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All about Taxifolin

The bioflavonoid dihydroquercetin (taxifolin) is the most promising natural antioxidant. The initial raw material is the wood of Siberian and Dahurian larches which grow abundantly and can provide steady supply.

The antioxidative activity of taxifolin exceeds that of most common antioxidants such as tocopherols (vitamin E) and carotenoids (vitamin A). In addition, taxifolin is much more resistant to the effects of oxidation and light.

Health benefits of taxifolin include capillary, liver, and radiation protection. By «trapping» free radicals, taxifolin helps to protect the body against adverse environmental factors. Regular consumption of taxifolin helps to sustain antioxidant reserves in the human body. Exhaustion of these reserves may be caused by an unbalanced diet and environmental factors. As a consequence, the human organism experiences oxidative stress, which may result in different pathologies.

The daily physiological need for bioflavonoids (natural antioxidants) equates to 150-250 mg for children over 7 years of age and 200-250 mg for adults (according to Guidelines MR 2.3.1.2432 −08 Physiological Needs for Energy and Nutrition of Different Population Groups within the Russian Federation).

Toxicological studies demonstrated that taxifolin is non-toxic and produces no side effects in human organism.

Daily consumption of taxifolin helps to maintain the body’s physiological functions at high levels.

Taxifolin Activity

Dihydroquercetin (taxifolin, 3,5,7,3’,4’-pentahydroxyffavanone) /CAS No. 480-18-2/ is one of the most powerful antioxidants of natural origin.

Dihydroquercetin was discovered in 1936, by Albert, an American biochemist. Since then, its biological and antioxidative activities have been studied for several decades. More active than tocopherol and carotene, it is also more stable. Dihydroquercetin belongs to a limited flavanone class of flavonoid compounds. It is a fine crystalline or amorphous powder of white to white-cream color depending on the method of preparation and the presence of other substances.

Dihydroquercetin has a good solubility in acetone, methyl and ethyl alcohol, 1,2-propylene glycol, acetic ether, and hydrocarbons, but is insoluble in chloroform, sulphuric ether, and hydrocarbons. The solubility in water increases when more pure dihydroquercetin is used. While conventional commercial products have a solubility of 0.1 percent by weight at 20oC and 5.20 percent by weight at 90oC, highly purified dihydroquercetin provides more than threefold increase over these solubility levels (see below).

Basic Physical and Chemical Properties of Taxifolin

Molecular formula — С15Н1207

Molecular weight — 304.25 daltons

Melting point: 222 — 224oС. Buchi, Melting Point B-250

UV spectrum: λmax=289±2nm, log Emax=4.25±0.05.

A solution of 0.1 g of dihydroquercetin in 5 ml of 95% alcohol, with 0.5 ml of concentrated chlorohydric acid and 0.05 g of granulated zinc added, yields a crimson color, signifying the presence of the flavanoid (flavonoid qualitative test).

Although there are a considerable number of patents related to the extraction of dihydroquercetin, no adequate technology has been available to achieve the high purification of the substance until now. Solvent reprecipitation methods result in an amorphous product with a tar-like residue, which is impossible to identify. This is responsible for the low solubility of dihydroquercetin even in hot water.

Standard Chromatogram of Highly Purified Taxifolin

[pic]

Dihydroquercetin 99.6%

Aromadendrin 0.40%

Eriodictyol 0%

Naringenin 0%

Analysis Conditions:

Column: 4.6×250 mm, Kromasil-100-C18, 5 µm

Eluent: A — ACN/2%CH3COOH (30:70), B — 100% ACN

Gradient: from 100% A to 100% B in 13 min

Detection: UV-288 nm

Flow rate: 1 ml/min

Injection — 10 µl

Higher purity of dihydroquercetin result to significant impact on its physical and chemical properties. Dihydroquercetin, as part of bioflavonoid complex, differs from the other known products because of its ability to become crystallized in highly pure state.

Taxifolin Crystals:

 

 

 

 

 

 

 

The removal of foreign substances improves significantly its solubility as compared to the solubility of the other known products. Such significant modifications in physical and chemical properties show that dihydroquercetin manufactured using this new technology can be considered as new generation product with new technological possibilities and expanded applications.

Taxifolin — new possibilities in sports nutrition

Performance and endurance training, required in professional sports, is closely related to the training of one’s cardiovascular system in order to adapt it to exercise workload. This is especially important during the competition period, when physical demands are at their peak and athletes strive to push their limits.

An individual, undergoing intense physical training, utilizes oxygen at levels exceeding 75% of maximum values. The challenge here is that sustained physical exercise may result in an inadequate supply of oxygen to working muscles (known as tissue hypoxia), a result of insufficient blood supply to the tissues due to poor microcirculation.

Moreover, during maximal exercise, the metabolism of the tissue is violated. Muscles accumulate lactic acid, which causes fatigue and complicates recovery after training.

Studies show that the application of taxifolin is able to solve these problems very efficiently. Specifically, taxifolin is able to:

• Improve intracardial hemodynaimcs and intensify blood flow to the myocardium

• Help to return pathologic microcirculation to normal, thus, optimizing tissue blood flow

• Contribute to the redistribution of blood flow within small arteries, thus, enhancing blood supply to ischemia-affected tissues

• Enhance blood flow to muscles

• Enhance pulmonary mechanics and improve lung ventilation and blood gas composition

• Help to increase РО2 (oxygen partial pressure) and blood oxygenation

Studies of taxifolin were conducted during the training period of the Russian Olympic Team prior to the 2008 Olympic Games. The studies were supervised by S. A. Parastaev, M. D., a member of the medical commission of the Russian Olympic Committee, Professor of Physical Therapy, Sports Medicine, and Physical Education of the Russian State Medical University.

The studies showed that taxifolin can be utilized by professional athletes in daily doses of up to 100-200 mg during the training period, which requires aerobic and anaerobic endurance, as well as during the competition period when the workload is at its maximum.

