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Vitamin B12 Basic information outline Chemical properties Characters The structure of vitamin B12 Uses Physiologic function vitamin B12 deficiency Main Application Content Analysis Toxicity Limited use Production method Product Name: Vitamin B12 Synonyms: hemomin;hepacon-b12;hepagon;hepavis;hepcovite;lactobacilluslactisdornerfactor;lldfactor;macrabin CAS: 68-19-9 MF: C63H88CoN14O14P MW: 1355.37 EINECS: 200-680-0 Product Categories: Pharmaceutical intermediates;Inhibitors;Mainly used in the treatment of giant young red blood cell anemia, nutritional bad blood loss anemia, neuralgia and obstructive disease;Vitamin series;Cobalamin, vitamin B-12;vitamin;Organometallics;Nutritional Supplements;Vitamins and derivatives;Vitamin Ingredients;Carbohydrates & Derivatives;Chiral Reagents;Intermediates & Fine Chemicals;Pharmaceuticals;Biochemistry;Classes of Metal Compounds;Co (Cobalt) Compounds;Porphyrins;Transition Metal Compounds;Vitamins Mol File: 68-19-9.mol   Vitamin B12 Chemical Properties Melting point  >300°C alpha  23656 -59 ± 9° (dil aq soln) Boiling point  >300 °C Fp  9℃ storage temp.  2-8°C solubility  Sparingly soluble in water and in ethanol (96 per cent), practically insoluble in acetone. The anhydrous substance is very hygroscopic. pka pKa 3.28±0.04(H2O,D2O t=23±0.5 Iunspeci ed) (Uncertain) form  Crystalline Powder or Crystals color  Red to dark red Water Solubility  Soluble Sensitive  Hygroscopic Merck  14,10014 BRN  4122889 Stability: Hygroscopic. Keep cold and dry. InChIKey RMRCNWBMXRMIRW-WZHZPDAFSA-L EPA Substance Registry System Vitamin B12 (68-19-9)   Safety Information Hazard Codes    Hazardous Substances Data 68-19-9(Hazardous Substances Data) Toxicity LD50 intravenous in mouse: 2gm/kg MSDS Information Provider Language SigmaAldrich English ACROS English ALFA English   Vitamin B12 Usage And Synthesis outline Vitamin B12, which is called VB12 for short, also known as cobalamin, and is one of the B vitamins, is a class of complex organic compounds containing cobalt Corrin class ,and contained trivalent cobalt in similar porphyrin Corrin plane at the center of the ring.It is the largest and most complex vitamin molecule that has been discovered. It is also the only vitamin with metal ion. The crystal is red, it is also called red vitamin.The plant does not contain VB12, and can not produce VB12. The liver is the best source of VB12, then from milk, meat, eggs, fish and so on.VB12 is an essential coenzyme in the synthesis of RNA and DNA. The lack of VB12 in vivo can cause pathological changes in the nervous system such as peripheral nerve and central nervous system. The discovery of vitamin B12, first of all, should be attributed to the research work carried out by the people in the treatment of pernicious anemia named by British physician Addison.The pernicious anemia at that time is a type of cancer that is incurable. In 1926, Minot and Murphy found it can cure the disease by ingestion of large amounts of raw liver , for which they won the 1934 Nobel Prize in physiology and medicine prize. Following the discovery of Minot and Murphy, people successfully cured the disease by liver concentrate. In 1948, the riches, British Smith and Parker et al, respectively from the liver concentrate isolated a red crystal, named for vitamin B12. In the same year, R. west of Columbia University in the United States confirmed by injections of vitamin B12 to effective treatment of pernicious anemia.Then in 1955,  D. Hodgkin,et al. using X-ray analysis to determine the crystal structure of vitamin B12. He also won the 1964 Nobel Prize in chemistry in 1972, Woodward successfully completed the total synthesis of vitamin B12. Figure 1 is the source of vitamin B12 Chemical properties Deep red crystalline or amorphous crystalline powder, odorless and tasteless. Melting point is 210~220 ℃ (carbonized to black). 1g product can be dissolved in 80mL water, soluble in alcohol, insoluble in acetone, ethyl ether or chloroform. Anhydrous is easy to absorb moisture, crystallization of Vitamin B12 in neutral and acidic solution to air and better thermal stability, in alkali, strong acid and reducing agent is not stable, not resistant to light and ultraviolet. Characters It is the deep red crystal or crystalline powder, odorless, tasteless, hygroscopic strong. Slightly soluble in water or ethanol, insoluble in chloroform or ether.  