Pharmacological composition for treating secondary amyloidosis

FIELD: medicine.

SUBSTANCE: oral pharmacological composition for treating secondary amyloidosis contains alkaloid curcumin, betulin and piperine taken in certain proportions.

EFFECT: composition is effective for treating secondary amyloidosis.

 

The invention relates to pharmacology and medicine and is intended for the treatment of secondary amyloidosis.

Known drug "Fluorouracil" /7/, which is a white or slightly yellowish slightly soluble in water and in alcohol crystalline powder, which is an antimetabolite, antitumor activity which is determined by its transformation into cancer cells in a competitive inhibitor involved in the synthesis of nucleic acids. This drug by intravenous injection is used in inoperable and recurrent gastric cancer, cancer of the colon and rectum, breast, ovary, and pancreas, however, the drug is highly toxic and its use may cause bone marrow suppression, diarrhea, loss of appetite, vomiting, ulcerative stomatitis. In addition, this drug is contraindicated in General condition of the patient, gastric ulcer and duodenal ulcer, severe functional liver failure.

Famous drug melphalan used for the treatment of amyloidoses. Thus for the treatment of amyloidoses apply intermittent scheme as melphalan - toxic medicine and among long-term consequences of its use may develop a second tumor (acute leukemia or myelodysplastic Sindh�Ohm. More sparing scheme is the use of melphalan every 4-6 weeks, 7-day course (0.15 mg/kg body weight) in combination with prednisolone (0.8 mg/kg body weight). Treatment for a long period, at least 1 year. The worse results of treatment in patients with chronic heart failure (CHF) and significantly better in patients with nephrotic syndrome. So, the patients that responded to treatment, the life expectancy of up to 5 years. /8/

Also known drug "Calepin" for the treatment of amyloidoses. However, the drug has a very pronounced side effects, and it does not have sufficient therapeutic effect, see the Internet site www.bsmu.by A. E. Makarevich, N. And. etc., "Amyloidosis of the heart: pathomorphology, clinic, diagnostics, differential diagnosis, treatment", Belarusian state medical University, the 10th clinical hospital of Minsk/.

Also known derivatives of tri-n-aminodiphenylamine, such as tetramethylene, pentamethylene and hexamethylene derivatives / EN JNs 2257200, 2004/. The disadvantages of this drug is short term, low efficiency in the treatment of several tumors, low efficiency in the treatment of amyloidoses and relative toxicity.

Object of the invention is the creation of a pharmaceutical composition for treating amyloidosis, which allows to increase therapeutic �effect and reduce (eliminate) toxic effect and the occurrence of harmful side effects when using it.

The invention consists in that the pharmaceutical composition for the treatment of secondary amyloidosis, intended for oral administration, comprises an alkaloid curcumin in an amount of 200 mg as the basis, piperine 20 mg as a potentiating agent that improves the bioavailability and betulin 10 mg as a stabilizer of the membrane of liposomes.

Curcumin is a biologically active agent with multiple effects. He intensively investigated as an anticancer drug for the treatment of some forms of cancer. In the experiment in vitro on cell cultures curcumin is able to induce apoptosis in cancer cells without cytotoxic effects on healthy cells [1-3]. It is known that curcumin has antioxidant and anti-inflammatory effects. Explores antidepressant properties of curcumin, which is comparable to the efficacy of tricyclic antidepressants. It is assumed that the antidepressant effect of curcumin is mediated through the inhibition of monoamine oxidase [4].

In addition, curcumin is a potential therapeutic agent for the treatment of Alzheimer's disease, the pathogenesis of which is accumulation in brain tissue of certain species of amyloid protein [5, 6].

Curcumin, administered in pure form per os, has a low bioavailability, which �that the use of high doses. It is on the basis of this pharmacological composition and method of its liposomal packaging, consisting of three components.

Curcumin is in an amount of 200 mg - based composition, is a fine yellow powder. Is the main curcuminoid, which is part of the turmeric root.

Piperine 20 mg is an alkaloid found in various kinds of pepper. Is potentiating agent, which allows to increase the bioavailability.

