RU2482862C2 - Therapeutic preparation 'aqueous-alcoholic solution of purified mumiyo' - Google Patents

Abstract

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutical industry, particularly to therapeutic preparations of mumiyo. The therapeutic preparation which contains purified mumiyo, grapefruit citrosept, edible glycerol, ethanol and water at specific proportions.

EFFECT: preparation has a prolonged shelf life.

8 tbl

Description

The invention relates to the parapharmaceutical industry, in particular to mummy preparations in the form of a solution.

Known biologically active additive "Mumivit" in the form of tablets, including, wt.%: Purified mummy 25-30, starch 10-15, calcium stearate 5-10, the rest is sugar. The need for the introduction of inert additives is due to the specific physicomechanical properties of the mummy, namely, high adhesive properties and high viscosity, which is why tabletting of pure mummy is practically impossible, while the introduction of inert additives reduces the quality of the product (RF patent No. 2238100, IPC A61K 35/78, A61K 9/20, A23L 1/30, publ. 2004.10.20).

Known drug with anti-inflammatory and antimicrobial effects based on mummies and ascorbic acid in the presence of talc, starch, calcium stearate and sugar, providing disintegration and pressing time (talc, starch), improving the fluidity of the granulate and increasing the compressive strength (calcium stearate), sugar as a filler (RF patent No. 2174840, IPC А61К 35/02, А61К 9/06, publ. 200.10.20).

Known drug mummy in the form of a powder, in which powdered cellulose is introduced into the mummy extract in a ratio of 2: 1, while the mummy extract is transformed from a sticky mass into a loose powder, stickiness, ductility and moisture permeability disappear. The drug in this form serves as an active substance in the composition of ointments, suppositories, tablets, etc. (RF patent No. 2068264, IPC A61K 35/00 publ. 1996.10.27).

As can be seen from the above analogues, the tabletting process is practically impossible without inert additives due to the high viscosity and high adhesive properties of the mummy, and when storing such tablets at an ambient humidity of over 50%, the drug gains some fluidity, the tablets stick to the package, losing up to 20% mass upon extraction, which violates the dosage during its use.

A liquid form of a water-based dietary supplement is known that contains mummies, pine nutshell products, crushed to a finely dispersed state of Artemia salina cysts and water in the following ratios of ingredients, wt.: Mummy 1-20, processed products of pine nutshell 1-20, Artemia salina cysts 1-20, the rest is water (RF patent No. 2345572, publ. 02/10/2009 - prototype). However, the presence in the aqueous solution of this drug of such an ingredient as Artemia salina cyst determines a short shelf life of the drug due to the fact that any protein compounds can only be stored in lyophilized form (subjected to freeze drying), or in canned form, because . protein in the presence of water undergoes natural decomposition.

Thus, currently in the pharmacological practice of the manufacture of the drug Mummy there is no convenient in the preparation and use of the dosage form of the drug with a long shelf life of qualitative indicators of the mummy. In the form of an aqueous solution, the drug can be prepared only for 1-2-fold use during the day, because the shelf life of aqueous solutions of mumiye is short. Table 1 shows the study of the shelf life of aqueous solutions of mumieum of various concentrations.

Table 1 The concentration of the aqueous solution of the mummy,% Storage time of an aqueous solution of mummy, days 5 0.5 10 1,0 thirty 2.0

As can be seen from table 1, the shelf life of aqueous solutions of mummy although increases with increasing concentration of mumie in solution, but even at a relatively high concentration is a single-use dosage form.

As for the use of mummy tablets, among other things, the manufacturers of the drug, when selling it, were faced with the fact that the supply and sale of the tablet form of mumie to regions with high humidity and even more so at high temperatures were almost impossible, since tablets in these conditions ( despite the presence of sealed packaging) lose their presentation and consumer properties (liquefy and adhere to the packaging).

The objective of the invention is to develop a simple and technologically low cost in the manufacture of the dosage form of the mummy, convenient to use, with a long shelf life, ensuring high quality of the drug and dosage accuracy when using.

