WO2022048015A1 - 一种采用混合填料精准控制大豆油中硬脂酸含量的方法 - Google Patents

一种采用混合填料精准控制大豆油中硬脂酸含量的方法 Download PDF

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WO2022048015A1
WO2022048015A1 PCT/CN2020/128414 CN2020128414W WO2022048015A1 WO 2022048015 A1 WO2022048015 A1 WO 2022048015A1 CN 2020128414 W CN2020128414 W CN 2020128414W WO 2022048015 A1 WO2022048015 A1 WO 2022048015A1
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soybean oil
stearic acid
lipase
content
mixed
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PCT/CN2020/128414
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English (en)
French (fr)
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袁诚
许文东
唐顺之
牛亚伟
牟肖男
李遥
莫嘉伟
傅玉萍
关伟键
王国财
彭万才
满兴战
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广州白云山汉方现代药业有限公司
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Publication of WO2022048015A1 publication Critical patent/WO2022048015A1/zh

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    • C—CHEMISTRY; METALLURGY
    • C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
    • C11B—PRODUCING, e.g. BY PRESSING RAW MATERIALS OR BY EXTRACTION FROM WASTE MATERIALS, REFINING OR PRESERVING FATS, FATTY SUBSTANCES, e.g. LANOLIN, FATTY OILS OR WAXES; ESSENTIAL OILS; PERFUMES
    • C11B3/00—Refining fats or fatty oils
    • C11B3/003—Refining fats or fatty oils by enzymes or microorganisms, living or dead
    • C—CHEMISTRY; METALLURGY
    • C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
    • C11B—PRODUCING, e.g. BY PRESSING RAW MATERIALS OR BY EXTRACTION FROM WASTE MATERIALS, REFINING OR PRESERVING FATS, FATTY SUBSTANCES, e.g. LANOLIN, FATTY OILS OR WAXES; ESSENTIAL OILS; PERFUMES
    • C11B3/00—Refining fats or fatty oils
    • C11B3/008—Refining fats or fatty oils by filtration, e.g. including ultra filtration, dialysis
    • C—CHEMISTRY; METALLURGY
    • C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
    • C11B—PRODUCING, e.g. BY PRESSING RAW MATERIALS OR BY EXTRACTION FROM WASTE MATERIALS, REFINING OR PRESERVING FATS, FATTY SUBSTANCES, e.g. LANOLIN, FATTY OILS OR WAXES; ESSENTIAL OILS; PERFUMES
    • C11B3/00—Refining fats or fatty oils
    • C11B3/02—Refining fats or fatty oils by chemical reaction
    • C11B3/06—Refining fats or fatty oils by chemical reaction with bases
    • C—CHEMISTRY; METALLURGY
    • C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
    • C11B—PRODUCING, e.g. BY PRESSING RAW MATERIALS OR BY EXTRACTION FROM WASTE MATERIALS, REFINING OR PRESERVING FATS, FATTY SUBSTANCES, e.g. LANOLIN, FATTY OILS OR WAXES; ESSENTIAL OILS; PERFUMES
    • C11B3/00—Refining fats or fatty oils
    • C11B3/10—Refining fats or fatty oils by adsorption

