WO2019128156A1 - 一种海藻酸钠及其制备方法和应用 - Google Patents

一种海藻酸钠及其制备方法和应用 Download PDF

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Publication number
WO2019128156A1
WO2019128156A1 PCT/CN2018/092471 CN2018092471W WO2019128156A1 WO 2019128156 A1 WO2019128156 A1 WO 2019128156A1 CN 2018092471 W CN2018092471 W CN 2018092471W WO 2019128156 A1 WO2019128156 A1 WO 2019128156A1
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sodium alginate
alginic acid
less
powder
water
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PCT/CN2018/092471
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English (en)
French (fr)
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王超
杨照悦
张德蒙
徐泽斌
张健
王鹏
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青岛明月海藻集团有限公司
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Priority to JP2020539775A priority Critical patent/JP6891352B2/ja
Publication of WO2019128156A1 publication Critical patent/WO2019128156A1/zh

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    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
    • C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
    • C08B37/006—Heteroglycans, i.e. polysaccharides having more than one sugar residue in the main chain in either alternating or less regular sequence; Gellans; Succinoglycans; Arabinogalactans; Tragacanth or gum tragacanth or traganth from Astragalus; Gum Karaya from Sterculia urens; Gum Ghatti from Anogeissus latifolia; Derivatives thereof
    • C08B37/0084—Guluromannuronans, e.g. alginic acid, i.e. D-mannuronic acid and D-guluronic acid units linked with alternating alpha- and beta-1,4-glycosidic bonds; Derivatives thereof, e.g. alginates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin

