WO2017206703A1 - 一种蛋氨酸新晶型i及其制备方法 - Google Patents

一种蛋氨酸新晶型i及其制备方法 Download PDF

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WO2017206703A1
WO2017206703A1 PCT/CN2017/084383 CN2017084383W WO2017206703A1 WO 2017206703 A1 WO2017206703 A1 WO 2017206703A1 CN 2017084383 W CN2017084383 W CN 2017084383W WO 2017206703 A1 WO2017206703 A1 WO 2017206703A1
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methionine
crystal form
solution
preparation
ray powder
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PCT/CN2017/084383
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French (fr)
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吴传隆
万霞
刘丹
刘桢
李华萍
金海琴
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宁夏紫光天化蛋氨酸有限责任公司
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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
    • 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

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  • 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 methionine granule product currently produced has a low solubility of about 3g/100g, and its production efficiency in liquid preparations is not high and has certain limitations.
  • Another object of the present invention is to provide a process for the preparation of the above novel methionine form I.
  • a methionine crystal form I characterized in that the crystal form is at a diffraction angle 2 ⁇ of 21.751 ⁇ 0.2°, 22.168 ⁇ 0.2°, 21.186 ⁇ 0.2°, 25.426 ⁇ 0.2°, 18.395 ⁇ 0.2°, 32.879 ⁇ 0.2°. There are diffraction peaks.
  • the crystal form product is excellent in solubility.
  • the methionine crystal form I of the present invention has a diffraction angle 2 ⁇ of 18.395 ⁇ 0.2°, 21.186 ⁇ 0.2°, 21.751 ⁇ 0.2°, 22.168 ⁇ 0.2°, 23.301 ⁇ 0.2°, 25.426 ⁇ 0.2°, 32.879 ⁇ 0.2°, There are diffraction peaks at 33.775 ⁇ 0.2°, 37.054 ⁇ 0.2°, and 42.455 ⁇ 0.2°.
  • the above methionine crystal form I 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 I 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 I is characterized in that it has the structure shown in FIG. The X-ray powder diffraction pattern shown.
  • the above-mentioned methionine crystal form I has a melting point peak temperature of 282 ° C, and this crystal form has a DSC/TG pattern as shown in FIG. 2 .
  • the methionine crystal form I of the present invention has the same chemical structure as methionine, has good quality, and is highly efficient for producing liquid preparations.
  • the preparation method of the methionine crystal form I of the invention adopts the following steps:
  • the above crude methionine is dissolved in a sec-butanol solvent at a concentration of 10 mg/mL to 50 mg/mL, continuously stirred, heated to 60 ° C to 100 ° C to dissolve, filtered to form a supersaturated solution; the solution is sealed and placed in - The crystal was cooled in an environment of 5 ° C to -10 ° C for 1-3 hours to obtain white crystals.
  • the methionine crystal form I of the invention is white crystal particles, has good light reflectivity, has large particles, is spherical like, and has a particle size concentration of 110-130 micrometers, is relatively uniform, has excellent quality, and has good solubility, and solubility in water is 4.5 g. /100g water or more, it is used in the production of liquid preparations with high efficiency and is advantageous for large-scale industrial production.
  • 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 300 times.
  • the preparation method of methionine crystal form I is as follows:
  • the above crude methionine is dissolved in a sec-butanol solvent at a concentration of 25 mg/mL to 28 mg/mL, continuously stirred, heated to 70 ° C to 75 ° C to dissolve, and filtered to form a supersaturated solution; the solution is sealed at -6 ° C The crystals were cooled and crystallized for 2.5 hours to give white crystals.
  • 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 118.395 ⁇ 0.2°, 21.186 ⁇ 0.2°, 21.751 ⁇ 0.2°, 22.168 ⁇ 0.2°, 23.301 ⁇ 0.2°, 25.426 ⁇ 0.2°, 32.879 ⁇ 0.2°, 33.775 ⁇ 0.2°, There are diffraction peaks at 37.054 ⁇ 0.2° and 42.455 ⁇ 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:
  • the differential scanning thermal analysis (DSC) of the crystalline methionine of the present invention is shown in Fig. 2, and the endothermic transition temperature is 282 ° C; the thermogravimetric analysis chart (TG) is shown in Fig. 2, about 240 ° C The first reaction was started, and the second reaction was carried out at 282 ° C, and the reaction was completed at 380 ° C.
  • DSC differential scanning thermal analysis
  • TG thermogravimetric analysis chart
  • the scanning electron micrograph of the methionine crystalline particles at 300 times is shown in Fig. 3.
  • the particles are large, spherical, and the particle size is concentrated at 110-130 microns, which is relatively uniform and excellent in quality.
  • the solubility in water is determined. 5.0 g / 100 g of water.
  • the above crude methionine is dissolved in a sec-butanol solvent at a concentration of 10 mg/mL to 20 mg/mL, continuously stirred, heated to 60 ° C to 65 ° C to dissolve, filtered to form a supersaturated solution; the solution is sealed at -10 ° C The crystals were cooled and crystallized for 3 hours to give white crystals.
  • Example 2 It was identified by the method of Example 2 that it is the methionine crystal form I of the present invention, and its solubility in water is 5.2 g / 100 g of water.
  • the above crude methionine is dissolved in sec-butanol at a concentration of 40 mg/mL to 50 mg/mL.
  • stirring was continued, and the mixture was heated to 95 ° C to 100 ° C to dissolve, and filtered to form a supersaturated solution; the solution was sealed and placed in an environment of -5 ° C to cool and crystallize for 1 hour to obtain white crystals.
  • Example 2 It was identified by the method of Example 2 that it was the methionine crystal form I of the present invention, and its solubility in water was 4.6 g / 100 g of water.
  • the above crude methionine is dissolved in a sec-butanol solvent at a concentration of 25 mg/mL to 35 mg/mL, continuously stirred, heated to 70 ° C to 80 ° C to dissolve, filtered to form a supersaturated solution; the solution is sealed at -7 ° C The crystals were cooled and cooled in an environment of ⁇ -8 ° C for 2 hours to obtain white crystals.
  • Example 2 It was identified by the method of Example 2 that it is the methionine crystal form I of the present invention, and its solubility in water is 4.8 g / 100 g of water.

