RU2223107C2 - Phytoagent eliciting antituberculosis effect - Google Patents

Abstract

FIELD: medicine, phytotherapy. SUBSTANCE: invention relates to medicinal vegetable agents eliciting an antituberculosis effect. Proposed phytoagent comprises aloe leaves, sweet flag rhizomes, birch leaves, flower-of-an-hour (Hibiscus trionum L.) flowers, elecampane roots and rhizomes, linden flowers, shizandra fruits, nettle leaves, violet herb, mint leaves, licorice roots, horse-tail herb and bur-marigold herb taken in the definite ratio of components. Agent can be made as granule, tablet and syrup and can be used as decoction and infusion. In treatment with the claimed agent the tuberculosis proceeds with prevalence of productive tissue response and the following foci healing symptoms by their sclerosis and resolution. EFFECT: enhanced effectiveness of phytoagent. 7 cl, 2 tbl

Description

 The invention relates to medicine and herbal medicine, namely to herbal medicines with anti-tuberculosis action, and can be used in the pharmacotherapy of tuberculosis.

 Tuberculosis is a chronic infectious disease caused by tuberculosis bacteria (MBT). The most common tuberculosis of the respiratory system, in particular the lungs.

 Modern pharmacotherapy of tuberculosis is based on the integrated use of antibacterial drugs and immunostimulants, hormonal drugs and mucolytic agents.

 The chemotherapeutic agents used to treat various forms of tuberculosis are known, the main of which is isonicotinic acid hydrazide, isoniazid and its derivatives, as well as antibiotics rifampicin, streptomycin, PASK and its derivatives (M.D. Mashkovsky. Medicines, ed. 13th, Kharkov, 1997, vol. 2, p. 313-347). Known anti-tuberculosis chemotherapeutic agents are highly effective, but have several disadvantages. With their use, the resistance of tuberculosis mycobacteria develops quite rapidly. With the isolated use of one drug, resistant forms of mycobacteria can appear after 2-4 months. The development of resistance of mycobacteria occurs much more slowly with the simultaneous use of different drugs. In this regard, at present, combined antibacterial therapy of tuberculosis is being carried out, prescribing the patient at the same time 2-3 drugs. In addition, with the use of isoniazid and other drugs of this series, side effects are observed: headache, nausea, vomiting, allergic reactions, pain in the heart, sleep deprivation, psychosis, peripheral neuritis, muscle atrophy and limb paralysis. An absolute contraindication when taking these drugs is severe atherosclerosis, impaired liver and kidney function, epilepsy, a tendency to convulsive seizures.

 In recent years, the attention of developers has been attracted to medicinal plants that can prevent or reduce side effects that occur during pharmacotherapy of tuberculosis. Herbal compositions have already been created, used against the background of antibiotic therapy for pulmonary tuberculosis.

 So, in the application of Russia 96121489, 1996, a method for the treatment of pulmonary tuberculosis is proposed, which includes laser exposure against antibacterial therapy using a herbal composition containing Ledum flowers, plantain leaf, thyme leaf, nettle leaf, valerian root, blackcurrant leaf, calendula flowers and dandelion root in a certain ratio of components.

 Russian patent 2050855 1992 describes a method for treating patients with infiltrative pulmonary tuberculosis, including oral administration of an extract of fir paws during treatment with tuberculostats; plant extract contributes to the disappearance of side effects arising from the introduction of tuberculostatics, stimulates cellular immunity.

 An object of the present invention is to provide an agent having an anti-tuberculosis effect and not causing serious side effects when introduced into the body.

This object is achieved by the fact that the proposed anti-tuberculosis drug containing aloe leaf, calamus rhizome, birch leaves, hibiscus flowers, rhizomes and elecampane roots, linden flowers, magnolia vine fruits, nettle leaf, violet grass, mint leaf, licorice root, grass horsetail and grass sequences, with the following ingredients, in parts:
Aloe leaf - 1-30
Calamus rhizomes - 1-30
Birch Leaf - 1-30
Hibiscus flowers - 1-30
Rhizomes and roots of elecampane - 1-30
Linden flowers - 1-30
Schisandra fruits - 1-30
Nettle leaf - 1-30
Violet grass - 1-30
Mint leaf - 1-30
Licorice Root - 1-30
Horsetail grass - 1-30
Series grass - 1-30
Means (collection) can be used in the form of a decoction and infusion.