Definitions

  • the invention relates to the technical field of sodium alginate for sustained release agents, in particular to a sodium alginate and a preparation method and application thereof.
  • Sodium alginate is used as a sustained release agent and a binder in tablets, and forms an insoluble gel layer under acidic conditions for sustained release.
  • M/G gel strength
  • the powder properties affect the permeation effect of the gel layer. The consistency of these factors in production is difficult to control, resulting in a problem of a linear relationship between the amount of sodium alginate and the release rate of the tablet when used by the pharmaceutical company, which is not conducive to the formulation adjustment of the pharmaceutical factory, or even Not available.
  • the sodium alginate extraction process is a brown algae water washing soaking, alkali digestion, dilution with water, filtration to obtain a liquid sodium alginate mixture, calcification, acidification to obtain alginic acid monomer, dehydration, neutralization to obtain sodium alginate monomer, granulation, drying to obtain a product .
  • Degradation of sodium alginate exists in each step, in which the sodium alginate concentration is the largest and the degradation unevenness is the largest.
  • Two modes of neutralization First, alginic acid reacts in ethanol medium (mass ratio of alginic acid to ethanol solution ⁇ 1) and liquid sodium hydroxide. The advantage is that sodium alginate is completely converted, the viscosity is stable, and ethanol has a purifying effect.
  • the deficiency is that the sodium hydroxide has a high degree of structural damage to the sodium alginate, and the ethanol structure makes the alginate fiber structure strengthen the powder properties of the final product.
  • the second is the reaction of alginic acid and solid sodium carbonate.
  • the advantage is that the structure of sodium alginate is less damaged by sodium carbonate.
  • the weakening of the structure of sodium alginate fiber is beneficial to the powder characteristics of the product.
  • the deficiency is the incomplete conversion of sodium alginate.
  • the drying step is sodium alginate. The degree of degradation is not uniform.
  • the object of the present invention is to provide a sodium alginate and a preparation method and application thereof, so as to solve the defects that the prior sodium alginate has unstable viscosity, large molecular weight distribution and large particle size distribution.
  • the present invention provides a method for preparing sodium alginate, the method comprising the steps of:
  • the brown algae comprises one or more of kelp, wakame, solanaceous, sargasso, and macroalgae
  • the soaking time is 3-15 h
  • the amount of water is the brown algae.
  • the alkali agent comprises sodium carbonate and/or sodium hydroxide
  • the alkaline agent is used in an amount of 40%-50% of the mass of the brown algae
  • the digestion temperature is 45-60 ° C
  • the digestion time is 3 -6h.
  • the alginic acid monomer has a water content of 60% to 75%.
  • the ethanol solution has a mass concentration of 30%-100%, and the amount is 5%-10% of the mass of the alginic acid.
  • the solid sodium carbonate is added in an amount of 8% to 10% by mass of the alginic acid, and the neutralization time is 30 to 60 minutes.
  • the drying temperature is less than 90°.
  • the invention also provides sodium alginate prepared by the preparation method of the sodium alginate, wherein the sodium alginate has a viscosity of 200-700 mpas, a viscosity decrease rate of less than 5%, a Mw/Mn of less than 1.85, and a water content of less than 11 %, the transparency is more than 30 cm, the specific gravity of the powder is 0.65-0.75 g/cm 3 , the particle size is 120 mesh, and the powder particle size distribution is narrow.
  • the sodium alginate of the present invention is used for a sustained release agent.
