WO2022048014A1 - 一种橄榄油中棕榈酸含量的精准控制方法 - Google Patents

一种橄榄油中棕榈酸含量的精准控制方法 Download PDF

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WO2022048014A1
WO2022048014A1 PCT/CN2020/128412 CN2020128412W WO2022048014A1 WO 2022048014 A1 WO2022048014 A1 WO 2022048014A1 CN 2020128412 W CN2020128412 W CN 2020128412W WO 2022048014 A1 WO2022048014 A1 WO 2022048014A1
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olive oil
palmitic acid
lipase
acid content
precise control
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PCT/CN2020/128412
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English (en)
French (fr)
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许文东
袁诚
唐顺之
牛亚伟
刘菊妍
傅玉萍
李遥
牟肖男
王国财
刘春芳
李咏华
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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 WO2022048014A1 publication Critical patent/WO2022048014A1/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
    • C11B3/001—Refining fats or fatty oils by a combination of two or more of the means hereafter
    • 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 oil refining, in particular to a method for accurately controlling the content of palmitic acid in olive oil.
  • Olive oil is a kind of natural oil extracted and refined from the mature stone fruit of oleifera, and it is the main energy component of parenteral nutrition fat emulsion injection.
  • a kind of oil-fat emulsion injection (SMOF) is used as an energy substance.
  • Olive oil can provide essential fatty acids for the human body, the main fatty acids include palmitic acid, palmitoleic acid, palmitic acid, oleic acid, linoleic acid, linolenic acid, arachidic acid, eicosenoic acid, behenic acid, tetracosane acid etc.
  • the 2015 edition of the Chinese Pharmacopoeia stipulates the fatty acid content of olive oil as follows: saturated fatty acids less than 16 carbons should be no more than 0.1%, palmitic acid should be 7.5-20.0%, palmitoleic acid should be no more than 3.5%, palmitic acid should be 0.5-5.0% %, oleic acid should be 56.0-85.0%, linoleic acid should be 3.5-20.0%, linolenic acid should be no more than 1.2%, arachidic acid should be no more than 0.7%, eicosenoic acid should be no more than 0.4%, and behenic acid should be no more than 0.4% 0.2%, tetracosanoic acid is not more than 0.2%.
  • Olive oil has been cultivated in Mediterranean countries for about 6,000 years, where 95% of the world's olive germplasm resources are distributed. Since its introduction in the 1960s, my country has experienced a development stage from the introduction experiment to the initial stage of industrialization.
  • the olive oil preparations already on the market in China all rely on foreign imports or imported sub-packages.
  • the palmitic acid content of olive oil in domestically marketed imported olive oil preparations is usually between 7.5 and 12.0%, while the palmitic acid content of domestic olive oil raw materials is usually between 12.0 and 20.0%.
  • the fatty acid composition of olive oil obtained by the traditional olive oil preparation process is highly dependent on the olive oil raw material, and its quality is restricted by the maturity of the olive fruit, the picking season, and the planting area. Therefore, how to control the quality of olive oil more precisely and realize the controllability of the fatty acid composition of olive oil through the technological process is currently facing a huge challenge to the traditional production process.
  • the traditional production process of medicinal-grade olive oil is only to control the impurities in its oil.
  • the acid value, peroxide value and methoxyaniline value of natural olive oil can be effectively controlled.
  • microorganisms and other key physical and chemical properties in addition, it can effectively control toxic and harmful impurities such as benzopyridine, but it cannot specifically change the composition and proportion of its fatty acids.
  • the fatty acid composition mostly retains the state of natural fatty acids, that is, the traditional oil refining process. There is no way to control the content of a single fatty acid in olive oil.
  • the traditional olive oil production process can meet the quality requirements of 7.5-20.0% of the palmitic acid content in the Chinese Pharmacopoeia
  • the palmitic acid content is basically more than 12%, which is mainly dependent on the characteristics of the olive oil raw materials. Controlled from the production process.
