RU2585108C1 - Composition for recovery of cartilaginous and bone tissue in osteoporosis - Google Patents

Abstract

FIELD: medicine; pharmaceuticals.

SUBSTANCE: invention refers to pharmaceutical industry, namely to composition for recovery of cartilaginous and bone tissue in osteoporosis, consisting of certain dried plants powder in certain proportions.

EFFECT: composition described above is characterised by high regeneration of cartilage and bone tissues in osteoporosis.

3 cl, 10 dwg, 8 tbl, 5 ex

Description

The invention relates to medicine, more specifically to pharmacy and pharmacology, and can be used to create a medicinal product or dietary supplement for the prevention and treatment of osteoporosis.

Osteoporosis is one of the most urgent problems of modern health care. According to WHO, about 75 million citizens of Europe, the USA and Japan suffer from this disease. Osteoporosis takes the fourth place in the frequency of disability after diseases of the cardiovascular system, diabetes and oncological diseases [Rudenko E.V., Buglova A.E., Rudenko E.V., Samokhovets O.Yu. Medication for osteoporosis in adults. Teaching aid, Minsk: BelMAPO, 2011 - 22 pp.]. In Russia, 33.8% of women and 26.9% of men over 50 suffer from osteoporosis. Another 43.3% of women and 44.1% of men show signs of osteopenia [Mikhailov E.E., Benevolenskaya L.I. In: A Guide to Osteoporosis. Ed. L.I. Benevolenskaya. M: BINOM, 2003; 10-55]. Mortality in the most characteristic fracture of the femoral neck for osteoporosis exceeds 30%. Osteoporosis is often the cause of the development of aseptic necrosis of bone tissue.

Osteoporosis is a polyetiological disease, the pathogenesis of which is not well understood. Age-related deficiency of sex hormones released during stress and used for medicinal purposes glucocorticoids, sedentary lifestyle, unbalanced diet, frequent antibiotic use, smoking and alcohol abuse are called important causes of osteoporosis [Consensus development conference: diagnosis, prophylaxis, and treatment of osteoporosis . Am J Med. 1993 Jun; 94 (6): 646-50. NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis, and Therapy, March 7-29, 2000: highlights of the conference. South Med J. 2001, Jun; 94 (6): 569-73].

Effective therapy of osteoporosis remains an unresolved problem [Chernov, Yu.N., Peshekhonova LK, Batishcheva GA Osteoporosis: critical links in pathogenesis and pharmacological correction. http://medi.ru/doc/7200210.htm], which necessitates further research in this area.

A comprehensive in-depth analysis of hormonal status and metabolic processes in bone tissue using modern diagnostic test systems for osteoporosis indicates violations in the state and regulation of calcium-phosphorus metabolism: the development of hypocalcemia, increased excretion of calcium and phosphorus in the urine, activation of total alkaline phosphatase. In parallel, the pathology of calcium-regulating systems is noted: an increase in the secretion of parathyroid hormone and a tendency to a decrease in the level of calcidiol. Deficiency of sex steroids progesterone and androgens, as well as changes in the secretion of other systemic hormones (cortisol and thyroxine) in the genesis of osteopenic phenomena are characteristic. A redistribution of the cytokine profile and release of IL-1, IL-6 and TNFα is observed in cases of bone remodeling disorders, which are expressed in the activation of resorptive processes.

Preparations for the treatment of osteoporosis can be divided into three groups:

- preventing bone resorption (resorption);

- contributing to bone formation;

- combined action.

A number of drugs are known to compensate for calcium deficiency, for example, calcium gluconate (radar, http://www.rlsnet.ru/tn_index_id_1170.htm?nocache=yes), calcium carbonate (radar, http://www.rlsnet.ru/tn_index_id_43815 .htm and calcium lactate (radar, http://www.rlsnet.ru/mnn_index_id_718.htm).

Known compositions containing mixtures taken in different ratios of vitamins and minerals, including calcium and iodine, are described in US patents - US 6562378, US 6572903, US 6565891, Germany - DE 10109798, European patent - EP 1214893.