Definitions

  • the invention relates to the technical field of medicinal oils and fats refining, in particular to a method for accurately controlling the content of stearic acid in soybean oil by using mixed fillers.
  • Soybean oil is a natural oil extracted and refined from soybean. It is the main energy component of parenteral nutrition fat emulsion injection and the oil phase matrix of drug-loaded fat emulsion. Soybean oil can provide essential fatty acids for the human body, and its main fatty acids include palmitic acid, palmitoleic acid, stearic acid, oleic acid, linoleic acid, linolenic acid, arachidic acid, eicosenoic acid, behenic acid, twenty-four Alkanoic acid etc.
  • the Chinese Pharmacopoeia stipulates the fatty acid content of soybean oil as follows: the saturated fatty acid less than 14 carbons is not more than 0.1%, the tetradecanoic acid is not more than 0.2%, the palmitic acid should be 9-13%, the palmitoleic acid is not more than 0.3%, Stearic acid should be 3.0-5.0%, oleic acid should be 17.0-30.0%, linoleic acid should be 48.0-58.0%, linolenic acid should be 5.0-11.0%, arachidic acid should be no more than 1.0%, eicosenoic acid not more than 1.0%, and behenic acid not more than 1.0%.
  • Soybean oil has been used in fat emulsion for 60 years. Its rich fatty acid composition can provide necessary nutritional support for clinical special patients. At present, the traditional production process of medicinal grade soybean oil only controls the impurities in the oil, and cannot change the composition and proportion of its fatty acids. content control. Although the production process of traditional soybean oil can meet the quality requirements of 3-5% of the Chinese Pharmacopoeia in the soybean oil, the stearic acid content is basically 4-5%, mainly depending on the quality of the soybean oil raw material, It cannot be controlled from the production process.
  • soybean oil triglycerides are mainly saturated fatty acids such as palmitic acid, stearic acid, etc.
  • the 2 positions are mainly unsaturated fatty acids such as oleic acid, linoleic acid, linolenic acid, etc.
  • the purpose of the present invention is to solve the problems that the traditional soybean oil production process cannot accurately control the stearic acid content and cannot meet the requirements for preparing high-quality fat emulsion formulations.
  • the present invention adopts the following technical solutions:
  • a method for accurately controlling the content of stearic acid in soybean oil by using mixed fillers comprising the following steps:
  • the proportion of each component of the mixed filler and the soybean oil is as follows: 0.1-5% of the lipase, 0.1-5% of the solid alkali, 1-20% of the filter aid, 1-20% of the adsorbent 20%.
  • the present invention can achieve three effects of deacidification, enzymatic hydrolysis and adsorption and impurity removal at the same time by adopting a method for accurately controlling the content of stearic acid in soybean oil by using a mixed filler. And by physically mixing lipase, solid alkali, filter aid, and adsorbent to make them uniformly dispersed, the free fatty acid in soybean oil is neutralized with the solid alkali to deacidify and produce water; Sn-1 ,3-specific lipase uses the water produced by the deacidification process to hydrolyze the triglycerides in soybean oil to generate free fatty acids; the free fatty acids are neutralized by solid alkali to form a microcirculation process.
  • the filter aid mixed in it can effectively avoid the problem of difficult filtration caused by the saponin produced in the alkali refining process. If there is a lack of filter aids, the saponin produced in the alkali refining process will increase the flow resistance of soybean oil, making it difficult or even impossible to flow through the mixed filler, and it is difficult to control the degree of hydrolysis of soybean oil, and at the same time greatly prolong the refining process. Lipase, solid alkali, filter aid and adsorbent are evenly mixed and complementary to each other. Neutralization and hydrolysis form a microcirculation reaction.
  • Impurities such as stearic acid, monoester and oxide are adsorbed by the adsorbent in time, making it possible to precisely control the stearic acid content in soybean oil.
  • the precise control of the above process can be achieved by controlling the temperature, the pressure of the equipment, and the contact time between the raw materials and the filler, and finally the precise control of the stearic acid content in soybean oil within a very narrow range can satisfy the Different medicinal needs.
  • the preferred dosage is that the proportion of each component of the mixed filler and soybean oil is as follows: 0.1-5% of lipase, 0.1-5% of the solid alkali, 1% of the filter aid ⁇ 20%, 1 ⁇ 20% of the adsorbent, at this time, the slow reduction of the stearic acid content in the soybean oil can be better controlled, and the acid value, peroxide value, etc. are controlled within a reasonable range at the same time, until reaching Refined soybean oil requirement.
  • the stearic acid content of the refined soybean oil is 3-4%; the peroxide value of the refined soybean oil is less than 1.
  • the stearic acid content in soybean oil has a greater influence on the quality of the soybean oil fat emulsion preparation.
  • the present invention utilizes the characteristics that stearic acid is mainly distributed in the 1 and 3 positions of triglycerides in soybean oil, and selects the triglycerides 1, 3, and 3 in the soybean oil.
  • the 3-position selective lipase hydrolyzes soybean oil, and removes impurities such as diester, monoester, oxide, etc. through solid alkali deacidification and adsorbent adsorption, so as to reduce the content of stearic acid and control the content of stearic acid.
  • the content is in the range of 3 to 4%.
  • the method of the present invention can control the stearic acid content of any source of soybean oil within a very narrow range of 3-4%, and at the same time control the peroxide value below 1, and get rid of the dependence on the source of soybean oil in the study of fat emulsion formulations. It will have a huge impact on pharmaceutical research.
  • the standard deviation of the mixing uniformity of the mixed filler is not greater than 0.05%; the particle sizes of the lipase, the inorganic base, the filter aid, and the adsorbent are all less than 250 ⁇ m.
  • the filler particles of lipase, inorganic base, filter aid and adsorbent should be controlled to be roughly the same size and the particle size should be less than 250 ⁇ m. If the particle size of the filler is different, it is difficult to achieve the purpose of uniform mixing. At the same time, controlling the filler in a smaller particle size range can increase the contact area between the raw material and the filler and improve the contact efficiency. The smaller the particle size, the more helpful the four components of lipase, inorganic base, filter aid, and adsorbent are mixed with each other and have a synergistic effect. When the standard deviation of mixing uniformity is not more than 0.05%, soybean oil can have the smoothest microcirculation reaction in the mixed filler without blocking, which is an ideal mixing state.
  • the step A further comprises: packing the mixed filler in a chromatography column.
  • the operation of the step B is as follows: the soybean oil enters the chromatography column and flows out to obtain the refined soybean oil.
  • the temperature of the chromatography column is 30-60° C.
  • the pressure is 0.02-0.5 MPa
  • the contact time with the soybean oil is 1-10 h; the soybean oil is circulated into the chromatography column for 1-10 h. 10 times.
  • the Sn-1,3-specific lipase includes one or more of TLIM, 435 lipase, Lipase lipase, and RMIM lipase.
  • the solid base includes one or more of sodium hydroxide, potassium hydroxide and calcium hydroxide.
  • the adsorbent includes one or more of alumina, silica gel, clay, and gel.
  • the filter aid includes one or more of diatomaceous earth and bentonite.
  • the present invention realizes three effects of enzymatic hydrolysis, acid reduction, and impurity removal through one-step reaction, and realizes the removal of diglyceride and monoglyceride by controlling the temperature, pressure, and the contact time of the raw material and the filler that are equipped with mixed fillers, free fatty acids, oxides, etc.
  • the disadvantage of cumbersome industrialization steps is greatly reduced.
  • the indicators of a low-content stearic acid soybean oil prepared by the present invention meet the Chinese Pharmacopoeia standard, and the stearic acid content of the soybean oil can be strictly controlled between 3-4% through this process. It avoids the fluctuation of stearic acid content in soybean oil due to differences in starting materials, and at the same time meets the specific raw material requirements of domestic preparation companies for soybean oil with a stearic acid content of 3-4%, and can produce higher quality fat emulsion preparations . Through this process, the dependence on the starting material of soybean oil can be solved.
  • the present invention adopts the method of adding a filter aid to the uniformly dispersed mixed filler formed by physical mixing including lipase, solid alkali, and adsorbent to avoid the formation of
  • the saponin causes the whole system to fail to be chromatographed smoothly, which further ensures that the one-step operation method can simultaneously achieve the three effects of enzymatic hydrolysis, deacidification and impurity removal.
  • the lipase realizes the localized hydrolysis of triglycerides in soybean oil. It is also possible to control the temperature, the pressure of the equipment, and the contact time between the raw material and the filler to achieve precise and controllable control of the above process, and finally achieve precise control of the stearic acid content in soybean oil within a very narrow range.
  • Fig. 1 is the mixed filler schematic diagram of the present invention
  • Fig. 2 is the investigation result graph that adopts the mixed packing method to pass the column time
  • Fig. 3 is the schematic diagram of the filler of Comparative Example 1;
  • Fig. 4 is the investigation result graph of adopting comparative example 1 packing method to pass the column time
  • Fig. 5 is the schematic diagram of the filler of Comparative Example 2.
  • Fig. 6 is the investigation result graph that adopts comparative example 2 packing method to pass the column time
  • Fig. 7 is the schematic diagram of the filler of Comparative Example 3.
  • Fig. 8 is the investigation result graph of adopting comparative example 3 packing method to pass the column time
  • Figure 9 is a graph of the results of investigation of the amount of lipase and solid alkali in Comparative Example 4.
  • the stearic acid content can still be accurately controlled within 3-4%. Within the range, it meets the requirements for preparing high-quality fat emulsion preparations (wherein, the acid value, peroxide value, and methoxyaniline value are measured and calculated according to the methods shown in the Pharmacopoeia).
  • the stearic acid content can still be accurately controlled within 3-4% after the process of the present invention. Within the range, it meets the requirements for preparing high-quality fat emulsion preparations (wherein, the acid value, peroxide value, and methoxyaniline value are measured and calculated according to the methods shown in the Pharmacopoeia).
  • the technical solution of the present invention can effectively control the stearic acid content between 3% and 4%, and at the same time, because the technical solution of the present invention does not require external introduction of water, the adsorption effect of silica gel is guaranteed. The ability of oxides will not be destroyed.
  • the stearic acid content of soybean oil can be guaranteed to be between 3 and 4% within 1 to 10 hours of column passing time, and the peroxide value can meet the requirements of pharmacopoeia standards.
  • a comparative test of layered packing is also carried out.
  • the positions of the filter aid and the adsorbent need to be fixed.
  • the filter aid In order to ensure the passability of soybean oil flowing through the chromatography column, the filter aid should be below the formation of saponin to ensure the filtering effect.
  • the adsorbent In order to ensure the refining effect of soybean oil after flowing through the chromatography column, the adsorbent should be at the bottom layer. Therefore, based on the effects of filter aids and adsorbents in the chromatographic column, the experimental protocols of Comparative Example 1 and Comparative Example 2 were designed.
  • the lipase, solid base, filter aid and adsorbent are added together into the same chromatography column, and the order of packing is lipase, solid base, filter aid and adsorbent from top to bottom to form a layered packing method
  • Multiple sets of data tests were performed, and the detailed schematic diagram of the filler is shown in Figure 3.
  • Condition control, filler ratio and soybean oil dosage are as in Example 1, and the test results are integrated into a line graph, as shown in Figure 4.
  • the content of stearic acid is directly lower than 3%, which does not meet the requirements of 3-5% in the pharmacopoeia. It can also be seen from the results of peroxide value determination that in order to meet the Pharmacopoeia standard, the column passing time must be more than 4h to meet the requirements.
  • the scheme design of the comparative example 3 is also designed.
  • the method of fully mixing lipase and solid alkali, and layering fillers of filter aid and adsorbent was used to investigate the effect of reducing the content of stearic acid in soybean oil.
  • the schematic diagram of the filler is shown in Figure 7, the condition control, the ratio and amount of the filler are as in Example 1, and the test results are integrated into a line graph, as shown in Figure 8.
  • the stearic acid content of soybean oil in the solution of Comparative Example 3 is still uncontrollable, and the main reason for the sudden drop in the stearic acid content may be the formation of a large amount of saponin in the mixed layer of lipase and solid alkali , so that the soybean oil flow through the mixed layer is blocked, resulting in too high contact degree of soybean oil and lipase per unit time, and excessive hydrolysis.
  • the single-factor control variable method was used to conduct multiple experiments on the dosage range of lipase and solid alkali, and two experimental groups were designed: the dosage of lipase in experimental group 1 was 0.1%, 0.5%, 1%, 2.5%, 5%, 7.5%, the contact time is 1h, the other is the indicated material ratio and the condition control is the same as in Example 1; the dosage of solid alkali in experimental group 2 is 0.1%, 0.5%, 1%, 2.5% %, 5%, 7.5%, the contact time is 1h, and the other is the indicated material ratio and the condition control is the same as that of Example 1.
  • the results of the study are shown in Figure 9.
  • the solid alkali in this process is relatively excessive relative to lipase, and soybean oil
  • the effect of alkali refining is mainly, so the effect of reducing the content of stearic acid is relatively slight.
  • water will be generated, which will affect the adsorption effect of the adsorbent to a certain extent, resulting in methoxyl groups.
  • the aniline value and peroxide value are relatively high; when the amount of lipase is 1-5%, when the soybean oil flows through the mixed filler, the interaction between alkali refining and hydrolysis makes the content of stearic acid decrease significantly.
  • the adsorption performance of the adsorbent is less affected by water; with the further increase of the amount of solid alkali, the mixed filler system becomes an environment with excess alkali, so the excess water in the alkali refining process is significantly affected.
  • the adsorption performance of the adsorbent when the amount of solid alkali exceeds 5%, the final soybean oil peroxide value that flows through the mixed packing layer exceeds the internal control standard of 1.0. Therefore, the solid base dosage of 0.1% to 5% is a better choice.