  • OO long-chain fat emulsion injection
  • SMOF oil fat emulsion injection
  • the lipase hydrolysis step is added to the traditional olive oil production process, the accuracy of the enzymatic hydrolysis cannot be controlled, resulting in a sharp decrease in the content of palmitic acid in the final product, which cannot meet the Chinese Pharmacopoeia standard. It can be seen that the technology that lipase is used in the oil production process to specifically reduce the content of a certain fatty acid from the perspective of industrialization has not been studied.
  • the purpose of the present invention is to solve the problems that the traditional olive oil production process cannot precisely control the content of palmitic acid and cannot meet the requirements for preparing high-quality fat emulsion preparations.
  • the present invention adopts the following technical solutions:
  • a method for precise control of palmitic acid content in olive oil comprising the following steps:
  • the proportion of each component of the mixed filler to the olive oil is as follows: 0.1-7.5% of the lipase, 0.1-7.5% 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 palmitic acid in olive oil by using a mixed filler. Moreover, by physically mixing lipase, solid base, filter aid and adsorbent to make them uniformly dispersed, the free fatty acid in olive oil and the solid base undergo a neutralization reaction to deacidify and produce water; lipase utilizes The water produced in the deacidification process conducts localized hydrolysis of triglycerides in olive 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 the olive oil, making it difficult or even impossible to flow through the mixed filler, and it is difficult to control the degree of hydrolysis of the olive 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 monoesters, monoesters and oxides are adsorbed by the adsorbent in time, making it possible to precisely control the palmitic acid content in olive 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 material and the filler, and finally the precise control of the palmitic acid content in olive oil within a very narrow range can meet the needs of different Medicinal needs.
  • the preferred dosage is that the proportion of each component of the mixed filler and the olive oil is as follows: lipase 0.1-7.5%, solid alkali 0.1-7.5%, filter aid 1-20%, adsorption At this time, the slow reduction of palmitic acid content in olive oil can be better controlled, and the acid value and peroxide value are controlled within a reasonable range until the requirements of refined olive oil are met.
  • the palmitic acid content of the refined olive oil is 7.5-12%; the peroxide value of the refined olive oil is less than 3.
  • the palmitic acid content in the olive oil has a great influence on the quality of the olive oil fat emulsion preparation.
  • the palmitic acid content of any source of olive oil can be controlled within a very narrow range of 7.5-12%, while the peroxidation The value is controlled below 3 to get rid of the dependence on the source of olive oil in the study of fat emulsion preparations, which will have a huge impact on the research of pharmaceuticals.
  • the standard deviation of the mixing uniformity of the mixed fillers 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 the mixing uniformity is not more than 0.05%, the olive 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: the olive oil enters the chromatography column, and the refined olive oil is obtained after flowing out.
  • the temperature of the chromatography column is 30-60° C.
  • the pressure is 0.02-0.5 MPa
  • the contact time with the olive oil is 1-10 h; the olive oil is circulated into the chromatography column for 1-10 h. 10 times.
  • the lipase is Sn-1,3-specific lipase.
  • the distribution of palmitic acid triglycerides in olive oil is randomly assigned, and may or may not be at all three sites. However, it is found through research that palmitic acid is mainly distributed in the 1 and 3 positions of triglycerides in olive oil.
  • the present invention utilizes this characteristic and preferentially selects a lipase with selectivity to the 1 and 3 positions of triglycerides to hydrolyze olive oil.
  • the solid alkali deacidification and adsorbents remove impurities such as diesters, monoesters, oxides, etc., so as to reduce the content of palmitic acid and control the content of palmitic acid in the range of 7.5-12%.
  • the lipase includes one or more of TLIM, 435 lipase, Lipase lipase or RMIM lipase;
  • the solid alkali includes one or more of sodium hydroxide, potassium hydroxide, calcium hydroxide or
  • 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.
  • a refined olive oil product obtained according to the precise control method of palmitic acid content in the above-mentioned olive oil obtained according to the precise control method of palmitic acid content in the above-mentioned olive oil.
