RU2330679C1 - Composition for prevention and treatment of asthma and upper airways diseases and method of production thereof - Google Patents

Abstract

FIELD: medicine; pharmacology.

SUBSTANCE: composition for prevention and treatment of asthma and upper airways diseases is characterised by that it includes incense tree Boswellia serrata dry extract solution with Boswellia acids content in terms of β- Boswellia acid not less than 80%, in wheat germs oil mixed with pharmaceutically acceptable selenium source and encapsulated containing glycerine, gelatin, pharmaceutically acceptable zinc source and chicory dry extract. Composition production implies that pharmaceutically acceptable zinc source, chicory dry extract gelatin, glycerine are sequentially dissolved renovated water. Agitated mixture is used to make capsule thereafter filled with capsulation solution produced by stirring of wheat germs oil and pharmaceutically acceptable selenium source followed by gradual addition of incense tree Boswellia serrata dry extract, with Boswellia acids content in terms of β- Boswellia acid not less than 80% till it is completely dissolved. Produced capsules are kept at temperature 5-10°C and dried out.

EFFECT: produced composition has improved efficiency.

4 cl, 4 ex

Description

The invention relates to the field of medicine and the food industry.

Upper respiratory tract diseases represent a significant group of pathologies, including rhinitis, laryngotracheitis, bronchitis, bronchopneumonia, acute respiratory viral infections - SARS, etc.

One of the currently common diseases of the upper respiratory tract is bronchial asthma (BA), a chronic inflammatory disease that is a serious public health problem in all countries of the world. Asthma is common in all age groups and often has a severe fatal course. More than 100 million people suffer from this disease, and their number is constantly increasing.

In recent decades, in all economically developed countries, there has been a significant increase in the severity of bronchial asthma, characterized by an earlier onset of the disease. According to some reports, the frequency of bronchial asthma in the structure of childhood morbidity in Russia is from 0.2-0.5% to 8%.

That is why there are many international programs and consensus for the prevention and control of the spread of AD.

The treatment of bronchial asthma is a long process. The etiology of it is still not completely clear. Therefore, the effect of most asthma medications is mainly aimed not at eliminating the cause of the disease, but at eliminating the seizures and their prevention.

For this purpose, many compositions have been developed, including those based on natural substances.

Known, for example, is a biologically active additive for the prevention and maintenance treatment of bronchial asthma and inflammatory diseases of the respiratory system based on medicinal plants, containing dry extract of licorice root, dry aqueous concentrates of elecampane root, sage grass, hyssop grass, dry concentrate of tinted peppermint, ground root ginger, zinc sulfate, calcium gluconate, starch, calcium stearate and sugar (RU 2207143).

According to modern concepts, bronchial asthma develops as a multifactorial pathology, in which the initial role is played by the activation of inflammatory mediators - interleukins (IL-4, -5, etc.), which stimulate the growth, differentiation and mobilization of mast cells, basophils, eosinophils and B cells, as cellular components of an allergic response.

From the prior art, works are known according to which compositions based on Boswellia extract and active compounds isolated from it can be recognized as effective agents affecting these factors.

In particular, in double-blind, placebo-controlled studies by German scientists in 40 patients with bronchial asthma, an improvement in the course of the disease was found in 70% of patients taking Boswellia extract. The improvement in the control group (placebo) was only 27% (Gupta I, Gupta V, Parihar A, Gupta S, Ludtke R, Safayhi H, Ammon HP. // Effects of Boswellia serrata gum resin in patients with bronchial asthma: results of a double-blind, placebo-controlled, 6-week clinical study. Eur J Med Res. 1998 Nov 17; 3 (11): 511-4).

Boswellia serrata gum resin containing boswellic acids is known to be used traditionally in India to treat inflammatory diseases. Boswellic acids block the biosynthesis of leukotrienes, elastase in leukocytes and, accordingly, proliferation. In clinical trials, promising results were observed in patients with rheumatoid arthritis, chronic colitis, Crohn's disease and bronchial asthma (Ammon HP, Boswelliasauren (Inhaltsstoffe des Weihrauchs) als wirksame Prinzipien zur Behandlung chronisch entzundlicher Erkrankincense components. principle in treatment of chronic inflammatory diseases], Wien-Med-Wochenschr. 2002; 152 (15-16): 373-8).

