Stereostructured lipid, preparation method thereof and application of stereostructured lipid in preparation of nutritional therapeutic product for improving cancer and hyperlipidemia

Abstract

The invention relates to the field of synthetic biology, in particular to stereostructured lipid, a preparation method of the stereostructured lipid and application of the stereostructured lipid in preparation of nutritional treatment products for improving cancers and hyperlipidemia. The three-dimensional structure lipid comprises third structure fat and a third antioxidant; the third structure fat is prepared from the following raw materials in parts by weight: 3-4 parts of first structure fat, 1-2 parts of second structure fat, 5-6 parts of borage seed oil and third lipase; the second structure fat is prepared from the following raw materials in parts by weight: 3-40 parts of polyunsaturated fatty acid, 0.2-4 parts of second glycerol, 0.2-0.3 part of water and second lipase; the first structure fat is prepared from the following raw materials: 90 parts of ethyl ester type fish oil, 9-13 parts of first glycerol, first lipase and a first antioxidant. The stereostructured lipid provided by the invention not only can provide nutrition urgently needed by severe patients, but also can resist tumor growth and inhibit cancer cell metastasis, and can also eliminate side effect complications of radiotherapy and chemotherapy targeted drugs.

Description

[0001] This application claims the priority of a Chinese patent application with the application number 2024104444560 and the title "Stereostructured Lipids and Their Preparation Methods and Applications", filed on April 12, 2024, the entire text of which is hereby incorporated by reference. Technical Field

[0002] This application relates to the field of synthetic biology. Specifically, it relates to a stereostructured lipid, its preparation method, and its application in the preparation of nutritional therapy products for improving cancer and hyperlipidemia. Background Art

[0003] As an important component of the three major nutrients in the human body, the nutrition community has been studying the beneficial effects of the balanced single-component content of fatty acids for many years. However, simply providing fatty acid balance and single-component content is not enough. Structured fats represent an advanced stage of oil research. Combining multiple functional fatty acids on one oil molecule to form a new three-dimensional structure and preparing a composition with good hydrophilicity, rapid absorption, and precise and unique efficacy is a new topic in the field of biosynthesis.

[0004] The structured fat emulsion C6-24, an imported injectable parenteral nutrition drug, has provided inspiration. By incorporating 1-2 medium-chain fatty acids into each long chain, the long chain exhibits hydrophilic portal vein absorption characteristics, which can provide energy and nutritional support for saving lives. To prepare the 16-24 carbon long chain to be hydrophilic, it is necessary to first achieve the three-dimensional structure of some core fatty acids, that is, hydrolyze pure triglycerides into glyceride-structured fats containing triglycerides, diglycerides, and monoglycerides coexisting, and then stack multiple functional fatty acids to incorporate essential fatty acids into the sn-2 position, presenting a fatty acid configuration with coexistence of positions 1, 3 and 2. The absorption mechanism is equivalent to that of medium- and long-chain fatty acids. The 1,3 positions are absorbed by the portal vein, and the sn-2 position monoglyceride is absorbed by mucosal cells, and are released into the liver and blood in a 1:1 ratio to exert the greatest effect.

[0005] With the change of lifestyle, the incidence of hypertension and coronary heart disease caused by dyslipidemia due to overnutrition has gradually increased, showing a trend of getting younger, and it is called "the first killer of mankind". The "Report on Cardiovascular Health and Diseases in China 2019" shows that currently, the number of patients with vascular diseases in China reaches 330 million. Among them, there are 13 million cases of stroke, 11 million cases of coronary heart disease, 5 million cases of pulmonary heart disease, 8.9 million cases of heart failure, 2.5 million cases of rheumatic heart disease, 2 million cases of congenital heart disease, 45.3 million cases of lower extremity arterial diseases, and 245 million cases of hypertension. Among every 8 people who die from diseases, 2 are due to cardiovascular diseases, far higher than cancer. Once heart disease recurs, it will affect multiple organs and is difficult to reverse. Preparing new structured fatty acids from animal and plant components will become the preferred choice for nutritional therapy and prevention.

[0006] Tumors are the biggest killers. According to the current consensus among clinicians, in addition to surgery, radiotherapy, chemotherapy, and targeted drugs are essential means for treating tumors. For patients, medical insurance bears most of the burden, seemingly temporarily reducing the economic burden. However, the harm of radiotherapy, chemotherapy, and targeted drugs to healthy cells and the consequence of shortening the survival period have been manifested in the serious decline in the quality of life in the later stage. Therefore, developing nutrients to achieve anti-tumor growth, inhibit cancer cell metastasis, combine to eliminate the side effects and complications of radiotherapy, chemotherapy, and targeted drugs, and replace chemotherapy and targeted drugs to enable patients to spend the dangerous recovery period comfortably and recover at low cost with a new type of structured lipid has great social and economic significance, and it is also the highlight of changing the concept of rehabilitation in clinical medical nutrition education.

