Menaquinone 4

444.65

444.65

234-264-5

27Y876D139

DTXSID6048969

C52194

Light yellow microcrystalline plates from petroleum ether|Crystals|LIGHT-YELLOW SOLIDS OR OILS

2914699000

34.1

10.94

yellow crystals

1.0±0.1 g/cm3

35 °C

200 °C at 0.0002 mm Hg (some decomposition)

2℃

1.539

Slightly less soluble than vitamin K1 in the same organic solvents

−20°C

LD50 intravenous in dog: > 40mL/kg

198.66 Ų [M+H]+ [CCS Type: DT, Method: stepped-field]|197.4 Ų [M+H]+

Ⅱ

UN 1648 3 / PGII

3

3

22-24/25

QL9279500

P210-P280-P305 + P351 + P338

H225-H302 + H312 + H332-H319

SRP: Criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

... MK-7 induced more complete carboxylation of osteocalcin, and hematologists should be aware that preparations supplying 50 ug/d or more of MK-7 may interfere with oral anticoagulant treatment in a clinically relevant way.|Broad specturm antibiotics may sterilize the bowel and decrease the vitamin K contribution to the body by the intestinal microflora. /Vitamin K/|Cephalosporins containing side chains of N-methylthiotetrazole (cefmenoxime, cefoperazone, cefotetan, cefamandole, latamoxef) or methylthiadiazole (cefazolin) can cause vitamin K deficiency and hypoprothombinemia. These cephalosporins are inhibitors of hepatic vitamin K epoxide reductase. /Vitamin K/|Concomitant intake of cholestyramine and vitamin K may reduce the absorption of vitamin K. /Vitamin K/|For more Interactions (Complete) data for Vitamin K2 (16 total), please visit the HSDB record page.

Group of prenylated naphthoquinone derivatives having the physiological activity of vitamin K1 ... Compounds of varying chain length are produced by bacteria, particularly by normal intestinal flora, and may serve as a source of vitamin K for humans. Birds and mammals are capable of alkylating mendione ... to produce menaquinone 4 /Menaquinones/|Vitamin K functions as a coenzyme during the synthesis of the biologically active form of a number of proteins involved with blood coagulation and bone metabolism. /Vitamin K/

Vitamin K content of milk and meat products(1). /Vitamin K/ [Table#2773]

There is no typical dosage for vitamin K. Some multivitamin preparations contain vitamin K as vitamin K1 (phylloquinone or phytonadione) or vitamin K2 (menaquinones) at doses of 25 to 100 ug.|Vitamin K is used to treat anticoagulant-induced prothrombin deficiency caused by warfarin, hyporprothrombinemia secondary to antibiotic therapy and hypoprothrombinemia secondary to vitamin C deficiency from various causes, including malabsorption syndromes. /Vitamin K/|Because hemorrhagic disease of the newborn can be effectively prevented by administrating vitamin K, infants born in the US and Canada routinely receive 0.5-1 mg pf phylloquinone intramuscularly or 2.0 mg orally within 6 hours of birth. This practice is supported by both US and Canadian pediatric societies. /Phylloquinone/|The current recommendations of the American Academy of Pediatrics advise that "vitamin K (phylloquinone) should be given to all newborns as a single, intramuscular dose of 0.5-1 mg" and if this advice is followed, the disease /Vitamin K deficiency bleeding/ is effectively prevented. /Vitamin K/|For more Therapeutic Uses (Complete) data for Vitamin K2 (8 total), please visit the HSDB record page.

... MK-7 induced more complete carboxylation of osteocalcin, and hematologists should be aware that preparations supplying 50 ug/d or more of MK-7 may interfere with oral anticoagulant treatment in a clinically relevant way.|It has been suggested that vitamin K may have roles in osteoporosis and vascular health. However, this is difficult to establish on the basis of the studies performed thus far. /Vitamin K/|Pregnant women and nursing mothers should avoid supplemental intakes of vitamin K greater than RDA amounts (65 ug daily) unless higher amounts are prescribed by their physicians. /Vitamin K/|Individuals on chronic warfarin therapy may require dietary counseling on how to maintain steady vitamin K intake levels. Because habitual vitamin K intake may modulate warfarin dosage in patients using this anticoagulant, these individuals should maintain their normal dietary and supplementation patterns once an effective dose of warfarin has been established. /Vitamin K/|For more Drug Warnings (Complete) data for Vitamin K2 (6 total), please visit the HSDB record page.

Agents acting to arrest the flow of blood. Absorbable hemostatics arrest bleeding either by the formation of an artificial clot or by providing a mechanical matrix that facilitates clotting when applied directly to the bleeding surface. These agents function more at the capillary level and are not effective at stemming arterial or venous bleeding under any significant intravascular pressure. (See all compounds classified as Hemostatics.)