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Abstract

本发明属于药用油脂精炼技术领域，公开一种采用混合填料精准控制大豆油中硬脂酸含量的方法，包括如下步骤：A、将脂肪酶、无机碱、助滤剂、吸附剂以物理方式混合均匀，形成混合填料，所述脂肪酶为Sn-1,3位特异性脂肪酶；B、使大豆油流经所述混合填料，获得精制大豆油。本发明解决传统大豆油生产工艺无法精准控制硬脂酸含量、无法满足制备高质量脂肪乳制剂的要求的问题。

Description

一种采用混合填料精准控制大豆油中硬脂酸含量的方法 技术领域
本发明涉及药用油脂精炼技术领域，具体涉及一种采用混合填料精准控制大豆油中硬脂酸含量的方法。
背景技术
油脂中存在少量的游离态脂肪酸和大量的结合态脂肪酸，其中，游离态脂肪酸较容易除去与控制，但结合态脂肪酸则以酯的形式作为油脂的构成成分之一，往往无法除去与控制，只能依赖于原料本身，其组成比例具有天然性和随机性。
大豆油是一种从大豆提取，精炼而成的天然油脂，是目前肠外营养型脂肪乳注射液的主要能量成分，以及载药脂肪乳的油相基质。大豆油能够提供人体必须的脂肪酸，其主要脂肪酸包括棕榈酸，棕榈油酸，硬脂酸，油酸，亚油酸，亚麻酸，花生酸，二十碳烯酸，山嵛酸，二十四烷酸等。中国药典中对于大豆油脂肪酸含量的规定如下：小于十四碳的饱和脂肪酸不大于0.1％，十四烷酸不大于0.2％，棕榈酸应为9～13％，棕榈油酸不大于0.3％，硬脂酸应为3.0～5.0％，油酸应为17.0～30.0％，亚油酸应为48.0～58.0％，亚麻酸应为5.0～11.0％，花生酸不大于1.0％，二十碳烯酸不大于1.0％，山嵛酸不大于1.0％。
近年来，随着国家开展仿制注射剂一致性评价，对于注射剂质量与疗效要求越来越严格，尤其是对于脂肪乳，脂质体，微球等复杂注射剂。因为这类复杂注射剂所用原辅料多属于具有功能性，且成分复杂的天然来源物质，如大豆油、橄榄油等油脂类产品。如何精确控制这类天然来源的原辅料质量的一致性，目前对于传统生产工艺来说，面临着巨大挑战。
大豆油用于脂肪乳已有了60年的历史，其丰富的脂肪酸组成，可以为临床特殊病患提供必要的营养支持。目前药用级别大豆油传统的生产工艺仅是针对其油脂中存在的杂质成分进行控制，无法改变其脂肪酸的组成及比例，脂肪酸 组成多保留了天然脂肪酸状态，没有针对天然油脂中某一种脂肪酸含量的控制。传统大豆油的生产工艺虽然能够满足大豆油中硬脂酸含量符合中国药典3～5％的质量要求，但是硬脂酸含量基本上为4～5％，主要是依赖于大豆油原料的质量，无法从生产工艺中得到控制。目前越来越多的制剂企业寻求硬脂酸含量为3～4％的大豆油，以期能够生产出更高质量的脂肪乳制剂，但是截至目前为止尚未有关于控制大豆油中硬脂酸含量的工艺报导，阻碍我国药用脂质及脂肪乳领域的发展。
随着近年来在油脂领域的研究越来越深入，研究人员发现大豆油中甘油三酯三个碳链的分布有着一定的规律。研究表明，大豆油甘油三酯中1，3位脂肪酸残基主要分布饱和的脂肪酸如棕榈酸，硬脂酸等，2位主要为不饱和的脂肪酸如油酸，亚油酸，亚麻酸等。虽然脂肪酶水解甘油三酯用于甘油三酯结果确证已经有了诸多报道，但基本都是利用酶水解得到甘油单酯，进而对甘油单酯中脂肪酸组成进行研究。研究人员已经做过尝试，如果在传统大豆油生产工艺中加入脂肪酶水解步骤，无法控制其酶水解的精确度，使得最终产品硬脂酸含量急剧降低，无法满足脂肪乳制剂的要求。如果在传统的大豆油精炼工序中引入酶水解过程，来制备硬脂酸含量在3～4％之间的大豆油，会使得大豆油精炼工序变得十分冗长。传统大豆油单独增加酶水解过程主要有如下几点问题：①水解过程需进行搅拌，工业化机械搅拌强大的机械能会使得酶被搅碎，增加酶活性保障的不确定性；②增加酶水解过程，必然要增加后续酶去除工序，进一步延长工时；③由于酶在水解过程中被机械能搅碎，后续对酶是否能够去除完全需增加酶残留工艺验证问题。
可见，如何精准控制大豆油中的硬脂酸含量，一直是业内急待解决的难题。
发明内容
本发明的目的在于，解决传统大豆油生产工艺无法精准控制硬脂酸含量、无法满足制备高质量脂肪乳制剂的要求的问题。
为了解决上述技术问题，本发明采用如下技术方案：
一种采用混合填料精准控制大豆油中硬脂酸含量的方法，包括如下步骤：
A、将脂肪酶、无机碱、助滤剂、吸附剂以物理方式混合均匀，形成混合填料，所述脂肪酶为Sn-1,3位特异性脂肪酶；
B、使大豆油流经所述混合填料，获得精制大豆油；
所述混合填料各组分与所述大豆油的比重如下：所述脂肪酶0.1～5％、所述固体碱0.1～5％、所述助滤剂1～20％、所述吸附剂1～20％。
从现行药典标准以及各种国际组织可查询到的标准来看，现行标准对大豆油中硬脂酸含量的要求较为宽松，一般都是根据当地大豆油产出的天然性质进行制定(如药典要求为3％～5％)，只有部分与当地性质差异较大或较为劣质的油脂才不被接受。但是，在实际合作与研发过程中，特别是药用产品的合作开发与生产中，大豆油这一常用脂肪乳制剂原料实际还需要满足无法提前获知的企业内部标准。企业内部标准往往比可查询到的当地标准更为严格而无法普遍满足，其主要目的在于减少竞争对手、提高药用产品质量。