When dissolved, taxifolin is rapidly and completely absorbed by the human body (bioavailability), thus promoting antioxidative activity.

We provide our own methods of qualitative and quantitative testing of taxifolin in premixes and in any type of end products. End product control is performed utilizing ultraviolet spectrophotometry and high performance liquid chromatography (HPLC) subject to the state reference standard (GSO No. 9054-20080).

Federal State Educational Institution of Higher Professional Training

RUSSIAN STATE UNIVERSITY OF PHYSICAL EDUCATION, SPORT AND TOURISM (RGUFKSMIT)

Sport Research Institute

RESEARCH REPORT

Effect of Taxifolin (Dihydroquercetin) on physical work capacity in top athletes practicing cyclic sports

Project Director S.K. Sarsania, M.D., Prof.

INTRODUCTION

Topicality of the research. Professional sport training and participation in competitions involve strenuous efforts and constantly growing training loads to be executed by athletes. For this reason we feel the need to detect and investigate specific factors, which may help improve physical work capacity in top athletes and speed up the recovery after training exertion. On the one hand, these factors are related to optimal planning of both competition and training loads according to biological adaptation laws with the use of pharmacological support. On the other hand, these factors comprise efficient recovery of the organism after physical training. The recovery process is based on well-balanced nutrition and intake of food supplements of high biological value and high metabolic capacity, which intensify the synthesis of morphological structures and activate favourable physiological reactions. In a long list of biologically active additives, we found it interesting to study a product with the trade name Taxifolin, chemical name (Dihydroquercetin)-98%, produced by the company "Taxifolia" Ltd., Belgorod (Registration #77.99.11.3.У.7914.8.09; date of registration 24.08.2009). A preliminary information study showed that this product might be called a model antioxidant free of admixtures (pitches, essential oils), its purity being not less than 98%. The base substance is found in the bottom part of Siberian larch and Dahurian larch [18].

Principal properties of Taxifolin:

• improvement of microcirculation;

• preventing thrombus formation;

• enhancement of work capacity and intensification of recovery processes after high physical and psycho-emotional loads;

• strengthening of capillary walls;

• bringing triglycerides and cholesterol concentrations in blood to normal level;

• improvement of coronary blood flow and myocardial contractility, normalization of excitability and conductivity in cardiomyocytes.

Hypothesis. Taking into account the ability of Taxifolin to protect capillaries and improve microcirculation, we suggest that the use of Taxifolin increases oxygen supply and utilization in skeletal muscles, thus resulting in development of aerobic capacities and growth of results in endurance sports.

Purpose. The purpose of our research was to estimate short-term and long-term effects of Taxifolin intake on aerobic capacity of working muscles, functional capacity of the cardiovascular system, and short-term recovery after maximal physical exertion.

Subjects. 5 top-class male athletes (Masters of Sport; Masters of sport, International Class) participated in the research. The age of the subjects varied from 23 to 28 years; all the subjects have been practicing skiing, cycling, and mountain running for many years.

Object of investigation: aerobic capacity of skeletal muscles and functional capacity of the cardiovascular system.

Principal tasks:

1. estimate short-term adaptive effects of Taxifolin intake on 1) functional capacity of the cardiovascular system at rest and 2) immediate recovery of physiological parameters after physical exertion;

2. estimate long-term adaptive effects of Taxifolin intake on 1) functional capacity of the cardiovascular system at rest and 2) immediate recovery of physiological parameters after physical exertion;

3. estimate short-term adaptive effects of Taxifolin intake on aerobic capacity of skeletal muscles;

4. estimate long-term adaptive effects of Taxifolin intake on aerobic capacity of skeletal muscles.

Expiration date — 3 years.

Application of Flavomix Taxifolin Premixes in Food

1. Antioxidant for various fat-containing food products (dairy, fish, meat, confectionary, etc.)

2. Therapeutic dietary supplements

Application of Flavomix Taxifolin Premixes in Dairy Products

Taxifolin (dihydroquercetin), registered in the RF National Standard — GOST R 52791-2007, has been approved for application in dairy products.

Taxifolin (dihydroquercetin), when used as an antioxidant in dairy products, performs two functions simultaneously:

ü Consumed with food, Taxifolin slows the body’s oxidation processes

ü Taxifolin also slows the oxidation process in foods, doubling or tripling normal shelf life.

Studies, conducted in the RF Dairy Research Institute, show that taxifolin, added to dairy products in amounts of 0.08% to 0.2% of the product’s fat mass, slows the oxidation process thus, reducing the accumulation of toxic substances resulting from oxidation. As a result, dairy products acquire more stability and a more than twofold increase of shelf life without alteration in their organoleptic properties. Only highly-purified taxifolin (≥98%), free from foreign substances, may be utilized in the dairy industry.

Dissolved taxifolin (premix) is convenient for integration in products at any stage of production.

A dairy product combined with 40 — 100 mg of dihydroquercetin acquires medicinal properties

Bibliography:

1. RF National Standard GOST R 52791-2007 ‘Canned Dairy Products. Powdered Milk.’ Specifications. Effective since 01/01/2009, eligible for early application.

2. Process Regulations. Osoboye Whole Cow’s Milk. Istra-Nutritsiya, RF, 1998

3. Dihydroquercetin protection of powdered milk against free radical oxidation. I. V. Babenkova, G. I. Klebanov, Yu. A. Kolesnik, and others. Biotechnology and Management periodical, 1994, No. 3-4, p. 254-256

4. Inhibition of free radical lipid oxidation in powdered milk by dihydroquercetin. I. V. Babenkova, G. I. Klebanov, Yu. A. Kolesnik, I. A. Radayeva, and others. Biotechnology and Management periodical,1995, No. 1, p. 36-39

RF National Standard GOST R 52791-2007 ‘Canned Dairy Products. Powdered Milk.’ Specifications. Effective since 01/01/2009, eligible for early application.