The specified technical result is achieved by the fact that the therapeutic and prophylactic preparation based on the mummy is made in the form of a solution and contains purified mummy, ethyl alcohol, food glycerin, grapefruit citrocept, water in the following ratio, wt.%:

peeled mummy 25-30 ethanol 18-22 food glycerin 8-10 citrosept 1-6 water rest

The invention consists in the following. As you know, mummies are poorly soluble in alcohol, while alcohol, as a good preservative, can extend the shelf life of a highly concentrated mummy solution. However, its high concentration can lead to denaturation of the protein part of the mummy, reducing the quality of the product. In addition, the high alcohol content of the drug is contraindicated in adults who cannot tolerate alcohol and in children. The claimed invention provides a composition of ingredients in conjunction with a high concentration mummy, ensuring its good solubility, low alcohol content in solution, long shelf life with a high level of therapeutic properties of the drug.

Targeted additives to the mummy (citrosept, glycerin, alcohol) are not inert components of the solution. In the proposed combination of components, each of them brings a positive component in solving the problem, providing a combined multifunctional effect.

Mumiye is a complex, multicomponent combination of organic compounds and their mineral complexes, including more than 50 macro- and microelements, essential oils, B vitamins, organic, including humic, acids, carbohydrates, albumin, amino acids, including glycine, wax-like and resinous substances, gums, alkaloids, polyphenols, fatty acids, phospholipids and other substances. Mumiye belongs to the means of non-specific immunostimulating action, is a powerful biostimulant, about 3.5 times more effective than taiga ginseng, with a wider range of biological effects. Trace elements contained in physiological proportions have a beneficial effect on biochemical and physiological processes, metabolism, the functioning of enzyme systems, which helps to increase resistance and adaptation of the body. Due to the presence of a high concentration of minerals and trace elements, mummy is an excellent antimicrobial, antiseptic. Mumiye is actively involved in the biosynthesis of DNA in the cell, therefore, it has powerful wound healing properties and stimulates blood formation. Mumiye has an antispasmodic and calming effect, exhibits a pronounced anticoagulant and antitoxic effect, protects against radiation, radiation, poisons, and has antioxidant properties. Mumiye stimulates all the functions of the liver, exhibits a distinct choleretic effect, helps reduce cholesterol and blood sugar. Mumiye has an antitumor effect, which is associated with its ability to enhance adaptive properties and increase immunity. Humic acids in the composition of the mummy suppress inflammation, lower capillary reactivity, regulate vascular permeability, reducing tissue exudation and swelling, reduce redness, and reduce intoxication. Essential oils in mummies are analgesic, and the biologically active substances that make up the mummy increase local and general immunity. According to the recommendations of oriental medicine, the mummy is used for surgical (bone fractures, dislocations, bruises, wounds, atrophic ulcers, hemorrhoids), therapeutic (acute and chronic gastritis, colitis, peptic ulcer disease, hepatitis, cholecystitis, anemia, hypotension), nervous (epilepsy, migraine , inflammation and paralysis of peripheral nerves, stuttering, hearing loss), infectious and inflammatory and allergic (tonsillitis, stomatitis, otitis, bronchitis, rheumatism, bronchial asthma, endometritis, salpingitis, cystitis) diseases, poisoning of plants and live poison poisons (insect bite, scorpion), as well as chronic alcoholism.

The mummy in terms of elemental and organic composition is non-toxic and belongs to the 4th category of hazard drugs, i.e. almost safe (according to the toxicology laboratory of NPO “Karbolit”, Novosibirsk, 1989). It is used in the form of powder, tablets or freshly prepared solutions, it is highly soluble in water and poorly soluble in alcohol. The most common dose is 0.1-0.3 g of mummy.