[0007] Malignant tumors are described in four stages:

[0008] The first stage: discovering the tumor, before surgery, the observation period, entering the fear period;

[0009] The second stage: surgery, radiotherapy, chemotherapy, multiple complications, a serious decline in the quality of life, nausea, vomiting, abdominal distension, abdominal pain, diarrhea, constipation, anorexia, oral ulcers, low mental and emotional state, and the fear still exists.

[0010] The third stage: the end of radiotherapy and chemotherapy: multiple complications of targeted drugs, a serious decline in the quality of life, the formation of cachexia and muscle atrophy, and the physique still cannot recover quickly. Worried about the regrowth and metastasis of tumor cells, fear still brings heavy pressure to the spirit.

[0011] The fourth stage: the five-year survival period after surgery, the exhaustion of medical insurance resources and family resources, and the person still cannot be saved due to precise malnutrition.

[0012] Although tumors are the biggest killers, malnutrition that makes the body and mind ill will exacerbate complications and medical costs. Only by understanding the code of malnutrition can the dreams of cancer patients come true. Cancer patients are a group in need of care. Malnutrition is a common and most easily ignored demon. Precise nutrition is not dispensable but completely indispensable.

[0013] The preparation processes of traditional structured fats, such as a method for preparing a polyunsaturated fatty acid structured lipid described in the invention patent application with the application number 201811158595.8, and another method for preparing a fatty acid structured lipid with anti-tumor growth and cancer cell migration described in the invention patent application with the application number 202110289998.1, have functional limitations. Summary of the Invention

[0014] The purpose of one or more embodiments of the present application includes providing a three-dimensional structured lipid, its preparation method, and application. It includes the following contents:

[0015] One or more embodiments of the present application provide a three-dimensional structured lipid, which includes a third structured fat and a third antioxidant;

[0016] By weight,

[0017] The raw materials for preparing the third structured fat include 3 parts - 4 parts of the first structured fat, 1 part - 2 parts of the second structured fat, 5 parts - 6 parts of borage oil, and a third lipase;

[0018] The raw materials for preparing the second structured fat include 3 parts - 40 parts of polyunsaturated fatty acids, 0.2 parts - 4 parts of second glycerol, 0.2 parts - 0.3 parts of water, and a second lipase;

[0019] The raw materials for preparing the first structured fat include 90 parts of ethyl ester type fish oil, 9 parts - 13 parts of first glycerol, a first lipase, and a first antioxidant.

[0020] In some embodiments of the present application, the third antioxidant satisfies one or more of the following conditions:

[0021] (1) The third antioxidant includes ascorbyl palmitate, astaxanthin oil, or a combination thereof; and,

[0022] (2) The dosage of the third antioxidant is 0.2 wt‰ - 3 wt‰ of the weight of the third structured fat.

[0023] In some embodiments of the present application, the third structured fat satisfies one or more of the following conditions:

[0024] 1) The third lipase is an immobilized lipase; optionally, the third lipase is one or more of IMNE-100 immobilized lipase, Novozym immobilized lipase 435, and NS400190 immobilized lipase; and,

[0025] 2) The dosage of the third lipase is 3 wt% - 5 wt% of the total weight of the first structured fat, the second structured fat, and the borage oil.

[0026] In some embodiments of the present application, the first structured fat satisfies one or more of the following conditions:

[0027] (Ⅰ) The first antioxidant is astaxanthin oil; and,

[0028] (Ⅱ) The dosage of the first antioxidant is 0.2 wt‰ - 1.5 wt‰ of the total weight of the ethyl ester type fish oil and the first glycerol;

[0029] (III) The first lipase is an immobilized lipase; optionally, the first lipase is one or more of Novozym immobilized enzyme 435 and IMNE-100 immobilized lipase; and,

[0030] (IV) The dosage of the first lipase is 3wt% - 5wt% of the total weight of the ethyl ester type fish oil and the glycerol.

[0031] In some embodiments of the present application, the second structured fat satisfies one or more of the following conditions:

[0032] I) The second lipase is an immobilized lipase; optionally, the second lipase is NS400190;

[0033] II) The dosage of the second lipase is 3wt% - 5wt% of the total weight of the polyunsaturated fatty acid and the second glycerol; and,

[0034] III) The polyunsaturated fatty acid is selected from two or more of almond oil, Acer truncatum Bunge seed oil, Xanthoceras sorbifolia Bunge oil, pine seed oil, evening primrose oil, and blackcurrant oil.

