrochloricum is known as an undisputed spasmolitic. It removes the bronchospasm and relieves the respiration center and the cough center /Martinedale, 1989/. The atropinum sulfuricum is implemented for healing of the lung asthma /Paterson J.W. and Tara RA., Med. J.Aust. 1985, 143.390/.
The zincum sulfuricum is known. In the recent years a significant attention is paid to the zinc salts having in mind their effects influencing the immunity and the metabolic process in the organism. The quantity of the microelement zinc in the organism is approximately 2g. Dependant on the zinc are important ferments as: corticotropinum, somatotropinum, gonadotropinum, insulin /Bjojovski, R., Tatalay, M. etc. "News in the pharmacology and the medicine", 1995, No 3, p.72-76/. The zinc deficiency in the organism results in an immunity decrease. In the central nervous system the zinc is mainly accumulated around the centers regulating the respiration rhythm, the rhythm cheerfulness - sleep, the rhythm of the heart activity, intestinal tract etc. Nowadays zinc salts are used for treatment of the lung, heart-vessel etc. systems. The original moment in the lung asthma treatment is the adding of a zincum sulfuricum.
The aminophyllinum is a medicament for a treatment of the lung asthma. It removes the bronchospasm, reduces the resistance of the blood vessels, reduces the pressure in the lung artery system, expands the coronary vessels. The glaucinum hydrochloricum is known - it has an anti-cough effect. Unlike the codeine, it does not suppress the respiration center, does not influence the motoricity of the intestinal tract and does not result in habitation and infatuation. The sulfaguajacolas is known. It is used for treatment of the respiration organs, especially in childish age.
The chlorpyraminum is known. It is a competitive blockator of the histamine in term of Hl- receptors. It is used for treatment of the lung asthma in the intervals between the ebullitions.
Each of the above medicines has the disadvantage that influences only separate components of the symptomatic of the lung asthma without interrupting the disease development.
The corticosteroids preparations are known used for treatment of the lung asthma /Martindale, 1989/. They have the disadvantage that they may result in symptoms of medicamentous hypercorticismus - obesity, arterial hypertonia, osteoporosis, stomach and duodendal infections etc. After commencing the treatment the patient becomes completely dependant on exogenous corticosteroids and although an improvement to a certain extent of his condition is demonstrated, the appearance of new ebullitions are not prevented.
SUMMARY OF THE INVENTION
The invention seeks to provide an anti-asthmatic medicine, to be able to stop the attacks of the disease and to result in prolonged remission in the course of 10-20 years i.e. healing in practice and at the same time not to produce the acute side effects of the corticosteroids. In accordance with the invention, this object is accomplished in an antiasthmatic medicine, containing coffeinum purum, ergotamintartarat, zincum sulfuricum, papaverinum hydrochloricum, atropinum sulfuricum, aminophyllinum, glaucinum hydrochloricum, kalium sulfaguajacolicum and chlorpyraminum, having quantity proportions [in mg] as follows:
- coffeinum purum from 30,00 to 250,00
- ergotamintartarat from 0,25 to 2,00
- zincum sulfuricum from iθ,00 to 400,00
- papaverinum hydrochloricum from 30,00 to 200,00 - atropinum sulfuricum from 0,25 to 1,00
- aminophyllinum from 40,00 to 250,00
- glaucinum hydrochloricum from 30,00 to 200,00
- kalium sulfaguajacolicum from 100,00 to 600,00
- chlorpyraminum from 30,00 to 200,00
The anti-asthmatic medicine in accordance with the invention has a number of advantages, as follows: - even the acutest asthmatic ebullitions are being put under control in the course of 30-40 minutes;
- prevented is a new appearance of a painful asthmatic respiration and of consequent asthmatic attacks for periods of 10-20 and more years i.e. in practice a treatment of the disease is achieved;
- prevented are the acute side effects and complications of the corticosteroids ;
- the anti-asthmatic medicine has a good bearing and does not result in complications.
DETAILED DESCRIPTION OF THE EMBODIMENTS
The invention is explained more detailed with the examples shown below:
Example 1. The medicine contains, in mg:
- coffeinum purum 50,00
- ergotamintartarat 0,25 - zineum sulfuricum 40,00
- papaverimim hydrochloricum 40,00
- atropinum sulfuricum 0,25
- aminophyllinum 50,00
- glaueinum hydrochloricum 40,00 - kalium sulfaguajacolicum 50,00
- chlorpyraminum 50,00
Example 2. The medicine contains, in mg:
- coffeinum purum 100,00
- ergotamintartarat 1,00
- zineum sulfuricum 200,00
- papaverinum hydrochloricum 100,00
- atropinum sulfuricum 1,00 - aminophyllinum 100,00
- glaueinum hydrochloricum 80,00
- kalium sulfaguajacolicum 250,00
- chlorpyraminum 100,00
Example 3. The medicine contains, in mg:
- coffeinum purum 100,00
- ergotamjntartarat 0,25 - zincum sulfurieum 400,00
- papaverinum hydrochloricum 40,00
- atropinum sulfurieum 0,25
- aminophyliinum 50,00 - glaucinum hydrochloricum 40,00
- kalium sulfaguajacolicum 50,00
- chlorpyraminum 50,00