Grapefruit citrocept (standard 33% grapefruit seed extract) is a plant-based antiseptic and can be used as a plant preservative with beneficial properties. Registration certificate No. 77.99.20.916. B.000428.11.03. Manufacturer: Norway, Chintamani International AS. Ingredients: grapefruit seed bioflavonoid extract (33%) and vitamin C (4.9 g), palm glycerol and water. Compared with conventional alcohol and iodine-containing antiseptics, citrosept has a wider spectrum of effects on microorganisms (more than 800 strains of gram-positive and gram-negative bacteria, more than 100 types of fungi and yeast, some viruses). 100 ml of citrosept contains 19.37 g of bioflavonoids (quercetin, hesperidin, naringin, etc.), which determine its antiseptic properties. The antifungal effect of the standardized 33% grapefruit seed extract is based on the delay of the cytochrome P-450 enzyme, and the antibacterial and antiparasitic effects are based on damage to the cytoplasmic membrane, cell wall and on the inhibition of the synthesis of amino acids of microorganisms (in the absence of toxicity to living organisms). Citrosept has a wide spectrum of action, a good disinfecting property and is effective even in low concentrations (0.7%). The drug is non-toxic, biodegradable, non-addictive, addictive and does not destroy the beneficial microflora, goes well with other natural medicines. In combination with mummy, it enhances the healing properties of the drug and, due to its disinfecting properties, reduces the amount of alcohol in the solution.

In medical practice, citrocept is used (according to the instructions for use) for candidiasis and other fungal diseases of the skin, mucous membranes and nails, dermatoses, mixed fungal and bacterial infections of the skin and nail plates, diseases of the respiratory tract (sinusitis, influenza, SARS, tonsillitis, asthma, bronchitis), diseases of the oral cavity (stomatitis, gingivitis, periodontal disease), intestinal diseases (dysbiosis, gastritis), hepatitis, liver failure, acute intoxication, immunodeficiency, parasitosis, insect bites, p anah, cuts, burns, varicose veins and trophic ulcers, female fungal and bacterial infections, etc., therefore, citrosept goes well with the mummy as a therapeutic effect, enhances the antimicrobial activity of the mummy and expands its spectrum (due to antiviral and antifungal effects citrosept).

Glycerin (in the presence of an aqueous solution of mummy in the preparation) promotes the digestibility of the drug due to the fact that its molecules, having small sizes and having a high agent with water molecules (having a hydration shell), contribute to the saturation of the cells of the drug component of the drug. Its molecules structure the extracellular fluid and protect the cell from adverse ultrahigh osmotic effects, i.e. enhance the function of macronutrients to maintain optimal osmotic pressure. Glycerin mixes with water and alcohol in every way and is a thickener and solvent for many organic and inorganic substances.

To determine the optimal combination of ingredients in the preparation, experimental studies of the preparations by shelf life were carried out with an alcohol content of 16 to 28% and a citrosept of 1 to 10%. The mummy content in this case was 25-30% (almost the maximum solubility level) and 10% food glycerin. The research results are shown in table 2.

table 2 The alcohol content,% The content of citrosept,% Shelf life of the drug, months With citrosept at 30% mummy content With citrosept at 25% mummy content Without citrosept at 30% mummy content 16 6 9.7 9.1 3,5 eighteen 4-6 12.1-12.4 11.9-12.1 5.5 twenty 2-4 12.2-12.6 12.0-12.4 6.9 22 1-2 12.4-12.9 12.2-12.6 8.7 24 - - - 10.1 26 - - - 11.5 28 - - - 12.7

Table 2 shows the expiration dates (from the entire array of combinations of ingredients) of drugs with a shelf life of 12.5 + 0.4 months. This shelf life of highly concentrated mummies in solution is due to time: production, formation of a batch of the drug, delivery to the consumer (especially in remote regions), use, as well as other unforeseen circumstances. The exception is the data on the experimental samples with 16% alcohol, in the presence of which in the preparation with the content of 6% citrosept the shelf life was 9.7 months and the data on the experimental samples without the introduction of citrocept, where the required shelf life was achieved only at 28 % alcohol in solution.

As can be seen from table 2, with an increase in the amount of citrocept in the preparation from 1 to 6%, the required amount of alcohol to maintain the required shelf life is reduced. So without a citrocept, to maintain a 12-month shelf life of the drug, 28% alcohol is required, while a content of 1-2% citrocept in a solution provides this shelf life already at 22% alcohol, and 4-6% citrocept - at 18% alcohol in the drug. The optimal ratio of ingredients according to the task should be considered the following ratio, wt.%: Purified mummy according to TU 9197-002-01898825-05-25-30%, glycerol according to GOST 6824 10%, citrosept 1-6%, alcohol according to GOST 51652 18 -22%, water according to GOST R51232, SanPiN 2.1.4.1074-2001. Studies have shown that the qualitative indicators of the drug with a glycerol content of 8 to 10% were identical, which allowed to expand the limits of glycerol input in the drug.