Abstract

一种蛋氨酸晶型I，所述晶型I在衍射角度2θ在21.751±0.2°、22.168±0.2°、21.186±0.2°、25.426±0.2°、18.395±0.2°、32.879±0.2°处有衍射峰。本发明蛋氨酸晶型I为白色结晶颗粒、反光性好，其颗粒大、呈类球状、且粒度集中在110-130微米、较均匀、品质优异，同时其溶解性好，在水中溶解度在4.5g/100g水以上，将其用于液体制剂生产中效率高、利于规模化工业使用生产。

Description

一种蛋氨酸新晶型I及其制备方法 技术领域
本发明涉及一种蛋氨酸新晶型及其制备方法。
背景技术
蛋氨酸(DL-Methionine)化学式为C5H11O2NS，白色薄片状结晶或结晶性粉末，有特殊气味，味微甜。用于营养增补剂，添于燕麦、黑麦、米、玉米、小麦、花生粉、大豆、土豆、菠菜等食品中以改善氨基酸平衡，需要量随胱氨酸摄入量而异，成人男子需要量为1.1g/d。也用于氨基酸输液，综合氨基酸制剂，按我国GB2760-86规定可用作香料，它还是一种必不可少的动物饲料添加剂，加有蛋氨酸的动物饲料可以在短时间内帮助动物快速成长，使其节省大约40％的饲料。畜禽缺乏蛋氨酸,会引起发育不良,体重减轻,肝肾机能减弱,肌肉萎缩，皮毛变质等。
中国专利CN104926701 A公开了一种蛋氨酸的纯化工艺，采用大孔吸附树脂分离蛋氨酸和副产盐类物质，蛋氨酸被吸附在大孔吸附树脂上然后用解吸剂解吸树脂回收蛋氨酸，副产盐类物质在吸附过程中不被大孔吸附树脂吸附进入吸附流出液中，主要包括以下步骤：1)树脂吸附：蛋氨酸溶液自上而下通过大孔吸附树脂层，当树脂柱流出液中含蛋氨酸含量大于等于进口含量的10％(w/w)时，停止树脂吸附；树脂吸附流出液作为副产盐类物质；2)树脂解吸：步骤1)中完成了吸附的树脂，用解吸剂自上而下通过，解吸树脂，并收集解吸液；3)后续工艺过程：解吸液按照现有工艺流程后续处理。经 过吸附、解吸工艺，可得到纯度≥99％的蛋氨酸产品，副产盐类物质中蛋氨酸含量≤0.03％，树脂提取蛋氨酸收率≥98％。中国专利CN104177280 A公开了一种蛋氨酸生产工艺，步骤1：将蛋氨酸结晶母液通过填充有钠型或者钾型色谱树脂的连续色谱分离系统分离，得蛋氨酸溶液和无机盐溶液；步骤2：将蛋氨酸溶液采用反渗透系统浓缩得蛋氨酸反渗透浓缩液，将得到的蛋氨酸反渗透浓缩液返回结晶工序；该工艺简单、分离效果好，蛋氨酸纯度高、浓缩成本低等优点。
中国授权专利CN101480385 B公开了一种蛋氨酸的用途，蛋氨酸在制备治疗或预防内耳前庭毛细胞疾病的组合物中的用途，其药物组合物中含有：(a)50-200重量份蛋氨酸和/或其多肽；(b)400-2000重量份药学上可接受的载体；且(a)+(b)的重量是药物组合物总重量的50-99％，所述的药物组合物是固体制剂或液体制剂，所述的液体制剂包括乳浊剂、溶液剂、悬浮剂、糖浆剂、滴剂等。
目前生产的蛋氨酸颗粒产品溶解度较低、在3g/100g左右，将其用于液体制剂中生产效率不高、存在一定局限性。
发明内容
本发明的目的在于提供一种溶解性好的蛋氨酸新晶型I。
本发明另一目的在于提供上述蛋氨酸新晶型I的制备方法。
本发明目的通过如下技术方案实现：