[0035] One or more embodiments of the present application also provide a method for preparing the steric structured lipid, and the preparation method includes the following steps:

[0036] Prepare the first structured fat with the ethyl ester type fish oil, the first glycerol, the first lipase, and the first antioxidant;

[0037] Prepare the second structured fat with the polyunsaturated fatty acid, the second glycerol, water, and the second lipase;

[0038] Prepare the third structured fat with the first structured fat, the second structured fat, borage oil, and the third lipase; and,

[0039] Mix the third structured fat and the third antioxidant to prepare the steric structured lipid.

[0040] In some embodiments of the present application, the preparation method satisfies one or more of the following conditions:

[0041] (A) In the process of preparing the first structured fat, the conditions for the transesterification reaction participated by the first lipase include: the vacuum degree is 50Pa - 200Pa, the temperature is 55°C - 65°C, and the time is 22h - 24h;

[0042] (B) In the process of preparing the second structured fat, the conditions for the transesterification reaction participated by the second lipase include: normal pressure, the temperature is 55°C - 65°C, and the time is 5h - 24h;

[0043] (C) In the process of preparing the third structured fat, the conditions for the transesterification reaction participated by the third lipase include: the vacuum degree is 50 Pa - 200 Pa, the temperature is 55 °C - 65 °C, and the time is 3 h - 24 h; and

[0044] (D) The third structured fat is treated with absolute ethanol and then mixed with the third antioxidant; the treatment with absolute ethanol satisfies one or more of the following conditions:

[0045] D1) The volume ratio of the third structured fat to the absolute ethanol is 1:(0.5 - 1.5); and,

[0046] D2) At normal pressure, the temperature is higher than 65 °C, and the time is 8 h - 11 h; further, the temperature of the thermal reaction is 68 °C - 75 °C.

[0047] One or more embodiments of the present application further provide a stereostructured lipid composition, including:

[0048] The stereostructured lipid as described above; and,

[0049] Excipients acceptable in food science or pharmacy.

[0050] In some embodiments of the present application, the stereostructured lipid composition is a granule, a capsule, a gummy candy, a fluid type or an emulsion.

[0051] One or more embodiments of the present application further provide a preparation method of the stereostructured lipid composition as described above, and the preparation method includes the following steps:

[0052] Provide the stereostructured lipid as described above, or prepare the stereostructured lipid according to the preparation method as described above; and,

[0053] Prepare the stereostructured lipid composition with the stereostructured lipid and the excipient.

[0054] Details of one or more embodiments of the present application are set forth in the following description, and other features, objects, and advantages of the present application will become apparent from the specification and its claims. BRIEF DESCRIPTION OF THE DRAWINGS

[0055] In order to more clearly illustrate the technical solutions in the embodiments of the present application and to more fully understand the present application and its beneficial effects, the following will briefly introduce the drawings required for the description of the embodiments. Obviously, the drawings in the following description are only some embodiments of the present application, and those skilled in the art can obtain other drawings based on these drawings without creative efforts.

[0056] Figure 1Experimental report on the analysis of the three-dimensional structured lipid composition prepared in Example 4;

[0057] Figure 2 Schematic diagram of the decomposition structure of the three-dimensional structured lipid in the human body;

[0058] Figure 3 Metabolic mechanism diagram of the absorption pathway;

[0059] Figure 4 A technical roadmap for effect verification;

[0060] Figure 5 Another technical roadmap for effect verification. Detailed implementation manners

[0061] The present invention will be further described in detail below with reference to the accompanying drawings, implementation manners and examples. It should be understood that these implementation manners and examples are only used to illustrate the present invention and not to limit the scope of the present invention. The purpose of providing these implementation manners and examples is to make the disclosure of the present invention more thoroughly and comprehensively understood. It should also be understood that the present invention can be implemented in many different forms and is not limited to the implementation manners and examples described herein. Those skilled in the art can make various changes or modifications without departing from the connotation of the present invention, and the equivalent forms obtained also fall within the protection scope of this application. In addition, in the following description, a large number of specific details are given to provide a more thorough understanding of the present invention. It should be understood that the present invention can be implemented without one or more of these details.

[0062] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the technical field to which the present invention belongs. The terms used in the specification of the present invention herein are only for the purpose of describing the implementation manners and examples and are not intended to limit the present invention.