Vitamin K, mainly in the form of vitamin K1, is principally absorbed from the jejunum and ileum. ... Vitamin K is delivered to the enterocytes in micelles formed from bile salts and other substances. Vitamin K is secreted by enterocytes into the lymphatics in the form of chylomicrons. It enters the circulation via the thoracic duct and is carried in the circulation to various tissues including hepatic, bone and spleen, in the form of chylomicron remnants. In the liver, some vitamin K is stored, some is oxidized to inactive end products and some is secreted with VLDL (very low density lipoprotein). Approximately 50% of vitamin K is carried in the plasma in the form of VLDL, about 25% in LDL (low-density lopoprotein) and about 25% in HDL (high-density lipoprotein). /Vitamin K/|Excretion of vitamin K and its metabolites is mainly via the feces. Some urinary excretion of vitamin K also occurs. /Vitamin K/|...Menaquinones are adequately absorbed from the GI tract only if bile salts are present. Menaquinones and its water-soluble derivatives, however, are absorbed even in the absence of bile. ... Menaquinones are absorbed almost entirely by way of the lymph. /Menaquinones/|Menaquinone forms of vitamin K are produced by bacteria in the lower bowel, where the forms appear in large amounts. However, their contributuion to the maintenance of vitamin K status has been difficult to assess. Although the content is extremely variable, the human liver contains about 10 times as much vitamin K as a mixture of menaquinones than as phylloquinone. /Menaquinones/

A major pathway of vitamin K metabolism is that which is involved in the reduction and recycling of the epoxide formed by the carboxylase. /Vitamin K/|Vitamin K undergoes some oxidative metabolism. /Vitamin K/

In vivo and in vitro studies have shown that vitamin K may directly act on bone metabolism. In vitro studies have demonstrated that vitamin K2 inhibits bone resorption by, in part, inhibiting the production of bone resorbing substances such as prostaglandin E2 and interleukin-6. Vitamin K2 has been reported to enhance human osteoblast-induced mineralization in vitro and to inhibit bone loss in steroid-treated rats and ovariectomized rats.|Certain naphthoquinones, in particular the synthetic vitamin K menadione, have been found to have antitumor activity in vitro and in vivo. Vitamin K2 has been found to induce the in vitro differentiation of myeloid leukemic cell lines. The mechanism of the possible anticarcinogenic activity of vitamin K is not well understood. Menadione is an oxidative stress inducer and its possible anticarcinogenic activity may, in part, be explained by induction of apoptotic cell death. One study suggested that the induction of apoptosis by menadione is mediated by the Fas/Fas ligand system. Another study reported that menadione induces cell cycle arrest and cell death by inhibiting Cda 25 phosphatase.|Vitamin K is involved as a cofactor in the posttranslational gamma-carboxylation of glutamic acid residues of certain proteins in the body. These proteins include the vitamin K-dependent coagulation factors II (prothrombin), VII (proconvertin), IX (Christmas factor), X (Stuart factor), protein C, protein S, protein Zv and a growth-arrest-specific factor (Gas6). In contrast to the other vitamin K-dependent proteins in the blood coagulation cascade, protein C and protein X serve anticoagulant roles. The two vitamin K-dependent proteins found in bone are osteocalcin, also known as bone G1a (gamma-carboxyglutamate) protein or BGP, and the matrix G1a protein or MGP. Gamma-carboxylation is catalyzed by the vitamin K-dependent gamma-carboxylases. /Vitamin K/|The primary gene product of the vitamin K-dependent proteins contains a very homologous domain between the amino terminus of the mature protein and the signal sequence that targets the polypeptide for the secretory pathway. This "propeptide" region appears to be both a "docking" or "recognition " site for the enzyme and a modulator of the activity of the enzyme by decreasing the apparent Km of the Glu site substrate. ... A key finding essential to a complete understanding of the detailed mechanism of action of this enzyme has been the identification of an intermediate chemical form of vitamin K, which could be sufficiently basic to abstract the gamma-hydrogen of the glutamyl residue. It has been proposed that the initial attack of O(2) at the naphthoquinone carbonyl carbon adjacent to the methyl group results in the formation of a dioxetane ring, which generates an alkoxide intermediate. /Vitamin K/|For more Mechanism of Action (Complete) data for Vitamin K2 (8 total), please visit the HSDB record page.