As the closest analogue, a source describing the use of 11-keto-beta-boswellic acid for the treatment of inflammatory diseases, for example, bronchial asthma (DE 10053056) can be indicated. However, this tool is not a tool with an effective preventive effect and does not provide the level of safe intake, which is possible when taking biologically active additives.

The objective of the invention is to develop a composition and a method for its preparation, which can be more effectively used both in the treatment or prevention of asthma, and other inflammatory diseases of the upper respiratory tract.

This problem is solved by the present invention.

As the basis of the composition, a solution of the dry Boswellia serrata Boswellia extract (frankincense resin) in wheat germ oil was selected. In addition, to enhance the biological effect of the agent, it includes a pharmaceutically acceptable source of selenium, preferably in a fat-soluble form, a pharmaceutically acceptable source of zinc, preferably in the form of zinc lactate, as well as dry chicory extract. Composition per capsule (mg / capsule)

Wheat germ oil 200.0-300.0 Boswellia serrata dry Boswellia extract, with the content of boswellic acids in terms of on β-boswellic acid not less than 80% 20,0-40,0 pharmaceutically acceptable source selenium in terms of selenium 0.004-0.006 Shell Composition Gelatin 17.3-21.1 Glycerol 5.7-6.9 Pharmaceutically acceptable source of zinc in terms of zinc 0.5-0.6 Dry chicory extract 2.2-2.6

Sacred Boswellia (frankincense) - Boswellia serrata, a family of burseridae, grows on the slopes of the mountains of the Somali Peninsula in India. Boswellia exhibits pronounced anti-inflammatory properties, the ability to restore damaged blood vessels, antimicrobial activity.

As noted above, to date, a sufficient amount of scientific data has been accumulated indicating the anti-inflammatory effect of Boswellic acids.

A study of the molecular mechanisms of the anti-inflammatory effect of Boswellic acids has established that their main property is the ability to inhibit the biochemical pathway of arachidonic acid metabolism by inhibition of 5-lipoxygenase and thereby prevent the formation of leukotrienes. The inhibition of the biosynthesis of leukotrienes, as well as the release of leukocyte elastase, is an important mechanism that impedes the development of pro-inflammatory and hypersensitizing processes in the body (Safayhi ea, 1997). At the same time, boswellic acid does not block the activity of two other enzymes involved in the metabolism of arachidonic acid, 12-lipoxygenase and cyclooxygenase. This circumstance fundamentally distinguishes the pharmacological effect of Boswellia from the known non-steroidal anti-inflammatory drugs that block the cyclooxygenase pathway of the conversion of arachidonic acid to prostaglandins and thromboxanes, which are important substances for regulating hemostasis and microhemodynamics.

Boswellia's anti-inflammatory activity has also been confirmed in studies related to the pro-inflammatory effect of tumor necrosis factor (TNF-alpha), (Royea, 2005).

Another aspect of the anti-inflammatory effect of Boswellia extract is associated with inhibition of nitric oxide production from activated macrophage lipopolysaccharides (Pandey ea, 2005).

The efficacy of Boswellic acid preparations for chronic colitis (Gupta ea, 2001), in patients with chronic polyarthritis, knee osteoarthritis and inflammatory neuropathology of spinal origin (Kimmatkar ea, 2003; Kulkami ea, 1991; Reichling ea) and, what is especially important for bronchial asthma.

According to the invention, a dry Boswellia extract obtained by conventional methods known per se can be used, for example, “Boswellia food grade serat, New Ambadi Estates PVT. LTD, India ”, state registration certificate No. 77.99.3.U.8128.04.

The dry Boswellia extract is a fluffy powder of a yellowish-grayish color with a characteristic odor that has low solubility. In this regard, in accordance with the present invention, a form of an oily solution of Boswellia extract in wheat germ oil has been developed.