[0063] Terms

[0064] Unless otherwise specified or there is a contradiction, the terms or phrases used herein have the following meanings:

[0065] As used herein, the terms "and / or", "or / and", and "and / or" cover any one of two or more of the related listed items, as well as any and all combinations of the related listed items. The said any and all combinations include combinations of any two of the related listed items, any more than two of the related listed items, or all of the related listed items. It should be noted that when at least three items are connected by at least two conjunctions selected from "and / or", "or / and", and "and / or", it should be understood that in this application, this technical solution undoubtedly includes the technical solution connected by "logical AND", and undoubtedly also includes the technical solution connected by "logical OR". For example, "A and / or B" includes three parallel solutions: A, B, and A + B. Another example, the technical solution of "A, and / or, B, and / or, C, and / or, D" includes any one of A, B, C, and D (i.e., the technical solution connected by "logical OR"), and also includes any and all combinations of A, B, C, and D, that is, combinations of any two or any three of A, B, C, and D, and also includes the combination of all four items A, B, C, and D (i.e., the technical solution connected by "logical AND").

[0066] In the present invention, terms such as "multiple", "multiple types", "multiple times", "multiple elements", etc., unless otherwise specified, mean greater than or equal to 2 in quantity. For example, "one or more" means one or greater than or equal to two kinds.

[0067] As used herein, "its combination", "any combination thereof", "any combination mode thereof", etc. include all suitable combination modes of any two or more of the listed items.

[0068] In this article, the "suitable" in "suitable combination mode", "suitable mode", "any suitable mode", etc. is subject to being able to implement the technical solution of the present invention, solve the technical problems of the present invention, and achieve the expected technical effects of the present invention.

[0069] In this article, "preferred", "better", "more preferable", "it is advisable" are only used to describe embodiments or examples with better effects. It should be understood that they do not constitute a limitation on the protection scope of the present invention.

[0070] In the present invention, "further", "even further", "especially", etc. are used for descriptive purposes and represent differences in content, but should not be construed as a limitation on the protection scope of the present invention.

[0071] In the present invention, "optionally", "optional", "optional" mean that it can be either present or absent, that is, any one of two parallel solutions selected from "present" or "absent". If "optional" appears multiple times in a technical solution, unless otherwise specified and there is no contradiction or mutual restriction relationship, each "optional" is independent of each other.

[0072] In the present invention, in "the first aspect", "the second aspect", "the third aspect", "the fourth aspect", etc., the terms "first", "second", "third", "fourth", etc. are only for descriptive purposes, and cannot be construed as indicating or implying relative importance or quantity, nor can they be construed as implicitly indicating the importance or quantity of the indicated technical features. Moreover, "first", "second", "third", "fourth", etc. only serve the purpose of non-exhaustive listing and description, and it should be understood that they do not constitute a closed limitation on quantity.

[0073] In the present invention, among the technical features described in an open-ended manner, it includes a closed technical solution composed of the listed features, and also includes an open technical solution containing the listed features.

[0074] In the present invention, regarding numerical intervals (i.e., numerical ranges), unless otherwise specified, the selectable numerical values are considered continuous within the above numerical intervals, and include the two numerical endpoints (i.e., the minimum value and the maximum value) of the numerical range, as well as each numerical value between these two numerical endpoints. Unless otherwise specified, when the numerical interval only refers to integers within the numerical interval, it includes the two endpoint integers of the numerical range, as well as each integer between the two endpoints. In this article, it is equivalent to directly listing each integer. For example, t being an integer selected from 1 to 10 means that t is any integer selected from the integer group consisting of 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10. In addition, when providing multiple range descriptions for features or characteristics, these ranges can be combined. In other words, unless otherwise specified, the ranges disclosed herein should be understood to include any and all sub-ranges subsumed therein.

[0075] For the temperature parameter in the present invention, unless otherwise specified, it allows both constant temperature treatment and variation within a certain temperature range. It should be understood that the so-called constant temperature treatment allows the temperature to fluctuate within the accuracy range controlled by the instrument. It is allowed to fluctuate within a range such as ±5°C, ±4°C, ±3°C, ±2°C, ±1°C.

[0076] In the present invention, %(w / w) and wt% both represent weight percentages, %(v / v) refers to volume percentage, and %(w / v) refers to mass-volume percentage.

[0077] All documents mentioned in the present invention are incorporated herein by reference as if each document was individually incorporated by reference. Unless it conflicts with the object and / or technical solution of the present application, the cited documents involved in the present invention are incorporated by reference in their entirety and for all purposes. When the present invention involves cited documents, the definitions of relevant technical features, terms, nouns, phrases, etc. in the cited documents are also incorporated by reference. When the present invention involves cited documents, examples and preferred modes of the relevant technical features cited can also be incorporated into the present application as references, but only to the extent that the present invention can be implemented. It should be understood that when the cited content conflicts with the description in the present application, the present application shall prevail or be amended adaptively according to the description in the present application.