Heat-resistant, but in the case of oxidizing or reducing substances (such as vitamin C or hydrogen peroxide, etc.), heavy metal salts and strong acids, alkalis, it can become invalid. The structure of vitamin B12 Vitamin B12 is octahedral compound containing cobalt ions, its center structure is composed of four pyrrole (pyrrole) connected to the composition of the plane goo phen ring corrinring.Vitamin B12 molecule generally consists of three parts: four N atoms and the central cobalt ion is chelated to Corrin ring; 5,6-dimethylbenzimidazole (5, 6-dimethylbenzimidazole,DMBI) by N-7 atoms and cobalt ions linked to low vitamin B12 molecule as a (alpha) ligand, in addition, DMBI is by phosphate groups and aminopropanol aminopropanol connected and ammonia alcohol and pyrrole D of the propionic acid side chains covalently connected; adenosine (adenosylgroup) or methyl (methylgroup) and cobalt ions linked to vitamin B12 molecules of the host (beta) ligand. Ligands above corrin ring axial are different forms of vitamin B12 substances of different types. The hydroxyl (-OH) is connected with the cobalt Corrin ring in the formation of hydroxocobalamin (hydroxycobalamin), similarly, deoxyadenosine (5 '-deoxyadenosyl), methyl (-CH3), cyano (-CN) connected with cobalt ions each generat to deoxyadenosylcobalamin (deoxyadenosylcobalamin), methyl cobalamin (methylcobalamin) and Vitamin B12e (Vitamin B12). In nature, the final form of vitamin B12 is microbial biosynthesis of deoxyadenosylcobalamin (coenzyme B12), methyl cobalamin and hydroxycobalamin. But because their character is not stable,  artificially adding sodium cyanide in industrial purification process, can make the natural form of vitamin B12 into more stable Vitamin B12e. Figure 2  the structure of vitamin B12 Uses 1. Vitamin B12 deficiency can cause anemia, nervous system disorders. It can be used in infant foods, used amount is 10~30μg/kg; use in strengthening drink liquid and the amount  is 2~6μg/kg. 2. Mainly used to treat megaloblastic anemia, poor nutrition, blood loss anemia, neuralgia and obstructive disorders. 3. As the feed nutrition fortifier, with anti-anemia effects of pernicious anemia, nutritional anemia, parasites and anemia and effective dosage is 15-30mg/t. 4. Vitamin B12 is essential for the metabolism of the human body. The average total amount of vitamin B12 in the human body is 2-5mg, 50-90% of which is stored in the liver, the body needs to release into the blood in the formation of red blood cells. Chronic lack of B12 can cause pernicious anemia. B12 and folic acid are important  fear of enzymes during cell nucleic acid synthesis, involved in the synthesis of purines, pyrimidines, nucleic acids and methionine; and allows methyltransferase to promote the synthesis of the base; at the same time to increase the synthesis of sugar yuan, thus eliminating the role of liver fat. Clinical often as a drug for the treatment of liver diseases. Human need vitamin B121 micrograms per day, every day foods provide 2 micrograms, to ensure the normal needs. Hydroxocobalamin in Vitamin B12 reacts with cyanide to generate Vitamin B12, to eliminate cyanide toxicity. Therefore, the lack of vitamin B12 for cyanide sensitivity is higher than the average person.  Thus, vitamin B12 deficiency sensitivity to cyanide higher than the average person. Vitamin B12 is mainly used to treat pernicious anemia, megaloblastic anemia, antifolate drugs starting from anemia and multiple neuritis. Physiologic function 1. To improve the utilization of folic acid, it and folic acid are together with the synthesis of methionine (from high cysteine synthetase) and choline, producing Vitamin B12 application based pioneer substances such as methyl cobalamin and coenzyme B12 in purine and pyrimidine synthesis process, participating in the methylation process in many important compounds. When vitamin B12 deficiency, activities which transferred methyl groups from the methylenetetrahydrofolate reduced to make folic acid into no use of form, leading to folate deficiency. 2.Maintain the metabolism and function of the nerve myelin sheath. Lack of vitamin B12, can cause neurological disorders, degeneration of spinal cord, and can cause severe psychiatric symptoms. Vitamin B12 deficiency can cause peripheral neuritis. Children's lack of vitamin B12 early performance is emotional, dull, slow response, and finally leads to anemia. 