  • the present invention provides a sodium alginate and a preparation method and application thereof, and the preparation method comprises the following steps: (1) soaking brown algae with water and washing with alkali agent Mixing and digesting, then diluting with water, adding diatomaceous earth to filter, and then obtaining alginic acid monomer by calcium coagulating method; (2) degrading alginic acid monomer at 30-50 ° C, the degradation time is less than 2 h; (3) The semi-finished sodium alginate is obtained by mixing and stirring solid sodium carbonate as a neutralizing agent and alginic acid, and then stirring with an ethanol solution to disperse the semi-finished sodium alginate into a powder, and then granulating, drying and pulverizing to obtain sodium alginate.
  • Sodium alginate viscosity is 200-700mpas, viscosity reduction rate is less than 5%, Mw/Mn is less than 1.85, water content is less than 11%, transparency is greater than 30cm, powder specific gravity is 0.65-0.75g/cm 3 , particle size is less than 120 mesh, powder The body particle size distribution is narrow.
  • the sodium alginate of the invention can be used for a sustained release agent. The greater the relative molecular mass of sodium alginate, the higher the viscosity and the slower the release rate; the higher the gel strength, the slower the release rate; the more the powder particle size Fine, the slower the release rate.
  • the sodium alginate of the invention has stable viscosity, narrow molecular weight distribution and narrow particle size distribution, so the sustained release effect of the formula is stable, and the release requirement is achieved, and the problem of poor reproducibility of the sustained release effect of the sodium alginate sustained release agent formulation is solved.
  • the preparation method of the sodium alginate of the invention comprises the following steps:
  • the brown algae comprises one or more of kelp, wakame, solanaceous, sargasso and macroalgae, the soaking time is 3-15 h, the water amount is 3-6 times that of the brown algae, and the brown algae Soaking and washing with water can remove impurity particles and the like in brown algae.
  • the alkaline agent comprises sodium carbonate and/or sodium hydroxide, the alkali agent is used in an amount of 40%-50% of the mass of the brown algae, the digestion temperature is 45-75 ° C, the digestion time is 3-24 h; the brown algae and sodium carbonate and/or hydroxide are used.
  • the sodium is uniformly mixed to convert the insoluble alginate in the brown algae into sodium alginate.
  • step (1) by adding diatomaceous earth filtration, impurities such as a pigment or a water-insoluble matter in the sodium alginate extract can be removed, and the purity of the sodium alginate can be improved.
  • the step of the calcium coagulating method comprises: reacting the filtered product of the diatomaceous earth with a calcium chloride solution to obtain calcium alginate, and then adding calcium alginate to hydrochloric acid for decalcification to obtain an alginic acid monomer.
  • Extrusion dehydration of alginic acid monomer to control the moisture content of 60%-75%, and the sodium alginate obtained by reacting alginic acid and sodium carbonate is not sticky when the moisture exceeds 75%, and the algae when the moisture is less than 60% Acid and sodium carbonate react slowly and incompletely.
  • the mass concentration of the ethanol solution is 30%-100%, and the amount added is 5%-10% of the mass of the alginic acid.
  • Ethanol can be used as a solid phase to neutralize the anti-adhesive of sodium alginate, a semi-finished product of the reaction product, so that sodium alginate loses its viscosity and is stirred into a powder form by long fibers to increase the specific gravity of sodium alginate.
  • Improve the pulverization efficiency of sodium alginate reduce the particle size distribution of sodium alginate, and also strengthen the kneading effect of sodium alginate material, improve the neutralization degree of sodium alginate, and make the viscosity of sodium alginate more stable.
