WO2017206704A1 - Nouvelle forme cristalline ii de la méthionine et son procédé de préparation - Google Patents

Nouvelle forme cristalline ii de la méthionine et son procédé de préparation Download PDF

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Publication number
WO2017206704A1
WO2017206704A1 PCT/CN2017/084385 CN2017084385W WO2017206704A1 WO 2017206704 A1 WO2017206704 A1 WO 2017206704A1 CN 2017084385 W CN2017084385 W CN 2017084385W WO 2017206704 A1 WO2017206704 A1 WO 2017206704A1
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Prior art keywords
methionine
crystal form
crystallization
particles
hours
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English (en)
Chinese (zh)
Inventor
吴传隆
万霞
刘桢
刘丹
李华萍
金海琴
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Ningxia Unisplendour Tianhua Methionine Co Ltd
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Ningxia Unisplendour Tianhua Methionine Co Ltd
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
    • C07C319/26—Separation; Purification; Stabilisation; Use of additives
    • C07C319/28—Separation; Purification
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
    • C07C319/14—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
    • C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
    • C07C323/51—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton
    • C07C323/57—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being further substituted by nitrogen atoms, not being part of nitro or nitroso groups
    • C07C323/58—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being further substituted by nitrogen atoms, not being part of nitro or nitroso groups with amino groups bound to the carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/13—Crystalline forms, e.g. polymorphs