3. Promote the development and maturation of red blood cells. The two acyl coenzyme A is converted to succinate coenzyme A, which is involved in the synthesis of three carboxylic acid cycle, in which the synthesis of A is related to the synthesis of heme. 4. Vitamin B12 is also involved in synthesis of deoxy nucleic acid (DNA), metabolism of fat, carbohydrate and protein, increasing the synthesis of nucleic acids and proteins. An overview of vitamin B12, traits, physiological function, application are compiled by  Eastern of Chemicalbook . (2016-12-10) vitamin B12 deficiency 1. The causes of vitamin B12 deficiency (1) Too little intake  body can not synthesize vitamin B12. Dietary vitamin B12 is  from animal food, milk and less content of dairy products , vegetable foods are basically no vitamin B12. Vegetarians are more prone to vitamin B12 deficiency than non vegetarians.. Vitamin B12 intake and serum vitamin B12 levels were positively correlated..Maternal vitamin B12 deficiency or lack of intake, may be due to low vitamin B12 in the milk causing vitamin B12 deficiency in infants. (2) malabsorption  The Elderly people are prone to vitamin B12 deficiency, about 60% is due to gastrointestinal reasons causing food bound cobalamin malabsorption. Taking more than 12 to 30 g of synthetic vitamin B12 per day can make older people's low vitamin B12, the risk of high MMA reduced. Oral administration of high doses of vitamin MMA can make most of the vitamin B12 deficiency in the elderly to return to normal. (3) The lack of intrinsic factor vitamin B12  needs to be combined with the internal factor to eventually be absorbed. Pernicious anemia patients have intrinsic factor autoantibodies, it can lead to serious vitamin B12 deficiency. (4) Others taking anti-epileptic drugs, metformin, histamine H2 receptor blockers and proton pump inhibitors, hereditary cobalt amine transfer protein II deficiency, tropical sprue, Helicobacter pylori infections, parasitic infections, also It can lead to be lack of vitamin B12. 2. Vitamin B12 deficiency and disease (1) anemia, vitamin B12 deficiency anemia caused by lack of vitamin B12 like the same as lack of folic acid, just as megaloblastic anemia. However, whether the elderly people or less intake of food of animal origin in the crowd, vitamin B12 deficiency anemia is not associated with the state.  People that are lack of vitamin B12 supplement vitamin B12 and this does not affect the whole blood cell count. (2) homocysteine Blood total homocysteine concentration is more than 10μmol /L, can increase the risk of atherosclerosis and venous thrombosis. Vitamin B12 is involved in homocysteine metabolic methylation process, is essential cofactors for the methionine synthase (enzyme catalytic homocysteine methyl). Vitamin B12, folic acid concentration in the blood and homocysteine concentration. Vitamin B12, folic acid concentrations are relation to homocysteine concentration in the blood. In Indian the vegetarian population, high incidence of vitamin B12 deficiency is related to coronary artery disease. For diabetic retinopathy population, vitamin B12 deficiency associated with high homocysteine and vitamin B12 deficiency may be an independent risk factor for diabetic retinopathy. However, vitamin B12 did not reduce the risk of cardiovascular disease or diabetes. (3) nervous and mental diseases Vitamin B12 and folic acid have a pivotal role in maintaining the normal function of the central nervous system (CNS). SAM is an important donor in the brain, and the  imbalance of methylation is one of the causes of neurological and psychiatric disorders. Homocysteine is also one of the reasons of CNS disorders, associated with cognitive impairment. Vitamin B12 or folic acid deficiency can make homocysteine concentration increased and interfere with the methylation status. MMA is toxic to the nervous system. Vitamin B12 and folic acid can protect the elderly CNS disease, mood disorders and dementia (including Alzheimer's disease, vascular dementia and dementia), other studies was negative results. Despite the extensive literature  show that B-group vitamins and homocysteine, and cognitive and mood disorders, dementia related but even if they can reduce homocysteine levels and in randomized controlled trials, there is no clear evidence that supplement of folic acid and vitamin B12 could improve cognitive impairment and dementia, can not improve the symptoms of depression. (4) fertility