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Sopharma
Phytin Phytin

Phytin® is a nutrient supplement which contains a calcium-magnesium salt of phytic acid. As a natural component of animal tissues and organs, this salt is of great value for the human body, being also isolated in some plant products where it serves as a phosphate depot. Decades of studies have highlighted the role of phytic acid for the increased oxygen transportation capacity of the human erythrocytic hemoglobin. Evidence exists that Phytin® improves and regulates cell metabolism, especially in phosphorus deficiency-related conditions in humans. It stimulates the hemopoietic system and bone tissue production, and improves the tone of the nervous system.


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The comprehensive effect of Phytin® is demonstrated by an improved intensity and stability of attention, and an increased capacity for work, with elimination of the sense of fatigue.

As a nutrient supplement, Phytin® is a very good preventive agent in conditions of physical and mental overloading, and it enhances human body endurance during intensive exercise.

Sopharma AD manufactures Phytin® in the form of 250 mg tablets which may be taken 30 minutes before meals, with the following dose regimen:

Adults: from 4 to 6 tablets daily
Children 2 to 6 years of age: from 1 to 2 tablets daily
Children 6 years or older: from 2 to 4 tablets daily

Simultaneous higher intake of calcium-containing foods and supplements is recommended to children.

Supplement Facts:
Serving Size: 4 Filmtabs
Servings Per Container: 10
Phytic Acid: 1,000mg

Inactive Ingredients: Starch Wheat, Talc, Magnesium Stearate, Lactose.

Warning: Persons diagnosed with obesity, cancer, and pregnant and nursing women should consult a physician before use.

PHYTIN® - A TONIC AND GENERAL STIMULANT NATURAL PRODUCT WITH PRESENT, PAST AND FUTURE

Phytin isolated from plants belongs to the group of organic phosphates and is a mixture of calcium-magnesium salt of inositol hexaphosphoric acid, also known as phytic acid. The name Phytin was first used by S. Posternak in the beginning of this century (1902) for the phosphorous-containing compounds obtained from various plant seeds, suggesting them to be intermediary products of chlorophyll synthesis. This suggestion was rebuked later, but the name Phytin remained as a designation of those products isolated from the seeds of cereal grains (wheat, corn, etc.), and leguminous (lentils, beans, peas) and oil (sunflower, rape, soy, sesame) plants. Phytic acid contents were found to be higher in the outer coverings of seeds than in the whole seeds (Mukhamedova, H.S. et al., 1977).

In plant organs, phytic acid has the function of phosphate depot. Under the action of phytase, which belongs to the group of phosphatases occurring in the gastro-intestinal tract and in plants, phytic acid is broken down to myo-inositol as the absorbable form. Studies on the action of Phytin focus on the above-mentioned biologically active form of phytic acid.

Like the other phosphorous-containing preparations, Phytin stimulates hemopoiesis, potentiates bone growth and development, and improves the functions of the nervous system.

Literature data show that interest towards the isolation and assay of Phytin, phytic acid, and its utilizable forms has continued for nearly a century. More recent publications on the mechanism of action and the new areas of application support the need for Phytin production and its use as active ingredient in novel one-component and multi-component dosage forms.

Sopharma AD manufactures Phytin® in the form of tablets of 250 mg. Phytin® and its finished dosage form can be used for their therapeutic and prophylactic effects, and as food supplement to various diets depending on the condition of the organism.

ISOLATION AND IDENTIFICATION

Phytin is a white amorphous powder, odorless and tasteless, almost insoluble in water, soluble in dilute mineral acids and in some organic acids. One part Phytin dissolves in 10 parts of 1 n hydrochloric acid and forms a clear solution. According to some authors, Phytin contains 36% organically bound phosphoric acid. Upon heating with dilute acids, alkali and water, Phytin hydrolyzes to give ortho-phosphoric acid and the cyclitol myo-inositol as end products. These are obtained together with some other products of semi-degradation.

The first patents for Phytin isolation were filed by S. Posternak and date back to 1902 and 1903 (DRP 147968, 147969, 159749, 160470). In his extensive studies S. Posternak (1921) established that the salts (magnesium, calcium, manganese, etc.) of phytic acid he obtained were likely to lose 3 molecules of water upon vacuum drying and suggested the following gross formula for phytic acid. Structural identification of phytic acid

The structural identification of phytic acid and, consequently, Phytin structure remained questionable for long time. The following two tentative structures were commented: Neuberg's (1908) asymmetric tri-pyrophosphate structure and Anderson's (1914) symmetric hexa-orthophosphate structure.