本发明通过采用一种混合填料用于精准控制大豆油中硬脂酸含量的方法，能够同时实现脱酸，酶水解，吸附除杂三个效果。而且通过将脂肪酶、固体碱、助滤剂、吸附剂通过物理混合使其均匀分散的混合在一起，大豆油中游离的脂肪酸与固体碱发生中和反应，脱酸并产生水；Sn-1,3位特异性脂肪酶利用脱酸过程产生的水对大豆油中甘油三酯进行定位水解，产生游离的脂肪酸；游离的脂肪酸又被固体碱中和，形成一个微循环过程。混合在其中的助滤剂又能有效地避免碱炼过程产生的皂角而造成过滤较难的问题。如果缺少助滤剂，则碱炼过程产生的皂角会使得大豆油流动阻力增大，很难甚至无法流经混合填料，对大豆油的水解程度难以控制，同时大大延长精制工序时长。脂肪酶、固体碱、助滤剂、吸附剂四种物质均匀混合、相辅相成，中和与水解形成微循环反应，碱炼过程中形成的皂角又被助滤剂所阻隔，水解产生的二酯、一酯和氧化物等杂质则被吸附剂及时吸附，使精准控制大豆油中的硬脂酸含量成为可能。在这个基础上，可以通过控制温度，控制设备压力，以及控制原料与填料的接触时间实现上述过程的精准可控，最终实现大豆油中硬脂酸含量在极窄范围内的精确控制，能满足不同药用需求。
对于大豆油中降低硬脂酸含量的工艺，优选的用量是混合填料各组分与大豆油的比重如下：脂肪酶0.1～5％、所述固体碱0.1～5％、所述助滤剂1～20％、所述吸附剂1～20％，此时，能较好的控制大豆油中硬脂酸含量的缓慢减少，并同时将酸值、过氧化值等控制在合理范围内，直到达到精制大豆油要求。
优选的，所述精制大豆油的硬脂酸含量为3～4％；所述精制大豆油的过氧化值小于1。
对于大豆油脂肪乳制剂质量影响较大的是大豆油中的硬脂酸含量，本发明利用硬脂酸主要分布在大豆油中甘油三酯1，3位的特性，选用对甘油三酯1，3位具有选择性的脂肪酶对大豆油进行水解，而且通过固体碱脱酸以及吸附剂吸附除去二酯，一酯，氧化物等杂质，以达到降低硬脂酸的含量，控制硬脂酸的含量在3～4％范围。通过本发明的方法能将任意来源的大豆油控制硬脂酸含量在3～4％的极窄范围内，同时将过氧化值控制在1以下，摆脱脂肪乳制剂研究对大豆油来源的依赖，对药剂研究将产生巨大的影响。
优选的，所述混合填料的混合均匀度的标准差均不大于0.05％；所述脂肪酶、所述无机碱、所述助滤剂、所述吸附剂的粒径均小于250μm。
脂肪酶、无机碱、助滤剂、吸附剂几种填料颗粒应控制大小大致相同并且粒径均小于250μm，如果填料粒径不一，很难达到混合均匀的目的。同时控制填料在较小的粒径范围，可以增加原料与填料的接触面积，提高接触效率。粒径越小，越有助于脂肪酶、无机碱、助滤剂、吸附剂4种成分相互混匀、协同发生作用。在混合均匀度的标准差均不大于0.05％的情况下，大豆油能在混合填料中发生最流畅的微循环反应而不会产生阻滞，是较理想的混合状态。
优选的，所述步骤A还包括：将所述混合填料填充在层析柱中。
优选的，所述步骤B的操作为：所述大豆油进入所述层析柱中，流出后获得所述精制大豆油。
优选的，所述层析柱的温度为30～60℃，压力为0.02～0.5MPa，与所述大豆油的接触时间为1～10h；所述大豆油循环进入所述层析柱中1～10次。
优选的，所述Sn-1,3位特异性脂肪酶包括TLIM、435脂肪酶、Lipase脂肪酶、RMIM脂肪酶中的一种或多种。
优选的，所述固体碱包括氢氧化钠、氢氧化钾、氢氧化钙中的一种或多种。
优选的，所述吸附剂包括氧化铝、硅胶、白土、凝胶中的一种或多种。
优选的，所述助滤剂包括硅藻土、膨润土中的一种或多种。
一种根据上述采用混合填料精准控制大豆油中硬脂酸含量的方法获得的精制大豆油产品。
与现有技术相比较，实施本发明，具有如下有益效果：
1.本发明经过一步反应实现酶水解，降酸，除杂三个效果，通过控制装有混合填料设备的温度，压力，原料与填料的接触时间来实现脱除甘油二酯，甘油单酯，游离脂肪酸，氧化物等效果。大大降低了工业化步骤繁琐的缺点。
2.本发明制备的一种低含量硬脂酸大豆油各项指标满足中国药典标准，通过该工艺能够严格控制大豆油硬脂酸含量在3～4％之间。避免了大豆油因为起始物料差异造成的硬脂酸含量波动，同时满足国内制剂企业对于3～4％硬脂酸含量大豆油的特定原料需求，进而能够生产出与更高质量的脂肪乳制剂。通过该工艺可以解决大豆油的起始物料的依赖。
3.为保证上述过程的可操作性，本发明采用了在包含脂肪酶，固体碱，吸附剂通过物理混合形成的均匀分散的混合填料中添加助滤剂的方法，避免碱炼过程中形成的皂角导致整个体系无法顺利层析，进一步保障了一步操作法同时实现酶水解，脱酸，除杂三个效果。
4.通过将脂肪酶，固体碱，助滤剂，吸附剂通过物理混合使其均匀分散的混合在一起，使用脱酸过程产生的水，脂肪酶实现对大豆油中甘油三酯的定位水解。还可以控制温度，控制设备压力，以及控制原料与填料的接触时间实现上述过程的精准可控，最终实现大豆油中硬脂酸含量在极窄范围内的精确控制。
附图说明
图1为本发明混合填料示意图；
图2为采用混合填料法过柱时间的考察结果图；
图3为对比例1填料示意图；
图4为采用对比例1填料法过柱时间的考察结果图；
图5为对比例2填料示意图；
图6为采用对比例2填料法过柱时间的考察结果图；
图7为对比例3填料示意图；
图8为采用对比例3填料法过柱时间的考察结果图；
图9为对比例4脂肪酶和固体碱用量考察结果图。
具体实施方式
为使本发明的目的、技术方案和优点更加清楚，下面将结合附图对本发明作进一步地详细描述。
实施例1
称取Sn-1,3位特异性脂肪酶435脂肪酶1g，氢氧化钠1g，硅藻土10g，氧化铝10g，经过物理混合均匀，添加至层析柱中。取食用大豆油1kg，进行上述混合填料柱层析柱操作，柱温控制在50±2℃，压力控制在0.04±0.02mPa，过柱时间为10h。检测食用大豆油和过柱后精制大豆油的酸值，甲氧基苯胺值，过氧化值，硬脂酸含量。测定结果如表1所示(其中，酸值、过氧化值、甲氧基苯胺值按药典所示方法进行测定与计算)。
表1 实施例1食用大豆油精制前后关键指标测定结果
Figure PCTCN2020128414-appb-000001
Figure PCTCN2020128414-appb-000002
实施例2