Microbiological studies of the drug after 12 months of storage are shown in table 3.

Table 3 No. p / p Defined indicators Research results, units Permissible level value, units ND on research methods one 2 3 four 5 one KMAFAMM Less than 1 × 10 ² CFU / g Not more than 1 × 10 ⁴ CFU / g GOST 10444.15-94 2 BGKP (coliforms) 1.0 g undetected 1.0 g not detected GOST 30518-97 (GOST R 50474-93) 3 S.aureus 1.0 g not detected 1.0 g not allowed GOST 10444.2-93 four Pathogenic, including salmonella 1.0 g not detected 1.0 g not allowed GOST 30518-97 (GOST R 50474-93) 5 Yeast mold Less than 10 cfu / g No more than 100 CFU / g GOST 10444.12-88 6 V.parahaemolyticus Less than 10 cfu / g No more than 200 CFU / g MUK 4.2.1793-03

As can be seen from table 3, the drug according to microbiological indicators complies with SanPiN 2.3.2.1078-01 "Hygienic requirements for the safety of the nutritional value of products" (ind. 1.10.6.1).

The biological value of the drug is presented in table 4.

Table 4 Indicator MG in a daily dose (30 drops = 1.5 ml) % of the adequate level of consumption per day Humic Acid Content 16 (16) * one hundred The content of flavonoids (in terms of luteolin) 1.5-4.5 (5) * 30-90 The content of free organic acids (in terms of malic acid) 6 (500) * 1.2 * - An adequate level of consumption per day according to MU 2.3.2.1915-04

As can be seen from table 4, the daily dose of the claimed drug 100% satisfies the daily requirement of the body for humic acids and 30-90% of the need for flavonoids.

Organoleptic and physico-chemical characteristics of the drug based on the mummy are shown in table 5.

Table 5 Name of indicator The indicator of the drug based on the mummy Appearance Homogeneous, thick solution from dark brown to black Taste Bittersweet Smell Specific resinous with a light citrus aroma Density, g / cm ³ , not less 1,1 pH of 1% aqueous solution 7.5-7.9 Solids content,% not less than 40,0 The content of free organic acids,%, not less 0.4 The content of flavonoids (in terms of luteolin),%, not less 0.1 The content of humic acids,%, not less 1,0 Total ash content,%, not less 6.0 The content of ash insoluble in 10% hydrochloric acid,% not less 0.3

A therapeutic and prophylactic drug based on the mummy is prepared as follows.

Example 1. 25 kg of crushed purified mummy is loaded into an industrial mixer, 42 liters of water are added. The operation of the mixer continues until the mummy is completely dissolved within 3-4 hours. The resulting solution is pumped into the blender with a stirrer, 2 kg of grapefruit citrocept, 9 kg of food glycerin, 22 kg of ethyl alcohol are introduced there. The mixture is thoroughly mixed for at least 30 minutes and packaged in sterile glass bottles (sterilized at a temperature of 140 ± 5 ° C for 40 minutes) or in polypropylene bottles (sterilization at 60 ± 1 ° C for 3 hours) with dropper caps , pipette lids.

Example 2. The sequence of technological operations was carried out as in example 1 with the following ratio of components: purified mummy - 30 kg, ethyl alcohol 18 kg, grapefruit citrocept 5 kg, food glycerin 10 kg, water 37 kg.

Example 3. The sequence of technological operations according to example 1 with the following ratio of components: purified mummy 27 kg, ethyl alcohol 20 kg, grapefruit cytosept 4 kg, food glycerin 10 kg, water 39 kg.