Known drug "Divina" containing estradiol valeriate (white tablets) and estradiol valeriate with progestogen medroxyprogesterone acetate (blue tablets). The tool is used for menopausal disorders, for disorders of the menstrual cycle, for the prevention of osteoporosis in the period after menopause. Contraindications are the same as with other estrogen drugs.

However, the optimistic expectations associated with the widespread introduction into practice of many drugs for the treatment of osteoporosis are not fully justified. This is due to the numerous side effects of treatment, the high cost of drugs and lack of effectiveness. Therefore, an active search is underway for alternative approaches to the correction of bone metabolism, including in the arsenal of methods of diet therapy, laser therapy, herbal medicine, etc.

To suppress bone resorption, along with estrogens, preparations of calcitonin, a thyroid hormone, for example, myacalcyclic, wild boar, calcitonin depot, alostin, osteover, are widely used.

There are a number of effective drugs from the group of bisphosphonates: Alendronate (fosamax), Bonviva, Aklast. They not only reduce bone resorption, but also increase the calcium content in it.

A known tool is a complex drug osteogenon that improves bone adhesion after spinal injuries.

In recent years, the recombinant human parathyroid hormone (PTH) FORSTEO, which provides an anabolic effect in the bone and the fully human monoclonal antibody JgG2 PROLIA, which inhibits the activation of osteoclasts, has begun to be used. The term and experience of use are insufficient.

The disadvantage of these drugs is that the immediate effect of therapy can be expected only after a few years of constant administration of the drugs, after discontinuation of the drugs, after some time, bone density can again decrease to the initial level. Long-term treatment, in addition to high cost, is fraught with a delay in these drugs (bisphosphonates) in the newly formed bone. The frequency of side effects occurs in at least 20% of cases. Almost all anti-osteoporotic drugs require additional intake of calcium and vitamin D.

From patents of the Russian Federation No. 2349339 and No. 2239438 known funds based on chondroitin sulfate and glucosamine, which according to the patents stimulate the regeneration of cartilage and connective tissue. However, existing observations have shown that drugs of this series have a mild therapeutic effect. Nevertheless, at present, preparations containing chondroitin sulfate and glucosamine are priority in the methods of prevention and treatment of osteoporosis.

From the patent of the Russian Federation No. 2527042, dietary supplement is known for the prevention of diseases of osteoporosis, which includes calcium and magnesium salts, vitamin D3, as well as salts of boron and zinc. In this case, the specified calcium salt is normal calcium phosphate, the magnesium salt is magnesium phosphate.

For 10 years, the Cheng zai wan dietary supplement, made from plant and animal components used in traditional Chinese medicine, has been successfully used in the aseptic necrosis treatment center [Lang FP, Huang H, Huang H, Huang KQ, Zhang JC. Retrospective analysis of therapeutic efficacy in 1 425 cases of femoral head necrosis. // Zhonggou Gongcheng Yanjiu yu Linchuang Kangfu 2008; 12 (33): 6500-6504]. However, most of the ingredients included in it are absent in the territory of the Russian Federation. In addition, the preparation technology of this tool is also not known.

Closest to the claimed agent is the agent described in RF patent 2521227. According to this patent, a composition is proposed for eliminating the phenomena of osteoporosis and osteoarthrosis, characterized in that it contains an extract or powder of a dried plant selected from the group: burdock, dandelion, marsh cinquefoil, birch , St. John's wort, goldenrod, nettle, mint, licorice, white cinquefoil, upright cinquefoil, rose hip, cyanosis blue, valerian, corn, milk thistle, oats, repeshchit, immortelle, ginseng, sage, asterisk, pumpkin, willow , Strawberries, chicory, Agropyron, Jerusalem artichoke, bilberry, calendula, horseradish, garlic, aspen, knot-grass (knotgrass), plantain, elecampane, krasnostebelnaya buckwheat, chamomile flowers, lemon balm, Centaurea cyanus, cudweed, tripartite series; drone brood lyophilisate and quercetin or dihydroquercetin or rutin powder in the following ratio of components in parts (1-5) :( 1-4): 1, respectively.

However, as follows from the patent, a well-known tool has only a proven antianginal effect (see the task section of the invention of patent No. 2521227). The authors explain this effect as an effect on the circulatory system, and the ability of the drug to increase the number of chondrocytes. Since the cited document claims the use of funds for all types of osteoporosis, this technical solution can be taken as a prototype.