and birth defects folic acid is a protective factor to neural tube defects (NTD), folate metabolism closely linked to vitamin B12 is also an independent risk factor of the NTD. Vitamin B12 deficiency is a risk factor for early pregnancy abortion, recurrent abortion. In the neonatal period, vitamin B12 deficiency can seriously damage the development and function of the nervous system, more performance for infant growth retardation and nervous system disabilities but not anemia. Once the baby of vitamin B12 deficiency occurs, low levels of vitamin B12 will continue for at least a year. Even if corrected early vitamin B12 deficiency, these children still may appear to be long-term neurological, cognitive impairment, including irritability, anorexia, growth retardation, mental retardation and developmental regression. (5) Others  vitamin B12 deficiency may increase the chance of occurrence of some cancers. Vitamin B12 and bone density may be related, but different conclusions are not consistent. Main Application 1. Applications for medical and health care Used in the treatment of various VB12 deficiency, for example: treat megaloblastic anemia, anemia caused by poisoning, aplastic anemia and leukopenia psychosis; and with the use of pantothenic acid, which can prevent malignant anemia, helps Fe2+ uptake and secretion of gastric acid; also used to treat arthritis, facial nerve paralysis, trigeminal neuralgia, hepatitis, herpes, asthma and other allergies, atopic dermatitis, hives, eczema and bursitis; VB12 can also be used for the nervousness, irritability, insomnia, memory loss, depression disorder treatment. New research shows that, VB12 deficiency can also cause depression mental illness. VB12 as a therapeutic agent or health products ,is very safe,more than thousands of times of RDA VB12 is not found poisoning phenomenon in intravenous or intramuscular. 2. Applications in respect of feed VB12 can promote growth and development of the poultry, livestock especially poult, young animals , improve the utilization of feed protein, and thus it may be used as feed additives. Treatment of eggs and fry with vitamin B12 solution to improve fish of toxic substances in the water such as tolerance to benzene and heavy metal and reducing mortality. Since the  "mad cow" incident in European, the use of the chemical structure of vitamins and other nutritional supplements to replace the clear "MBM" has more room for development. Currently the world's production of VB12 is mostly used for the feed industry. 3. In other aspects of the application In developed countries, VB12 complex with other substances are used in cosmetics; in the food industry, VB12 is used as ham, sausage, ice cream, fish, meat and other food colorants. In family life, the VB12 solution is adsorbed on activated carbon, zeolites, non-woven fabric or paper to be made into soap, toothpaste, etc; it can be used for deodorant toilet, refrigerator, eliminating the smell of sulfide and aldehydes; VB12 is also available in dehalogenation of environmental protection soil and  common pollutants in surface water-organic halides. Content Analysis Weighed accurately sample of about 30 mg, and it is taken transferred to a 1000ml volumetric flask to volume with water and mix. Another Weigh Pharmaceutical grade vitamin B12 as reference standard sample, dissolved in water, and then gradually diluted with water to a concentration of about 30μg/ml of the standard solution. Make a blank test with water, with a suitable spectrophotometer, and measured at the maximum absorption wavelength (about 361nm), the absorbance of the two solutions in 1 cm Colorimetric pool . According to the following formula to calculate the sample of vitamin B12 (C63 H88CoNl4O14P) content (mg). Content of vitamin B12 (mg) = C × Au/As Where c is the concentration of reference standard solution, in units of μg/ml; Au and As are the absorbance of the sample solution and reference standard solution, respectively. Toxicity GRAS(FDA，§182．5945，2000)。 Limited use GB 14880-94: infant food, fortified beverages 10~15μg/kg. FDA, §184.1945 (2000): In (3MP) limit. GB 2760-2002 (μg/kg): soft drinks 0.6-1.8 ; instant breakfast cereal, 5-10; jelly 2.0-6.0; cocoa powder and other solid nutritional beverage flavors, 1-6.6 (corresponding nutritious milk drink by diluting reduce multiple usage). Production method 1. A large number of synthetic vitamin B12 can be produced by actinomycetes, such as Streptomyces sp., and the production of vitamin B12. in the culture solution of this kind of bacteria is used in industry. The whole synthesis of vitamin B12 has been completed in 1973 by R.B. Wood, which is a very outstanding work in organic synthesis. 