Different arguments have been proposed for each structure.

Smith and Clark (1951) confirmed the heterogeneity of phytic acid by ion-exchange methods. Cosgrove (1966) identified it as a complex mixture of polyphosphates, including esters of inositol and myo-inositol. Tate (1968) studied phytic acid by electrophoresis and nuclear magnetic resonance and verified its structure as myo-inositol-hexa-phosphoric acid.

Synthesis (Courtois, J. et al. 1951); Diemair and Becker, 1955) and modern chromatographic and spectrographic techniques (Johnson, L.F. et al. 1969) have ascertained that the gross formula of phytic acid is C6H6[OPO(OH)2]6, whereas its structural formula is recognized as:

The raw material for Phytin production is rice bran and cereal grains bran, as well as oil plant cakes obtained as by-products of the food processing and oil-producing industries.

Structural formula

When processing the raw plant material, it should be known that many plant seeds (especially of the bean species) contain the enzyme phytase together with Phytin. In aqueous solutions phytase causes partial or complete hydrolysis of Phytin to intermediary products, such as inositol-mono-, inositol-di-, and inositol-tri-ortho-phosphates.

Different technological processes are available for industrial Phytin isolation. They can be classified in two groups, according to the extracting medium used. Most methods include extraction of the plant material with acidulated water, using some organic acids (formic, trichloroacetic, lactic, oxalic, citric, etc.) (Sarma, 1942) or dilute mineral acids (hydrochloric, nitric) (Schormoeller, J. et al., 1956); Pavlov L., S. Stanev, V. Kamedulski, 1969; Zakharov V. P. 1993).

The aqueous -acid extracts, in addition to the main product, yield also protein substances, inorganic salts, sugars, etc. some of the proteins precipitate with time and can be further separated by filtration. Phytin itself falls as a white amorphous precipitate after neutralization and mild alkalization with alkaline base, lime water, ammonia, basic carbonate or acetate, etc. The precipitated crude product is filtered, washed, and purified by subsequent dissolution and precipitation, boiling with activated charcoal and intermediary treatments to remove specific admixtures (Posternak, 1903, Pavlov et al., 1969).

PHARAMACOLOGY AND ACTION

Inositol hexaphosphoric acid (phytic acid, INN Fytine acid Roempps Chemie Lexicon, 1983) serves as a phosphate depot in the body and is broken down by phytase to myo-inositol. The human body contains about 40 g of myo-inositol. It also plays the role of a growth factor and is identical in action to the formerly designated as "bios I" factor, necessary for optimal growth. Based on its mode of action, myo-inositol can be classified to the vitamin complex of ht B-group (Roempps Chemie Lexicon, 1983). In the body, myo-inositol can be synthesized from glucose-6-phosphate, but human requirements are chiefly covered through consumption of fruit and cereals, where it occurs in the form of inositol-hexaphosphate (phytic acid).

By competitive chelate formation phytic acid participates in the process of intestinal absorption of calcium, magnesium and iron ions. The formation of insoluble chelate complexes of phytic acid accounts for some of its extremely important properties.

Myo-inositol increases the oxygen transporting capacity of hemoglobin in red blood cells, improves and regulates cellular metabolism, especially in conditions of phosphorus deficiency in the body, stimulates hemopoiesis and bone tissue formation, and improves the tone of the nervous system.

The overall complex effect of Phytin is expressed in a general tonic action which, combined with its involvement in the regulatory metabolic processes, improves the intensity and stability of attention, increases performance and work capacity, removes the feeling of fatigue, and stimulates the organism's defenses through yet not entirely clear mechanisms (Torre et al., 1991).

Phytin® as a food supplement is very good for prophylaxis in conditions of physical and mental strain, and for increasing general endurance during active exercise and sports.

Several studies (Nicoletti F. et al. 1989) have demonstrated an increase of calcium ion influx in cerebellar neurons. They provide evidence for a direct activating effect of phytic acid and its salts on the functional activity of the central nervous system. These data are further confirmed by other authors, who established an important role of phytic acid in the regulation of cell metabolism.