  • the solid sodium carbonate is added in an amount of 8% to 10% by mass of the alginic acid, and the neutralization time is 30 to 60 minutes.
  • the drying temperature is less than 90 °C.
  • the sodium alginate prepared by the method for preparing sodium alginate of the invention has a viscosity of 200-700 mpas, a viscosity decrease rate of less than 5%, a Mw/Mn of less than 1.85, a water content of less than 11%, a transparency of more than 30 cm, and a powder.
  • the specific gravity is 0.65-0.75 g/cm 3 , the particle size is 120 mesh, and the powder particle size distribution is narrow.
  • the sodium alginate of the invention can be used for a sustained release agent.
  • the sodium alginate of the invention has stable viscosity, narrow molecular weight distribution and narrow particle size distribution, so the sustained release effect of the formula is stable, and the release requirement is achieved, and the problem of poor reproducibility of the sustained release effect of the sodium alginate sustained release agent formulation is solved.
  • Casing method (visual measurement) determination the sodium alginate of the invention is dissolved in water to prepare a sodium alginate glue of 1% by mass, and the sodium alginate glue is poured into the colorimetric tube with the scale. Place the colorimetric tube on the white paper with 15 black lines with a tooth gap of 1mm; take a 50ml colorimetric tube inside the above colorimetric tube, and move the 50ml color tube sleeve up and down to see the white paper. Up to the black line, repeat the operation three times, and measure the distance between the bottoms of the two colorimetric tubes, that is, the transparency (in cm) of sodium alginate.
  • Viscosity reduction rate (%) (E 0 - E 1 ) ⁇ 100% / E 0
  • the obtained sodium alginate had a viscosity of 320 mPa.s, a viscosity reduction rate of 3.2%, a Mw/Mn of 1.70, a water content of 9.5%, a transparency of 45 cm, a powder specific gravity of 0.7 g/cm 3 and a gel strength of 290 g/cm 2 . .
  • the obtained sodium alginate had a viscosity of 350 mPa.s, a viscosity reduction rate of 2.1%, a Mw/Mn of 1.65, a water content of 8.0%, a transparency of 60 cm, a powder specific gravity of 0.67 g/cm 3 and a gel strength of 400 g/cm 2 . .
  • the preparation method of sodium alginate of the present comparative example was basically the same as that of Example 1, except that the step (1) was not filtered with diatomaceous earth.
  • the obtained sodium alginate has a brownish yellow appearance, a viscosity of 320 mPa.s, a viscosity reduction rate of 3.0%, a Mw/Mn of 1.70, a water content of 9.5%, a transparency of 5 cm, a powder specific gravity of 0.7 g/cm 3 , and a gel strength. It is 290 g/cm 2 .
  • the sodium alginate prepared in Comparative Example 1 had a dark color appearance, low transparency, and low purity.
  • the preparation method of the sodium alginate of the present comparative example is basically the same as that of the first embodiment, except that the step (3) is: the alginic acid is reacted with 30% by mass of liquid sodium hydroxide in an ethanol medium, and the mass ratio of the alginic acid to the ethanol solution is 1:3, the amount of liquid sodium hydroxide added is 18-25% of the mass of alginic acid.
  • the obtained sodium alginate had a milky white appearance, a viscosity of 320 mPa.s, a viscosity decrease rate of 9.8%, a Mw/Mn of 1.95, a water content of 9.5%, a transparency of 35 cm, a powder specific gravity of 0.4 g/cm 3 , and a gel strength of 290 g/cm 2 .
  • the sodium alginate prepared in Comparative Example 2 has a low specific gravity, indicating that the sodium alginate has low pulverization efficiency, a fine particle size, a wide particle size distribution, and a high Mw/Mn ratio.
  • the molecular weight dispersibility is relatively high, indicating that the molecular weight is not uniform.
  • the preparation method of sodium alginate of the present comparative example was basically the same as that of Example 1, except that the step (3) was stirred and mixed without adding an ethanol solution.