  • the present invention utilizes the characteristic that palmitic acid is mainly distributed in the triglyceride 1,3 position in olive oil, selects the lipase that has selectivity to triglyceride 1,3 position to hydrolyze olive oil, realizes enzymatic hydrolysis through one-step reaction , acid reduction, impurity removal three effects, through solid alkali deacidification and adsorbent adsorption to remove diesters, monoesters, oxides and other impurities, in order to reduce the content of palmitic acid, by controlling the temperature and pressure of the mixed packing equipment , the contact time between the raw material and the filler to achieve the removal of diglycerides, monoglycerides, free fatty acids, oxides and other effects.
  • the disadvantage of cumbersome industrialization steps is greatly reduced.
  • the indexes of the low-content palmitic olive oil prepared by the present invention meet the Chinese Pharmacopoeia standards, and the palmitic acid content of the olive oil can be strictly controlled to be between 7.5% and 12% through this process. It avoids the fluctuation of palmitic acid content in olive oil due to differences in starting materials, and at the same time meets the specific raw material requirements of domestic preparation companies for olive oil with a palmitic acid content of 7.5 to 12%, and can produce higher quality fat emulsion preparations. The dependence of the starting material of olive oil can be solved by this process.
  • 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.
  • lipase realizes the localized hydrolysis of triglycerides in olive oil. It is also possible to control the temperature, control the pressure of the equipment, and control the contact time between the raw material and the filler to achieve the precise and controllable process of the above, and finally achieve the precise control of the palmitic acid content in the olive oil within a very narrow range.
  • Figure 1 is a schematic diagram of the mixed filler 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 investigating the amount of lipase and solid alkali in Comparative Example 4.
  • Table 1 embodiment 1 virgin olive oil before and after refining key index measurement results
  • Table 2 embodiment 2 virgin olive oil before and after refining key index measurement results
  • the content of palmitic acid can be effectively controlled between 7.5% and 12%.
  • the technical solution of the present invention does not require external introduction of water, the adsorption effect of silica gel is guaranteed, and its adsorption peroxidation The ability of things will not be destroyed.
  • the palmitic acid content of the olive oil can be guaranteed to be between 7.5 and 12%, and the peroxide value can meet the standard requirements.
  • 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 olive 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 olive 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 olive oil consumption are as in Example 1, and the test results are integrated into a line graph, as shown in Figure 4.
  • Comparative Example 3 In addition to Comparative Example 1 and Comparative Example 2, the scheme design of Comparative Example 3 was also designed. The method of fully mixing lipase and solid alkali, and layering filter aids and adsorbents was used to investigate the effect of reducing the content of palmitic acid in olive oil.
  • the schematic diagram of the filler is shown in Figure 7, the condition control, the ratio of the filler and the amount of olive oil are as in Example 1, and the test results are integrated into a line graph, as shown in Figure 8.
  • 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 0.05%, 0.1%, and 0.5%, 1%, 2%, 4%, 6%, 8%, 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 0.05%, 0.1 %, 0.5%, 1%, 2%, 4%, 6%, 8%, the contact time is 1h, and the proportions and conditions of other unspecified materials are the same as those in Example 1. The results of the study are shown in Figure 9.
  • lipase is relatively high; when the amount of lipase is 1-5%, when the olive oil flows through the mixed filler, the interaction between alkali refining and hydrolysis makes the palmitic acid content significantly reduced.
  • the moisture of lipase is absorbed by the adsorbent, so that the adsorption effect of the adsorbent is not greatly affected, which is reflected in the obvious reduction effect of the peroxide value; with the further increase of the amount of lipase, the degree of hydrolysis gradually increases.
  • the amount of lipase exceeds 7.5 %, the palmitic acid content drops below 7.5%, which does not meet the requirements of the Chinese Pharmacopoeia for palmitic acid content of 7.5-20% in olive oil. Therefore, lipase dosage of 0.1% to 7.5% is a better choice.
  • the reduction effect of palmitic acid content is not obvious, and the adsorption effect of the adsorbent is high, and the peroxide value is small; as the amount of solid alkali increases, the water generated in the alkali refining process increases, and the lipase hydrolysis effect is improved.