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

/HUMAN EXPOSURE STUDIES/ The supplemental forms of vitamin K, vitamin K1 and vitamin K2 are well tolerated. In one study, doses of 90 mg daily of vitamin K2 were given for 24 weeks. Few adverse effects were noted. Reversible elevations of some liver tests were noted in a few subjects in the study.|/HUMAN EXPOSURE STUDIES/ ... The synthetic short-chain vitamin K(1) is commonly used in food supplements, but recently the natural long-chain menaquinone-7 (MK-7) has also become available as an over-the-counter (OTC) supplement. The purpose of this paper was to compare in healthy volunteers the absorption and efficacy of K(1) and MK-7. Serum vitamin K species were used as a marker for absorption and osteocalcin carboxylation as a marker for activity. Both K(1) and MK-7 were absorbed well, with peak serum concentrations at 4 hours after intake. A major difference between the 2 vitamin K species is the very long half-life time of MK-7, resulting in much more stable serum levels, and accumulation of MK-7 to higher levels (7- to 8-fold) during prolonged intake. MK-7 induced more complete carboxylation of osteocalcin, and hematologists should be aware that preparations supplying 50 ug/d or more of MK-7 may interfere with oral anticoagulant treatment in a clinically relevant way.|/SIGNS AND SYMPTOMS/ No adverse effects have been reported with high intakes of vitamin K from food or supplements in healthy individuals who are not intentionally blocking vitamin K activity with anticoagulation medications. /Vitamin K/|/OTHER TOXICITY INFORMATION/ ... This study ... measured circulating levels of vitamin K1, menaquinone-4 (MK-4) and menaquinone-7 (MK-7) in 23 normal healthy women aged 52-93 years (mean +/- SD: 80.1 +/- 3.5), 13 female patients with vertebral fractures aged 66-93 years (80.3 +/- 7.8) and 38 female patients with hip fractures aged 76-87 years (79.8 +/- 9.2), (all Japanese) ... . Serum circulating levels of MK-4 was undetectable in most subjects (only one out of 74). Appreciable numbers from these three groups had undetectable levels of MK-7 (52% of the control group, 23% of the vertebral fracture group and 24% of the hip fracture group). Eight subjects from the normal control group (35%) and five patients from the vertebral group (38%) had undetectable levels of vitamin K1. ... A significant difference in the measurable levels of vitamin K1, MK-4 and MK-7 in patients with vertebral fractures or patients with hip fractures /was not found/ compared to age-matched normal controls...

(E,E,E)-isomer of menatetrenone

In the early 1930s, Henrik Dam observed that chicks consuming very low lipid diets developed subdural or muscular hemorrhages and that blood taken from these animals clotted slowly. This hemorrhagic disease could not be cured by supplementation with any other known dietary factor, and Dam proposed the existence of a new fat-soluble factor, vitamin K. ... The term vitamin K is now used as a generic descriptor of 2-methyl-1,4-naphthoquinone (menadione) and all derivatives of this compound that exhibit antihemorrhagic activities in animals fed a vitamin K-deficient diet. /Vitamin K/|The compound, 2-methyl-3-farnesyl-geranylgeranyl-1,4-naphthaquinone, first isolated from putrefied fish meal, is one of a series of vitamin K compounds with unsaturated side chains called multiprenylmenaquinones, which are produced by a limited number of anaerobic bacteria and are present in large quantities in the lower bowel. This particular menaquinone has 7 isoprenoid units in the side chain and was once called vitamin K2. That term is currently used to describe any of the vitamers with an unsaturated side chain, and this compound is more correctly identified as menaquinone-7 (MK-7). The predominant menaquinones found in the gut are MK-7 through MK-9, but smaller amounts of others are also present.|Nomenclature is based on the number of isoprene residues comprising the side chain. /Menaquinones/|Vitamin K is a generic term for a group of substances which contain the 2-methyl-1,4-naphthoquinone ring structure and which possess hemostatic activity. ... Vitamin K1 or phylloquinone is the principal dietary source of vitamin K and its predominant circulating form. ... Vitamin K1 is a fat-soluble substance. Vitamin K2, which is also fat soluble, is the collective term for a number of substances known as menaquinones. The dietary contribution of vitamin K2 is much less than that of vitamin K1. The amount of vitamin K contributed to the body by the intestinal microflora remains unclear. Vitamin K3 or menadione is a fat-soluble synthetic compound which is used in animal feed and dog and cat food. It is metabolized to vitamin K2.|For more General Manufacturing Information (Complete) data for Vitamin K2 (6 total), please visit the HSDB record page.

As a result of its high selectivity and sensitivity, high performance liquid chromatography (HPLC) is the method of choice for the determination of phylloquinone and menaquinones in the blood, tissues, milk, and in foods. Various procedures for extraction and preliminary purification, internal standardization, HPLC conditions (with normal or reversed phase) and possibilities for UV, electrochemical, and fluorescence detection (both after electrochemical or chemical reduction and after photochemical decomposition) of the vitamins K have been described. /Phylloquinone and Menaquinones/|A sensitive and highly selective high-performance liquid chromatography (HPLC) method was developed for the determination of vitamin K homologues including phylloquinone (PK), menaquinone-4 (MK-4) and menaquinone-7 (MK-7) in human plasma using post-column peroxyoxalate chemiluminescence (PO-CL) detection following on-line ultraviolet (UV) irradiation...