一种蛋氨酸晶型I，其特征在于：所述晶型在衍射角度2θ在21.751±0.2°、22.168±0.2°、21.186±0.2°、25.426±0.2°、18.395±0.2°、32.879±0.2°处有衍射峰。该晶型产品溶解性优异。
具体地说，本发明蛋氨酸晶型I在衍射角度2θ在18.395±0.2°、21.186±0.2°、21.751±0.2°、22.168±0.2°、23.301±0.2°、25.426±0.2°、32.879±0.2°、33.775±0.2°、37.054±0.2°、42.455±0.2°处有衍射峰。
上述蛋氨酸晶型I，其特征在于：它具有下列
Figure PCTCN2017084383-appb-000001
值和相对强度百分比I(％)值表达的-X射线粉末衍射数据，
Figure PCTCN2017084383-appb-000002
具体地说，上述蛋氨酸晶型I，其特征在于：它具有下列
Figure PCTCN2017084383-appb-000003
值和相对强度百分比I(％)值表达的-X射线粉末衍射数据，
Figure PCTCN2017084383-appb-000004
更具体地说，上述蛋氨酸晶型I，其特征在于：它具有如图1所 示的X-射线粉末衍射图。
上述蛋氨酸晶型I的熔点峰值温度为282℃，该晶型具有如图2所示的DSC/TG图谱。
本发明所述的蛋氨酸晶型I与蛋氨酸化学结构相同，品质好、用于生产液体制剂生产效率高。
本发明蛋氨酸晶型I的制备方法，采用如下步骤：
1、在5-(β-甲巯基乙基)乙内酰脲与碳酸钾溶液反应得到的含甲硫氨酸钾水解液中加入50-1000ppm的羟丙基甲基纤维素，边搅拌边通入CO2、CO2的通入压力为0.2-0.6Mpa，进行结晶析出得到蛋氨酸粗品；
2、将上述蛋氨酸粗品以10mg/mL-50mg/mL的浓度溶解在仲丁醇溶剂中，不断搅拌，加热至60℃～100℃溶解，过滤，形成过饱和溶液；将此溶液密封放置在-5℃～-10℃环境中冷却结晶1-3小时，得到白色晶体。
本发明具有如下的有益效果：
本发明蛋氨酸晶型I为白色结晶颗粒、反光性好，其颗粒大、呈类球状、且粒度集中在110-130微米、较均匀、品质优异，同时其溶解性好，在水中溶解度在4.5g/100g水以上，将其用于液体制剂生产中效率高、利于规模化工业使用生产。
附图说明
图1为本发明结晶型蛋氨酸X射线粉末衍射图；
图2为本发明结晶型蛋氨酸的差示扫描热分析(DSC)/热重分析(TG)图；
图3为本发明结晶型蛋氨酸在300倍下的扫描电镜图。
具体实施方式
下面通过实施例对本发明进行具体的描述，有必要在此指出的是以下实施例只用于对本发明进行进一步说明，不能理解为对本发明保护范围的限制，该领域的技术人员可以根据上述本发明内容对本发明作出一些非本质的改进和调整。
实施例1
蛋氨酸晶型I的制备方法，按如下步骤：
在5-(β-甲巯基乙基)乙内酰脲与碳酸钾溶液反应得到的含甲硫氨酸钾水解液中加入200-300ppm的羟丙基甲基纤维素，边搅拌边通入CO2、CO2的通入压力为0.3Mpa，进行结晶析出得到蛋氨酸粗品；
将上述蛋氨酸粗品以25mg/mL-28mg/mL的浓度溶解在仲丁醇溶剂中，不断搅拌，加热至70℃～75℃溶解，过滤，形成过饱和溶液；将此溶液密封放置在-6℃环境中冷却结晶2.5小时，得到白色晶体。