Betulin in the amount of 10 mg - crystalline organic substance contained in large quantities in the cells of the pith tissue in the bark of a birch. A powerful antioxidant, it stabilizes the lipid membrane of liposomes.

To improve the bioavailability of the pharmaceutical composition used liposomal delivery method. Liposomal delivery method of the composition is carried out by processing the ultrasound component composition at a frequency of 40 kHz, thermal drying of the obtained substance for 48 hours in a thermostat at a temperature of 120°C and dispersing the mixture.

The obtained substance before use diluted in 1 ml of saline and injected per os 0.1 grams per day.

All substances that are included in the pharmaceutical composition are widespread and can be used in the produc�TVE in large volumes.

Experimental confirmation of protivoallergennoy activity of curcumin with the development of secondary amyloidosis was conducted on 48 white outbred male rats kept in standard conditions of vivarium Amur GMA. The animals were divided into intact and experimental group. Experimental group was divided into 2 subgroups: control and experimental. In each subgroup to 16 animals.

The experimental group was simulated secondary systemic amyloidosis the introduction of native egg albumin with the complete adjuvant of franda, in our modification in the dose of 1 ml intraperitoneally for 30 days by entering the amyloidogenic substatio through days (15 doses). Criteria for the development of amyloidosis served: dysproteinemia, change of cytokine profile, histologically positive staining kangaroom with the use of polarized light microscopy, hematoxylin and eosin. Systemic amyloidosis was simulated for 30 days. With 31 days of the experiment daily for 15 days the test group was administered per os pharmacological composition is dissolved in the form of an emulsion in 1 ml of physiological solution, 0.1 grams a day, and control group, saline per os at a dose of 1 ml within 15 days.

45 the day of the experiment all animals were removed from the experiment in compliance with the requirements of humanity, with�their request No. 4 to the Application to carry out work with experimental animals (Annex to order of the USSR Ministry of health No. 755 from 12.08.1977 "On the procedure for euthanasia (the right of killing an animal)". For biochemical studies took the serum, morphological studies were taken lungs, kidneys, liver, spleen, heart. Determination of the cytokine profile was performed by solid-phase ELISA on the car, "Anthos 2020", the fraction of proteins in the serum was determined by the method of pseudosections with concentrated solutions of dihydrophosphate sodium. For histology were preparing the preparations according to the standard method. In the future, paraffin blocks were made serial sections with a thickness of 5 μm. For optical microscopy were used routine stained with hematoxylin and eosin, which were estimated General structure of the gland, the presence or absence of inflammation, damage and repair of cells. To assess the presence of amyloid protein, its localization was used paint kangaroom, including with the use of polarization filters

In the study of cytokine profile,the level of proinflammatory cytokines IL-6, TNF-alpha increased in the control group in 2 times in comparison with the group treated with the drug, and in 3 times in comparison with the intact group. According to electrophoresis, the amount of alpha-2 globulins, gamma-globulins in 1 and 2 times lower in the experimental group compared with the control group, the decrease in the level of albumin in 1.5 times the control group compared with the group sex�of awsa pharmacological substance. According to the histological study of the lesions of amyloidosis was found in all subgroups of the experimental group. In the lungs, liver and kidneys of the control group density lesions of amyloidosis is 4-5 times higher than in the group treated with a pharmacological substance. In the spleen and heart are statistically significant differences between subgroups were found.

The increase in the number of Pro-inflammatory cytokines speaks of actively penetrating the inflammation under simulated pathology, reducing the amount of cytokines in the action of pharmacological substances reduce phase inflammatory response, possibly through the suppression factor signal transduction STAT-3. The increase in the number of alpha-globulins and gamma-globulins and a decrease in albumin in the blood serum of the control subgroups indicates chronic inflammation and nephrotic syndrome and increase of resistance in treated groups developed a pharmacological composition based polyphenol curcumin. We identified a dose-dependent nature of the pharmacological action of the composition in treatment of systemic amyloidosis, in the absence of side effects in the laboratory animals.