1. Process Regulations. Osoboye Whole Cow’s Milk. Istra-Nutritsiya, RF, 1998

2. Dihydroquercetin protection of powdered milk against free radical oxidation. I. V. Babenkova, G. I. Klebanov, Yu. A. Kolesnik, and others. Biotechnology and Management periodical, 1994, No. 3-4, p. 254-256

3. Inhibition of free radical lipid oxidation in powdered milk by dihydroquercetin. I. V. Babenkova, G. I. Klebanov, Yu. A. Kolesnik, I. A. Radayeva, and others. Biotechnology and Management periodical,1995, No. 1, p. 36-39

Application of Flavomix Taxifolin Premixes in Confectionary

Studies, conducted jointly by the Red October Moscow Confectionary Factory and the Sechenov Moscow Medical Academy, demonstrated that:

The inhibitory effect on lipid peroxidation, produced by a taxifolin dosage of 0.05% to 0.2% of the fat mass of the confection, will extend product shelf life by 250%.

The studies included the following products:

1. Primary components of sugar-based fat-containing confections (confectionary fat, cocoa butter, lipids of grated cocoa, lipids of cocoa powder, lipids of grated nut kernels, lipid fraction of powdered milk)

2. Finished confectionary products: chocolate (Pushkin’s Fairy Tales, Alenka, Jubilee Chocolate, Red October) and candies. The components listed under item a) constitute a part of these products in various proportions depending upon the recipe, i.e. the composition and quantities of lipid mass in the products varied.

The studies also showed that the confections containing taxifolin in amounts up to 1% of their fat mass, acquire distinctive medicinal effects, thus, chocolate becomes a parapharmaceutical product (e.g., Sibirsky chocolate with a taxifolin content of 0.75%).

Findings:

• Taxifolin antioxidative activity is manifested regardless of the nature or composition of lipid fractions in the confectionary components.

• Taxifolin antioxidative activity is not affected by confectionary components of a non-lipid nature.

• Taxifolin content in confections does not diminish over time with storage (Taxifolin catalytic effect).

• The presence of Taxifolin in confections in the amount up to 1% of the product’s fat mass does not affect organoleptic properties of the product.

• Only highly-purified taxifolin (≥96%) free from foreign substances (resins) may be utilized in confectionary.

Bibliography:

1. Confections containing dietary supplements. 1. Dihydroquercetin. Yu. A. Kolesnik, I. A. Rulenko, N. A. Tyukavkina, and others. Biotechnology and Management periodical, 1993, No. 3-4, p. 24-43.

2. Application of dihydroquercetin as antioxidative agent in confectionary products designed for medicinal purposes. A. M. Daursky, Yu. A. Kolesnik, I. A. Rulenko, and others. The 3rd International Symposium ‘Human Ecology: Challenges and Status of Therapeutic Nutrition’, Moscow, 1994, p. 189-192.

3. Biological activity of dihydroquercetin-containing confectionary products. A. M. Daursky, Yu. A. Kolesnik, I. A. Rulenko, and others. The 3rd International Symposium ‘Human Ecology: Challenges and Status of Therapeutic Nutrition’, Moscow, 1994, p. 198-200.

4. Sibirsky Chocolate — New Type of medicinal confection. The 3rd International Symposium ‘Human Ecology: Food and Food Processing’, Moscow, 1995, p. 293-294.

Application of Flavomix Taxifolin Premixes in Cosmetics and Perfumes

The Flavomix taxifolin premixes can be utilized in cosmetics and perfumes, specifically, to:

• Preserve raw material, oil and fat components, as well as the finished products

• Render therapeutic effects to products

The Flavomix taxifolin premixes, utilized in cosmetics:

• Enhance protective functions of the skin against external and internal toxicity, radiation, germs, and other environmental factors.

• Normalize general metabolic processes through topical application, specifically, those in lymphatic and blood system, thus, slowing skin aging.

The Flavomix taxifolin premixes are a promising component to be utilized in cosmetics intended for intensive care after:

• Dry and aging body and facial skin

• Sensitive skin prone to irritation and allergy

• Skin with weakened microcirculation

• Capillaropathy

The Flavomix taxifolin premixes, introduced in creams and shampoos, help to renew skin. Taxifolin-based hair conditioners contribute to the general health of hair and hair growth.

The Flavomix taxifolin premixes are quickly and completely absorbed by the skin, which maximizes their antioxidative effect.

Bibliography:

1. Use of flavonoids in hair protection and (or) enhancement of its mechanical properties. L’OREAL,FR 949405539,05.05.94.

2. Bioflavonoid-based hair cosmetics. L`OREAL.FR94905540 05.05.94.

3. Use of flavonoids to protect unstable active substances and ingredients in cosmetic and dermatologic products. Beiersdorf AG, DE944444238,13.12.94.

4. Substances curing hyperactive and hypoactive skin conditions and dermatitis. Beiersdorf AG, DE944444238, 13 Dec 94.

5. Use of flavonoids as immunomodulators or immune protectors in cosmetic and dermatologic products. Biersdorf AG, DE944444238, 13.12.94.

6. Cosmetic and medical preparations containing flavonoid-phospholipid complex. Enr.Pa+ Appl EP275.005(CL,CO779)10,20.07.88.) Bombardeli et al. Chem.Ab,v.111,1989. Gen.S u b Ind, 45279Z

7. Clinical studies of the dihydroquercetin-enriched drinking water efficiency. ‘Beauty Institute’ cosmetic center, Moscow, 2006

8. Assessing dynamics of blood microcirculation by laser Doppler flowmetry upon application of taxifolin-enriched body cream. The Peoples’ Friendship University of Russia, Moscow, 2004.

9. Studies of cosmetic and perfume products efficiency. ‘Cosmetology’ laboratory testing center, Moscow, 2006.

Application of Flavomix Taxifolin Premixes in Dietary Supplements and Pharmaceutical Products

Due to its powerful antioxidative and capillary protection activities taxifolin is most widely used in dietary supplements and pharmaceutical products. Taxifolin is compatible with vitamins, mineral complexes, and medicinal plant extracts.