实施例2
将实施例1所制得的蛋氨酸晶体，做XRD测试：
辐射源为Cu靶，波长为1.54060nm，扫描角度为10°～70°，电压为30kV，电流为20mA，扫描速度为2.4°/min。其X射线粉末衍射图如图1所示。
所述结晶型蛋氨酸在衍射角度2θ在118.395±0.2°、21.186±0.2°、21.751±0.2°、22.168±0.2°、23.301±0.2°、25.426±0.2°、32.879±0.2°、33.775±0.2°、37.054±0.2°、42.455±0.2°处有衍射峰。
本发明的结晶型蛋氨酸，其粉末X射线图以晶面间距D、Bragg角(2θ)、相对强度的百分比I(％)以及强度(I值)晶型表达，如下所示：
Figure PCTCN2017084383-appb-000005
本发明结晶型蛋氨酸的差示扫描热分析(DSC)如图2所示，其吸热转变温度在282℃；其热重分析图(TG)如图2所示，240℃左右 开始进行第一个反应，282℃进行第二个反应，到380℃时反应结束。
蛋氨酸结晶型颗粒在300倍下的扫描电镜图如图3所示，其颗粒较大、呈类球状、且粒度集中在110-130微米、较均匀、品质优异；经测定，其在水中溶解度在5.0g/100g水。
实施例3
蛋氨酸晶型I的制备方法，采用如下步骤：
在5-(β-甲巯基乙基)乙内酰脲与碳酸钾溶液反应得到的含甲硫氨酸钾水解液中加入50-100ppm的羟丙基甲基纤维素，边搅拌边通入CO2、CO2的通入压力为0.6Mpa，进行结晶析出得到蛋氨酸粗品；
将上述蛋氨酸粗品以10mg/mL-20mg/mL的浓度溶解在仲丁醇溶剂中，不断搅拌，加热至60℃～65℃溶解，过滤，形成过饱和溶液；将此溶液密封放置在-10℃环境中冷却结晶3小时，得到白色晶体。
用实施例2的方法鉴定，为本发明蛋氨酸晶型I，其在水中溶解度在5.2g/100g水。
实施例4
蛋氨酸晶型I的制备方法，采用如下步骤：
在5-(β-甲巯基乙基)乙内酰脲与碳酸钾溶液反应得到的含甲硫氨酸钾水解液中加入900-1000ppm的羟丙基甲基纤维素，边搅拌边通入CO2、CO2的通入压力为0.2Mpa，进行结晶析出得到蛋氨酸粗品；
将上述蛋氨酸粗品以40mg/mL-50mg/mL的浓度溶解在仲丁醇溶 剂中，不断搅拌，加热至95℃～100℃溶解，过滤，形成过饱和溶液；将此溶液密封放置在-5℃环境中冷却结晶1小时，得到白色晶体。
用实施例2的方法鉴定，为本发明蛋氨酸晶型I，其在水中溶解度在4.6g/100g水。
实施例5
蛋氨酸晶型I的制备方法，采用如下步骤：
在5-(β-甲巯基乙基)乙内酰脲与碳酸钾溶液反应得到的含甲硫氨酸钾水解液中加入500-600ppm的羟丙基甲基纤维素，边搅拌边通入CO2、CO2的通入压力为0.4Mpa，进行结晶析出得到蛋氨酸粗品；
将上述蛋氨酸粗品以25mg/mL-35mg/mL的浓度溶解在仲丁醇溶剂中，不断搅拌，加热至70℃～80℃溶解，过滤，形成过饱和溶液；将此溶液密封放置在-7℃～-8℃环境中冷却结晶2小时，得到白色晶体。
用实施例2的方法鉴定，为本发明蛋氨酸晶型I，其在水中溶解度在4.8g/100g水。