In the known patent there is no data on the direct effect of the claimed funds on reparative processes in cartilage and bone tissue. However, increased proliferation of chondrocytes is not always an indicator of the restoration of cartilage. For example, in a model of experimental osteoporosis, chondrocytes are actively proliferated by introducing prednisolone into animals, leading ultimately to cartilage degeneration.

The technical result of the claimed invention is the creation of a drug that provides higher regeneration of cartilage and bone tissue in osteoporosis.

This technical result is achieved by the fact that in the known composition for the restoration of cartilage and bone tissue in osteoporosis, containing powder of dried plants selected from the group: birch, mint, willow, aspen, mountaineer bird (knotweed), plantain, chamomile flowers, lemon balm, dried mussel , a series of tripartite crushed powder from bees, the composition additionally contains veronica grass, water pepper (pepper), grass, golden grass, geranium blood-red grass, geranium forest grass, geranium meadow grass, ivory grass leaf grass, gorse, grass dwarf, common grass, oregano common grass, angelica root, blackberry grass, goldenroot grass, centaury umbelliferous grass, dentate late grass, European bark grass, Ivan tea (fireweed narrow leaved) leaf, hyssopa medicinal red root root, red brush root, buckthorn bark, alfalfa grass, common grass cuffs, Lungwort grass, woodlice grass, spearmint long leaf grass, peppermint leaf, primrose grass, pikulnik grass, peony root , bedstraw tenacious grass, plantain big leaf, wormwood God's tree grass, saplings grass, motherwort grass, common grass flax, duckweed small grass, senna leaf, blueberry grass, currant leaf, common grass, colza common grass, meadowsweet (labaz) and grass, thyme grass, a series of drooping grass, blueberry shoots, Chernobyl grass, sage purple grass, echinacea purple grass, licorice roots, astragalus grass, dead bees, finely chopped in the following ratio, weight. %:

The composition may take the form of tablets of 0.5-1.0 grams

The daily dose of the composition is 7-8 grams.

The composition is prepared as follows.

According to the recipe, high-quality dry vegetable raw materials are taken, they are decontaminated (roasted), weighed on a VK 3000 benchtop electronic scale. Then they are cut on a Corsar P-190 universal grinder to a minimum particle size of 2 mm. The next step is to grind the raw materials in a PL10G Plasma micromill to a powder state, then sift them on a VAEM-USh-300 sorting machine, and then powder can be pressed into tablets.

Were prepared 2 composition containing the minimum and maximum amounts of the ingredients of the claimed funds.

Composition number 1.

EXAMPLE 1

Composition No. 2

The most important properties of this drug are: the restoration and maintenance of metabolic processes, the activation of metabolism in the Krebs cycle, the cytoprotective effect and antioxidant protection due to the induction of superoxide dismutase, the activation of regenerative processes, the anti-stress effect that regulates the effect on the processes of excitation and inhibition in the central nervous system and normalization of activity autonomic nervous system, restoration of sensitivity of tissue receptors to female and male sex hormones us gain tissue perfusion due to the effect of the receptacles (different gauge) and improve blood rheology (viscosity decrease), regulation of mineral metabolism, enhance mineralization of bone, its density and increase bone mass. The ingredients of the composition have cardiotonic and diuretic effects, support the motility of the gastrointestinal tract, have bile-forming, choleretic, hepatoprotective, anti-inflammatory and immunomodulating effects. It normalizes carbohydrate and fat metabolism, provides a general strengthening effect, tones skeletal muscles, improves performance and endurance, which ultimately stimulates osteogenesis.

Studies have shown that the claimed composition contains herbal remedies that act on the central regulatory mechanisms of the hormonal background (growth hormone, insulin, parathyroid hormone, sex hormones, vitamin D, thyroid hormones T3 and T4, thyrotropin) and the tone of the sympathetic nervous system that transforms changes in function hypothalamic neurons in the regulatory effect on bone tissue. With the participation of neurotransmitters (neurotransmitters and neuropeptides), a coordinated interaction of nerve impulses and biochemical processes is achieved, which implements the regulatory effect of the nervous system on bone tissue.