Taxifolin’s proven biological effects include:

• Antioxidative activity

• Vitamin P activity

• Capillary protection: improving microcirculation and blood flow at the capillary level, promoting the development of new capillaries

• Helping to maintain blood pressure at physiological levels, providing a mild hypotension effect

• Improvement of the elasticity of red blood cells, reduction of blood viscosity

• Improvement of the coronary blood flow and myocardial contractility, reduction of the affected zone of the cardiac muscle

• Anti-ischemic effect

• Antidepressant effect

• Reduction of the low density lipoprotein levels in blood plasma

• Stomach protection

• Liver protection

• Immune system regulation

• Inactivation of cytotoxic substances

• Radiation protection

• Synergist to vitamins А, С, Е

Bibliography:

Free radicals scavenging and protection from peroxidation (extending life of cell membranes and organelles):

1. Dihydroquercetin — new antioxidant and capillary protector. V. K. Kolkhir, N. A. Tyukavkina, V. A. Bykov, and other. Chemical & pharmaceutical periodical, 1995, No. 9, p. 61-64.

2. Antioxidative activity of dihydroquercetin. Yu. O. Teselkin, B. A. Zhambalova, I. V. Babenkova, G. I. Klebanov, N. A. Tyukavkina, Biophysics guide, 1996, Vol. 41, No. 3, p. 620-624.

3. Natural flavonoids as food antioxidants and dietary supplements. N. A. Tyukavkina, I. A. Rulenko, Yu. A. Kolesnik. Nutrition Issues periodical, 1996, No. 2, p. 33-38.

4. Interaction of flavonoids with 1,1-diphenyl-2-picrylhydrazyl free radical, liposomal membranes and soybean lipoxygenase-1. Ratty A.K, Sunamoto J., Das N.P., Biochem. Pharmacol., 1988, Mar 15;37(6), p.989-995.

5. Protection against oxidative damage by dihydroflavonols in Engelhardtia chrysolepis. Haraguchi H., Mochida Y., Sakai S., Masuda H., Tamura Y., Mizutani K., Tanaka O., Chou W.H., Biosci. Biotechnol. Biochem., 1996 Jun;60(6), p.945-948.

6. Effects of flavonoids on nonenzymatic lipid peroxidation: structure-activity relationship. Ratty A.K., Das N.P., Biochem. Med. Metab. Biol. 1988, Feb;39(1), p.69-79.

7. How flavonoids inhibit the generation of luminol-dependent chemiluminescence by activated human neutrophils. Hart B.A., Ip Via Ching T.R., Van Dijk H., Labadie R.P., Chem. Biol. Interac.t 1990, 73(2-3), p.323-335.

8. Mutagenicities of 61 flavonoids and 11 related compounds. Nagao M., Morita N., Yahagi T., Shimizu M., Kuroyanagi M., Fukuoka M., Yoshihira K., Natori S., Fujino T., Sugimura T., Environ. Mutagen., 1981, No 3(4), p.401-419

Inactivation of cytotoxic substances

1. Flavonoids as inhibitors or enhancers of the cytotoxicity of tumor necrosis factor-alpha in L-929 tumor cells. Habtemariam S., J. Nat. Prod., 1997, Aug;60(8), p.775-778.

2. Differences in the serum levels of acetaldehyde and cytotoxic acetaldehyde-albumin complexes after the consumption of red and white wine: in vitro effects of flavonoids, vitamin E, and other dietary antioxidants on cytotoxic complexes. Wickramasinghe S.N, Hasan R., Khalpey Z., Alcohol. Clin. Exp. Res., 1996 Aug, No 20(5), p.799-803.

Antidiabetic Activity

1. Inhibition of aldose reductase and sorbitol accumulation by astilbin and taxifolin dihydroflavonols in Engelhardtia chrysolepis. Haraguchi H., Ohmi I., Fukuda A., Tamura Y., Mizutani K., Tanaka O., Chou W.H., Biosci. Biotechnol. Biochem., 1997, Apr, No 61(4), p.651-654.

2. An intensely sweet dihydroflavonol derivative based on a natural product lead compound. Nanayakkara N.P., Hussain R.A., Pezzuto J.M., Soejarto D.D., Kinghorn A.D., J. Med. Chem. 1988, Jun, No 31(6), p. 1250-1253.

Reduction of low-density lipid concentrations in liver and blood plasma without affecting body’s own antioxidant enzyme systems

1. Effect of astilbin in tea processed from leaves of Engelhardtia chrysolepis on the serum and liver lipid concentrations and on the erythrocyte and liver antioxidative enzyme activities of rats. Igarashi K., Uchida Y., Murakami N., Mizutani K., Masuda H., Biosci. Biotechnol. Biochem., 1996, Mar, No 60(3), p.513-515.

Antitumor activity

1. Inhibitory effects of flavonoids on Moloney murine leukemia virus reverse transcriptase activity. Chu S.C., Hsieh Y.S., Lin J.Y., J. Nat. Prod., 1992. Feb., No 55(2), p.179-183.

2. Differential inhibition of proliferation of human squamous cell carcinoma, gliosarcoma and embryonic fibroblast-like lung cells in culture by plant flavonoids. Kandaswami C., Perkins E., Drzewiecki G., Soloniuk D.S., Middleton E. Jr., Anticancer. Drugs, 1992, Oct., No 3(5), p.525-530.

3. In vitro effects of natural plant polyphenols on the proliferation of normal and abnormal human lymphocytes and their secretions of interleukin-2. Devi M.A., Das N.P., Cancer. Lett., 1993, May, No 69(3), p.191-196.

Antimutagenic effect

1. Inhibition of the mutagenicity of bay-region diol-epoxides of polycyclic aromatic hydrocarbons by phenolic plant flavonoids. Huang M.T., Wood A.W., Newmark H.L., Sayer J.M., Yagi H., Jerina D.M., Conney A.H., Carcinogenesis, 1983, Dec. No4(12), p.1631-1637.