Definitions

  • the invention relates to a new crystalline form of methionine and a preparation method thereof.
  • the chemical formula of DL-Methionine is C 5 H 11 O 2 NS, white flake crystal or crystalline powder with special odor and slightly sweet taste.
  • Also used for amino acid infusion, comprehensive amino acid preparations, can be used as spices according to China's GB2760-86 regulations, it is also an essential animal feed additive, animal feed with methionine can help animals grow quickly in a short time, so that It saves about 40% of the feed. Lack of methionine in livestock and poultry can cause stunting, weight loss, liver and kidney function weakening, muscle atrophy, and skin deterioration.
  • Chinese patent CN104926701 A discloses a purification process of methionine, which uses a macroporous adsorption resin to separate methionine and by-product salts, methionine is adsorbed on a macroporous adsorption resin and then desorbed by a desorbent to recover methionine, a by-product salt substance.
  • the adsorption process it is not adsorbed into the adsorption effluent by the macroporous adsorption resin, and mainly includes the following steps: 1) Resin adsorption: the methionine solution passes through the macroporous adsorption resin layer from top to bottom, and the methionine content in the resin column effluent is greater than When it is equal to 10% (w/w) of the inlet content, the resin adsorption is stopped; the resin adsorbs the effluent as a by-product salt; 2) the resin is desorbed: the adsorbed resin is completed in step 1), and the desorbent is used from top to bottom.
  • the desorbed liquid is subsequently processed according to the existing process flow.
  • the methionine product with purity ⁇ 99% can be obtained, the content of methionine in the by-product salt substance is ⁇ 0.03%, and the yield of resin extraction methionine is ⁇ 98%.
  • Cisoka patent CN104177280 A discloses a methionine production process, step 1: separating the methionine crystallization mother liquor through a continuous chromatographic separation system filled with sodium or potassium type chromatography resin to obtain a methionine solution and an inorganic salt solution; Step 2: methionine solution
  • the reverse osmosis system is used to concentrate the methionine reverse osmosis concentrate, and the obtained methionine reverse osmosis concentrate is returned to the crystallization process; the process is simple, the separation effect is good, the purity of methionine is high, and the concentration cost is low.
  • Chinese Patent No. CN101480385 B discloses the use of methionine for the preparation of a composition for treating or preventing vestibular hair cell disease of the inner ear, the pharmaceutical composition comprising: (a) 50-200 parts by weight of methionine and/or a polypeptide thereof; (b) 400-2000 parts by weight of a pharmaceutically acceptable carrier; and the weight of (a) + (b) is 50-99% by weight based on the total weight of the pharmaceutical composition, the pharmaceutical composition being a solid preparation or A liquid preparation comprising an opacifying agent, a solution, a suspending agent, a syrup, a drop, and the like.
  • the currently produced methionine granule products have poor processing flowability, low bulk density, and increased packaging and transportation costs.
  • Another object of the present invention is to provide a process for preparing the above methionine crystal form II.
  • a methionine crystal form II characterized in that the crystal form has a diffraction angle 2 ⁇ of 22.304 ⁇ 0.2°, 33.757 ⁇ 0.2°, 45.674 ⁇ 0.2°, 28.104 ⁇ 0.2°, 18.615 ⁇ 0.2°, There is a diffraction peak at 42.739 ⁇ 0.2°.
  • the methionine crystal form II of the present invention has a diffraction angle 2 ⁇ of 11.145 ⁇ 0.2°, 16.716 ⁇ 0.2°, 18.615 ⁇ 0.2°, 22.304 ⁇ 0.2°, 25.203 ⁇ 0.2°, 28.104 ⁇ 0.2°, 33.757 ⁇ 0.2°, There are diffraction peaks at 42.739 ⁇ 0.2°, 45.674 ⁇ 0.2°, and 51.812 ⁇ 0.2°.
  • methionine crystal form II is characterized in that it has the following Value and relative intensity percentage I (%) value expressed by -X-ray powder diffraction data,
  • methionine crystal form II is characterized in that it has the following Value and relative intensity percentage I (%) value expressed by -X-ray powder diffraction data,
  • the above methionine crystal form II is characterized in that it has the structure shown in FIG. The X-ray powder diffraction pattern shown.
  • the above-mentioned methionine crystal form II has a melting point peak temperature of 287 ° C, and the crystal form has a DSC/TG pattern as shown in FIG. 2 .
  • the methionine crystal form II of the present invention has the same chemical structure as methionine, and has good quality and excellent processing flowability.
  • the preparation method of the methionine crystal form II of the invention adopts the following steps:
  • the above methionine neutralization solution is added to the isopropanol solvent, the methionine neutralization solution in the concentration of isopropanol 0.3-1.0 mg / mL, continuously stirring at 55 ° C ⁇ 65 ° C, stirring time 0.5-1.5 hours;
  • the solution is pre-cooled in an environment of -1 ° C - 5 ° C for 1-2 hours; then vacuum crystallization, the cooling medium for crystallization is ethylene glycol, the temperature of the cooling medium is -10 ° C, and the crystallization temperature is 0 ° C to -5 ° C.
  • the stirring rate is 30-60 r/min, the degree of vacuum is 19-30 kPa, and the crystallization time is 3-6 hours.
  • the methionine crystal form II of the invention is white crystal particles, has good light reflectivity, and has large and relatively uniform particles, and has a flat block shape with a length to width ratio of about 2:1, and the particle length is concentrated in the range of 450-550 micrometers, and the single particles.
  • the appearance is a complete and dense crystal with excellent quality.