2.1)It is prepared by the chain of gray mold fermentation broth after acidification with a weak acid exchange acrylic cationic resin--122 adsorption, and then eluted, purified, transformed with 1% cyanide by solvent and water extraction repeatedly, lead oxide layer analysis, crystallized from acetone to obtain the finished product. (2) Glucose, corn syrup as the raw material, vaccination Hsueh Propionibacterium (Propionibacterium shermarii) fermentation, the fermentation broth was added cobalt chloride, 5,6-2-methyl benzimidazole, were extracted and dried to obtain product. Chemical Properties Dark red, crystalline powder or dark red crystals. Originator Berubigen,Upjohn,US,1949 History VITAMIN B12 (Cobalamin), Sometimes also called cyanocobalamin, this vitamin is one of the more recent of the major B complex vitamins to be fully identified, with its structure not definitized (by Hodkin et al.) Uses vitamin, coenzyme B12 Uses Prototype of the family of naturally occurring cobalt coordination compounds knows as corrinoids. Analogs of vitamin B12 which differ only in the β-ligand of the cobalt are termed cobalamins. Synthesi zed almost exclusively by bacteria. Dietary sources include fish, meat, liver, and dairy products; plants have little or no cobalamins. Converted by the body into its bioactive forms, methylcobalamin and cobamamide, which serve as enzyme cofactors. Severe deficiency may result in megaloblastic anemia and/or neurological impairment. Uses A coenzyme for synthesis of nucleic acids and metabolism carbohydrates. Uses Vitamin B12 is water-soluble required for the normal development of red blood cells. Its deficiency causes pernicious anemia. It is stable in neutral conditions and is more stable for storage than for processing conditions. It is found in meat, fish, and milk. Production Methods Vitamin B12 dietary supplements are often prepared commercially by the fermentation of S. griseus, S. aureofaciens, Propionibacterium; or as a by-product of antibiotic production. Manufacturing Process The following is taken from US Patent 3,057,851. Milorganite was extracted with water to obtain an aqueous extract containing vitamin B12 active substances. This aqueous extract was purified by treatment with an ion exchange resin according to the following method. An aqueous extract of milorganite, 100 ml containing 300 μg of vitamin B12 active substances and 4.5 grams of total solids, was combined with 0.5 gram of sodium nitrite and 0.4 gram of potassium cyanide. The resulting solution was adjusted to pH 4.0 with hydrochloric acid and heated to boiling. The boiled solution was filtered through a Super-Cel filter surface, and the filter was then washed with water. The filtrate was obtained in a total volume of 130 ml including the washings. Amerlite XE-97, an ion exchange resin of the carboxyl type (Rohm and Haas), was classified to an average wet particle size of 100 to 150 mesh. The classified resin was utilized in the hydrogen form, and was not buffered during the ion exchange fractionation. The classified resin, in the amount of 35 ml, was packed into a glass column having a diameter of 25 mm and a height of 250 mm. The cyanide-treated aqueous extract of milorganite was infused gravitationally into the ion exchange bed at a rate of 3 ml per minute. The effluent was discarded and the resin bed was then washed with the following solutions in the specified sequence: (1) 120 ml of an aqueous 0.1 N hydrochloric acid solution; (2) 75 ml of an aqueous 85% acetone solution; and (3) 70 ml of an aqueous 0.1 N hydrochloric acid solution. After washing, the resin bed was eluted with an aqueous 60% dioxane solution containing 0.1 N of hydrochloric acid. In this elution, 8 ml of colored eluate was collected. This portion of the eluate was found to contain 295 μg of cyanocobalamin and 9 mg of total solids. Brand name Nascobal (QOL). Therapeutic Function Hematinic General Description Pharmaceutical secondary standards for application in quality control, provide pharma laboratories and manufacturers with a convenient and cost-effective alternative to the preparation of in-house working standards. Cyanocobalamin, also