Since 15 drops of the mummy-based therapeutic and prophylactic drug correspond to the mummy content of one tablet weighing 0.2 g, which is most often used in medical practice, the treatment and prevention of diseases with the claimed drug is carried out similarly to the existing treatment practice. In the presence of bioflavonoids that complement and enhance the properties of the mummy, the claimed drug is especially effective for infectious and inflammatory diseases of bacterial, fungal, viral etiology (candidiasis, dermatosis, genital infections, tonsillitis, acute respiratory viral infections, stomatitis, gastritis, colitis, etc.), disorders metabolism (diabetes mellitus, hypercholesterolemia, obesity, etc.), increased blood viscosity (diseases of the cardiovascular system, their complications, etc.), vascular diseases (inflammation, atherosclerosis, varicose expansion etc.), dysbiosis, immunodeficiency, for the prevention of secondary infections, after chemo-, radiation and antibacterial therapy, etc.

The results of comparative tests for the treatment of a number of diseases with mummy tablets according to known methods and the claimed drug are shown in tables 6 and 7.

Clinical studies were conducted on a group of probants aged 21-59 years (20 people) with the following diagnoses: chronic gastritis with various secretory activity, HP +, chronic colitis and deep vein thrombophlebitis of the lower extremities, table 6.

Table 6 Disease Dosage and route of administration by author Dosage and method of use of the claimed drug Author Application Results The results of the use of the claimed drug Chronic gastritis with various secretions of gastric juice Inside, at a dose of 100 mg 3 times a day (morning, afternoon and evening) for 15-20 days, 30 minutes before meals at a low, 40-45 minutes before meals at normal and 1.5 hours before meals at high secretion of gastric juice. Askarov U.A., 1980. Inside, at a dose of 15 drops 3 times a day (morning, afternoon and evening) for 21 days 30 minutes before meals at a low, 40-45 minutes before meals at normal and 1.5 hours before meals with increased gastric secretion juice. Before use, the drug must be previously dissolved in a volume of 1 tablespoon of boiled water. A decrease in pain in patients was observed on the 4th-6th day of treatment, and its complete disappearance, including local pain, on the 9th-12th day. All dyspeptic symptoms (nausea, vomiting, heartburn, belching, etc.) took place on the 7-10th day of treatment. Stool normalization - on the 6-15th day of treatment. 15-20 minutes after taking the drug, in almost all patients the pain decreased or disappeared, and its complete disappearance - on 4-9 days. Palpation pain disappeared on the 9-12th day of treatment. All dyspeptic symptoms (nausea, vomiting, heartburn, belching, etc.) took place on the 6-9th day of treatment. Stool normalization - on the 5-12th day of treatment. Chronic colitis Inside, at a dose of 200 mg 1 time per day for 10 days 30 minutes before meals. Abdurakhmanov T.R., 1970. Inside, at a dose of 15 drops, 1 time per day for 10 days 30 minutes before meals. Before use, the drug is previously The main symptoms of the disease disappeared on the 5-10th day of treatment. A decrease in pain was observed on 3-4 days of treatment, the disappearance of phenomena Dissolve in a volume of 1 tablespoon of boiled water. gastrointestinal dyspepsia, cramping - on the 8-9th day of treatment. Stool normalization within 1-2 weeks. Thrombophlebitis of the deep veins of the lower extremities Inside, at a dose of 300 mg once a day for 10 days 30 minutes before meals. Abdurakhmanov T.R. et al., 1970. Inside, at a dose of 15 drops, 1 time per day for 10 days 30 minutes before meals. Before use, the drug must be previously dissolved in a volume of 1 tablespoon of boiled water. Reducing the feeling of pain, the degree of swelling and the volume of the diseased limb - by 3-6 days of treatment. On day 8-10, skin temperature returned to normal, other symptoms of the disease disappeared. Reduction of soreness, degree of swelling and volume of the diseased limb - by 2-4 days of treatment. On the 6-8th day of treatment, skin temperature returned to normal, other symptoms of the disease disappeared.

The therapeutic and prophylactic drug based on mummy can be used without special technological methods in the production of medicines, being their basis. Replacing part of the water in this preparation with targeted additives (concentrated juices, decoctions, infusions), it is possible to purposefully enrich the preparation with components to enhance the effect on a particular disease. So, the developers of the claimed drug based on it created a spray for the treatment of diseases of the oral cavity and upper respiratory tract by replacing 10-15% of water in liquid mummy with cherry concentrated juice, which is an antiseptic and has expectorant and antipyretic properties, and introducing orange essential oil into the spray (0.05%) and grapefruit essential oil (0.03%) as flavorings. In addition, essential oils also have a disinfectant and anti-inflammatory effect.