  • the inventors found that the fluidity and bulk density are closely related to the key peak position and relative peak intensity of the X-ray powder diffraction pattern.
  • the methionine crystal form II of the present invention has a high bulk density of 1-2 g/cm 3 and processing fluidity.
  • the injection angle method (fixed funnel method) is used to determine the angle of repose of the crystal particles, ⁇ ⁇ 40 degrees, which is advantageous for subsequent large-scale industrial production applications.
  • Figure 1 is a crystalline methionine X-ray powder diffraction pattern of the present invention
  • Figure 2 is a differential scanning thermal analysis (DSC) / thermogravimetric analysis (TG) diagram of crystalline methionine of the present invention
  • Figure 3 is a scanning electron micrograph of the crystalline methionine of the present invention at 100 times.
  • the preparation method of methionine crystal form II is carried out as follows:
  • the above methionine neutralization solution is added to the isopropanol solvent, the methionine neutralization solution is at a concentration of 0.5-0.6 mg/mL of isopropanol, and the mixture is continuously stirred and stirred at 60 ° C for 1 hour; Pre-cooling in the environment of 0 ° C -1 ° C for 1.5 hours; vacuum crystallization, the cooling medium for crystallization is ethylene glycol, cooling medium temperature -10 ° C, crystallization temperature -2 ° C, stirring rate 40-45 r / min, vacuum Degree 22-25 kPa, crystallization time 4.5 hours.
  • Example 1 The methionine crystals prepared in Example 1 were subjected to XRD test:
  • the radiation source is a Cu target with a wavelength of 1.54060 nm, a scanning angle of 10 to 70 degrees, a voltage of 30 kV, a current of 20 mA, and a scanning speed of 2.4°/min. Its X-ray powder diffraction pattern is shown in Figure 1.
  • the crystalline methionine has a diffraction angle 2 ⁇ of 11.145 ⁇ 0.2°, 16.716 ⁇ 0.2°, 18.615 ⁇ 0.2°, 22.304 ⁇ 0.2°, 25.203 ⁇ 0.2°, 28.104 ⁇ 0.2°, 33.757 ⁇ 0.2°, 42.739 ⁇ 0.2°, There are diffraction peaks at 45.674 ⁇ 0.2° and 51.812 ⁇ 0.2°.
  • the crystalline methionine of the present invention has a powder X-ray pattern expressed by a crystal plane spacing D, a Bragg angle (2 ⁇ ), a percentage of relative intensity I (%), and an intensity (I value) crystal form, as follows:
  • DSC differential scanning thermal analysis
  • TG thermogravimetric analysis chart
  • the scanning electron micrograph of the methionine crystalline particles at 100 times is shown in Fig. 3.
  • the particles are large and uniform, and have a flat block shape with a length to width ratio of about 2:1.
  • the particle length is concentrated in the range of 450-550 ⁇ m.
  • the individual particles appear as intact and dense crystals.
  • the methionine crystal form II bulk density was determined to be 2 g/cm 3 , and the methionine crystal obtained above was measured for the angle of repose:
  • the angle of repose of the methionine crystal prepared above was measured by an injection method (fixed funnel method). Pour the sample to be tested into the funnel, and gently and evenly fall into the center of the disc to form a cone. When the material falls freely from the oblique edge of the powder along the edge of the disc, the feeding is stopped, and the angle of repose is determined by a protractor. The three angles of repose were measured repeatedly: 36.4, 34.7, and 33.5 degrees, and the crystal particles were excellent in fluidity.
  • the preparation method of methionine crystal form II adopts the following steps:
  • the above methionine neutralization solution is added to the isopropanol solvent, the methionine neutralization solution is at a concentration of 0.9-1.0 mg/mL of isopropanol, and the mixture is continuously stirred and stirred at 65 ° C for 0.5 hour; Pre-cooling for 1 hour in an environment of -1 ° C; vacuum crystallization, crystal cooling medium is ethylene glycol, cooling medium temperature -10 ° C, crystallization temperature -5 ° C, stirring rate 30-35 r / min, vacuum degree 19 - 21 kPa, crystallization time 6 hours.
  • Example 2 It was identified by the method of Example 2 that it was the methionine crystal form II of the present invention, the bulk density was 1.5 g/cm 3 , and the angle of repose ⁇ was 37.1 degrees.
  • the preparation method of methionine crystal form II adopts the following steps:
  • the above methionine neutralization solution is added to the isopropanol solvent, the methionine neutralization solution is at a concentration of 0.3-0.4 mg/mL of isopropanol, and the mixture is continuously stirred and stirred at 55 ° C for 1.5 hours; Pre-cooling for 2 hours in an environment of 4 ° C - 5 ° C; vacuum crystallization, the cooling medium for crystallization is ethylene glycol, cooling medium temperature -10 ° C, crystallization temperature 0 ° C, stirring rate 55-60 r / min, vacuum 28-30 kPa, crystallization time 3 hours.
  • Example 2 It was identified by the method of Example 2 that it was the methionine crystal form II of the present invention, the bulk density was 1.0 g/cm 3 , and the angle of repose ⁇ was 35.9 degrees.
  • the preparation method of methionine crystal form II adopts the following steps:
  • the above methionine neutralization solution is added to the isopropanol solvent, the methionine neutralization solution is at a concentration of 0.7-0.8 mg/mL of isopropanol, and the mixture is continuously stirred and stirred for 0.8 hours at 62 ° C; Pre-cooling in the environment of 2 ° C -3 ° C for 1-2 hours; then vacuum crystallization, the cooling medium for crystallization is ethylene glycol, cooling medium temperature -10 ° C, crystallization temperature -1 ° C, stirring rate 50 r / min, vacuum Degree 20-22 kPa, crystallization time 5 hours.
  • Example 2 It was identified by the method of Example 2 that it was the methionine crystal form II of the present invention, the bulk density was 1.3 g/cm 3 , and the angle of repose ⁇ was 34.3 degrees.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Fodder In General (AREA)