known as vitamin B12, belongs to a group of organic compounds important for the normal growth and development of human and animal bodies. It is used for the treatment of trigeminal neuralgia and multiple sclerosis. Health Hazard Deficiency diseases or disorders include retarded growth; pernicious anemia; megaloblastic anemia; macrocytic, hyperchromic anemia; glossitis; spinal cord degeneration; and sprue. Biological Activity Principal physiological functions include: (1) Coenzyme in nucleic acid, protein, and lipid synthesis; (2) maintains growth; (3) participates in methylations; (4) maintains epithelial cells and nervous system (myelin sheath); (5) erythropoiesis (with folic acid); (6) leukopoiesis. Biochem/physiol Actions Vitamin B12 is metabolized to its active form, methylcobalamin. Hindered vitamin B12 uptake is observed in pernicious anemia. Vitamin B12 is essential for erythroblast development. Pregnancy reduces the levels of vitamin B12. Aging reduces vitamin B12 absorption. It works as a coenzyme in fat, carbohydrate and protein metabolism. It is required for growth, genetic stability and survival of cells in vitro. Functions to support one-carbon metabolism. Present in many classical and serum-free formulations. Safety Profile Poison by subcutaneous route. Moderately toxic by intraperitoneal route. An experimental teratogen. Experimental reproductive effects. When heated to decomposition it emits very toxic fumes of POx and NOx. See also COBALT COMPOUNDS. Veterinary Drugs and Treatments Cyanocobalamin is used for treating deficiencies of vitamin B12. Malabsorption of the nutrient secondary to gastrointestinal tract disease, or dietary chromium deficiencies (in ruminants) can be associated with dietary deficiencies of vitamin B12. As there appears to be a high percentage of cats with exocrine pancreatic insufficiency or gastrointestinal disease that are deficient in cobalamin, there is considerable interest in evaluating serum cobalamin (vitamin B12) in these patients. Giant schnauzers may have a genetic defect affecting the location of the cobalamin-intrinsic factor, causing cobalamin deficiency. Dogs with inflammatory bowel disease may also develop cobalamin deficiency. Purification Methods Vitamin B12 crystallises from de-ionized H2O, with a solubility in H2O of 1g/80g, and is dried under vacuum over Mg(ClO4)2. The dry red crystals are hygroscopic and can absorb 12% of 2O. A solution at pH 4.5-5 can be autoclaved for 20minutes at 120o without decomposition. Aqueous solutions are stabilised by addition of (NH4)2SO4. [Golding Comprehensive Organic Chem Vol 5 (Ed. Haslam; Pergamon Press, NY, 1979) pp 549584.] Alternatively an aqueous solution of the coenzyme can be concentrated, if necessary in a vacuum at 25o or less, until the concentration is 0.005 to 0.01M (as estimated by the OD at 522nm of an aliquot diluted with 0.01M K-phosphate buffer pH 7.0). If crystals begin to form on the walls of the container, they should be re-dissolved with a little H2O. The concentrated solution is placed in a glass stoppered flask and diluted with 5volumes of Me2CO. After 2-3hours at 3o it is centrifuged (10,000xg/10minutes) in Me2CO-insoluble plastic tubes to remove some amorphous precipitate. The clear supernatant is inoculated with a small crystal of the vitamin and allowed to crystallise overnight at 3o. Crystals are formed on the walls and the bottom of the container. A further 2volumes of Me2CO are added and set aside at 3o to further crystallise. Crystallisation is followed by observing the OD522 of the supernatant. When the OD falls to 0.27, then ca 94% of the crystals have separated. The supernatant is decanted (saved for obtaining a second crop), and the crystals are washed with a little cold 90% aqueous Me2CO (2x), 100% Me2CO (2x), Et2O (2x) at which time the crystals separate from the glass walls. Allow them to settle and remove residual Et2O with a stream of dry N2. The process can be repeated if necessary. The crystals can be dried in air or in a vacuum for 2hours over silica gel at 100o with an 8-9% weight loss. [Barker et al. Biochemical Preparations 10 33 1963.] This material gives a single spot on paper chromatography [see Weissbach et al. J Biol Chem 235 1462 1960.] The vitamin is soluble in H2O (16.4mM at 24o, 6.4mM at 1o), in EtOH and PhOH but insoluble in Me2CO, Et2O, CH2Cl2 and dioxane. UV: max at 260, 375 and 522nm ( 34.7 x 106, 10.9 x 106 and 8.0 x 106 / mole) in H2O. The dry crystals are stable for months in the dark, but aqueous solutions decompose on exposure to VIS or UV light or alkaline CN-, but are stable in the dark at pH 6-7. The vitamin is inactivated by strong acids or alkalies. [Barker et al. J Biol Chem 235 480 1960, see also Vitamin B12 (Zagalak & Friedrich Eds) Walter de Gruyter, Berlin 1979, Beilstein 2 6 IV 3117.]   