Wheat germ oil is obtained by double cold pressing from selected fresh embryos without any auxiliary materials using a technology that ensures the complete preservation of biologically active substances inherent in grain in nature.

The uniqueness of the properties of wheat germ oil is due to the presence of at least 3 active complexes in its composition

- antioxidants - tocopherols, carotenoids, moreover, in terms of vitamin E content, oil is a champion among all natural compounds (from 200 to 600 mg%);

- Essential polyunsaturated fatty acids (including linoleic, linolenic), as well as lecithin in a ratio optimal for lipid metabolism in the human body;

- vitamins of group B, D, PP; pantheon and folic (2-3 mg%) acid; amino acid methionine.

It is widely known that wheat germ oil has a general healing effect; normalizes the functions of the immune and endocrine systems; It is a stimulant of reproductive function; increases working capacity; increases vitality and resistance to stress. It promotes the rapid healing of wounds, burns, ulcers and diseases of the gastrointestinal tract, has anti-sclerotic and cardioprotective properties, lowers cholesterol in the blood and liver, and regulates hormonal balance.

The biological activity of α-tocopherol and its analogues is based on high efficiency and the ability to eliminate lipid peroxyl radicals by transferring the hydrogen atom of the hydroxyl group (one-electron transfer) to the radical and lipid reduction (antiradical potential). Thus, vitamin E prevents the oxidation of unsaturated lipids and protects biological membranes from oxidation.

Unlike other antioxidants, vitamin E is a fat-soluble (lipophilic) compound and therefore can easily be integrated directly into the structure of low density lipoproteins and cell membranes and, thus, most effectively prevents the oxidation of lipoproteins and lipid peroxidation of cell membranes.

In contrast to α-tocopherol, β- and γ-tocopherols of oil have lower antiradical activity, but their antioxidant activity in the absence of reducing antioxidants is significantly higher than that of α-tocopherol. Therefore, the presence in the oil of wheat germ (α, β, γ γ tocopherols (24%, 10% and 10% respectively), along with α tocopherol, significantly increases the antioxidant effect of the oil on membrane lipids of various tissues.

The significance of the third component of the composition, selenium, as an essential factor in human nutrition was established about half a century ago. This stimulated the appearance in the arsenal of doctors of numerous selenium-containing biologically active food additives and official preparations. In our country, the practical use of selenium in medical practice began relatively recently.

Selenium may be included as any pharmaceutically acceptable source, for example, as selenomethionine, selenocysteine, sodium selenite. Particularly preferred is the use of selexene. Selexen-9-phenyl-symmetric octahydroselenoxanthene is a powerful antioxidant. Selexen - the only antioxidant capable of self-healing. It is a prolonged form, a metabolically active functioning depot of selenium.

The antioxidant effect of selenium is significantly enhanced in combination with vitamin E.

The inclusion of zinc in the composition of the composition is due primarily to its antioxidant properties. Being part of the Zn-dependent superoxide dismutase, it protects endogenous nitric oxide from its radical conversion into toxic peroxynitrite. The antioxidant activity of zinc is multifaceted. When the body is enriched with zinc, the concentration of peroxide lipids, including atherogenic low density lipoproteins, decreases. It is known that zinc also has a significant effect on the hormonal functions of the body, including the production and action of androgens and extragens; insulin production and function; the state of the thymus and the production of its hormones, with which the state of the body's immune system is closely related.

Recently, the need for zinc has increased due to the dominance of high-carbohydrate foods in the diet, requiring increased insulin production and a high prevalence of diabetes.

As a pharmaceutically acceptable source of zinc, in particular zinc sulfate, zinc carbonate, zinc oxide, zinc acetate, zinc ascorbate and others can be used. Preferably, in the form of zinc lactate. For example, the source may be Puramex ZN (PURAC Biochem B.V., Netherlands).

Chicory has been used in folk medicine since ancient times. It improves the function of the spleen, normalizes the heart rhythm and increases the force of contraction of the heart muscle, acts soothingly on the central nervous system, improves the outflow of bile, removes cholesterol, eliminates nausea, lowers blood glucose, has a diuretic effect, activates the metabolism, has a thyrotropic effect, has analgesic property.