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Abstract

本发明公开了一种海藻酸钠及其制备方法和应用，制备方法包括如下：(1)将褐藻加水浸泡洗涤、与碱剂混合消化，加水稀释、加硅藻土过滤，通过钙凝酸化法得到海藻酸单体；(2)将海藻酸单体在30-50℃下进行降解；(3)以固体碳酸钠作为中和剂和海藻酸混合搅拌反应得到半成品海藻酸钠，再加乙醇溶液搅拌，使得半成品海藻酸钠分散成粉末状，然后造粒、干燥、粉碎得到海藻酸钠。海藻酸钠粘度为200-700mpas，粘度下降率小于5％，Mw/Mn小于1.85，含水量小于11％，透明度大于30cm，粉体比重为0.65-0.75g/cm 3，粒度120目，粉体粒度分布窄。本发明的海藻酸钠可以用于缓释剂，缓释效果稳定。

Description

一种海藻酸钠及其制备方法和应用 技术领域
本发明涉及缓释剂用海藻酸钠技术领域，具体来说涉及一种海藻酸钠及其制备方法和应用。
背景技术
海藻酸钠用于片剂中作为缓释剂和粘结剂，在酸性条件下形成不溶凝胶层起到缓释作用，海藻酸钠的粘度(分子量)、凝胶强度(M/G)、粉体特性等影响凝胶层的透过效果，生产中这些因素的一致性难以控制，导致药厂使用时出现海藻酸钠用量和药片释放度线性关系差问题，不利于药厂配方调整，甚至无法使用。
海藻酸钠提取流程是褐藻水洗浸泡、碱消化、加水稀释、过滤得到液体海藻酸钠混合物，钙化、酸化得到海藻酸单体，脱水、中和得到海藻酸钠单体，造粒、干燥得到产品。每个步骤都存在着海藻酸钠的降解，其中中和步骤海藻酸钠浓度最大，降解不均匀程度最大。中和的两种模式：一是海藻酸在乙醇介质中(海藻酸和乙醇溶液质量比＜1)和液体氢氧化钠反应，优势是海藻酸钠转化完全，粘度稳定，乙醇具有提纯效果。不足是氢氧化钠对海藻酸钠结构破坏程度高、不均匀，同时乙醇使海藻酸钠纤维结构强化影响最终产品的粉体特性。二是海藻酸和固体碳酸钠反应，优势是碳酸钠对海藻酸钠结构破坏程度小，海藻酸钠纤维结构弱化有利于产品粉体特性，不足是海藻酸钠转化不完全，干燥步骤海藻酸钠降解不均匀程度大。
发明内容
本发明的目的在于提供一种海藻酸钠及其制备方法和应用，以解决现有海藻酸钠粘度不稳定、分子量分布大、粒度分布大的缺陷。
为此，本发明提供了一种海藻酸钠的制备方法，所述方法包括如下步骤：
(1)将褐藻加水浸泡洗涤、与碱剂混合消化，然后加水稀释、加入硅藻土过滤，然后通过钙凝酸化法得到海藻酸单体；
(2)将海藻酸单体在30-50℃下进行降解，降解时间小于2h；
(3)以固体碳酸钠作为中和剂和海藻酸混合搅拌反应得到半成品海藻酸钠，再加乙醇 溶液搅拌，使得半成品海藻酸钠分散成粉末状，然后造粒、干燥、粉碎得到海藻酸钠。
优选的，所述步骤(1)中，所述褐藻包括海带、裙带菜、泡叶藻、马尾藻和巨藻中的一种或多种，浸泡时间为3-15h，水用量为所述褐藻质量的3-6倍；所述碱剂包括碳酸钠和/或氢氧化钠，所述碱剂用量为所述褐藻质量的40％-50％，消化温度为45-60℃，消化时间为3-6h。
优选的，所述步骤(1)中，海藻酸单体的含水量为60％-75％。
优选的，所述步骤(3)中，乙醇溶液质量浓度30％-100％，加入量为海藻酸质量的5％-10％。
优选的，所述步骤(3)中，固体碳酸钠的加入量为海藻酸质量的8％-10％，中和时间为30-60min。
优选的，所述步骤(3)中，干燥温度小于90°。
本发明还提供了由所述的海藻酸钠的制备方法制备得到的海藻酸钠，所述海藻酸钠粘度为200-700mpas，粘度下降率小于5％，Mw/Mn小于1.85，含水量小于11％，透明度大于30cm，粉体比重为0.65-0.75g/cm 3，粒度120目，粉体粒度分布窄。
本发明的所述海藻酸钠用于缓释剂。