Claims (7)

  1. 一种蛋氨酸晶型I，其特征在于：所述晶型I在衍射角度2θ在21.751±0.2°、22.168±0.2°、21.186±0.2°、25.426±0.2°、18.395±0.2°、32.879±0.2°处有衍射峰。
  2. 如权利要求1所述蛋氨酸晶型I，其特征在于：所述晶型在衍射角度2θ在18.395±0.2°、21.186±0.2°、21.751±0.2°、22.168±0.2°、23.301±0.2°、25.426±0.2°、32.879±0.2°、33.775±0.2°、37.054±0.2°、42.455±0.2°处有衍射峰。
  3. 如权利要求1或2所述蛋氨酸晶型I，其特征在于：它具有如图1所示的X-射线粉末衍射图。
  4. 如权利要求1所述的蛋氨酸晶型I，其特征在于：它具有下列
    Figure PCTCN2017084383-appb-100001
    值和相对强度百分比I(％)值表达的-X射线粉末衍射数据，
    Figure PCTCN2017084383-appb-100002
  5. 如权利要求1、2、3或4所述的蛋氨酸晶型I，其特征在于：它具有下列
    Figure PCTCN2017084383-appb-100003
    值和相对强度百分比I(％)值表达的-X射线粉末衍射数据：
    Figure PCTCN2017084383-appb-100004
    Figure PCTCN2017084383-appb-100005
  6. 如权利要求1或2所述蛋氨酸晶型I，其特征在于：它具有如图2所示的DSC/TG图谱，其熔点峰值温度为282℃。
  7. 如权利要求1-6任一项所述蛋氨酸晶型I的制备方法，其特征在于，采用如下步骤：
    (1)、在5-(β-甲巯基乙基)乙内酰脲与碳酸钾溶液反应得到的含甲硫氨酸钾水解液中加入50-1000ppm的羟丙基甲基纤维素，边搅拌边通入CO2、CO2的通入压力为0.2-0.6Mpa左右，进行结晶析出得到蛋氨酸粗品；
    (2)、将上述蛋氨酸粗品以10mg/mL-50mg/mL的浓度溶解在仲丁醇溶剂中，不断搅拌，加热至60℃～100℃溶解，过滤，形成过饱和溶液；将此溶液密封放置在-5℃～-10℃环境中冷却结晶1-3小时，得到白色晶体。
PCT/CN2017/084383 2016-06-03 2017-05-15 一种蛋氨酸新晶型i及其制备方法 WO2017206703A1 (zh)

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