Currently, various chicory preparations are used, including dry extract of Extractum siccum radix Cichorium inthybus.

According to the invention, in particular, dry extract of chicory SEZ 78.22.59.919.11.000850.04.04 from 04/26/04 is used.

A method of obtaining an active additive composition for the prevention and treatment of asthma and diseases of the upper respiratory tract according to the invention is that a pharmaceutically acceptable source of zinc, dry chicory extract, gelatin, glycerin are successively dissolved in purified water, with stirring, a shell is formed from the resulting mass, which filled with an encapsulation solution obtained by mixing wheat germ oil and a pharmaceutically acceptable source of selenium, followed by gradual addition iem Boswellia dry extract of Boswellia serrata, containing boswellic acids with, based on the β-boswellic acid of at least 80%, up to its complete dissolution, allowed to stand at a temperature of obtained capsules 5-10 ° C and dried.

If necessary, after mixing, the gelatin mass is maintained until a mass viscosity of 500-600 mm ² / s is obtained. Determination of viscosity is carried out in a thermostat using a viscometer at a temperature of 60 ° C.

The optimal parameters of air for drying capsules are: temperature (17-22) ° C, humidity (45-60)%, drying time 18-24 hours.

The invention is illustrated by the following specific examples.

Example 1

The composition of the contents of the capsule, mg / capsule

Wheat germ oil 269,983

Boswellia serrata (dry Boswellia extract), the total content of Boswellic acids in terms of β-Boswellic acid is not less than 80% 30.00

"Selexen" 0.017 (in terms of selenium 0.004)

The composition of the shell (in terms of dry matter)

Gelatin 19.2

Glycerin 6.3

Food additive "Pyramiks" 2.12 (in terms of zinc 0.50)

Dry chicory extract 2.4

Production method

Cooking gelatin mass

26.69 kg of purified water are manually charged into the reactor. About 1.0 kg of water is drained into a container, heated to 60 ° C. In a hatch in parts, with the stirrer working, manually load 1.05 kg of zinc lactate, close the lid and mix until zinc lactate is completely dissolved within 10-20 minutes. Then download 1.19 kg of chicory extract and mix until completely dissolved. Then, 14.96 kg of gelatin and 4.49 kg of glycerin are loaded into the reactor. The lid is closed and the contents of the reactor are kept at a temperature of (40-45) ° C for 0.5-1 h until the gelatin is completely dissolved with stirring (stirrer rotation speed up to 30 rpm), avoiding strong foaming. If gelatin has come in the form of large conglomerates and rapid swelling and dissolution is difficult, it is allowed to increase the duration of heating and mixing by 30 minutes. The optimum pour point and storage of the gelatin mass (20-22) ° C.

The moisture loss during evaporation is 0.26 kg, the mechanical loss of the gelatinous mass is 1.25 kg. Get about 42.98 kg of gelatin mass, which is used as necessary.

Preparation of encapsulation solution

Wheat germ oil and selexen are weighed on the scales. 26.9 kg of wheat germ oil, 1.65 g of selexene are charged into the reactor. Turn on the stirrer and produce stirring for 2-3 hours. While stirring gradually, 3.3 kg of dry extract of Boswellia serrata is loaded in portions. After loading the entire volume of the extract, stirring is continued for 2 hours. Then the resulting mass is left until complete dissolution. The completeness of dissolution of the extract of Boswellia serrata is monitored visually. After a specified time, the mass should not contain lumps of extract and flocculent white particles. Then produce the unloading of the solution in the collection.

The output at the stage of 99.0%.

Getting gelatin capsules.

Soft seamless gelatin capsules are made on a capsulator from a molten gelatin mass filled with a product.

The output of the capsules is 27.59 kg.

The resulting capsules are kept at 5-10 ° C in a refrigerator and dried at a temperature of 17-22 ° C in an oven.

The shelf life of the product is 18 months from the date of manufacture.