与现有技术相比，本发明的优点和积极效果是：本发明提供了一种海藻酸钠及其制备方法和应用，制备方法包括如下步骤：(1)将褐藻加水浸泡洗涤、与碱剂混合消化，然后加水稀释、加入硅藻土过滤，然后通过钙凝酸化法得到海藻酸单体；(2)将海藻酸单体在30-50℃下进行降解，降解时间小于2h；(3)以固体碳酸钠作为中和剂和海藻酸混合搅拌反应得到半成品海藻酸钠，再加乙醇溶液搅拌，使得半成品海藻酸钠分散成粉末状，然后造粒、干燥、粉碎得到海藻酸钠。海藻酸钠粘度为200-700mpas，粘度下降率小于5％，Mw/Mn小于1.85，含水量小于11％，透明度大于30cm，粉体比重为0.65-0.75g/cm 3，粒度小于120目，粉体粒度分布窄。本发明的海藻酸钠可以用于缓释剂，海藻酸钠的相对分子质量越大，粘度则越高，释药速度越慢；凝胶强度越高，释药速度越慢；粉体粒度越细，释药速度越慢。本发明海藻酸钠的粘度稳定、分子量分布窄、粒度分布窄，所以配方缓释效果稳定，达到释放要求，解决了现海藻酸钠缓释剂配方缓释效果重现性差的问题。
具体实施方式
以下对本发明的具体实施方式进行详细说明，应当理解的是，此处所描述的具体实施方式仅用于说明和解释本发明，并不用于限制本发明。
本发明的海藻酸钠的制备方法包括如下步骤：
(1)将褐藻加水浸泡洗涤、与碱剂混合消化，然后加水稀释、加入硅藻土过滤，然后 通过钙凝酸化法得到海藻酸单体；
(2)将海藻酸单体在30-50℃下进行降解，降解时间小于2h；
(3)以固体碳酸钠作为中和剂和海藻酸混合搅拌反应得到半成品海藻酸钠，再加乙醇溶液搅拌，使得半成品海藻酸钠分散成粉末状，然后造粒、干燥、粉碎得到海藻酸钠。
步骤(1)中，褐藻包括海带、裙带菜、泡叶藻、马尾藻和巨藻中的一种或多种，浸泡时间为3-15h，水用量为褐藻质量的3-6倍，将褐藻加水浸泡、洗涤可以去除褐藻中的杂质颗粒等。碱剂包括碳酸钠和/或氢氧化钠，碱剂用量为褐藻质量的40％-50％，消化温度为45-75℃，消化时间为3-24h；将褐藻与碳酸钠和/或氢氧化钠混合均匀，可以使得褐藻中不溶性的海藻酸盐转化成海藻酸钠。
步骤(1)中，加入硅藻土过滤的方式，可以去掉海藻酸钠提取物中的色素、水不溶物等杂质，可以提高海藻酸钠的纯度。
步骤(1)中，钙凝酸化法的步骤包括：将硅藻土过滤后的产物与氯化钙溶液反应，得到海藻酸钙，然后将海藻酸钙加入盐酸进行脱钙，得到海藻酸单体，对海藻酸单体进行挤压脱水，使其水分控制在60％-75％，水分超出75％时海藻酸和碳酸钠反应得到的海藻酸钠发粘不好，水分低于60％时海藻酸和碳酸钠反应慢、转化不完全。
步骤(3)中，乙醇溶液质量浓度30％-100％，加入量为海藻酸质量的5％-10％。乙醇可以作为固相中和反应产物半成品海藻酸钠的抗粘结剂，使海藻酸钠失去黏性，并由长纤维状被搅拌成粉末状以提高海藻酸钠的粉体比重，还有利于提升海藻酸钠的粉碎效率、缩小海藻酸钠的粒度分布，同时也加强了海藻酸钠物料捏合效果，提高海藻酸钠中和转化程度，使得海藻酸钠的粘度更稳定。
步骤(3)中，固体碳酸钠的加入量为海藻酸质量的8％-10％，中和时间为30-60min。
步骤(3)中，干燥温度小于90℃。
由本发明的海藻酸钠的制备方法制备得到的海藻酸钠，海藻酸钠粘度为200-700mpas，粘度下降率小于5％，Mw/Mn小于1.85，含水量小于11％，透明度大于30cm，粉体比重为0.65-0.75g/cm 3，粒度120目，粉体粒度分布窄。
本发明的海藻酸钠可以用于缓释剂，海藻酸钠的相对分子质量越大，粘度则越高，释药速度越慢；凝胶强度越高，释药速度越慢；粉体粒度越细，释药速度越慢。本发明海藻酸钠的粘度稳定、分子量分布窄、粒度分布窄，所以配方缓释效果稳定，达到释放要求，解决了现海藻酸钠缓释剂配方缓释效果重现性差的问题。
检测方法
1、透明度测定
套管法(目测法)测定：将本发明的海藻酸钠溶于水，配制成质量分数为1％的海藻酸钠胶液，将海藻酸钠胶液倒至带有刻度的比色管中，将比色管放于划有牙距1mm的15条黑线的白纸上；另取一50ml比色管套在上述比色管内部，将50ml比色管套上下移动至能看清白纸上的黑线为止，重复操作三次，测出两比色管底的距离，即得海藻酸钠的透明度(以cm表示)。
2、粘度下降率测定
称取试样5g左右，置6×2cm的具塞试管中，塞好塞子，放入50℃的金属浴中，温度控制在50℃±0.5℃，保持48小时后，取出试样，测定其黏度。计算公式：