The tool (collection) with a fineness of 2 mm can be used packaged in filter bags of 2 g. This tool can be made in the form of granules, it additionally contains lactose and methyl cellulose, while medicinal plants are used in the form of a dry aqueous extract, with the contents of the ingredients per mass of 1 granule (in g):
Dry water extract - 0.1
Lactose - 0.067
Cellulose - 0.03
In granules, the main substance is used in the form of a dry aqueous extract. Dry water extract of aloe leaves, calamus rhizomes, birch leaves, hibiscus flowers, rhizomes and elecampane roots, linden flowers, magnolia vine, nettle leaf, violet grass, juniper fruit, mint leaf. licorice root, horsetail grass and grass string are prepared as follows. A method of obtaining a dry aqueous extract includes preparing the raw material, sequentially exhaustively extracting it with purified water, combining the obtained extracts, thickening the total extract and drying to the state of the dry extract. As a result of the tests, the optimal conditions for solid-phase extraction were selected: raw material fineness 2 mm, raw material: extractant ratio 1 (12-20), temperature regime not more than 90-95 ^o С, fractional extraction for 3 hours. Evaporation of the liquid extract is carried out in a circulating vacuum evaporator at a temperature of the reaction mass of 40 ± 5 ^o With up to approximately 1/10 of the original volume. The concentrated extract is dried in a spray dryer. The yield of the final product is 81.2.%.

 The phytochemical analysis of the claimed agent made it possible to establish the presence of such biologically active substances as flavonoids, tannins, polysaccharides, saponins, essential oils, vitamins, and organic acids.

 Upon receipt of the dry aqueous extract, stepwise extraction of the collection with hot purified water ensures the transition of all the above biologically active substances into the resulting dry aqueous extract.

 The main biologically active component are flavonoids and polysaccharides.

 Based on the data obtained, the content of the sum of flavonoids in the extract of the collection of anti-tuberculosis in terms of the routine standard is regulated by at least 1%.

 The resulting dry aqueous extract is an amorphous powder from yellowish-green to brownish in color with a specific odor, hygroscopic, crumple. Soluble in hydroalcoholic solutions (30%), in warm water.

The bulk density of the extract with free fall is 0.38-0.42 g / cm, with a seal of 0.65-0.69 g / cm, flowability 1.5-1.8 g / s, angle of repose 36-40 ^o . The loss in mass during drying at 100-105 ^o With does not exceed 5%.

 In the course of work, a dry aqueous extract from the claimed agent (collection) was used as the main active ingredient to obtain granules with anti-tuberculosis action.

 Given the moisture-absorbing ability of the extract, flowability, bulk density, the applicant developed a technology for producing granules. Granules in comparison with a dry aqueous extract have several advantages: good flowability, the ability to give more accurate dosing, maintain a uniform composition of the mixture, do not exfoliate. In addition, the granules have a more attractive and pleasant presentation, less hygroscopicity, do not dust.

 The technology for preparing granules is as follows. When developing granules as a result of research, lactose and methyl cellulose were selected as fillers in ratios with a dry aqueous extract of 1.5 and 3, respectively. As a binder, a 5% solution of methyl cellulose was selected. Wet granulation is carried out with fractional addition of a dry aqueous extract with calculated amounts: first 30%, then 70%.

 The content of flavonoids in terms of rutin in the granules is 0.01%, which corresponds to their content in a dry aqueous extract of 1%, this shows that when creating granules based on a dry aqueous extract, the active substances of the main component of the granules are completely preserved.

The proposed agent with anti-tuberculosis action can be made in the form of tablets, additionally contains calcium stearate and starch, while medicinal plants are used in the form of a dry aqueous extract, with the following ingredients per 1 tablet (in g):
Dry water extract - 0.05
Excipients (calcium stearate, starch) - Up to tablet weight 0.2
The tablets are convenient for dosing and administration. To obtain tablets, the dried granules are pressed on a tablet machine with the addition of starch and calcium stearate to the pressed mass. The resulting tablets are biconvex from yellow to brown.

 The flavonoid content in terms of rutin is 0.01%.

The claimed tool can be made in the form of a syrup. It provides high availability of active ingredients, taste correction and ease of administration. The syrup preparation additionally contains fructose, sorbitol and water, while medicinal plants are used in the form of a dry aqueous extract, with the contents of the ingredients per 100 ml of syrup (in g):
Dry water extract - 0.1-0.5
Fructose - 0.03-0.015
Sorbitol - 0.06-0.03
Water - Up to 100 ml
The technology for preparing syrup is generally accepted in pharmaceutical practice (State Pharmacopoeia, XIth ed .: Technology of medicines, I. Muravyov).

 The flavonoid content in terms of routine is at least 0.01%. The invention is illustrated by the examples presented in table 1.

 The use of the claimed funds in the form of a decoction and infusion.

 Decoction. 500 g of the product is poured 5 l of boiling water, boiled for 15 minutes, cooled for 30 minutes, filtered.

 Infusion. The claimed product (collection) is poured with boiled water in a ratio of 1:20, insisted for 1 hour, filtered.

 Broth and infusion take 50-100 ml 3 times a day (before, after) food. The duration of the course of treatment depending on the condition of the patient.

Bacterioscopic examination
We studied fingerprints from the internal organs of animals - guinea pigs. To count mycobacterium tuberculosis (MBT), thin smears of 2x1.5 cm in size were prepared from lung tissue, and smears were dried in air. They were fixed on fire and painted according to Zil-Nielsen. With a small number of MBTs in a smear, they were counted in 100 fields of view, with a large number of MBTs, 25-30 fields were scanned in different places and the arithmetic mean value of MBTs per 1 field of view was calculated.