  • the refining water just provides a hydrolysis environment for lipase, so that the adsorption performance of the adsorbent is less affected by moisture; as the amount of solid alkali further increases, the mixed filler system becomes an environment with excess alkali, so the excess water in the alkali refining process obviously affects the adsorbent.
  • the amount of solid alkali exceeds 7.5%, the final olive oil peroxide value that flows through the mixed packing layer exceeds the internal control standard of 3.0. 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，公开一种橄榄油中棕榈酸含量的精准控制方法，以初榨橄榄油为原料，以脂肪酶、无机碱、助滤剂、吸附剂等形成的混合填料除杂制备替代传统酶水解，降酸，除杂工艺，制备得到低含量棕榈酸的橄榄油。本发明的特点在于通过一步处理实现精准控制橄榄油中棕榈酸含量在7.5～12％之间的特定范围内，且能够满足工业化生产。

Description

一种橄榄油中棕榈酸含量的精准控制方法 技术领域
本发明涉及药用油脂精炼技术领域，具体涉及一种橄榄油中棕榈酸含量的精准控制方法。
背景技术
橄榄油是一种从油橄榄的成熟核果提炼，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，目前在已上市制剂长链脂肪乳注射液(OO)和多种油脂肪乳注射液(SMOF)作为能量物质使用。橄榄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，棕榈酸，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。2015版中国药典中对于橄榄油脂肪酸含量的规定如下：小于十六碳的饱和脂肪酸不大于0.1％，棕榈酸应为7.5～20.0％，棕榈油酸不大于3.5％，棕榈酸应为0.5～5.0％，油酸应为56.0～85.0％，亚油酸应为3.5～20.0％，亚麻酸不大于1.2％，花生酸不大于0.7％，二十碳烯酸不大于0.4％，山嵛酸不大于0.2％，二十四烷酸不大于0.2％。
油橄榄在地中海沿岸国家的栽培历史已经有约6000年，那里分布着世界95％的油橄榄种质资源。我国自20世纪60年代开始引种以来，经历了从引种试验到产业化建设初期的发展阶段。
近年来，国内药用脂质类原辅料行业崛起，开始有越来越多的脂肪乳制剂使用国产化的药用脂质原辅料。但是一些新型的脂肪乳制剂一直未能实现国产化，究其原因在于缺乏相应的油脂原料。长链脂肪乳注射液(OO)和多种油脂肪乳注射液(SMOF)就是其中的代表，国内由于缺乏橄榄油原料，所以这两种制剂一直未能实现真正意义上的国产化，国外企业通过垄断橄榄油原料钳制国内相应制剂的研发。随着国家开展注射剂仿制药一致性评价，其中制剂的药学一致性是首要解决的。目前国内已上市橄榄油制剂均依靠国外进口或者进口分装，国内制剂厂商积极开展仿制研究，但均未获上市批准，究其原因是因为现有橄榄油成分完全由橄榄树生长地的环境决定，难以人为控制，而国内制剂厂 商若不依赖进口则无法获得与原研制剂所用的橄榄油原料组分相同的橄榄油。从制剂角度分析，国内上市的进口橄榄油制剂中橄榄油的棕榈酸含量通常在7.5～12.0％，而目前国内橄榄油原料的棕榈酸含量通常在12.0～20.0％之间，尽管都符合中国药典7.5～20.0％的标准，但是国内橄榄油原料无法满足药学一致性要求。研究结果表明，棕榈酸会引起患者血清总胆固醇的升高，而血清总胆固醇水平越高，心血管疾病的发病率就越高，几乎没有例外，因此对于有心血管疾病并发症的患者采用橄榄油制剂进行肠外营养补充阶段，应尽可能使用低棕榈酸含量的橄榄油制剂，或许这就是原研制剂橄榄油棕榈酸含量在7.5～12.0％之间的原因。
然而橄榄油的传统精炼工艺不能降低脂肪酸含量，因此目前国内尚无符合原研制剂要求的橄榄油原料药，这极不利于国内橄榄油制剂的发展。国外制剂厂商很有可能是选择特定品种，特定种植范围，特定采摘时节的油橄榄获得特定脂肪酸比例的橄榄油，而这些信息原研制剂厂家出于商业机密不进行公开发布，使得国内制剂厂家开发受阻。如何能通过工艺控制实现与原研制剂一致的脂肪酸组成，减少橄榄油脂肪酸含量对于原料的严重依赖，进而实现更高质量的脂肪乳制剂的国产化，是摆在国内橄榄油原料生产企业门前的一座大山。传统的橄榄油制备工艺获得的橄榄油脂肪酸组成对于橄榄油原料的依赖程度较大，其质量受到橄榄果的成熟程度，采摘季节，种植地域等制约。因此如何更加精确控制橄榄油质量，通过工艺过程实现橄榄油脂肪酸组成的可控化，目前对于传统生产工艺来说，面临着巨大挑战。
