• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
  • 引用文献
  • 法律状态
  • 优先权
    • 专利摘要:
    Crystalline salts of beta -nicotinamide-adenine-dinucleotide ( beta -NAD), particularly alkali metal salts thereof are prepared in good yield and high quality to provide an analytically useful beta -NAD form.
    公开号:SU932992A3
    申请号:SU772511705
    申请日:1977-08-18
    公开日:1982-05-30
    发明作者:Мюлеггер Клаус；Вайманн Гюнтер；Нельбоэк-Хохштеттер Михаэль
    申请人:Берингер Маннхайм Гмбх (Фирма)；
    IPC主号:
    专利说明:

    (5) METHOD FOR OBTAINING ORTHORHOMBIC MONOLITHIUM SALT -NICOTINAMIDADENINDINO-NUCLEOTYDIDYDHYDRATE
    one
    The invention relates to a half-way method of a new compound — ortho-orthorhombic monolithium salt — nicotinamide adenine dinucleotide dihydrate
    ,) with space group g P 2/2-f with cell size
    0 10,, OOZA; y15;
    С 17,, siege and angles 0 / Ь T 90 which can be used in enzymatic analysis with JQ determination of enzymatic activities and substrate concentrations for clinical diagnosis.
    It is known to obtain crystalline nicotinamide adenine dinucleotide in the form of the free acid flj.
    However, this acid is very hygroscopic and rapidly spreads in air, which causes certain difficulties when used in enzymatic analysis in determining the activity and concentration of the substrate for clinical diagnosis. 2.26
    There is also known a method of obtaining crystalline salts and aqueous solutions by precipitating a target pro, product with an organic solvent 3j "
    The purpose of the invention is to obtain a new crystalline compound expanding the arsenal of a means of influencing a living organism.
    This goal is achieved by the fact that in the method of obtaining orthorhombic monolithium salt, P-nicotinamide adenine dinucleotide dihydrate with the space group P 2 / f 2 2f with cell sizes a 10,, OOZA; B 15.839 ± 0.00 “A; From 17,821
    0.004A and angles o11- / 90 ° to lithium hydroxide or cation exchange in lithium form to a pH of 3-7, preferably 3, 7.0, or to an aqueous solution of amorphous monolithium saltJJ- nicotinamide dendinucleotide add lithium hydroxide to pH 3-7.
    Preferably, to a pH of 3, 0, a water-miscible organic solvent is added to the half-sized aqueous solution, preferably at room temperature, before s begins to cloud the solution and the desired product crystallizes at 4-30 seconds. As a water miscible organic solvent in the proposed method, O can be used, generally any solvent having these properties. However, preference is given to low alcohols, ketones, nitriles and cyclic ethers, in particular methanol, ethanol, 15 H-propanol, isopropanol, acetone, acetonitrile or dioxane.
    Example 1. 1 g of lithium salt (obtained by passing a solution of free acid through 20 C gv-50 in the form of lithium, followed by lyophilization is dissolved in 2 ml of water, 1.2 ml of acetone is added dropwise with stirring at room temperature before starting turbidity. At 25–20–25 ° C, crystallization occurs. After 30 hours, the crystallized product is sucked off, washed twice with a small amount of acetone and water.
    (1: 2) and dried in a vacuum over zo. P2.05 Yield: 900 mg (90 using lyophilisate).
     -
    Example 2. 1g of a lyophilized lithium salt of p-NAD is dissolved in 2 ml of water and at room temperature, with stirring, 3.6 ml of methanol is added dropwise until cloudy. as in example 1. After drying, 900 mg of crystallized lithium salt are obtained.
    Example 3-1 g of Jb-NAD as a lyophilized free acid are dissolved in 0.75 ml of NlO and, with stirring, by dropping 1.3 ml of 1-M-lithium hydroxide, the pH is adjusted to. Then 2 ml of methanol are added and the mixture is left for 30 hours at 20-25 ° C. After treatment, analogous to Example 1, 900 mg (901 uses) of crystallized lithium salt p-NAD are obtained.
    Example t. 1 g of lyophized lithium salt (L-NAD is dissolved in 2 ml of water and 0.8 ml of isopropanol is added in the same way as in example 1. After 55 suction, washing and drying, 800 mg (80% use; crystallized lithium salt) are obtained.
    Example 5 0.5 mg of a lyophilized lithium salt / 3-NAD solution in 1 ml of water and 0.85 ml of dioxane are added in the same manner as in Example 1. The crystallization yield is 70 of the lyophilisate used.
    Example 6 0.5 g of the lyophilized lithium salt of R-NAD is dissolved in 1 ml of water and, as in Example 1, 0 ml of acetonitrile is slowly added. A lithium crystallization salt is obtained with a yield of 80 relative to the used lyophilisate.
    Example 7 0.5 g of the lyophilized lithium salt of p-NAD is dissolved in 1 ml of water and left at room temperature. After su to begin precipitation of crystals. For complete crystallization, it is left to stand still for 3 days at room temperature. The yield is kO% relative to the use of the lyophilisate.
    Analysis of the orthorhombic monolith salt
    Total formula
    . 2KgO
    Molar weight 705,
    NAD (enzymatic
    with ADH),% - 93.5
    Water 5.5
    Lithium, 1.17
    Mp., C203-203.5
    Elemental analysis:
    Found C, 35.28; H, 3.99; N 13.59
    . P 8.73.