The resulting composition is a more effective composition. In particular, it is known from the state of the art that 333 mg (Pharmacokinetic study of 11-Keto-Boswellic Acid, Sharmal SI; Thawani V.2; Hingorani L.3) is the optimal dosage of Boswellia extract that exhibits an anti-inflammatory effect without oral side effects. ; Shrivastava M.4; Bhate VR5; Khiyani R.6, Phytomedicine, Volume 11, Numbers 2-3, March 1, 2004, pp. 255-260 (6)). While according to the present invention, the dosage can be substantially reduced and amounts to 20-40 mg.

Example 2

Study of anti-asthma pharmacological activity.

The study of the proposed drug was conducted on 26 volunteers (21 women and 5 men) with chronic asthma. The patients were divided into 2 groups: the control group, which received Boswellia extract 300 mg in capsules, and the experimental group, which used the proposed composition according to Example 1 3 times a day for 6 weeks. In patients receiving dietary supplements, coughing and suffocation attacks stopped. In 2 patients in the experimental group and in 5 in the control, coughing attacks resumed after some time intervals. The results of subsequent observations showed that in terms of improvement in the condition of the experimental group on average 25-30% faster.

Example 3

The study of activity in diseases of the upper respiratory tract.

A patient, 8 years old, from the age of five was unsuccessfully treated for chronic bronchitis. Constantly bothered by a cough, periodically choking, which was removed by intal. Antibiotic treatment courses were prescribed. After taking the composition, two weeks later there was a significant improvement: stopped coughing, asthma attacks stopped. To date, exacerbations of the disease have not been observed.

The patient, 23 years old. He was treated for chronic tonsillitis, vasomotor rhinitis, frequent SARS. Complaints of persistent cough, tonsils enlarged, sometimes asthma attacks, difficulty in nasal breathing, runny nose. Took the composition according to example 1 3 times a day for a month. After 5-6 days, an improvement was observed. After treatment, coughing attacks, a significant reduction in tonsils, and free breathing disappeared.

Example 4

In another group of healthy volunteers (11 people) during the period of seasonal outbreaks of influenza and acute respiratory viral infections, the prophylactic properties of the new composition were investigated. Twice a day, the composition was taken as in Example 1. In the test group, these diseases were not registered.

Thus, the proposed new tool is effective and can be widely recommended for therapeutic purposes.

Claims (4)

1. Composition for the prevention and treatment of asthma and diseases of the upper respiratory tract, characterized in that it includes a solution of dry Boswellia serrata extract of Boswellia, with the content of Boswellic acid in terms of β-boswellic acid at least 80%, in wheat germ oil, concluded in mixtures with a pharmaceutically acceptable source of selenium in a shell containing glycerin, gelatin, a pharmaceutically acceptable source of zinc and chicory dry extract in the following components, mg per capsule: Wheat germ oil 200.0-300.0 Boswellia extract 20,0-40,0 Pharmaceutically acceptable source of selenium in terms of selenium 0.004-0.006 Gelatin 17.3-21.1 Glycerol 5.7-6.9 Pharmaceutically acceptable source of zinc in terms of zinc 0.5-0.6 Dry chicory extract 2.2-2.6 2. The composition according to claim 1, characterized in that as a pharmaceutically acceptable source of selenium contains selexene. 3. The composition according to claim 1 or 2, characterized in that as a pharmaceutically acceptable source of zinc contains zinc lactate. 4. A method of obtaining a composition for the prevention and treatment of asthma and diseases of the upper respiratory tract according to any one of claims 1 to 3, characterized in that a pharmaceutically acceptable source of zinc, dry chicory extract, gelatin, glycerin are sequentially dissolved in purified water with stirring from the obtained the masses form a shell, which is filled with an encapsulation solution obtained by mixing wheat germ oil and a pharmaceutically acceptable source of selenium, followed by the gradual addition of dry ex rakta Boswellia Boswellia serrata, containing boswellic acids with, based on the β-boswellic acid of at least 80%, up to its complete dissolution, allowed to stand at a temperature of obtained capsules 5-10 ° C and dried.