药用级别橄榄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，通过现有的油脂精炼工艺，可以有效的控制天然橄榄油的酸值，过氧化值，甲氧基苯胺值，微生物等关键的理化性质，此外还可以有效控制苯并吡等有毒有害的杂质，但是却无法特定的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，即传统的油脂精炼工艺无法针对橄榄油中某一种脂肪酸的含量进行控制。传统橄榄油的生产工艺虽然能够满足橄榄油中棕榈酸含量符合中国药典7.5～20.0％的质量要求，但是棕榈酸含量基本上为12％以上，这主要是依赖于橄榄油原料特性而言，无法从生产工艺中得到控制。目前，国内在开发长链脂肪乳注射液(OO)和多种油脂肪乳注射液(SMOF)过程时，由于每 种油的脂肪酸组成不尽相同，因此国内制剂企业在开发两种油以上的脂肪乳制剂时，开始对某一种油的某一种脂肪酸含量提出特定要求，而此要求通过传统油脂精炼工艺根本无法解决。目前国内开展含橄榄油脂肪乳制剂时，越来越多的制剂企业寻求特定棕榈酸含量在7.5～12％的橄榄油，以期能够生产出与原研产品一致的橄榄油脂肪乳制剂。但是截至目前为止尚未有关于控制橄榄油中棕榈酸含量的工艺报导，阻碍我国橄榄油类脂肪乳制剂的研发进度。
随着科研工作者对油脂领域的研究越来越深入，研究人员发现橄榄油中甘油三酯三个碳链的分布有着一定的规律。研究表明，橄榄油甘油三酯中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，如果在传统橄榄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，使得最终产品棕榈酸含量急剧降低，不能符合中国药典标准。可见脂肪酶用于油脂生产工艺从可产业化角度中特定降低某一种脂肪酸含量的技术尚未进行过研究。
发明内容
本发明的目的在于，解决传统橄榄油生产工艺无法精准控制棕榈酸含量、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：
一种橄榄油中棕榈酸含量的精准控制方法，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；
B、使橄榄油流经所述混合填料，获得精制橄榄油；
所述混合填料各组分与所述橄榄油的比重如下：所述脂肪酶0.1～7.5％、所述固体碱0.1～7.5％、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，现行标准对橄榄油中棕榈酸含量的要求较为宽松，一般都是根据当地橄榄油产出的天然性质进行制定(如药典要求为7.5％～12％)，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，橄榄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橄榄油中棕榈酸含量的方法，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，橄榄油中游离的脂肪酸与固体碱发生中和反应，脱酸并产生水；脂肪酶利用脱酸过程产生的水对橄榄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橄榄油流动阻力增大，很难甚至无法流经混合填料，对橄榄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，使精准控制橄榄油中的棕榈酸含量成为可能。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，最终实现橄榄油中棕榈酸含量在极窄范围内的精确控制，能满足不同药用需求。
对于橄榄油中降低棕榈酸含量的工艺，优选的用量是混合填料各组分与橄榄油的比重如下：脂肪酶0.1～7.5％、固体碱0.1～7.5％、助滤剂1～20％、吸附剂1～20％，此时，能较好的控制橄榄油中棕榈酸含量的缓慢减少，并同时将酸值、过氧化值等控制在合理范围内，直到达到精制橄榄油要求。
优选的，所述精制橄榄油的棕榈酸含量为7.5～12％；所述精制橄榄油的过氧化值小于3。
对于橄榄油脂肪乳制剂质量影响较大的是橄榄油中的棕榈酸含量，通过本发明的方法能将任意来源的橄榄油控制棕榈酸含量7.5～12％的极窄范围内，同时将过氧化值控制在3以下，摆脱脂肪乳制剂研究对橄榄油来源的依赖，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％。
优选的，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，橄榄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：所述橄榄油进入所述层析柱中，流出后获得所述精制橄榄油。
优选的，所述层析柱的温度为30～60℃，压力为0.02～0.5MPa，与所述橄榄油的接触时间为1～10h；所述橄榄油循环进入所述层析柱中1～10次。
优选的，所述脂肪酶为Sn-1,3位特异性脂肪酶。
棕榈酸在橄榄油中甘油三酯的分布是随机分配的，可能三个位点均是，也可能均不是。但经研究发现棕榈酸主要分布在橄榄油中甘油三酯1，3位，本发明利用这个特性，优先选用对甘油三酯1，3位具有选择性的脂肪酶对橄榄油进行水解，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，以达到降低棕榈酸的含量，控制棕榈酸的含量在7.5～12％范围。