Radiation protection

1. Pharmacological and radiation protection activities of some gamma-pyrone derivatives (flavanones and flavanols). T. Yu. Il’yuchenok, A. I. Khomenko, L. M. Frigidova, and others, Pharmacology and Toxicology periodical, 1975, 38, № 5, с.607-612.

Antiviral effect

1. Effect of antiviral substances on hepatitis A virus replication in vitro. Biziagos E, Crance J.M., Passagot J., Deloince R., J. Med. Virol., 1987, May, No22(1), p.57-66.

Immune regulation (anti-allergy effect) and anti-inflammatory activity

1. Kinetics of the inhibitory effect of flavonoids on histamine secretion from mast cells. Bronner C., Landry Y., Agents Actions, 1985, Apr. No16(3-4), p.147-151.

2. T. Yu. Il’yuchenok, A. I. Khomenko, L. M. Frigidova, and others, Pharmacology and Toxicology, 1975, Volume 38, No. 5, p. 607.

3. Comparison of the effects of quercetin with those of other flavonoids on the generation and effector function of cytotoxic T lymphocytes. Schwartz A., Middleton E.Jr., Immunopharmacology, 1984, No 7(2), p.115-126.

Normalizing influence on cell enzyme systems

1. Effects of flavonoids on enzyme secretion and endocytosis in normal and mucolipidosis II fibroblasts. Vladutiu G.D., Middleton E. Jr., Life Sci., 1986, Aug, No 25;39(8), p.717-726.

Low mutagenic activity and toxicity:

1. Pharmacological and radiation protection activities of some gamma-pyrone derivatives (flavanones and flavanols). T. Yu. Il’yuchenok, A. I. Khomenko, L. M. Frigidova, and others, Pharmacology and Toxicology periodical, 1975, 38, No. 5, p. 607-612.

2. Natural flavonoids as food antioxidants and dietary supplements. N. A. Tyukavkina, I. A. Rulenko, Yu. A. Kolesnik. Nutrition Issues periodical, 1996, No. 2, p. 33-38.

3. Study on the mutagenic activity of 13 bioflavonoids with the Salmonella Ara test. Jurado J., Alejandre-Duran E., Alonso-Moraga A., Pueyo C., Mutagenesis, 1991, Jul., No6(4), p. 289-295.

4. Mutagenicities of 61 flavonoids and 11 related compounds. Nagao M., Morita N., Yahagi T., Shimizu M., Kuroyanagi M., Fukuoka M., Yoshihira K., Natori S., Fujino T., Sugimura T., Environ. Mutagen., 1981, No3(4), p. 401-419.

5. Quercetin and DNA in solution: analysis of the dynamics of their interaction with a linear dichroism study. Solimani R., Int. J. Biol. Macromol., 1996, No18(4), p. 287-295.

6. Mutagenic activity of quercetin and related compounds. Bjeldanes L.F., Chang G.W., Science, 1977, Aug., No 5, 197(4303).,p.577-578.

Application of Flavomix Taxifolin Premixes in Agriculture

The Flavomix taxifolin premixes may be utilized as a plant growth regulator.

The premixes used in animal feed not only serve as a dietary supplement improving cardiovascular and immune systems, but also act as an antioxidant for fats and oils contained in the feed.

Bibliography:

1. Vitamins / under the editorship of M. I. Smirnov — M.: Medicine, 1974 — p. 495

2. Encyclopedia of chemistry: Vol. 5 — M.: Soviet Encyclopedia, 1988. — Vol. 1. — p. 556-557

3. Livestock feeding norms and rations: Reference guidelines / under the editorship of A. P. Kalashnikov, V. I. Fisin, V. V Shcheglov, N. I. Kleimenova — 3rd edition revised and amended — M., 2003 — p. 456

4. A. D. Orlov. Normal physiology /A. D Orlov, A. D. Nozdrachev. M.: GEOTAR Media, 2006 — p. 696

5. D. K. Kozyrev. Effect of milk, acidified with formic acid and enriched with chitosan, polisin (mixture of amino acids, vitamins, and minerals), and dihydroquercetin, on the calf growth and immunity during the milk-sustained growth period. Abstract of scientific paper by D. K. Kozyrev, Biology Ph.D. — M., 2007 — p. 24

6. A. D. Belov. Veterinary radiobiology / A. D. Belov, V. A. Kirshin. M.: Agropromizdat, 1987 — p. 287

7. S. P. Yarmonenko. Human and animal radiobiology: Textbook for biological institutes / S. P. Yarmonenko — 3rd edition revised and amended — M.: Vysshaya shkola, 1988 — p. 424

Flavomix Taxifolin Premixes

The physical and chemical properties of dihydroquercetin render it nearly insoluble in water and edible liquids (juices, milk, sunflower oil, dairy products, fat-containing canned food, etc.). Therefore, integration of dihydroquercetin into a finished product is extremely challenging.

Our premixes contain dihydroquercetin (taxifolin) without foreign substances (resin) and of a purification level exceeding 98%. This product has a higher-order crystal structure and all the attributes of a nanosystem. Specifically, it has a good solubility in water (up to 2 g/l) and stability in a water solution, ensuring its high bioavailability. These properties of high-purity taxifolin, combined with its strong antioxidative and capillary protection effects, make it attractive for food industry, including its application in the fabrication of water-based products.

Integration of taxifolin into a finished product in liquid form has an absolute advantage over the weight method.

The technology, developed by our specialists, allows for application of taxifolin in your production processes and facilitates the production of a standardized end product.

Drinking water properties:

1. Standard color (yellowy-orange)

2. No precipitate

3. Unaltered taste

Additionally, water may be boiled or frozen with no effect on the above properties.

Our premixes, utilized in other food products, allow integration of any required dose of taxifolin, thus, giving new therapeutic effects to these products.