The amount of MBT in the smear was carried out according to the method of O.O. Makeeva and G.N. Peak:
(0) - - lack of office
(±) - - from 1 MBT per 100 to 1 per 10 fields of view
(+) - - from 1 MBT per 9 fields to 1 per 1 field of view
(++) - - from 2 to 10 MBT in sight
(+++) - - from 11 to 50 MBT in sight
(++++) - - more than 50 MBT in sight
The number of crosses in all animals of the group was added up and divided by the number of animals in the group. The maximum possible index is 4.

 Guinea pigs weighing 400-500 g were divided into 3 groups of 3 animals in each group.

Group I - healthy control
Group II - infected untreated animals
Group III - infected animals treated with the claimed agent, starting from the 1st day of infection.

 Infection was carried out with a culture of bovine type Bovinus-8 mycobacterium tuberculosis at a dose of 0.0001 mg in 0.5 ml of saline subcutaneously in the right inguinal region. Group III animals received the claimed agent in a dose of 100 in the form of slurry, which was injected using a probe directly into the animals' esophagus. The data are presented in table 2.

 As follows from the data presented, the claimed drug has a pronounced anti-tuberculosis effect.

 The study of the anti-tuberculosis effect of the claimed drug during experimental infection (morphological studies).

 The experiments were performed on 20 guinea pigs. Infection was carried out by a culture of bovine type Bovinus-8 mycobacterium bovine tuberculosis, subcutaneously. After infection, all animals were divided into 3 groups: group I of 5 pigs was slaughtered 40 days after infection, group II of 5 pigs was observed before death. Animals of group III received orally in the form of gruel (through a probe) the claimed drug in a dose of 10 g, starting from the 1st day of infection and were killed after 6 days.

 For histological examination, inguinal lymph nodes, liver, lungs and spleen were taken. Sections were stained with hematoxylin-eosin according to Van Gieson and argyrophilic fibers were impregnated according to Foote.

 Results: in animals of group I (slaughtered after 40 days) and group II (animal death occurred after 60 days), massive caseous-necrotic lesions occurred. Common cirrhotic changes were found in the liver. Anemic heart attacks formed in the liver and spleen, as a result of vascular damage.

 The morphological picture of the organs of animals of group III treated with the claimed agent was characterized by focal sclerosis with hyalinosis in the pulp of the spleen. Hyperplasia of their lymphatic apparatus with the appearance of numerous accumulations of lymphocytes in the interstitial tissue was noted in the lungs.

 Thus, in the treatment with the claimed agent, the tuberculosis process proceeds with the predominance of a productive tissue reaction with subsequent healing phenomena of the foci by sclerotherapy and resorption.

Claims (7)

1. Herbal medicine with anti-tuberculosis action, characterized in that it contains a scarlet leaf, calamus rhizome, birch leaves, hibiscus flowers, rhizomes and elecampane roots, linden flowers, magnolia vine, nettle leaf, violet grass, mint leaf, licorice root, grass horsetail and grass sequences, with the following ingredients, including: Scarlet leaf 1 - 30 Rhizome of calamus 1 - 30 Birch Leaves 1 - 30 Hibiscus flowers 1 - 30 Rhizomes and roots of elecampane 1 - 30 Linden flowers 1 - 30 Schisandra fruits 1 - 30 Nettle leaf 1 - 30 Violet Grass 1 - 30 Mint leaf 1 - 30 Licorice Root 1 - 30 Horsetail Grass 1 - 30 Grass string 1 - 30 2. The herbal medicine according to claim 1, characterized in that it is made in the form of granules, additionally contains methyl cellulose and lactose, while it includes medicinal plants in the form of a dry aqueous extract with the contents of the ingredients per 1 granule, g: Dry water extract 0.1 Lactose 0.067 Cellulose 0.3 3. The herbal medicine according to claim 1, characterized in that it is made in the form of tablets, additionally contains auxiliary substances of calcium stearate and potato starch, while this includes medicinal plants in the form of a dry aqueous extract with the contents of the ingredients per 1 tablet, g: Dry water extract 0.05 Excipients (calcium stearate and potato starch) to a tablet mass of 0.2 4. The herbal remedy according to claim 1, characterized in that it is made in the form of a syrup, additionally contains fructose, sorbitol and water, and includes medicinal plants in the form of a dry aqueous extract with the contents of the ingredients per 100 ml of syrup, g: Dry aqueous extract 0.1 - 0.5 Fructose 0.015 - 0.03 Sorbitol 0.03 - 0.06 Water Up to 100 ml 5. Herbal medicine according to claim 1, characterized in that it is a decoction of medicinal plants. 6. Herbal medicine according to claim 1, characterized in that it is an infusion of medicinal plants. 7. The herbal remedy according to claim 1, characterized in that it is dosed with a mass of 2.0 g in filter bags.

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