In the regulation of cellular metabolism of bone tissue (stimulation of bone formation and resorption), prostaglandins play an important role, providing biochemical homeostasis and biomechanical stability of bone tissue.

The composition of the composition was determined by studying the numerous pharmacological properties of water extracts from more than 150 plants on models of various laboratory animals (anti-destructive, anti-inflammatory, stress-limiting, gonadotropic, hepatoprotective, corrective metabolism).

On these models, the most effective medicinal plants were determined, suitable for combining them together with the most pronounced effects on one or another link or several links in the pathogenesis of osteoporosis and aseptic necrosis.

Plants having the following properties were selected in the composition:

1. medicinal plants with anti-inflammatory properties: birch, veronica, long-leaf mint, peppermint, woodlice, licorice, willow, sage, blueberry, aspen, chamomile, senna, buckthorn, succession, hairworm, oregano, zyuznika, Ivan tea, hyssop , lemon balm, peony, wormwood, duckweed, bluehead, meadowsweet, thyme;

2. medicinal plants - hepatoprotectors: aspen, plantain, volodyushka, angelica, centaury, dentate, alfalfa, wormwood, repeshka, astragalus, licorice;

3. plants with an immunomodulatory effect: licorice, plantain, volodushka, gorse, gorse, angelica, cog, hyssop, red root, red brush, alfalfa, medunitsa, wormwood, groundnut, bluefin, currant, meadowsweet, thyme, echinacea;

4. medicinal plants that optimize tissue regeneration processes: licorice, bird highlander, plantain, coughweed, blood-red geranium, meadow geranium, forest geranium, gingerbread, golden rod, alfalfa, cuff, woodlice, picnic, cornstalk, currant, gum, astragalus ;

5. plants correctors of the functions of the endocrine glands (pituitary gland, adrenal glands, thyroid gland of the gonads): licorice, sage, blackberry, plantain, gorse, gingerbread, dentate, zyuznik, red root, red brush, alfalfa, cuff, currant, colza, meadowsweet, Chernobyl, echinacea, astragalus;

6. medicinal plants - vasoprotectants: pepper mountaineer, bird mountaineer, coughweed, window sill, astragalus;

7. plants with a stress-protective effect: long-leaf mint, peppermint, chamomile, sushnitsa, oregano, angelica, zyuznika, ivan-tea, red root, red brush, lemon balm, cuff, woodworm, peony, primrose, sapling, motherwort, blueberry , meadowsweet, thyme, Chernobyl;

8. plants with mineral-regulating properties: licorice, bird highlander, succession, blood-red geranium, meadow geranium, forest geranium, gingerbread, alfalfa, pikulnika, bedstraw, chickpea, currant;

9. Plants with proven cerebrovascular effect - astragalus, primrose, geranium, veronica, mint, currant, window sill, eye pupil;

10. The biological effects of the use of bee killing are manifested due to chitosan (bee colosan), which is an even more powerful biologically active substance than chitosan crustaceans. Its positive role in the regulation of all types of metabolism, strengthening, anti-inflammatory, adaptogenic, tonic, regulating the function of the endocrine and nervous systems has already been proven.

The results of experiments proving the regeneration of bone and cartilage tissue under the influence of the composition.

Materials and methods . The studies were conducted on males and females of mice of the Balb / c line of 2 months of age weighing 20 g (Stolbovaya Nursery, RAS). Mice were kept under standard conditions, 5 animals in a cage with controlled temperature (24 ° C) and lighting (for 12 hours) and with free access to water and food. To simulate experimental osteoporosis, a synthetic glucocorticoid prednisolone was used, which was administered to IM mice at a dose of 1 mg / mouse for 14 days. The dose of prednisolone administered was selected based on published data (Valeeva et al., 2002).