Integration of taxifolin in fat-containing products will extend their shelf life by 50 — 100%.

Highly technological production process of natural antioxidant from Larix sibirica based on modern chromatography purification technique gives the products with content of target compounds more than 99%.

 

• Highly purified "mono-component" Taxifolin (Dihydroquercetin) with the purity at least 99% for the production of pharmaceuticals;

• Taxifolin (Dihydroquercetin) with the purity at least 98% for the production of pharmaceuticals and foodstuffs;

• Taxifolin (Dihydroquercetin) containing Taxifolin at not less than 97% for beverages, dietary supplements and food products;

Bioflavonoid complex «Taxifolia®», containing the amount of related bioflavonoids of 98-99% (content of Taxifolin is 95-96,9%) for the production of dietary supplements, cosmetics and food.

ARKHYZ

Taxifolin-Enriched Beverage

Water with taxifolin — key to long and healthy life

ARKHYZ, a new antioxidant enriched beverage (taxifolin content — 80 mg per liter) — is the first drinking water available to contain a natural vitamin and mineral complex with a pure plant extract of taxifolin (dihydroquercetin content ≥98%).

The major advantage of taxifolin, dissolved in beverages, is its rapid and complete absorption by human body (bioavailability), which promotes antioxidative activity of the substance. As demonstrated by ultrasonic dopplerography of capillary blood flow, within a few minutes of ingesting 150-200 ml of taxifolin water solution (80 m per liter), the capillary blood flow velocity doubles.

Our odorless and tasteless beverage has a saturated orange color. When boiled, taxifolin retains its antioxidant properties, making it suitable for cooking and hot drinks (tea, coffee, soups, second courses, etc).

Daily consumption of taxifolin helps to maintain the body’s physiological functions at high levels.

According to L. Polling, the Nobel prize winner, regular consumption of food products with a preparation of vitamin P properties (dihydroquercetin) added to them would prolong the life significantly. The daily physiological need for bioflavonoids (natural antioxidants) equates to 150-250 mg for children over 7 years of age and 250 mg for adults (according to Guidelines MR 2.3.1.2432 −08 Physiological Needs for Energy and Nutrition of Different Population Groups within the Russian Federation).

Quality

Taxifolin from our company is produced by Taxifolia factory (State Registration Certificate 77.99.11.3.У.7914.8.09., 24 Aug 09) to utilize for development of premixes and therapeutic beverages. Taxifolin possesses a purification degree of at least 98% and is completely free from foreign substances (resins and ether oils), thus, enabling its application in the food industry without modifying organoleptical properties of the food products.

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Until now, taxifolin production had several considerable shortcomings, mostly related to the presence of non-flavonoid substances in taxifolin: resins, ether oils, etc. This resulted in peculiar and unpleasant taste, which limited application of non-purified taxifolin in food. Dihydroquercitin content in these products did not exceed 90-92%.

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The innovative nature of the technology, developed by Taxifolia company, has been certified by patents and honored with a gold medal at the IDEEN-ERFINDUNGEN-NEUHEITEN International Exhibition in Germany.

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Propylene glycol, utilized to manufacture our premixes, is a product of the German company — DOW EUROPE GmbH, (State Registration Certificate 77.99.26.9.У.7846.9.08, 15 Sep 2008). It complies with the Sanitary Regulations and Standards SANPIN 2.3.2.1293-03 Hygiene Requirements for Application of Dietary Supplements.

Water

To manufacture taxifolin-enriched beverages we utilize Arkhyz water. Arkhyz, the only mineral drinking water of natural origin, is produced and bottled in the North Caucasus mountains at the elevation of 1,507 m. Flowing through the mountain filter, this water becomes lightly mineralized, acquiring beneficial properties and amazing taste. Bacteriological purity within the water well is similar to that of vacuum, i.e. Arkhyz water is perfectly pure. The water is bottled on-site with its original nature preserved. Thus, we can rightfully say that Arkhyz is the water of original natural quality, providing considerable health benefits, as opposed to artificially mineralized water and regular water being purified almost to the level of distilled water. Arkhyz has been collaborating for 9 years with the Federal Agency for Physical Education and Sports of Russia and has been a partner of such events as Ski-Track of Russia (all-Russia amateur ski racing), Nation’s Cross-Country Run (amateur running race), and others. Arkhyz is the official partner of the Zenit Football Club.

Cardiovascular Pathology

TAXIFOLIN AND blood PRESSURE

The prevalence of hypertension shows continuous growth. By 2025, adult hypertension will increase by approximately 60%, affecting 1.56 billion people worldwide.

Hypertension affects both developed and developing nations. This is precursor to the global

epidemic of cardiovascular diseases.

In 2000, 26.4% of the world’s total adult population (972 million people) suffered from hypertension, including 333 million in developed countries and 639 million in developing countries.

It is expected that by 2025, the global hypertension rates among adult population will rise to 29.2% and it means that 1.54-1.58 billion people will suffer from high blood pressure. These rates reflect an increase of 24% in developed countries and of 80% in developing countries.

This forecast becomes all the more horrifying if one considers the fact that hypertension is currently responsible for 40% of the total death rate, 69 % of cerebral strokes, and 49% of coronary conditions.

Clinical studies were conducted among 40 second-degree hypertensive patients (all males). The individuals mentioned were undergoing the in-patient period of rehabilitation due to a hypertensive crisis and unstable blood pressure with astheno-neurotic syndrome. The average age of these patients was 49.6±4.5 years, while the average duration of hypertension was 8.8±1.9 years.

A control group of 20 patients received standard treatment, while an experimental group (20 persons as well) received a daily dose of 80 mg of taxifolin in addition to the standard therapy.

The patients’ risk factors included the following:

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The rehabilitation of all the hypertensive patients at the end of the treatment was successful in both groups; however, it was more effective in the experimental group.