Example 4. The medicine contains, in mg:
- coffeinum purum 100,00
- ergotamintartarat 1,00
- zincum sulfurieum 200,00
- papaverinum hydrochloricum 100,00 - atropinum sulfurieum 1,00
- aminophyliinum 100,00
- glaucinum hydrochloricum 80,00
- kalium sulfaguajacolicum 250,00
- chlorpyraminum 100,00
Example 5: Tests for the acute toxicology of the medicine combination. Tests representation:
For the tests were used male white rats, breed Wistar, having average weight from 130 to 2QQg. The animals were bred at standard conditions in terms of food and water supply. Taken as a whole 300 rats have been used for the tests. The used substances have been supplied by the applicant and they include: coffeinum purum, ergotaminum, zincum sulfurieum, papaverihum hydrochloricum atropinum sulfurieum. The substances were diluted in Tween 80 after good grind and were brought in by means of sound per orally in volume 1 ml/100g. corporal weight. For producing of the combination according to the invention were mixed respectively: 1 part ergotaminum, 1/4 part atropinum sulfurieum, 40 parts zincum sulfurieum, 40 parts papaverinum hydrochloricum and 50 parts coffeinum purum. The combination was brought in in the same way as the separate substances. After the preliminary defining the minimal and the maximal lethality dose for each substance for the fats. Divided into groups of 6 rats, different doses of the substances and the combinations were brought in. The lethality until the first 24 hours was controlled and until the 7th day (the represented results are reflecting only the data for the first 24 hours as they do not differ from those until the 7th day). The results were calculated by means of test analysis in the program for nonlinear regression REGRESS PC, thus LD50 was defined and the respective interval.
The tests results are generalized in Table 1. The table shows that the substances are classified, in term of their toxicity, as follows: most toxic is the ergotaminum, followed by coffeinum, papaverinum, atropinum and zincum sulfuricum. The combined preparation shows a toxicity, which is in the range of the toxicity of the papaverinum and the atropinum. On the basis of the analysis of the quantity of the separate components in the combination arid what part of the calculated values of LD50 represents it, the following calculations can be done: In lOOmg of the combination are contained, in mg: 0,762 ergotaminum (which is 1/105 part of the respective LD50); 30,470 zincum sulfuricum (1/50 part); 30,470 papaverinum hydrochloricum (1/14 part); 0,190 atropinum sulfuricum (1/3158 part); 30 and 38,090 coffeinum (1/5 part). Analysing the calculated values of the LD50 it can be seen that the quantities of the ergotaminum, atropinum, zincum sulfuricum and somewhat the papaverinum in the combined preparation are far away from the calculated values of the respective LD50. Thus a conclusion can be made that it is not very likely the toxicity of the combination to be defined by them.
100 mg of the medicine are representing approximately 1/5 of LD50 of the combination (5iO mg/kg), which is the sum of the respective parts of the zincum sulfuricum, papaverinum and coffeinum. This presents simple synergic effect of the separate components in terms of the acute peroral toxicity of the medicine, in accordance with the invention. Analysing the defined value of the acute peroral toxicity for white rats of the medicine combination and of the separate components, it can be concluded that the latter are in a quantity ratio that they neither enhance nor suppress its own toxic effects. The medicine in accordance with the invention is a combination having relatively low acute toxicity. The medicine according to Example 1 is implemented orally in the form of dragees. In the first 40 days was given four times a day, at intervals of at least four hours - 1 dragee. The next 60 days - 3 times a day, 1 dragee at intervals of 8 hours, Further 60 days - twice (in the mornings and in the evenings) 1 dragee, Further 90 days- 1 dragee only in the evenings before sleep. The anti-asthmatic medicine is tested on 2000 patients suffering from bronchial asthma and a chronic asthmatic bronchitis. The condition of all patients was improved after 30-40 minutes after the acceptance of the dragee. No side effects and complications characteristic of the corticosteroids were observed. The healing is lasting and no recidivations were observed.
The results are confirming the conclusion that the separate components of the combination not only have an additive effect but they are enhancing mutually their effect on the bronchia, which is proved by the numerous clinic tests.
Table !
Peroral acute toxicity of male white rats
Substance Dose Lethality LDSO mg/kg corp. weight died/ tested mg/kg
50 1/6
65 2/6
75 3/6
Ergotaminum 90 4/6 80
100 5/6 (63-97)
125 6/6
1000 0/6
1250 1/6
Zincum sulfuricum 1500 3/6 1500
1750 4/6 (1250-1750)
2000 5/6
2250 6/6
200 0/6
250 1/6
Papaverinum 300 2/6 440
350 3/6 (390- 490)
400 3/6
500 5/6
200 0/6
300 1/6
Atropinum 450 2/6 600
500 2/6 (485-725)
650 3/6
750 5/6
100 0/6
125 1/6
Coffeinum 150 3/6 192
200 4/6 (155-220)
250 5/6
300 6/6
Combination in 200 0/6 accordance with 350 1/6 the invention 500 3/6 510
600 4/6 (385-635)
700 5/6