称取Sn-1,3位特异性脂肪酶Lipase脂肪酶10g，氢氧化钠10g，硅藻土50g，硅胶50g，经过物理混合均匀，添加至层析柱中。取食用大豆油1kg，进行上述混合填料柱层析柱操作，柱温控制在40±2℃，压力控制在0.1±0.02mPa，过柱时间为5h。检测食用大豆油和过柱后精制大豆油的酸值，甲氧基苯胺值，过氧化值，硬脂酸含量。测定结果如表2所示(其中，酸值、过氧化值、甲氧基苯胺值按药典所示方法进行测定与计算)。
表2 实施例2食用大豆油精制前后关键指标测定结果
Figure PCTCN2020128414-appb-000003
实施例3
称取Sn-1,3位特异性脂肪酶RMIM脂肪酶100g，氢氧化钙100g，膨润土50g，白土750g，经过物理混合充分，添加至层析柱中。取食用大豆油5kg，经 过混合填料层析柱，柱温控制在40±2℃，压力控制在0.3±0.02mPa，过柱时间为5h。检测食用大豆油和过柱后精制大豆油的酸值，甲氧基苯胺值，过氧化值，硬脂酸含量。测定结果如表3所示(其中，酸值、过氧化值、甲氧基苯胺值按药典所示方法进行测定与计算)。
表3 实施例3食用大豆油精制前后关键指标测定结果
Figure PCTCN2020128414-appb-000004
实施例4
称取Sn-1,3位特异性脂肪酶TLIM脂肪酶300g，氢氧化钠400g，硅藻土1000g，凝胶1500g，经过物理混合充分，添加至层析柱中。取食用大豆油10kg，经过混合填料层析柱，柱温控制在30±2℃，压力控制在0.4±0.02mPa，过柱时间为1.5h。检测食用大豆油和过柱后精制大豆油的酸值，甲氧基苯胺值，过氧化值，硬脂酸含量。测定结果如表4所示(其中，酸值、过氧化值、甲氧基苯胺值按药典所示方法进行测定与计算)。
表4 实施例4食用大豆油精制前后关键指标测定结果
Figure PCTCN2020128414-appb-000005
Figure PCTCN2020128414-appb-000006
实施例5
称取Sn-1,3位特异性脂肪酶435脂肪酶750g，氢氧化钙750g，硅藻土3000g，硅胶3000g，经过物理混合充分，添加至层析柱中。取食用大豆油30kg，经过混合填料层析柱，柱温控制在35±2℃，压力控制在0.5±0.02mPa，过柱时间为1h。检测食用大豆油和过柱后精制大豆油的酸值，甲氧基苯胺值，过氧化值，硬脂酸含量。测定结果如表5所示(其中，酸值、过氧化值、甲氧基苯胺值按药典所示方法进行测定与计算)。
表5 实施例5食用大豆油精制前后关键指标测定结果
Figure PCTCN2020128414-appb-000007
实施例6
称取Sn-1,3位特异性脂肪酶435脂肪酶3kg，氢氧化钙3kg，硅藻土30kg，硅胶30kg，经过物理混合充分，添加至层析柱中。取食用大豆油3000kg，经过混合填料层析柱，柱温控制在35±2℃，压力控制在0.5±0.02mPa，过柱时间为1h，循环过柱5次，检测食用大豆油和过柱后精制大豆油的酸值，甲氧基苯胺值，过氧化值，硬脂酸含量。测定结果如表6所示(其中，酸值、过氧化值、 甲氧基苯胺值按药典所示方法进行测定与计算)。
表6 实施例6食用大豆油精制前后关键指标测定结果
Figure PCTCN2020128414-appb-000008
实施例7
称取Sn-1,3位特异性脂肪酶435脂肪酶50g，氢氧化钙50g，硅藻土200g，硅胶200g，经过物理混合充分，添加至层析柱中。取食用大豆油1kg，经过混合填料层析柱，柱温控制在40±2℃，压力控制在0.5±0.02mPa，过柱时间为5h，检测食用大豆油和过柱后精制大豆油的酸值，甲氧基苯胺值，过氧化值，硬脂酸含量。测定结果如表7所示(其中，酸值、过氧化值、甲氧基苯胺值按药典所示方法进行测定与计算)。
表7 实施例7食用大豆油精制前后关键指标测定结果
Figure PCTCN2020128414-appb-000009
Figure PCTCN2020128414-appb-000010
从本实施例可以看出，即使食用大豆油的原料品质较差(硬脂酸含量5.10％)，经过本发明的工艺处理后，依然能将其硬脂酸含量精确控制在3～4％的范围内，符合制备高质量脂肪乳制剂的要求(其中，酸值、过氧化值、甲氧基苯胺值按药典所示方法进行测定与计算)。
实施例8
称取Sn-1,3位特异性脂肪酶RMIM脂肪酶1.1g，氢氧化钠1g，硅藻土10g，氧化铝12g，经过物理混合均匀，添加至层析柱中。取食用大豆油1kg，进行上述混合填料柱层析柱操作，柱温控制在45±2℃，压力控制在0.05±0.02mPa，过柱时间为8h。检测食用大豆油和过柱后精制大豆油的酸值，甲氧基苯胺值，过氧化值，硬脂酸含量。测定结果如表8所示(其中，酸值、过氧化值、甲氧基苯胺值按药典所示方法进行测定与计算)。
表8 实施例8食用大豆油精制前后关键指标测定结果
Figure PCTCN2020128414-appb-000011
从本实施例可以看出，即使食用大豆油的原料品质较差(硬脂酸含量5.96％)，经过本发明的工艺处理后，依然能将其硬脂酸含量精确控制在3～4％的范围内，符合制备高质量脂肪乳制剂的要求(其中，酸值、过氧化值、甲氧基苯胺值按药典所示方法进行测定与计算)。
效果例1
采用将脂肪酶、固体碱、助滤剂、吸附剂以物理混合形成混合填料的方法进行多组数据测试，填料示意图如图1所示。条件控制、填料比例与大豆油用量如实施例1，测试结果整合成折线图，如图2所示。
从图2可以看出，采用本发明技术方案，能够有效控制硬脂酸含量在3～4％之间，同时由于本发明技术方案不需要外来引入水，使得硅胶吸附效果得到保障，其吸附过氧化物的能力不会被破坏。在过柱时间1～10h内，均可以保障大豆油的硬脂酸含量在3～4％之间，且过氧化值能够符合药典标准要求。