The rehabilitation of the individuals receiving taxifolin as part of the therapy was characterized by:

• Improvement of respiratory function

• Improvement of central and peripheral hemodynamics

• Enhancement of blood oxygenation

• Improvement of microcirculation

• Improvement of exercise tolerance

• Improvement of the emotional and psychological state of the patients

• Enhancement of rehabilitation efficiency

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Upon completion of treatment, both systolic and diastolic pressures decreased considerably in both groups. However, this decrease was more significant in the experimental group receiving taxifolin.

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HEALTHY HEART AND VESSELS – the simple secret to a long life

According to the WHO, more than 17 million people die due cardiovascular diseases each year, including over 7 million individuals with ischemic heart disease (IHD). By 2020, IHD is expected to become a killer of more than 11 million people every year.

For example, 5-6 million Americans are diagnosed with IHD each year and one third of total middle-aged deaths (in 35-64 age group) is attributed to coronary atherosclerosis, claiming the lives of more than 1 million people every year.

Acute myocardial infarction alone is the reason for hospitalizing over 200,000 people per year in the age group of 65 and over in the US.

Currently, myocardial infarction affects an estimated 900,000 people every year in the US, approximately 225,000 of them do not survive.

In Europe, IHD is one of the leading causes of death, with approximately 2 million cases annually. The percentage of deaths from this disease reaches 22% among European women and 21% among European men.

Changes in the blood microcirculation underlie the IHD pathogenesis. Therefore, the search for new medical preparations facilitating blood microcirculation remains of great importance.

Dihydroquercetin (taxifolin), being one of such preparations, has a stimulating effect on the tissue blood flow, stabilizing the barrier function of microvessels and reducing the permeability of the capillary walls, thus reducing stasis in the microcirculatory bloodstream.

Active life after heart surgery

An experimental group* included 30 patients aged 32-68 years (average age 47.6 ±3.2 years), who underwent coronary artery bypass surgery.

Patients consumed 80 mg of taxifolin daily for a 21 day period.

The most common complaints in these patients during the rehabilitation period included shortness of breath, caused by regular physical workload, and general weakness, which altered considerably the quality of their lives.

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The rehabilitation of the taxifolin taking patients resulted in improved central and peripheral hemodynamics, blood oxygenation, and microcirculation.

It’s remarkable that the most significant subjective improvement was the increased tolerance to exercise. This resulted in the patients‘ better emotional and psychological state which finally improved the rehabilitation outcome.

LIFE AFTER A HEART ATTACK

Studies were conducted among 30 patients, hospitalized for rehabilitation after acute myocardial infarction. The rehabilitation period lasted for 16- 28 days. All subjects were males aged 47-68 years (average age 57.6В±3.2 years). A substantial majority of the group was comprised of individuals whose work was associated with high emotional charge and mental labor.

53.3% of patients experienced angina attacks when they walked rapidly on horizontal surface or climbed upstairs, while 39.8% experienced angina attacks while walking on a level surface or ascended less than two flights of stairs at a moderate pace. Some patients (6.6%) experienced angina attacks at rest.

Repeated angina episodes (chest pains) often frighten patients who have recently experienced a potentially fatal heart attack. Their fear of a recurrent attack makes them emotionally suppressed.

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The number of angina attacks was significantly reduced among the experimental group patients receiving taxifolin.

This increased the number of patients who were able to cope psychologically with the disease or had minor difficulties with adaptability.

Thus, rehabilitation programs using taxifolin can be considered to be more efficient.

The positive dynamics in the control group was insignificant.

Taxifolin and ischemic heart disease

These studies were conducted among IHD male patients.

The average age of patients was 54.3 ± 2.3 years in the experimental group and 55.3 ± 1.9 years in the control group

The experimental group consumed 80 mg of taxifolin daily for a 21 day period, in an addition to the standard treatment.

The control group received the standard treatment only.

The studies showed that taxifolin consumption prevented and relieved spasms in both the normal and atherosclerotic coronary arteries, thus helping to eliminate microangiopathy.

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The rehabilitation program which included taxifolin resulted in improved rheological parameters, specifically:

• Increased blood flow velocity in microvessels

• Reduced stippling of the red blood cells and decreased aggregations of the cells

• In general, no focal stasis areas

• Improved hemodynamics

• Increased number of functioning capillaries

• Mitigated arteriolar spasm

• Normalizing arteriolar-to-venular diameter ratio

Additionally, the emotional state of the taxifolin taking patients improved significantly.

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Combination of the above positive changes in

• Microcirculation system

• Hemorheology

• Cardiorespiratory system

• Emotional and psychological state

finally resulted in the reduction or elimination of respiratory and heart insufficiency and a rapid recovery in patients.

Taxifolin improved intracardial hemodynamics, systemic and pulmonary circulations, respiratory function, and gas composition.

The preparation produces a positive effect on the peripheral microhemodynamics and facilitates the normalization of the pathological microcirculation, thus optimizing the tissue microflow.

Taxifolin facilitates the redistribution of the blood flow within the small arteries and enhances blood supply of ischemia-affected tissues such as myocardium. It also eliminates artery spasms which can alter the coronary arteries.

All patients reported good tolerance of the preparation and improved well-being, specifically:

• Reduction or elimination of the shortness of breath

• Reduction of retrosternal chest pain

• Increased activity level

• Improved sleep

Clinical Tests of DHQ in IHD Patients

Gerontology Center.

Objective:В  evaluation of DHQ antioxidative activity in medical patients.

Utilized materials and methods: 50 individuals participated in the studies. The first experimental group was comprised of 10 patients aged 50-73 years. The main medical condition of the patients was IHD often combined with

hypertension, diabetes, and obesity. The control group included 20 individuals.

Therapeutic approach: prior to application of DHQ, a complete clinical examination of the patients was conducted.

The patients consumed 250 mg of the preparation daily for a 10 day period.

The first control group included 14 people, matched by gender, age, and diseases.