Abstract

L'invention concerne une nouvelle forme cristalline II de la méthionine, les cristaux II manifestant des pics de diffraction à 22 304 ± 0,2°, 33 757 ± 0,2°, 45 674 ± 0,2°, 28 104 ± 0,2°, 18 615 ± 0,2° et 42 739 ± 0,2° à l'angle de diffraction 2θ. Les cristaux II de la méthionine selon la présente invention se présentent sous la forme de particules blanches ayant une bonne réflectivité de la lumière, les particules étant de grande taille, relativement uniformes et longues, et ayant une forme de bloc plat avec un rapport de largeur d'environ 2:1, la longueur des particules étant concentrée dans la plage allant de 450 à 550 microns, l'aspect d'une particule unique étant un cristal compact complet, et la qualité étant excellente. L'inventeur a découvert également que la fluidité et la densité en vrac sont liées à la position des pics et à l'intensité maximale relative du spectre de diffraction de poudre de rayons X, les cristaux II de la méthionine selon la présente invention ayant une densité en vrac importante, atteignant 1 à 2 g/cm3, la fluidité de traitement étant bonne, l'angle de repos des particules cristallines étant déterminé par un procédé d'injection (procédé d'entonnoir fixe), θ ≤ 40 degrés, et lesdits cristaux s'appliquant à la production industrielle à grande échelle.
PCT/CN2017/084385 2016-06-03 2017-05-15 Nouvelle forme cristalline ii de la méthionine et son procédé de préparation Ceased WO2017206704A1 (fr)

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CN201610387326.3A CN106008297B (zh) 2016-06-03 2016-06-03 一种蛋氨酸新晶型ⅱ及其制备方法
CN201610387326.3 2016-06-03

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106008297B (zh) * 2016-06-03 2018-11-30 宁夏紫光天化蛋氨酸有限责任公司 一种蛋氨酸新晶型ⅱ及其制备方法
CN108157908A (zh) * 2018-02-09 2018-06-15 武晓丹 一种利用抽真空制备高堆密度i+g混晶的方法

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS4324890B1 (fr) * 1966-08-25 1968-10-28
CN1274717A (zh) * 1999-05-21 2000-11-29 住友化学工业株式会社 蛋氨酸的制备方法
CN101602700A (zh) * 2008-06-09 2009-12-16 住友化学株式会社 生产蛋氨酸的方法
CN106008297A (zh) * 2016-06-03 2016-10-12 宁夏紫光天化蛋氨酸有限责任公司 一种蛋氨酸新晶型ⅱ及其制备方法

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2641898A1 (fr) * 2012-03-20 2013-09-25 Evonik Industries AG Procédé destiné à la fabrication de méthionine
CN104744326B (zh) * 2015-02-12 2016-08-10 山东新和成氨基酸有限公司 一种连续制备高堆积密度甲硫氨酸结晶的方法

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS4324890B1 (fr) * 1966-08-25 1968-10-28
CN1274717A (zh) * 1999-05-21 2000-11-29 住友化学工业株式会社 蛋氨酸的制备方法
CN101602700A (zh) * 2008-06-09 2009-12-16 住友化学株式会社 生产蛋氨酸的方法
CN106008297A (zh) * 2016-06-03 2016-10-12 宁夏紫光天化蛋氨酸有限责任公司 一种蛋氨酸新晶型ⅱ及其制备方法

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