Five presses on the dispenser lid (0.15 ml each press) corresponds to 0.75 ml of solution (15 drops). According to the scientific medical literature, for the treatment of inflammatory diseases of the oral cavity, many authors recommend applying the mummy topically in the form of lubrications, rinses, applications on the mucous membrane, which creates certain inconveniences and difficulties in use (the need to calculate the concentration and preparation of the solution only for 1-2-fold use during the day, because the shelf life of aqueous solutions of the mummy is short).

Table 7 shows the results of comparative tests for the treatment of diseases of the oral cavity with Mumiye tablets and a therapeutic and prophylactic drug based on Mumiye.

As can be seen from the test results, the therapeutic effect when using a therapeutic and prophylactic drug based on mummy in most cases exceeds the effectiveness of treating diseases with mummy tablets.

Table 8 shows the results of preventive measures in situations: seasonal exacerbation of chronic gastritis of any acidity, hypovitaminosis, complications of diseases associated with endothelial dysfunction (varicose veins, atherosclerosis, metabolic syndrome), osteoporosis.

Table 8 Situation Dosage and route of administration of the drug based on mummy Prevention of seasonal exacerbation of chronic gastritis of any acidity As part of complex therapy, a course intake 2 times a year (spring, autumn): inside at a dose of 15 drops 3 times a day (morning, afternoon and evening) for 21 days 30 minutes before meals. Before use, the drug must be previously dissolved in a volume of 1 tablespoon of boiled water. Hypovitaminosis Prevention As part of complex therapy, a course intake 2 times a year (spring, autumn): inside at a dose of 15 drops 3 times a day (morning, afternoon and evening) for 21 days 30 minutes before meals. Before use, the drug must be previously dissolved in a volume of 1 tablespoon of boiled water Prevention of complications of diseases associated with endothelial dysfunction (varicose veins, atherosclerosis, metabolic syndrome, etc.) As part of complex therapy, a course intake 2 times a year (spring, autumn): inside at a dose of 15 drops 3 times a day (morning, afternoon and evening) for 21 days 30 minutes before meals. Before use, the drug must be previously dissolved in a volume of 1 tablespoon of boiled water. Osteoporosis Prevention As part of complex therapy, a course intake 2 times a year (spring, autumn): inside at a dose of 15 drops 3 times a day (morning, afternoon and evening) for 21 days 30 minutes before meals. Before use, the drug must be previously dissolved in a volume of 1 tablespoon of boiled water. Prevention of seasonal incidence of ARVI and influenza During the epidemic, inside, at a dose of 15 drops 3 times a day (morning, afternoon and evening) for 21 days 30 minutes before meals. Before use, the drug previously dissolved in a volume of 1 tablespoon of boiled water. Upon contact with patients, add topical application: five presses on the dispenser lid in the oral cavity 2 times a day between meals for 10 days. Prevention of violations of the oral biocenosis with prolonged antibiotic therapy. Five taps on the dispenser lid in the oral cavity 2 times a day between meals for 10 days Prevention of inflammatory diseases of the oral cavity when wearing dentures 30 drops to 1 \ 2 cup boiled water to use as a mouthwash 1-2 times a day Periodontal Disease Prevention 30 drops to 1 \ 2 cup boiled water to use as a mouthwash 1-2 times a day Prevention of exacerbations of chronic tonsillitis During the epidemic and in contact with patients: five presses on the dispenser lid in the oral cavity 2 times a day between meals for 10 days

Thus, the claimed therapeutic and prophylactic drug based on mummy is convenient in the manufacture and use of the dosage form of mummy with a long shelf life with high quality and high metering accuracy when used.

Claims (1)

A therapeutic and prophylactic drug based on mummy, characterized in that it contains purified mummy, grapefruit citrocept, food glycerin, ethyl alcohol and water in the following ratio of components, wt.%:
peeled mummy 25-30 grapefruit citrose 1-6 food glycerin 8-10 ethanol 18-22 water rest