All animals were divided into 6 groups of 10 mice each (5 females +5 males). 1 - control group - intact mice. The animals of the remaining 5 groups were injected with prednisone. Animals of the 2nd group were killed using cervical dislocation 14 days after the 14-day administration of prednisolone. The femurs were removed, which were used for histological analysis and morphological assessment of the initial severity of the pathological process. Animals of the 3rd group after a 14-day administration of prednisone for 30 days received daily portions of porridge, which served as the basis for feeding the claimed funds. Animals from 4 to 6 groups at the same time received porridge with the claimed drug in different doses: 5.0, 50 and 250 mg / mouse. At the end of the course of taking the claimed funds, a histological analysis of the femurs was performed.

The bones of mice of all 6 groups were fixed in 10% formalin prepared on phosphate-buffered saline (PBS, 0.02 M, pH7.6) for 24 hours at room temperature. It was decalcified in 5% trichloroacetic acid for 24-48 hours, then washed in PBS and frozen in isopentane at -40 ° C. Next, sections with a thickness of 10 μm were prepared on a Leyca cryostat (Germany). Slices were dried at room temperature for 1 hour and stained with hematoxylin-eosin followed by image analysis using an Olympus Vanox AN BT3 light microscope (Germany), magnification (× 100) or (× 200). Images were photographed and morphological analysis of cells was performed in the field of view. To determine the significance of the differences between experience and control, the nonparametric two-sided Mann-Whitney test (U-test) was used.

Results. Analysis of histological data showed that a 14-day administration of prednisolone causes pronounced changes in both the cartilaginous tissue of the heads of the femurs of mice and directly bone tissue (FIG. 1-10). In the figures presented, the numbers indicate the following elements: 1 - bone marrow, 2 - perichondrium, 3 - chondroblasts, 4 - collagen fibers (matrix), 5 - blood vessels, 6 - chondrocytes, 7 - compact bone, 8 - osteocytes, 9 - breaks bone tissue, 10 - osteoblasts.

As can be seen from FIG. 2, under the influence of prednisolone, the proliferative activity of chondrocytes is significantly enhanced (112 ± 7) compared with the control group of animals that did not receive injections of prednisolone (12 ± 4,) FIG. 1 significance of differences between the experimental and control groups: M ± SEM; p <0.05.

A feature of articular cartilage in comparison with other types of tissues in the body is the presence of a small number of cells surrounded by a large area of intercellular space - a matrix represented by collagen fibers and the main substance. The increase in the number of chondrocytes occurs due to the extracellular matrix, which leads in the future to their qualitative changes.

After 30 days in the 3rd group of animals that received porridge without the declared means, the number of chondrocytes slightly decreased (83 ± 6, FIG. 3) compared with the 2nd group of animals slaughtered 14 days after the introduction of prednisolone. The claimed agent, taken at a dose of 5.0 mg / mouse, had a mild corrective effect on the cartilage tissue (the number of chondrocytes was 52 ± 6, FIG. 4). The restoration of hyaline cartilage almost to normal was observed when taking the claimed funds in doses of 50 and 250 mg / mouse (8 ± 3 and 20 ± 7, respectively, FIG. 5 and 6). The significance of differences between the experimental (5th and 6th) and control (2nd) groups was M ± SEM; p <0.05. They were the same for males and females.

The claimed agent at a dose of 250 mg / mouse had a corrective effect on bone tissue (FIG. 7-10). Under the action of the claimed funds was observed restoration of bone tissue to indicators of control animals (FIG. 7, 10). 14 days after the administration of prednisolone in the bone tissue, numerous sections of the gap were revealed (FIG. 8), which did not disappear even 30 days after the injection (FIG. 9). In addition, 14 days after the introduction of prednisone in the bone tissue, a random orientation of collagen fibers (FIG. 8) was detected, whereas after taking the claimed agent (FIG. 10), their location was similar to that of control intact animals (FIG. 7).

The positive effect of the claimed funds was also found by differences in the appearance and behavior of mice in the main groups of animals compared with mice of the 3rd group who did not take the drug.

Undesirable side effects when taking the claimed funds were not observed.

Clinical trials have been conducted in patients with osteoporosis with various pathologies.

Example 1

Patient V., male, born 1970

Diagnosis: Bilateral aseptic necrosis of the femoral heads on the right, II-III centuries, on the left, I centuries. Osteopenia, clinically significant (T = -2.3, Z = -2.3). The development of osteopenia as one of the complications of chemo- and radiation therapy of mediastinal B-cell lymphoma.