    Calculated,%: C 35.76; H 4.28;
    N 13.90; R 8.78. Crystallographic data: Orthorhombic crystal system 90 °
    Angle o1, p, Spatial
    P2x ,, group about cell dimensions, A
    a 10,, 003 b 15,, 00 + c 17.821 ± 0, crystal density, g / cm1.65 A crystal consists of a formula unit in asymmetric unity.
    权利要求:
    Claims (3)
    [1]
    Example 8. (Additional for upper pH limit value) 1 g of P-NAD of lyophilized free acid is dissolved in 0.8 ml and with stirring, k ml 1N. lithium hydroxide regulate pH to. 7- After this, 2.2 ml of methanol is added and the solution is left at 20-25 ° C for 2k-kB h. 5 After processing in the same manner as in Example 1, 900 mg (90% of water) of crystallized fr-NAD of the lithium salt are obtained. Example 9 is optional. 1 g of p-NAD (lyophilized free acid is dissolved in 1 ml of HjO at room temperature and using O, ml of 1N lithium hydroxide, with stirring, the pH is adjusted to 3.3. Then 1 ml of methanol is added and the mixture is left After being processed in analogy to example 1, 200 mg are obtained (20 injections of crystallized R-NAD lithium salt. Example 10. 1 g of lyophilized / J-NAD lithium salt is dissolved in 2 ml H „O (pH is 3.7) and mixed with 2 ml of methanol while cooling. After 30 hours of settling at 20-25 ° C, crystallized is processed in the same way as Example 1. 900 mg (90 inputs) of crystallized fi-NAD lithium salts are obtained. Example 11. Additional 1 g of lyophilized Jb-NAD lithium salt is dissolved in Z ml H-O The pH value is 3.7), the solution is heated to dou-50 ° C and 2 ml of methanol is added with stirring. The mixture is left for 2 -30 hours to crystallize at 20-25 ° C and then is worked up as in Example 1. 850 are obtained. mg (85 input) crista. lithium salt. 2 The claims The method of obtaining the orthorhombic monolithium salt | -nicotinamide adenine dinucleotide dihydrate with a space group of P2 f 2 - S cell size a 10 10,073tO, 003A; 1 15.839 ± 0, OOW; From 17.821 f O.OOjA and angles from /. ft 30, characterized in that lithium hydroxide or cation exchanger in lithium form is added to a pH of 3-7, preferably 3.7, O, or to an aqueous solution of an amorphous monolithium salt of p-nicotinamide adenine dinucleotide lithium hydroxide is added to a pH of 3-7, preferably 3.7-, O, to the resulting aqueous solution at 1050 0, preferably at room temperature, an organic solvent is added which is water-miscible before the solution begins to cloud. allizuyut desired product at. Sources of information taken into account in the examination 1.Winer A.D. Crystallization of nicotinic adenine dinucleotide.J. Biol. Chem, 239 (Yu) 3598, 196.
    [2]
    2.Dalziel K.Ocleaning. nicotinamide adenine dinucleotide and kinetic effects of nucleotide suspensions.J.Biol.Chem., 238, 1538 {19bЗ).
    [3]
    3. US patent number 370065, cl. 260-21-1,5, pub. 1972.
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    同族专利:
    公开号 | 公开日
    NL171809B|1982-12-16|
    DE2637598C3|1981-04-02|
    JPS5434759B2|1979-10-29|
    DK145826C|1983-08-29|
    DK145826B|1983-03-14|
    DE2637598A1|1978-02-23|
    SE442118B|1985-12-02|
    DE2637598B2|1980-07-03|
    IT1081815B|1985-05-21|
    GB1561954A|1980-03-05|
    HU179125B|1982-08-28|
    FR2362159B1|1980-05-16|
    JPS5325598A|1978-03-09|
    US4148994A|1979-04-10|
    DK351477A|1978-02-21|
    NL171809C|1983-05-16|
    FR2362159A1|1978-03-17|
    NL7707022A|1978-02-22|
    SE7707449L|1978-02-21|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    US3429868A|1956-03-12|1969-02-25|Kiyoshi Kominato|Method of preparing a series of prosthetic groups and coenzymes of a new redox-enzyme which are present in plants,animals,or foods and have vitamin-like activity|
    DE1767010A1|1968-03-20|1971-08-19|Boehringer Mannheim Gmbh|Process for the purification of reduced pyridine coenzymes on ion exchangers|
    US3700654A|1969-05-19|1972-10-24|Enzomedic Lab Inc|Nad salts and methods of preparation|
    DE2059429C2|1970-12-02|1986-10-23|Boehringer Mannheim Gmbh, 6800 Mannheim|Process for the preparation of nucleoside diphosphate esters|JPS624399B2|1980-10-15|1987-01-30|Kojin Kk|
    JPS63245002A|1987-03-31|1988-10-12|Nippon Zeon Co Ltd|Manufacture of electromagnetic reflecting body|
    US10654883B2|2018-05-15|2020-05-19|Jumpstart Fertility Pty Ltd|Inorganic salts of nicotinic acid mononucleotide as anti-aging agents|
    AU2019271858A1|2018-05-15|2021-01-14|Jumpstart Fertility Pty Ltd|Inorganic salts of nicotinic acid mononucleotide as anti-aging agents|
    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    DE2637598A|DE2637598C3|1976-08-20|1976-08-20|Orthorhombic monolithium salt of β-nicotinamide adenine dinucleotide and process for its preparation|
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