Repeated dose administration of Phytin® has revealed no changes in the body mass and electrolytic balance, and no signs of toxicity in the test animals, even at higher doses.

The inclusion of inositol-hexaphosphate (InsP6 or IP6) as an active ingredient of fiber-rich diets is being discussed in literature.

Increased consumption of calcium-containing products (milk and dairy products) and preparations is recommended for children with concomitant Phytin® administration.

Plasma calcium levels should be monitored during continued administration of high doses for possible formation of insoluble chelate complexes.

REFERENCES

1. Anderson, R. J., J. Biol. Chem. 1915, 20, 475
2. Angyal, S., A. F. Russel, Austr. J. Chem., 1968, 21, 391
3. Arbens, E., Lebensmittel Unters. u. Hyg., 1929, 13, 45
4. Assenov, I., S. Nikolov, Pharmacognosy, Sofia, Meditsina & Fizkultura, 1988 (in Bulgarian)
5. Berezovski, V.M., Vitamin Chemistry, Moscow, 1959 (n Russian)
6. Brown, E. C., M. I. Heit, D. E. Ryan, Can. J. Chem., vol. 39, 1961, 1290-1297
7. Cosgrove, D., J. Rev. Pure and Appl. Chem., 1966, 16, 209
8. Courtois et al., Bl. Soc. Chim. Biol., 1951, 33, 1075
9. Diemair, Becker, Dtsch. Lebennsmittel Rdsch., 1955, 51, 18-23
10. Fisher, F., F. Kurten, Biochem. Z., 1908, 9, 557
11. Graf, E., J.W. Eaton, Nutr. Cancer. 1993, 19(1), 11-9
12. Johnson, L.F., M.E. Tate, Can. J. Chem., 1969, vol. 47, 63-73
13. Mashkovski, M.D., Medicinal Products, 4th Edition, Moscow 1960 (in Russian)
14. Mukhamedova, H.S., S.T. Akramov, Chem. Nat. Comp., 1977, 4 (in Russian)
15. Neuberg, C., Biochem. Z., 1908, 9, 557
16. Nicoletti, F., B. V., Fiore L., Caballaro S., Canonico P.L., J.Nerurochem. 1989, 53(4), 1026-30
17. Owen R.W., U. Weisgerber, B. Spiegelhalder, H. Bartsch. Gut., 1966, 38(4), 591-7
18. Pavlov, L., S. Stanev, L. Kamedulski, Technology of Pharmaceutical Production, Sofia, Technika, 1969, vol. 2 (in Bulgarian)
19. Posternak S., DRP 147968, 147969/1902; 159749, 155798, 160470/1903; 331159/1919; Compt. Rend Soc. Biol., 1903, 55, 1190; Helv. Chim. Acta., 1921, 4, 150
20. Posternak, S., T. Posternak, Helv. Chem. Acta. 1929, 12, 1172
21. Posternak, T., The Cyclitols, Paris, 1965, 227
22. Phytin, R. Chemie Lexicon, Stuttgart, B.4, 1985, 3207
23. Rao, P.S., X. K. Liu et al., Ann. Thorac. Surg. 1991, 52(4), 908-12
24. R. Chemie Lexicon, B.1/1979, 446; B.3/1983, 1884; Biotin, Inosite
25. Zakharov, V. P., Medicinal Compounds of Plant Origin, Sofia, 1993 (in Bulgarian)
26. Sadulev, S.S., M.T. Turakhodjaev, T.T. Shakirov, Chem. Nat. Comp., 1976, 4 (in Russian)
27. Sarma, J., Indian chem. Soc., 1942, 19, 309
28. Shamsuddin, A.M., G.Y. Yang, I. Vucenik, Anticancer Res. 1996 16(6A); 3287-92
29. Shamsuddin, A.M., A. Ullah, Carcinogenesis, 1989, 10(8), 1461-3
30. Smith, D. H. E.S. Clark, Soil. Sci. 1951, 72,353
31. Tate, M.E., Anal. Biochem., 1968, 23, 141
32. Ullah, A., A.M. Shamsuddin, Carcinogenesis, 1990, 11(12), 2219-22
33. U.S Pat. 2493666/1945; 2732395/1952
34. Wrenshall, C., W. Dyer, Soil. Sci., 1941, 51, 235

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