The claimed agent (Composition 1) was prescribed at the rate of 5 tablets of 0.5 g 3 p. day.

The following dynamics was noted (see Tables 1 and 2). Table 1 shows the dynamics of blood counts; table 2 shows the results of ultrasonic densitometry (OmniSense 7000S).

MPT in dynamics from 07/09/2014 - 12/30/14 - the width of the joint spaces narrowed more to the right. GBK on the right is flattened with marginal growths; in the upper section, sections of usuration and reconstruction of the bone structure are preserved. Diffuse edema of the bone marrow of the neck and head of the right femur is less pronounced. In the upper part of the GBC on the left, the site of bone marrow edema decreased from 1.4 x 1.1 cm to 1.4 × 0.7 cm.

Example 2

Patient K., female, b. 1956

Diagnosis: aseptic necrosis of the femoral head on the left, stage II. Clinically significant osteopenia (T = -2.2 Z = -1.2); D-deficiency, type II-III.

The development of osteopenia on the background of surgical menopause with 48 liters. In 2004, the extirpation of the uterus with appendages was performed.

The following dynamics of blood indices was noted (see table 3). Ultrasonic densitometry (OmniSense 7000S) is shown in table 4. Against the background of the therapy, the composition contains: the claimed agent (composition 2) 5 tablets of 0.5 g 3 r. day; compliance with the orthopedic regimen. The dynamics of treatment are illustrated in tables 3 and 4.

On a series of X-ray diffraction patterns of TBS 2014 - Rg-picture without negative dynamics. On the right is perichondral sclerosis, GBK with even, clear contours, the structure is homogeneous. To the left, GBK is deformed, with bone growths along the edges of the articular surfaces, is heterogeneous due to edge defects with a sclerosis zone around, sizes from 7 to 13 mm, with no tendency to increase. The joint gap is unevenly narrowed to 3 mm on the left.

Example 3

Patient K.N.G., female, b. 1968

Diagnosis: hypertension 2 tbsp., Risk 3. CHD: angina pectoris. FC II. Atherosclerotic cardiosclerosis. XCH-I. FC-1. Hypercholesterolemia. Chronic cholecystitis, remission. Hepatitis C. Pancreatic steatosis. Obesity 3-4 tbsp. Urolithiasis disease. Hyperuricemia Fibrocystic mastopathy. Multiple uterine fibroids. Endometriosis Bilateral aseptic necrosis of the femoral heads on the left, stage II, on the right, stage I-II.

Clinically significant osteopenia, T-2.9; Z-2,3; D-deficiency type I-II.

Against the background of therapy in the composition: the claimed drug 5 tablets of 0.5 g 3 p. day; compliance with the orthopedic regimen.

The following dynamics of blood indices was noted (see table 5).

Ultrasonic densitometry (OmniSense 7000S) is shown in table 6. Series of TBS radiographs in 2014 - the joint spaces of the right and left hip joints are significantly and unevenly narrowed. The surfaces of the acetabulums are sclerosed, the contour is rough, the arches are flattened (more to the left), bone growths along the edges. The femoral heads are flattened along the upper contour, mushroom-shaped, flattened correspondingly to the depression, the contour is uneven, and the necks are shortened. In the structure of the femoral heads, the phenomena of small-cystic cystic bone remodeling (more on the left). In the structure of the bone tissue of the left GBK, the reduction in the area of small-cystic cystic reconstruction from 2/3 to 1/3 GBK.

Example 4

Patient I., b. 1945

Diagnosis: postmenopausal osteoporosis, T - -5.4; Z-3.2, the risk of injury is 99%. Against the background of therapy in the composition: the claimed drug 5 tablets of 0.5 g 3 p. day.

The following dynamics of blood indices was noted (see table 7). Ultrasonic densitometry (OmniSense 7000S) is shown in Table 8. General weakness decreased; lack of pain in the bones of the leg, knee joints. Increased physical activity.

The data obtained indicate the promising use of the developed composition in the complex non-surgical treatment of degenerative-dystrophic lesions of the joints and osteoporosis, as well as in the rehabilitation of patients suffering from them. The specified composition can be used as a dietary supplement for the prevention of degeneratively degenerative diseases.