粘度下降率(％)＝(E 0-E 1)×100％/E 0
式中：E 0───起始黏度；mPa.s
E 1───保温后测得的黏度；mPa.s
实施例1
本实施例的海藻酸钠的制备方法包括如下步骤：
(1)将海带加水浸泡、洗涤，然后与碳酸钠混合均匀，浸泡时间为10h，水用量为海带质量的6倍，碳酸钠用量为海带质量的40％，消化温度为54℃，消化时间为5h；然后加水稀释、加入硅藻土过滤，然后通过钙凝酸化法得到海藻酸单体，海藻酸单体的含水量为70％；
(2)将600Kg海藻酸单体在45℃下进行降解，降解时间1h；
(3)以54Kg固体碳酸钠作为中和剂和海藻酸混合搅拌反应30min，得到半成品海藻酸钠，再加20Kg、质量浓度为80％的乙醇溶液搅拌20min，使得半成品海藻酸钠分散成粉末状，然后造粒、干燥、粉碎，过120目筛，得到乳白色海藻酸钠。
得到的海藻酸钠粘度为320mpa.s，粘度下降率为3.2％，Mw/Mn为1.70，含水量9.5％，透明度为45cm，粉体比重0.7g/cm 3，凝胶强度为290g/cm 2。
实施例2
本实施例的海藻酸钠的制备方法包括如下步骤：
(1)将巨藻加水浸泡、洗涤，然后与碳酸钠混合均匀，浸泡时间为10h，水用量为巨藻质量的6倍，碳酸钠用量为海带质量的40％，消化温度为54℃，消化时间为5h；然后加水稀释、加入硅藻土过滤，然后通过钙凝酸化法得到海藻酸单体，海藻酸单体的含水量气为 75％；
(2)将500Kg海藻酸单体在45℃下进行降解，降解时间1h；
(3)以45Kg固体碳酸钠作为中和剂和海藻酸混合搅拌反应30min，得到半成品海藻酸钠，再加20Kg、质量浓度为80％的乙醇溶液搅拌20min，使得半成品海藻酸钠分散成粉末状，然后造粒、干燥、粉碎，过120目筛，得到乳白色海藻酸钠。
得到的海藻酸钠粘度为350mpa.s，粘度下降率为2.1％，Mw/Mn为1.65，含水量8.0％，透明度为60cm，粉体比重0.67g/cm 3，凝胶强度为400g/cm 2。
对比例1
本对比例的海藻酸钠的制备方法和实施例1基本相同，区别在于步骤(1)过滤时没有采用硅藻土助虑。
得到的海藻酸钠外观为棕黄色，粘度为320mpa.s，粘度下降率为3.0％，Mw/Mn为1.70，含水量9.5％，透明度为5cm，粉体比重0.7g/cm 3，凝胶强度为290g/cm 2。
与实施例1制得的海藻酸钠相比，对比例1制得的海藻酸钠的外观颜色深，透明度低，纯度低。
对比例2
本对比例的海藻酸钠的制备方法和实施例1基本相同，区别在于步骤(3)为：海藻酸在乙醇介质中和30％质量浓度液体氢氧化钠反应，海藻酸和乙醇溶液质量比为1:3，液体氢氧化钠加入量占海藻酸质量的18-25％。
得到的海藻酸钠外观为乳白色，粘度为320mpa.s，粘度下降率为9.8％，Mw/Mn为1.95，含水量9.5％，透明度为35cm，粉体比重0.4g/cm 3，凝胶强度为290g/cm 2。
与实施例1制得的海藻酸钠相比，对比例2制得的海藻酸钠的粉体比重低，表明海藻酸钠粉碎加工效率低、粒度偏絮状，粒度分布宽；Mw/Mn高，分子量分散性相对高，表明分子量不均匀程度高。
对比例3
本对比例的海藻酸钠的制备方法和实施例1基本相同，区别在于步骤(3)搅拌混合时没有加乙醇溶液。
得到的海藻酸钠外观乳白色，粘度320mpa.s，粘度下降率为17.3％，Mw/Mn＝1.85，含水量9.5％，透明度为35cm，透明度35cm，粉体比重0.5g/cm 3，凝胶强度290g/cm 2。
与实施例1制得的海藻酸钠相比，对比例3制得的海藻酸钠的粘度下降率明显增加，说明该反应条件海藻酸和碳酸钠反应转化不完全，制得的海藻酸钠稳定性相对差，不适合用在医药上。
以上实施例仅用以说明本发明的技术方案，而非对其进行限制；尽管参照前述实施例对本发明进行了详细的说明，对于本领域的普通技术人员来说，依然可以对前述实施例所记载的技术方案进行修改，或者对其中部分技术特征进行等同替换；而这些修改或替换，并不使相应技术方案的本质脱离本发明所要求保护的技术方案的精神和范围。