优选的，所述脂肪酶包括TLIM、435脂肪酶、Lipase脂肪酶或RMIM脂肪 酶中的一种或多种；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；所述吸附剂包括氧化铝，硅胶，白土，凝胶中的一种或多种；所述助滤剂包括硅藻土，膨润土中的一种或多种。
一种根据上述橄榄油中棕榈酸含量的精准控制方法获得的精制橄榄油产品。
与现有技术相比较，实施本发明，具有如下有益效果：
1.本发明利用棕榈酸主要分布在橄榄油中甘油三酯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橄榄油进行水解，经过一步反应实现酶水解，降酸，除杂三个效果，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，以达到降低棕榈酸的含量，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棕榈酸橄榄油各项指标满足中国药典标准，通过该工艺能够严格控制橄榄油棕榈酸含量在7.5～12％之间。避免了橄榄油因为起始物料差异造成的棕榈酸含量波动，同时满足国内制剂企业对于7.5～12％棕榈酸含量橄榄油的特定原料需求，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橄榄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，脂肪酶实现对橄榄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，最终实现橄榄油中棕榈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对比例4的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Lipase脂肪酶10g，氢氧化钠25g，硅藻土10g，硅胶90g，经过物理混合均匀，添加至层析柱中。取初榨橄榄油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0.15±0.02mPa，接触时间为8h。检测精制前后橄榄油的酸值，甲氧基苯胺值，过氧化值，棕榈酸含量。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初榨橄榄油精制前后关键指标测定结果
Figure PCTCN2020128412-appb-000001
Figure PCTCN2020128412-appb-000002
实施例2
称取Sn-1,3位特异性脂肪酶Lipase脂肪酶15g，氢氧化钠30g，硅藻土50g，硅胶50g，经过物理混合均匀，添加至层析柱中。取初榨橄榄油1kg，进行上述混合填料柱层析柱操作，柱温控制在60±2℃，压力控制在0.02mPa，过柱时间为10h。检测精制前后橄榄油的酸值，甲氧基苯胺值，过氧化值，棕榈酸含量。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初榨橄榄油精制前后关键指标测定结果
Figure PCTCN2020128412-appb-000003
实施例3
称取Sn-1,3位特异性脂肪酶435脂肪酶100g，氢氧化钾110g，膨润土50g，白土150g，经过物理混合充分，添加至层析柱中。取初榨橄榄油2kg，经过混 合填料层析柱，柱温控制在45±2℃，压力控制在0.4±0.02mPa，过柱时间为2h。检测精制前后的酸值，甲氧基苯胺值，过氧化值，棕榈酸含量。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初榨橄榄油精制前后关键指标测定结果
Figure PCTCN2020128412-appb-000004
实施例4
称取Sn-1,3位特异性脂肪酶435脂肪酶150g，氢氧化钾300g，膨润土500g，凝胶500g，经过物理混合充分，添加至层析柱中。取初榨橄榄油5kg，经过混合填料层析柱，柱温控制在35±2℃，压力控制在0.3±0.02mPa，过柱时间为5h。检测精制前后橄榄油的酸值，甲氧基苯胺值，过氧化值，棕榈酸含量。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初榨橄榄油精制前后关键指标测定结果
Figure PCTCN2020128412-appb-000005
Figure PCTCN2020128412-appb-000006
实施例5
称取Sn-1,3位特异性脂肪酶TLIM脂肪酶10g，氢氧化钙10g，硅藻土800g，硅胶800g，经过物理混合充分，添加至层析柱中。取初榨橄榄油10kg，经过混合填料层析柱，柱温控制在30±2℃，压力控制在0.05±0.02mPa，过柱时间为9h。检测精制前后橄榄油的酸值，甲氧基苯胺值，过氧化值，棕榈酸含量。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初榨橄榄油精制前后关键指标测定结果
Figure PCTCN2020128412-appb-000007
实施例6