Cited literature.

1. Lang FP, Huang H, Huang H, Huang KQ, Zhang JC. Retrospective analysis of therapeutic efficacy in 1 425 cases of femoral head necrosis. // Zhonggou Gongcheng Yanjiu yu Linchuang Kangfu 2008; 12 (33): 6500-6504 (China).

2. Valeeva I.E., Ziganshin L.E., Burnashova Z.A., Ziganshin A.U. The effect of dimephosphone and xidiphon on lipid peroxidation and the antioxidant system of rats treated with prednisone for a long time. // Experimental and clinical pharmacology. 2002.Vol. 65, No. 2. S. 40-43.

3. Chen Y, Huang K, Lang F, et al. Experimental study on cheng zai wan for treatment of necrosis of the femoral head. J Tradit Chin Med 2003; 23 (4): 292-298.

4. Harris WH. Traumatic arthritis of the hip after dislocation and acetabular fractures: treatment by mold arthroplasty. An end-result study using a new method of result evaluation. // J Bone Joint Surg Am. 1969 Jun; 51 (4): 737-55.

5. Zaitseva O.P. Errors and complications of hip arthroplasty // Autoref. diss. Cand. honey. Science. - Kurgan, 2009.

6. Davydov D.V. Treatment and prevention of hip joint failure // Joint Abstract of the dissertation for the degree of Doctor of Medical Sciences - Moscow, 2010 - 15 p.

7. Mironov SP., Rodionova S.S., Kolondaev A.F., Nuzhdin V.I., Popova T.P., Klyushnichenko I.V. The method of pharmacological correction of bone metabolism to improve the results of hip replacement // Osteoporosis and osteopathy - 2006 - No. 3: 44-47.

8. Corbett KL, Losina E, Nti AA, Prokopetz JJ, Katz JN. Population-based rates of revision of primary total hip arthroplasty: a systematic review // PLoS ONE - 2010 - vol. 5, issue 10, P. e13520.

9. Singh JA, Kundukulam JA, Bhandari M.A. systematic review of validated methods for identifying orthopedic implant removal and revision using administrative data // Pharmacoepidemiol Drug Saf. - 2012 - Jan; 21 Suppl 1 P. 265-73.

10. Lin T, Yan SG, Cai XZ, Ying ZM. Bisphosphonates for periprosthetic bone loss after joint arthroplasty: a meta-analysis of 14 randomized controlled trials // Osteoporos Int - 2012 - Jun; 23 (6) P. 1823-34.

Claims (3)

1. Composition for the restoration of cartilage and bone tissue in osteoporosis, containing a powder of dried plants selected from the group: birch, mint, willow, aspen, bird highlander (knotweed), plantain, chamomile flowers, lemon balm, sushnitsa, a series of tripartite crushed bee powder , characterized in that the composition additionally contains veronica grass, water pepper (pepper), grass, golden grass, geranium blood-red grass, geranium forest grass, geranium meadow grass, lilac loosestrife grass, gorse dyeing tr wu, common sorrel grass, oregano common grass, angelica officinalis root, blackberry grass, golden shank grass, centaury umbelliferous grass, dentate late grass, European bark grass, ivan tea (fireweed narrow leaved) leaf, hyssopa medicinal grass, red root root, red brush root, buckthorn bark, alfalfa grass, common grass cuffs, lungwort grass, woodlice grass, peppermint long leaf grass, peppermint leaf, primrose grass, picnic grass, peony root, bedstraw tenacious grass, podoro nickel of a large leaf, wormwood of God's tree grass, sapling grass, motherwort grass, common grass repeller, duckweed small grass, senna leaf, bluehead grass, currant leaf, common grass, grass colza grass, meadowsweet (meadowsweet) color and grass, thyme , a series of drooping grass, blueberry shoots, Chernobyl grass, clary sage grass, Echinacea purpurea grass, licorice roots, astragalus grass, dead bees, chopped finely in the following ratio, wt.%.

2. The composition according to p. 1, characterized in that it has the form of tablets of 0.5-1.0 grams 3. The composition according to p. 1, characterized in that its daily dose is 7-8 grams.

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