Claims

Anti-asthmatic medicine, characterised in that contains coffeinum puram, ergotamintartarat, zincum sulfuricum, papayerinum hydrochloricum, atropinum sulfuricum, aminophyllinum. glaucinum hydrochloricum, kalium sulfaguajacolicum and chiorpyraminum, having quantity proportions [in mg]: coffeinum purum 30,00 to 250,00; ergotamintartarat 0,25 to 2,00; zincum sulfuricum 10,00 to 400,00; papaverinum hydrochloricum 30,00 to 200,00; atropinum sulfuricum 0,25 to 1,00; aminophyllinum 40,00 to 250,00; glaucinum hydrochloricum 30,00 to 200,00; kalium sulfaguajacolicum 100,00 to 600,00; chiorpyraminum 30,00 to 200,00.
PCT/BG2007/000021 2006-09-26 2007-09-19 Anti-asthmatic medicine comprising i. a. caffeine, ergotamine, zinc, papaverine, atropine, aminophyyline, glaucine etc. WO2008037037A2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
BG109687 2006-09-26
BG109687A BG109687A (en) 2006-09-26 2006-09-26 Antiasthmatic drug

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WO2008037037A2 true WO2008037037A2 (en) 2008-04-03
WO2008037037A3 WO2008037037A3 (en) 2008-07-10

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PCT/BG2007/000021 WO2008037037A2 (en) 2006-09-26 2007-09-19 Anti-asthmatic medicine comprising i. a. caffeine, ergotamine, zinc, papaverine, atropine, aminophyyline, glaucine etc.

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113633710A (en) * 2021-09-29 2021-11-12 浙江养和健康管理科技有限公司 A Chinese medicinal composition for treating bronchitis, asthma and emphysema, and its preparation method

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
BG61430B1 (en) * 1994-03-23 1997-08-29 Иван ХРИСТОВ Antiasthma medicament
TWI257311B (en) * 1998-07-28 2006-07-01 Takeda Chemical Industries Ltd Rapidly disintegrable solid preparation
BG819Y1 (en) * 2001-07-10 2006-07-31 "Софарма" Ад Combined means for affecting the respiratory system

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113633710A (en) * 2021-09-29 2021-11-12 浙江养和健康管理科技有限公司 A Chinese medicinal composition for treating bronchitis, asthma and emphysema, and its preparation method

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BG109687A (en) 2008-03-31

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