称取Sn-1,3位特异性脂肪酶TLIM脂肪酶50g，氢氧化钙100g，膨润土600g，硅胶1400g，经过物理混合充分，添加至层析柱中。取初榨橄榄油10kg，经过混合填料层析柱，柱温控制在40±2℃，压力控制在0.2±0.02mPa，过柱时间为7h，检测精制前后的酸值，甲氧基苯胺值，过氧化值，棕榈酸含量。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初榨橄榄油精制前后关键指标测定结果
Figure PCTCN2020128412-appb-000008
实施例7
称取Sn-1,3位特异性脂肪酶RMIM脂肪酶300g，氢氧化钠300g，硅藻土3000g，氧化铝3000g，经过物理混合充分，添加至层析柱中。取初榨橄榄油15kg，经过混合填料层析柱，柱温控制在35±2℃，压力控制在0.3±0.02mPa，过柱时间为5h，循环次数2次，检测精制前后橄榄油的酸值，甲氧基苯胺值，过氧化值，棕榈酸含量。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初榨橄榄油精制前后关键指标测定结果
Figure PCTCN2020128412-appb-000009
实施例8
称取Sn-1,3位特异性脂肪酶435脂肪酶300g，氢氧化钠150g，硅藻土1200g，硅胶1800g，经过物理混合均匀，添加至层析柱中。取初榨橄榄油30kg，进行上述混合填料柱层析柱操作，柱温控制在35±2℃，压力控制在0.25±0.02mPa，过柱时间为6h。检测精制前后橄榄油的酸值，甲氧基苯胺值，过氧化值，棕榈酸含量。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初榨橄榄油精制前后关键指标测定结果
Figure PCTCN2020128412-appb-000010
实施例9
称取Sn-1,3位特异性脂肪酶TLIM脂肪酶7.5g，氢氧化钙8.0g，硅藻土10g，硅胶15g，经过物理混合均匀，添加至层析柱中。取初榨橄榄油100g，进行上述混合填料柱层析柱操作，柱温控制在60±2℃，压力控制在0.5±0.02mPa，过柱时间为1h。检测精制前后橄榄油的酸值，甲氧基苯胺值，过氧化值，棕榈酸含量。测定结果如表9所示。
表9 实施例9初榨橄榄油精制前后关键指标测定结果
Figure PCTCN2020128412-appb-000011
Figure PCTCN2020128412-appb-000012
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、填料比例与橄榄油用量如实施例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，能够有效控制棕榈酸含量在7.5～12％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，均可以保障橄榄油的棕榈酸含量在7.5～12％之间，且过氧化值能够符合标准要求。
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。为保证橄榄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，同时为保证橄榄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、填料比例与橄榄油用量如实施例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7.5～12％棕榈酸含量的橄榄油制备会使得棕榈酸含量不可控。可能是因为当橄榄油经过酶层时，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，棕榈酸含量直接低于7.5％，不符合药典中7.5～20％的要求。
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、填料比例与橄榄油用量如实施例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7.5～12％棕榈酸含量的橄榄油制备会使得棕榈酸含量降低不明显。可能是因为橄榄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，使得橄榄油棕榈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，导致橄榄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，用以考察其对橄榄油中棕榈酸含量的降低效果。