除本发明技术方案外，还进行了分层填料的对比试验，在设计分层填料试验方案时，为确保试验结果可对比性，需要固定助滤剂和吸附剂的位置。为保证大豆油流经层析柱的通过性，助滤剂要在皂角形成的下方，确保过滤效果，同时为保证大豆油流经层析柱后的精制效果，吸附剂要在最底层。因此，基于助滤剂和吸附剂在层析柱中的作用，设计了对比例1和对比例2试验方案。
对比例1
采用将脂肪酶、固体碱、助滤剂、吸附剂一起添加到同一层析柱中，填料顺序由上到下依次是脂肪酶、固体碱、助滤剂、吸附剂，形成分层填料的方法进行多组数据测试，填料详细示意图见图3。条件控制、填料比例与大豆油用量如实施例1，测试结果整合成折线图，如图4所示。
从图4可以看出，采用脂肪酶、固体碱、助滤剂、吸附剂，形成分层填料的方法进行3～4％硬脂酸含量的大豆油制备会使得硬脂酸含量不可控。可能是因为当大豆油经过酶层时，首先发生的是酶水解过程，容易使得甘油三酯水解过度。此外采用分层填料的方法，由于酶水解过程需要有水参与，因此酶层需要用适当比例水提前润湿，引入的水会使得后续硅胶吸附过氧化物效果变差。采用分层填料方法，硬脂酸含量直接低于3％，不符合药典中3～5％的要求。从过氧化值测定结果也可以看出，为满足药典标准，其过柱时间要大于4h以上才能符合要求。
对比例2
采用将固体碱、助滤剂、脂肪酶、吸附剂一起添加到同一层析柱中，填料顺序由上到下依次是固体碱、助滤剂、脂肪酶、吸附剂，形成分层填料的方法进行多组数据测试，填料详细示意图见图5。条件控制、填料比例与大豆油用量如实施例1，测试结果整合成折线图，如图6所示。
从图6可以看出，采用固体碱、助滤剂、脂肪酶、吸附剂，形成分层填料的方法制备3～4％硬脂酸含量的大豆油制备会使得硬脂酸含量降低不明显。可能是因为大豆油与固体碱反应后生成的水被助滤剂吸收，酶层由于缺乏水分导致其活性不足，使得大豆油硬脂酸含量没有发生明显改变。为保证酶的催化活性，若提前用水润湿又会使得吸附剂活性受到影响，导致大豆油的氧化指标不合格。
对比例3
除对比例1和对比例2外，还设计了对比例3的方案设计。采用了将脂肪酶和固体碱充分混合，助滤剂和吸附剂分层填料的方法，用以考察其对大豆油中硬脂酸含量的降低效果。填料示意图如图7所示，条件控制、填料比例与用量如实施例1，测试结果整合成折线图，如图8所示。
从图8可以看出，采用对比例3的方案大豆油硬脂酸含量仍然无法控制，造成其硬脂酸含量骤降的主要原因可能是在脂肪酶和固体碱混合层中形成了大量皂角，使得大豆油流经该混合层受阻，导致大豆油与脂肪酶单位时间接触程度过高，水解过度。
对比例4
除对比例1～3外，还采用单因素控制变量法对脂肪酶和固体碱用量范围进行了多组试验，设计了两个实验组：实验组1脂肪酶用量分别为0.1％，0.5％，1％，2.5％，5％，7.5％，接触时间1h，其他为注明的用料比例和条件控制同实施例1；实验组2固体碱用量分别为0.1％，0.5％，1％，2.5％，5％，7.5％，接触时间1h，其他为注明的用料比例和条件控制同实施例1。研究结果见图9所示。
从图9中实验组1硬脂酸和过氧化值测定结果来看，在其他成分用量不变 的前提下，其硬脂酸含量降低速度与脂肪酶用量总体上呈负相关，随着脂肪酶用量的增多，其硬脂酸含量降低得越多。但当脂肪酶用量超过5％时，即使只有1h的接触时间，其硬脂酸含量也会迅速降至3.0％以下，不符合中国药典对于大豆油硬脂酸含量的要求。这样的降低速度过快，对精准控制是极为不利的。从图9中还可以看出，在其他成分用量对硬脂酸含量的影响大致分为3个阶段，0.1～1％用量范围内，该过程固体碱相对于脂肪酶来说较为过量，大豆油流经混合填料时，碱炼效果为主，所以导致硬脂酸含量降低效果相对轻微，同样，由于碱炼过程会产生水分，这在一定程度上会影响吸附剂的吸附效果，导致甲氧基苯胺值过氧化值相对较高；当脂肪酶用量在1～5％时，大豆油流经混合填料时，碱炼与水解相互作用，使得硬脂酸含量降低明显，同时由于碱炼和水解过程发挥充分，较少的水分被吸附剂吸收，使得吸附剂的吸附效果不受太大影响，体现在甲氧基苯胺值过氧化值降低效果明显；随着脂肪酶用量进一步增加，使得其水解程度逐步加大，当脂肪酶用量超过5％时，其硬脂酸含量降至3.0％以下，不符合中国药典对于大豆油中硬脂酸含量3.0～5.0％的要求。因此，脂肪酶用量0.1％～5％是较优的选择。
从图9中实验组2硬脂酸和过氧化值测定结果来看，在其他成分用量不变的前提下，其硬脂酸含量降低速度与固体碱用量总体上也呈负相关，随着固体碱用量的增多，其硬脂酸含量降低得越多，但是其过氧化值与固体碱用量却呈正相关。开始时，由于混合填料体系中脂肪酶相对过量，但由于固体碱含量较少，使得碱炼过程产生的水分相对较少，这使得脂肪酶水解性能和硅胶吸附性能均受到较小的影响，所以呈现出的结果就是硬脂酸含量降低效果不明显，同时吸附剂的吸附效果较高，过氧化值较小；随着固体碱用量增多，碱炼过程产生的水分增多，脂肪酶水解效果提升，由于碱炼的水正好为脂肪酶提供水解环境，使得吸附剂吸附性能受水分影响较小；随着固体碱用量进一步增加，混合填料体系变为碱过量环境，这样碱炼过程多余的水明显影响吸附剂的吸附性能，当固体碱用量超过5％时，最终流经混合填料层的大豆油过氧化值超过内控标准1.0。因此，固体碱用量0.1％～5％是较优的选择。
从对比例4的实验组1和实验组2的一系列考察结果来看，当脂肪酶或固体碱含量超过5％以上时，无法同时满足控制硬脂酸含量和氧化值在合理范围 内，无法使最终大豆油产品满足标准要求。
以上所揭露的仅为本发明的较佳实施例而已，当然不能以此来限定本发明之权利范围，因此依本发明权利要求所作的等同变化，仍属本发明所涵盖的范围。

