High Quality Dry Vitamin K1 1% phytonadione / 84-80-0

Vitamin K

In 1929, a famous chemist Dam (Denmark) had first discovered and extracted a yellow crystalline substance from animal liver and linseed oil-vitamin K. Vitamin K is a the indispensable substance for hepatic synthesis of the four kinds of coagulation factors (active clotting factor Ⅱ (prothrombin), coagulation factor Ⅶ, coagulation factors Ⅺ and coagulation factor Ⅹ). Upon a lack of vitamin K1, the above four coagulation factors synthesized in liver synthesis become abnormal protein molecules while their ability to catalyze clotting effect dropped significantly. It is known that vitamin K is the cofactor for the glutamic acid γ-carboxylation. Lack of vitamin K disables the above γ-carboxylation of coagulation factors; in addition, these types of blood coagulation factors will reduce and will cause blood clotting slowing down and bleeding disorders. In addition, it is generally recognized that vitamin K was dissolved in mitochondrial membrane lipids, playing a role of electron transfer. Vitamin K can increase the intestinal motility and secretion property. Lack of vitamin will cause reduction in the tension and contraction of smooth muscle and can also affect the metabolism of some hormones, such as causing delay of the decomposition of glucocorticoids in the liver. It also has similar effects as hydrocortisone. Long-term injection of vitamin K can increase the thyroid and other endocrine activity. Vitamin K can be divided into two categories with both of them belonging to 2-methyl-1, 4-naphthoquinone derivatives. One class belongs to fat-soluble vitamins, namely vitamin K1 extracted from green plants (such as alfalfa, spinach and other leafy greens, etc.) and vitamin K2 extracted from microorganisms. Vitamin K2 can also be synthesized by human intestinal bacteria (such as E. coli). Vitamin K1 appears as yellow oil-like liquid while K2 appears pale yellow crystals. Both of them have heat resistance property, but are vulnerable to ultraviolet radiation to be destroyed, and therefore should be stored separately. Another class is water-soluble vitamins, namely artificially synthetic vitamin K3 and K4. The most important vitamins are K1 and K2. Vitamin K appears as oily liquid or solid and is insoluble in water but soluble in oils and organic solvents such as ether. It is chemically stable with heat and acid resistant, but being susceptible to alkali and UV degradation. The human body has a low demand. However, newborn infants are vulnerable to being lack of vitamin K that is an important vitamin for promoting blood clotting and normal bone growth. Dark green vegetables and yogurt are easily available vitamin K supplements obtained from the daily diet. Human has a very small demand for vitamin K but it is needed to maintain the normal function of blood coagulation, reduce heavy bleeding menstrual period, but also to prevent internal bleeding and hemorrhoids. Patients suffering frequent nosebleeds should be take more vitamin K from natural foods.This information is edited by Xiongfeng Dai from lookchem.

Limited use

Limited GB 14880-94: baby food, 420~475 μg/ku.

Production method

It can be obtained through the following process: o-naphthoquinone is mixed with acetic anhydride to have reduction, acetylation reaction to generate acetylated menadione in the presence of zinc; followed by hydrolysis in ammonia and further condensation reaction with phytol in ether with the catalysis of boron trifluoride to generate dihydro vitamin K1; and finally with hydrolysis, oxidation, purification and refining to derive the products.

Manufacturing Process

11 parts by weight of 2-methyl-1,4-naphthohydroquinone, 30 parts by volume of water-free dioxane and 1.5 parts by volume of boron trifluoride etherate are heated to 50°C. While agitating and introducing nitrogen, 10 parts by weight of phytol dissolved in 10 parts by volume of dioxane are added in the course of 15 minutes. Thereupon, the dark colored reaction mixture is stirred for 20 additional minutes at 50°C, cooled down and 60 parts by volume of ether are added. The reaction mixture is washed first with water, then with a mixture of 3 parts of N-sodium hydroxide and 2 parts of a 2.5% solution of sodium hydrosulfite and again with water. The aqueous extracts are washed with ether. The ether solutions are collected, dried over sodium sulfate and concentrated, toward the end under reduced pressure.The waxlike condensation product so obtained is mixed with 60 parts by volume of petroleum ether (boiling limits 30°C to 40°C) and agitated with hydrogen in the presence of a little active palladium lead catalyst (Pd-CaCO3catalyst, the activity of which is reduced by the addition of lead and quinoline). During the operation, the condensation product separates in the form of a voluminous white precipitate. The latter is separated by filtration in the absence of air while adding an inert coarse-grained adsorption agent (for example, aluminum silicate salt for filter purposes), and washed with cooled petroleum ether. Thereupon, the 2-methyl-3-phytyl-1,4-naphthohydroquinone is extracted from the filter cake by means of ether, the ethereal solution is concentrated to 100 parts by volume and the reaction product is oxidized by stirring the solution with 6.6 parts by weight of silver oxide during 30 minutes. The solution is filtered through sodium sulfate, the latter is rinsed with ether and the solvent is evaporated. There are obtained 5.7 parts by weight of 2-methyl-3-phytyl-1,4-naphthoquinone (vitamin K1) in the form of a golden yellow oil.

Biochem/physiol Actions

Vitamin K1 (Phylloquinone) is a lipid soluble polycyclic aromatic ketone used as a cofactor in the formation of coagulation factors II (prothrombin), VII, IX and X; anticoagulant factors protein C and S and as a cell signaling factor. Vitamin K1 is essential for blood coagulation, bone and vascular metabolism. Phylloquinone from green leafy vegetables and vegetable oil is the most important dietary source of vitamin K for humans.

Potential Exposure

Phylloquinone is a dietary component essential for normal biosynthesis of several factors required for clotting of blood; as a therapeutic drug used to correct bleeding tendency; and as a food supplement.

Veterinary Drugs and Treatments

The principal uses of exogenously administered phytonadione is in the treatment of anticoagulant rodenticide toxicity. It is also used for treating dicumarol toxicity associated with sweet clover ingestion in ruminants, sulfaquinoxaline toxicity, and in bleeding disorders associated with faulty formation of vitamin K-dependent coagulation factors.

Drug interactions

Potentially hazardous interactions with other drugs Antagonises effect of coumarins and phenindione.

Metabolism

Phytomenadione is rapidly metabolised to more polar metabolites and is excreted in bile and urine as glucuronide and sulphate conjugates.

Purification Methods

Vitamin K1 is a yellow viscous oil, which can be distilled at high vacuum practically unchanged. It is insoluble in H2O, but soluble in common organic solvents. Store it in the dark under N2 as it is oxygen sensitive. It has  1cm 328 at 248nm. [Fieser et al. J Am Chem Soc 61 2557 1939, Hirschmann et al. J Am Chem Soc 76 4592 1954, Isler & Doebel Helv Chim Acta 27 225 1954, Beilstein 7 IV 2496.]

Incompatibilities

Phylloquinone is photosensitive; decomposes in sunlight and is destroyed by alkali hydroxides and reducing agents such as hydrideds and active metals. Incompatible with oxidizers (chlorates, nitrates, peroxides, permanganates, perchlorates, chlorine, bromine, fluorine, etc.); contact may cause fires or explosions. Keep away from alkaline materials, strong bases, strong acids, oxoacids, epoxides.

General Description

Vitamin K1, also known as phylloquinone, consists of naphthalenoid and phytyl groups. Phylloquinone is present abundantly in photosynthetic plants and is a major dietary source. It is a fat-soluble vitamin.