填料示意图如图7所示，条件控制、填料比例与橄榄油用量如实施例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的方案橄榄油棕榈酸含量仍然无法控制，造成其棕榈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，使得橄榄油流经该混合层受阻，导致橄榄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0.05％，0.1％，0.5％，1％，2％，4％，6％，8％，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0.05％，0.1％，0.5％，1％，2％，4％，6％，8％，接触时间1h，其他未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棕榈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，其棕榈酸含量降低速度与脂肪酶用量总体上呈负相关，当脂肪酶用量小于0.1％时，橄榄油作为底物严重过量，脂肪酶催化作用明显减弱，其棕榈酸含量降低效果甚微；随着脂肪酶用量的增多，其棕榈酸含量降低得越多，但当脂肪酶用量超过7.5％时，即使只有1h的接触时间(1h为最小流出时间)，其棕榈酸含量也会迅速降至7.5％以下，不符合中国药典对于橄榄油棕榈酸含量的要求。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，在固定固体碱用量的前提下，其棕榈酸含量大致分为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，橄榄油流经混合填料时，碱炼效果为主，所以导致棕榈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，导致过氧化值相对较高；当脂肪酶用量在1～5％时，橄榄油流经混合填料时，碱炼与水解相互作用，使得棕榈酸含量降低明显，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7.5％时，其棕榈酸含量降至7.5％以下，不符合中国药典对于橄榄油中棕榈酸含量7.5～20％的要求。因此，脂肪酶用量0.1％～7.5％是较优的选择。
从图9中实验组2棕榈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，其棕榈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，其棕榈酸含量降低得越多，但是其过氧化值与固体碱用量却呈正相关。开始时，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不能充分发挥和硅胶吸附性能不受影响，所以呈现出的结果就是棕榈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7.5％时，最终流经混合填料层的橄榄油过氧化值超过内控标准3.0。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8％以上时，无法同时满足控制棕榈酸含量和氧化值在合理范围内，无法使最终橄榄油产品的标准要求。
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. 一种橄榄油中棕榈酸含量的精准控制方法，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；
    B、使橄榄油流经所述混合填料，获得精制橄榄油；
    所述混合填料各组分与所述橄榄油的比重如下：所述脂肪酶0.1～7.5％、所述固体碱0.1～7.5％、所述助滤剂1～20％、所述吸附剂1～20％。
  2. 根据权利要求1所述橄榄油中棕榈酸含量的精准控制方法，其特征在于，所述精制橄榄油的棕榈酸含量为7.5～12％；所述精制橄榄油的过氧化值小于3。
  3. 根据权利要求1所述橄榄油中棕榈酸含量的精准控制方法，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％。
  4. 根据权利要求1所述橄榄油中棕榈酸含量的精准控制方法，其特征在于，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。
  5. 根据权利要求1所述橄榄油中棕榈酸含量的精准控制方法，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。
  6. 根据权利要求1所述橄榄油中棕榈酸含量的精准控制方法，其特征在于，所述步骤B的操作为：所述橄榄油进入所述层析柱中，流出后获得所述精制橄榄油。
  7. 根据权利要求6所述橄榄油中棕榈酸含量的精准控制方法，其特征在于，所述层析柱的温度为30～60℃，压力为0.02～0.5MPa，与所述橄榄油的接触时间为1～10h；所述橄榄油循环进入所述层析柱中1～10次。
  8. 根据权利要求1所述橄榄油中棕榈酸含量的精准控制方法，其特征在于， 所述脂肪酶为Sn-1,3位特异性脂肪酶。
  9. 根据权利要求1所述橄榄油中棕榈酸含量的精准控制方法，其特征在于，所述脂肪酶包括TLIM、435脂肪酶、Lipase脂肪酶或RMIM脂肪酶中的一种或多种；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；所述吸附剂包括氧化铝，硅胶，白土，凝胶中的一种或多种；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所述橄榄油中棕榈酸含量的精准控制方法获得的精制橄榄油产品。
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