Claims (10)

  1. 一种采用混合填料精准控制大豆油中硬脂酸含量的方法，其特征在于，包括如下步骤：
    A、将脂肪酶、无机碱、助滤剂、吸附剂以物理方式混合均匀，形成混合填料，所述脂肪酶为Sn-1,3位特异性脂肪酶；
    B、使大豆油流经所述混合填料，获得精制大豆油；
    所述混合填料各组分与所述大豆油的比重如下：所述脂肪酶0.1～5％、所述固体碱0.1～5％、所述助滤剂1～20％、所述吸附剂1～20％。
  2. 根据权利要求1所述采用混合填料精准控制大豆油中硬脂酸含量的方法，其特征在于，所述精制大豆油的硬脂酸含量为3～4％；所述精制大豆油的过氧化值小于1。
  3. 根据权利要求1所述采用混合填料精准控制大豆油中硬脂酸含量的方法，其特征在于，所述混合填料的混合均匀度的标准差均不大于0.05％；所述脂肪酶、所述无机碱、所述助滤剂、所述吸附剂的粒径均小于250μm。
  4. 根据权利要求1所述采用混合填料精准控制大豆油中硬脂酸含量的方法，其特征在于，所述步骤A还包括：将所述混合填料填充在层析柱中；所述步骤B的操作为：所述大豆油进入所述层析柱中，流出后获得所述精制大豆油。
  5. 根据权利要求4所述采用混合填料精准控制大豆油中硬脂酸含量的方法，其特征在于，所述层析柱的温度为30～60℃，压力为0.02～0.5MPa，与所述大豆油的接触时间为1～10h；所述大豆油循环进入所述层析柱中1～10次。
  6. 根据权利要求1所述采用混合填料精准控制大豆油中硬脂酸含量的方法，其特征在于，所述Sn-1,3位特异性脂肪酶包括TLIM、435脂肪酶、Lipase脂肪酶、RMIM脂肪酶中的一种或多种。
  7. 根据权利要求1所述采用混合填料精准控制大豆油中硬脂酸含量的方法，其特征在于，所述固体碱包括氢氧化钠、氢氧化钾、氢氧化钙中的一种或多种。
  8. 根据权利要求1所述采用混合填料精准控制大豆油中硬脂酸含量的方法，其特征在于，所述吸附剂包括氧化铝、硅胶、白土、凝胶中的一种或多种。
  9. 根据权利要求1所述采用混合填料精准控制大豆油中硬脂酸含量的方法，其特征在于，所述助滤剂包括硅藻土、膨润土中的一种或多种。
  10. 一种根据权利要求1所述采用混合填料精准控制大豆油中硬脂酸含量的方法获得的精制大豆油产品。
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Publication number Priority date Publication date Assignee Title
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Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030013165A1 (en) * 2001-06-22 2003-01-16 Kao Corporation Hydrolytic process of oil and fat
CN101736047A (zh) * 2010-02-01 2010-06-16 国家粮食局科学研究院 一种茶油酶催化改性制备功能性油脂的方法
CN102660593A (zh) * 2012-04-28 2012-09-12 北京化工大学 酶法制备富含藻油n-3多不饱和脂肪酸的甘油酯的方法
CN106748615A (zh) * 2016-12-09 2017-05-31 广州白云山汉方现代药业有限公司 一种从油脂中提取角鲨烯的方法
CN106929501A (zh) * 2015-12-29 2017-07-07 丰益(上海)生物技术研发中心有限公司 脂肪酶固定化载体、固定化脂肪酶及其制备方法和应用
CN112029580A (zh) * 2020-09-03 2020-12-04 广州白云山汉方现代药业有限公司 一种采用微循环技术精准控制油脂中特定脂肪酸比例的方法