Studied parameters: cholesterol, triglyceride, conjugated dienes, conjugated trienes, Schiff base, and antioxidative activity index. The specified parameters were recorded within the timeline in accordance with the clinical observation protocols containing patients’ feedback as well as diagnosis of their primary diseases and co-morbid conditions.

Research approach: dynamics of lipid peroxidation resulting from the treatment was measured by the chemiluminescence method.

Results:within 10 days, the consulting physicians recognized the improved well-being and reduced intensity of cardiac chest pain and headache in the experimental group as compared to the control group. The evaluation of lipid peroxidation at elevated levels of molecular products (primary products — conjugated dienes, secondary products — conjugated trienes, final products — Schiff bases) showed prominent decrease in peroxidation against the chemiluminescence intensity rate. This decrease was expressed in a reduction of both Imax index and light sum (S), and was attributed to the reduced metabolic activity accompanied by the free-radical reactions. The Imax/S coefficient characterizing general antioxidative activity also decreased. After the DHQ therapy, none of the lipid peroxidation parameters analyzed deviated significantly from the norm (Table 1), while the same parameters in the control group patients not receiving the preparation treatment, demonstrated no marked changes (Table 2). Additionally, patients receiving DHQ treatment had a more significant decrease of cholesterol, triglyceride, and uric acid levels, and prothrombin time, which are crucial elements of the pathogenesis of the specified diseases. This demonstrates that the preparation is able to affect deep metabolic processes in the liver.

Table 1

Dynamics of Parameters in the Experimental Group of Atherosclerosis Patients Resulting from the DHQ Treatment

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Table 2

Control Group

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Application of taxifolin in treatment of the IHD patients. Several studies [1-3] have demonstrated that the IDH patients have both enhanced lipid peroxidation and reduced antioxidative protection levels, which suggests that these disorders constitute a link in the chain of the IHD pathogenesis. A significant amount of data regarding the crucial role of lipid peroxidation in the atherosclerosis pathogenesis is also available now [4]. In this connection, antioxidants become an important part of the comprehensive treatment of atherosclerosis and IHD, as they slow the lipid peroxidation and, thus, produce a positive effect on cell membrane and vessel wall health [5]. At the same time, antioxidative therapy for IHD patients is directly related to the lipid peroxidation levels and the antioxidative protection activity. The quicker membrane lipid peroxidation occurs and the weaker the level of the antioxidative protection, the lesser the therapeutic effect on the patient. [Р±].

Taxifolin is a bioflavanoid preparation [9]. Its antioxidative and capillary protective properities combine with the lipid-lowering, liver protective, and diuretic ones [10]. The DHQ produces neither allergic reaction, nor immunodepressive, embryotoxic, teratogenic, or mutagenic effects [II].

The objective of the above mentioned research was to justify the application of the DHQ as an antioxidant preparation in combination with the IHD therapy.

Materials and Methods

The data accumulated during the studies result from the observation of more than 56 IHD patients. The IHD diagnosis was developed on the basis of the WHO criteria, while angina functional class was determined in accordance with the Canadian Cardiovascular Society grading scale. Eighteen patients out of 56 (45 males and 11 females; average age 61.2 ±1.6 years) had a medical history of myocardial infarction. All the patients suffered from a stable exertional angina of the II or III functional class, which was diagnosed on the basis of the clinical symptoms and bicycle exercise test. The second-degree hypertensive disease has been diagnosed in 21 patients.

The patients received therapy including nitrates of long-lasting action, β-adrenergic receptor blocking agents, and angiotensin-converting enzyme inhibitors. Medication dosages were constant during the entire research process. All the patients continued to experience angina attacks during the therapy. Additionally, all the patients received taxifolin according to the following scheme: 0.04 g four times a day for 6 days; 0.04 g three times a day for 10 days; and 0.02 g three times a day for the remainder of the period. The therapy course continued for 40 days.

Examination of the IHD patients was performed prior to and after a 40-day taxifolin course which took place in parallel with the standard treatment. The evaluations included the patient’s general well-being, frequency of angina attacks, electrocardiographic examination data, and exercise tolerance as determined by the bicycle exercise test. The protocol of this test provided for a stepwise increasing workload (one workload level −25 Watt, duration — 3 min) until either the critical level (rhetrostanal chest pain and/or ischemic ST-segment displacement by 1 mm or more) or submaximal level (85 % of maximal heart rate) was reached.

Moreover, the blood lipid spectrum (total cholesterol), low-density lipoproteins, and triglycerides were measured in accordance with the unified procedure. Blood was obtained for analysis at the morning time following a 12-hour fasting period. The above study was combined with the diagnostic of thymus-dependant disregulatory immune deficiency, since this immune deficiency is recognized as one of the pathogenic components of most internal organ diseases, including IHD. Immune deficiency was determined through the method co-authored by M. V. Vogralik (1986). This method uses a thermal imager to scan the skin surface in the upper sternum area and the medial surface of the big toe in order to identify zones of reduced infrared radiation.

A decrease rate expressed in degrees demonstrates a statistically significant correlation with the decrease of quantitative and functional parameters of the T-cells. Additionally, the temperature gradient value has a negative correlation with the helper T-cells/suppressor T-cells ratio. Immune deficiency diagnosis was conducted with the help of the Helper device.

Clinical effect was evaluated on the basis of frequency of angina attacks, number of nitroglycerin pills consumed, and increase of the exercise tolerance. The effect was confirmed when less frequent or weaker angina attacks occurred, consumption of nitroglycerine was reduced by 50 % or more, pain thresholds decreased by 10% or more (as compared to the original levels), immunity increased, and blood lipids showed a marked reduction.

Results and Discussion

78% of the patients receiving taxifolin had mild symptoms of coronary failure. Specifically, the rate of angina attacks occurrence decreased by 50 %, resulting in a decrease of nitroglycerine consumption (Table 1). The data obtained confirm the crucial role of oxidative stress for the development of nitrate tolerance and, consequently, the beneficial effects of antioxidants included in the treatment.

Table 1. Dynamics of Angina Episodes in DHQ Patients

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