Claims (8)

  1. 一种海藻酸钠的制备方法，其特征在于，所述方法包括如下步骤：
    (1)将褐藻加水浸泡洗涤、与碱剂混合消化，然后加水稀释、加入硅藻土过滤，然后通过钙凝酸化法得到海藻酸单体；
    (2)将海藻酸单体在30-50℃下进行降解，降解时间小于2h；
    (3)以固体碳酸钠作为中和剂和海藻酸混合搅拌反应得到半成品海藻酸钠，再加乙醇溶液搅拌，使得半成品海藻酸钠分散成粉末状，然后造粒、干燥、粉碎得到海藻酸钠。
  2. 如权利要求1所述的海藻酸钠的制备方法，其特征在于，
    所述步骤(1)中，所述褐藻包括海带、裙带菜、泡叶藻、马尾藻和巨藻中的一种或多种，浸泡时间为3-15h，水用量为所述褐藻质量的3-6倍；
    所述碱剂包括碳酸钠和/或氢氧化钠，所述碱剂用量为所述褐藻质量的40％-50％，消化温度为45-60℃，消化时间为3-6h。
  3. 如权利要求1所述的海藻酸钠的制备方法，其特征在于，
    所述步骤(1)中，海藻酸单体的含水量为60％-75％。
  4. 如权利要求1所述的海藻酸钠的制备方法，其特征在于，
    所述步骤(3)中，乙醇溶液质量浓度30％-100％，加入量为海藻酸质量的5％-10％。
  5. 如权利要求1所述的海藻酸钠的制备方法，其特征在于，
    所述步骤(3)中，固体碳酸钠的加入量为海藻酸质量的8％-10％，中和时间为30-60min。
  6. 如权利要求1所述的海藻酸钠的制备方法，其特征在于，
    所述步骤(3)中，干燥温度小于90°。
  7. 一种如权利要求1-6中任一项所述的海藻酸钠的制备方法制备得到的海藻酸钠，其特征在于，所述海藻酸钠粘度为200-700mpas，粘度下降率小于5％，Mw/Mn小于1.85，含水量小于11％，透明度大于30cm，粉体比重为0.65-0.75g/cm 3，粒度120目，粉体粒度分布窄。
  8. 如权利要求7所述的海藻酸钠的应用，其特征在于，
    所述海藻酸钠用于缓释剂。
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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2022139115A1 (ko) * 2020-12-22 2022-06-30 (주)해림후코이단 알긴산 및 후코이단 제조방법
CN117659223A (zh) * 2024-01-31 2024-03-08 烟台泰和新材高分子新材料研究院有限公司 一种低钙离子含量海藻酸钠的提取方法

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113603809A (zh) * 2021-09-02 2021-11-05 青岛海之林生物科技开发有限公司 一种低乙醇残留的海藻酸钠的制备方法

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101456920A (zh) * 2008-12-02 2009-06-17 王永昌 一种高透明度褐藻酸钠的生产方法
CN103351440A (zh) * 2013-07-31 2013-10-16 青岛海之林生物科技开发有限公司 一种医药级海藻酸钠的生产工艺
CN103360511A (zh) * 2013-07-31 2013-10-23 青岛海之林生物科技开发有限公司 一种自凝型海藻酸钠的生产工艺
CN103586601A (zh) * 2013-11-27 2014-02-19 青岛明月海藻集团有限公司 一种焊接材料用海藻酸盐的制备方法
CN106749752A (zh) * 2016-12-20 2017-05-31 青岛明月海藻集团有限公司 一种超低粘度海藻酸盐的制备方法

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2009149734A (ja) * 2007-12-19 2009-07-09 Kao Corp 低分子量アルギン酸又はその誘導体の製造方法

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101456920A (zh) * 2008-12-02 2009-06-17 王永昌 一种高透明度褐藻酸钠的生产方法
CN103351440A (zh) * 2013-07-31 2013-10-16 青岛海之林生物科技开发有限公司 一种医药级海藻酸钠的生产工艺
CN103360511A (zh) * 2013-07-31 2013-10-23 青岛海之林生物科技开发有限公司 一种自凝型海藻酸钠的生产工艺
CN103586601A (zh) * 2013-11-27 2014-02-19 青岛明月海藻集团有限公司 一种焊接材料用海藻酸盐的制备方法
CN106749752A (zh) * 2016-12-20 2017-05-31 青岛明月海藻集团有限公司 一种超低粘度海藻酸盐的制备方法

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2022139115A1 (ko) * 2020-12-22 2022-06-30 (주)해림후코이단 알긴산 및 후코이단 제조방법
CN117659223A (zh) * 2024-01-31 2024-03-08 烟台泰和新材高分子新材料研究院有限公司 一种低钙离子含量海藻酸钠的提取方法
CN117659223B (zh) * 2024-01-31 2024-05-07 烟台泰和新材高分子新材料研究院有限公司 一种低钙离子含量海藻酸钠的提取方法

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