The technical result of the invention is that the components of the pharmaceutical composition in aggregate�ti potentiate the effect of each other, to reduce the recommended when the target application, the amounts of active ingredients necessary to achieve adequate therapeutic action of the composition as a whole, and thereby reduce the risk of side effects of active components of the composition, and to ensure the effectiveness of the treatment without compromising its quality. In addition, the choice of quantitative composition of the stabilizing agent is provided by an appropriate shape of the drug delivery composition, which allows to potentiate the biological effects exerted.

Thus, the developed farmakologicheskaya the composition has a high efficiency, the composition includes natural ingredients, it is easy to combine with other drugs in combination therapy, is easy and convenient for the patient admission scheme.

SOURCES of INFORMATION

[1] Dhillon, Navneet; et al. (2008). "Phase II Trial of Curcumin in Patients with Advanced Pancreatic Cancer". Clinical Cancer Research 14 (14): 4491-4499. DOI: 10.1158/1078-0432. CCR-08-0024.

[2] Patel, Vaishali B.; SabeenaMisra, Bhaumik B. Patel, Adhip P N Majumdar. (2010). "Colorectal cancer: chemopreventive role of curcumin and resveratrol". Nutrition and Cancer, 62 (7): 958-967.DOI:10.1080/01635581.2010.510259. ISSN 1532-7914.

[3] ↑ Curcumin Inhibits Hypoxia-Inducible Factor-1 by Degrading Aryl Hydrocarbon Receptor Nuclear Translocator: A Mechanism of Tumor Growth Inhibition (eng.). Molecular Pharmacology (2006).

[4] S. Kulkarni, A. Dhir, Akula KK. Potentials of curcumin as an antidepressant. // The Scientific World Journal. - Nov 2009. - No. 9. - P. 1233-1241. - PMID 19882093.

[5] Hishikawa N, Takahashi Y, Y. Amkusa Effects of turmeric on Alzheimer's disease with behavioral and psychological symptoms of dementia. Ayu. 2012 Oct; 33(4):499-504

[6] Wang Y, Yin H, Wang LCurcumin as a potential treatment for Alzheimer's disease: a study of the effects of curcumin on hippocampal expression of glial fibrillary acidic protein. Am J ChinMed. 2013; 41(1):59-70.

[7] Mashkovsky M. D. Medicines, Moscow, LLC "New Wave, 2002, V. 2, p. 425 Med. Oncol. 1999. - 16 (2) - p. 104-109.

Pharmacological composition for the treatment of secondary amyloidosis, intended for oral administration, comprising an alkaloid curcumin in an amount of 200 mg, betulin in the amount of 10 mg and piperine (20 mg as a potentiating agent that improves the bioavailability.



 

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,

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17 cl, 1 dwg, 6 tbl, 13 ex

FIELD: food industry.

SUBSTANCE: inventions group relates to food industry and may be used for drinking water production. For the said purpose water is drawn from a natural source, settled with access of atmospheric oxygen in 20-40 m3 vessels during 10-15 h and treated by way of passing through a device having an external and an internal cylinders. Water passes through the central cavity of the device from the dropping pipe and is whirled by counterflows spiralwise in the magnetic pipe. Then one proceeds with treatment with fullerenes by way of passing water through a cylindrical device containing an internal cylinder with holes whereto one periodically adds preliminarily prepared source water with hydrated fullerenes C60HyFn, such water produced as follows: into a 2 l flask one pours 2 l of source water and adds hydrated fullerene in a concentration of 14.4mg/l; the flask is rotated during 1 min counter-clockwise at a rate corresponding to a funnel formation. Then the water is settled during 2 min and repeatedly rotated during 30 sec and then again settled during 2 min; one takes 1 ml of the resultant solution and pours it into 1 l of source water; the procedure is repeated until production of a solution of fullerenes C60HyFn with concentration equal to 10-20 mol/l. the produced drinking water is bottled. A device for drinking water production is additionally produced.

EFFECT: inventions group ensures production of water suitable for regular consumption by man and having improved taste and organoleptic properties.

2 cl, 1 dwg, 1 tbl, 2 ex

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