Vitamin B12 Preparation Products And Raw materials Raw materials Cobalt chloride-->Lead monoxide-->streptomyces avermifilis-->Cyanide, Quant Test Strips-->Cation exchange resin,weak acidic acrylic acid-->2-Methylbenzimidazole-->5,6-Dimethylbenzimidazole Preparation Products Mecobalamin

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Leader Biochemical Group is a large leader incorporated industry manufacturers and suppliers of advanced refined raw materials From the year of 1996 when our factory was put into production to year of 2020, our group has successively invested in more than 52 factories with shares and subordinates.We focus on manufacture Pharm & chemicals, functional active ingredients, nutritional Ingredients, health care products, cosmetics, pharmaceutical and refined feed, oil, natural plant ingredients industries to provide top quality of GMP standards products.All the invested factories' product lines cover API and intermediates, vitamins, amino acids, plant extracts, daily chemical products, cosmetics raw materials, nutrition and health care products, food additives, feed additives, essential oil products, fine chemical products and agricultural chemical raw materials And flavors and fragrances. Especially in the field of vitamins, amino acids, pharmaceutical raw materials and cosmetic raw materials, we have more than 20 years of production and sales experience. All products meet the requirements of high international export standards and have been recognized by customers all over the world. Our manufacture basement & R&D center located in National Aerospace Economic & Technical Development Zone Xi`an Shaanxi China. Now not only relying on self-cultivation and development as well as maintains good cooperative relations with many famous research institutes and universities in China. Now, we have closely cooperation with Shanghai Institute of Organic Chemistry of Chinese Academy of Science, Beijing Institute of Material Medical of Chinese Academy of Medical Science, China Pharmaceutical University, Zhejiang University. Closely cooperation with them not only integrating Science and technology resources, but also increasing the R&D speed and improving our R&D power. Offering Powerful Tech supporting Platform for group development. Keep serve the manufacture and the market as the R&D central task, focus on the technical research.  Now there are 3 technology R & D platforms including biological extract, microorganism fermentation and chemical synthesis, and can independently research and develop kinds of difficult APIs and pharmaceutical intermediates. With the strong support of China State Institute of Pharmaceutical Industry (hereinafter short for CSIPI), earlier known as Shanghai Institute of Pharmaceutical Industry (SIPI), we have unique advantages in the R & D and industrialization of high-grade, precision and advanced products.  Now our Group technical force is abundant, existing staff more that 1000 people, senior professional and technical staff accounted for more than 50% of the total number of employees, including 15 PhD research and development personnel, 5 master′ S degree in technical and management personnel 9 people. We have advanced equipment like fermentation equipment and technology also extraction, isolation, purification, synthesis with rich production experience and strict quality control system, According to the GMP required, quickly transforming the R&D results to industrial production in time, it is our advantages and our products are exported to North and South America, Europe, Middle East, Africa, and other five continents and scale the forefront in the nation, won good international reputation.  We believe only good quality can bring good cooperation, quality is our key spirit during our production, we are warmly welcome clients and partner from all over the world contact us for everlasting cooperation, Leader will be your strong, sincere and reliable partner in China.

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