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2763789B2 (ja) * 1989-06-29 1998-06-11 旭電化工業株式会社 硬化油の改質方法
US8685680B2 (en) * 2005-05-13 2014-04-01 Thomas P. Binder Method for producing fats or oils
CN1965807A (zh) * 2006-11-21 2007-05-23 西安力邦制药有限公司 一种利用饱和脂肪酸卵磷脂制备的脂肪乳注射剂
JP5204776B2 (ja) * 2007-07-30 2013-06-05 日本水産株式会社 Ｅｐａ濃縮油およびｄｈａ濃縮油の製造方法
CN102586014B (zh) * 2012-02-24 2013-06-19 合肥工业大学 一种中长链脂肪酸甘油三酯的分离纯化方法
WO2014012548A1 (en) * 2012-07-18 2014-01-23 Aarhuskarlshamn Ab Reduction of mcpd-compounds in refined plant oil for food
CN105087157B (zh) * 2015-08-18 2018-11-13 沈阳药科大学 一种低甾醇注射用苏子油的精制工艺及其用途
CN106929150B (zh) * 2015-12-30 2020-11-10 丰益(上海)生物技术研发中心有限公司 油脂脱酸、脱色和精炼工艺

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030013165A1 (en) * 2001-06-22 2003-01-16 Kao Corporation Hydrolytic process of oil and fat
CN101736047A (zh) * 2010-02-01 2010-06-16 国家粮食局科学研究院 一种茶油酶催化改性制备功能性油脂的方法
CN102660593A (zh) * 2012-04-28 2012-09-12 北京化工大学 酶法制备富含藻油n-3多不饱和脂肪酸的甘油酯的方法
CN106929501A (zh) * 2015-12-29 2017-07-07 丰益(上海)生物技术研发中心有限公司 脂肪酶固定化载体、固定化脂肪酶及其制备方法和应用
CN106748615A (zh) * 2016-12-09 2017-05-31 广州白云山汉方现代药业有限公司 一种从油脂中提取角鲨烯的方法
CN112029580A (zh) * 2020-09-03 2020-12-04 广州白云山汉方现代药业有限公司 一种采用微循环技术精准控制油脂中特定脂肪酸比例的方法

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
"Bailey's Industrial Oil and Fat Products: 6th Edition, Vol. 2. Edible Oil and Fat Products: Edible Oils", 31 December 2010, CHINA LIGHT INDUSTRY PRESS, CN, ISBN: 978-7-5184-0895-5, article FEREIDOON SHAHIDI: "Edible Oil and Fat Products: Edible Oils", pages: 534, XP009534977 *
ZHAO YADONG, GUOCHENG HUO: "Production of Human Milk Fat Substitutes Through Immobilized Lipase-Catalyzed Interesterification", CHINA OILS AND FATS, vol. 35, no. 12, 31 December 2010 (2010-12-31), pages 12 - 15, XP055906100, ISSN: 1003-7969 *

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