[0078] The structured lipids prepared by the traditional preparation process of structured lipids have functional limitations. For example, the structured lipids prepared by the process described in 201811158595.8 do not play an effective role in balancing blood pressure indicators, increasing the blood flow velocity of the carotid artery, reducing blood flow resistance, thickening the inner wall diameter of blood vessels, and reducing or eliminating plaques in each main branch artery. For example, the structured lipids prepared by the process described in 202110289998.1 do not play an effective role in eliminating and alleviating the side effects and complications in the targeted drug stage of cancer radiotherapy and chemotherapy, reducing high medical costs, improving the quality of life, calming the mental state in the fear period, and preventing the formation of cachexia.

[0079] The embodiments of the present application aim to solve the risks brought by hypertension, hereditary low-pressure hypertension, coronary heart disease, and plaque stenosis in each branch segment of the coronary artery caused by dyslipidemia and replace anticoagulants, completely resolve the dependence on metal stents for arterial stenosis greater than 75%, and provide a precise nutrition treatment technical solution. The embodiments of the present application aim to solve the worldwide problem indicators of cardiovascular disease risks caused by coronary artery stenosis due to surface blood indicators and the resulting consequences, as well as the high-risk indicators of coronary artery stenosis caused by renal failure dialysis, anemia, and high low-density lipoprotein. The novel three-dimensional structured lipids prepared by combining omega-3 EPA / DHA with plant components by synthetic biology technology resolve the confusion of no effective solutions for coexisting multiple diseases, and completely provide a precise solution to the medical intractable problems such as cardiovascular disease, coronary heart disease, hypertension, and low blood pressure caused by external factors or nutritional excess and genetics. The embodiments of the present application provide a creative precise nutrition solution to meet the rehabilitation needs while supplementing essential fatty acids for the above clinically urgent problems to be solved. The embodiments of the present application are new technological achievements achieved under the above background, providing a basic theoretical basis for the technological upgrading of structured lipids and completely replacing chemotherapy drugs and targeted drugs.

[0080] In a first aspect of the embodiments of the present application, a three-dimensional structured lipid is provided, and the three-dimensional structured lipid includes a third structured fat and a third antioxidant;

[0081] By weight,

[0082] The raw materials for preparing the third structured fat include 3 to 4 parts of the first structured fat, 1 to 2 parts of the second structured fat, 5 to 6 parts of borage seed oil, and a third lipase;

[0083] The raw materials for preparing the second structured fat include 3 to 40 parts of polyunsaturated fatty acids, 0.2 to 4 parts of second glycerol, 0.2 to 0.3 parts of water, and a second lipase;

[0084] The raw materials for preparing the first structured fat include 90 parts of ethyl ester type fish oil, 9 to 13 parts of first glycerol, a first lipase, and a first antioxidant.

[0085] The steric structured lipid developed in the embodiments of the present application is a food that can not only provide the nutrients urgently needed by critically ill patients, but also has the functions of anti-tumor growth, inhibiting cancer cell metastasis, eliminating the side effects and complications of radiotherapy, chemotherapy and targeted drugs, and is safe without any side effects. It is an important way to shorten the hospital stay, extend the survival period, improve the quality of life, and reduce medical consumption, and has great social and economic significance. It is also an urgent need for future clinical anti-consumption, anti-inflammatory, anti-tumor, and immune-enhancing nutritional therapy.

[0086] The steric structured lipid provided by the embodiments of the present application is applied to reduce hyperlipidemia, increase high-density lipoprotein, balance various blood indicators, reduce low-density lipoprotein, high cholesterol, reduce high blood pressure, and at the same time reduce hereditary low blood pressure and high pressure; the carotid artery PSV blood flow velocity increases, and the R1 resistance decreases; the blood vessel inner diameter thickens, the deposition on the blood vessel wall decreases, and the clarity of the blood vessel wall image is significantly improved. It can clear or reduce the stenosis plaques in each segment of the coronary artery, reduce the risk of coronary atherosclerotic heart disease, and obtain obvious effects.

[0087] The decomposition path and absorption path of the steric structured lipid provided by the embodiments of the present application in the human body are shown in Figure 2 and Figure 3 .

[0088] In the embodiments of the present application, the essential fatty acids omega-3 EPA / DHA, plant components, and functional components required by the fatty acid gene direction corresponding to diseases are prepared into steric structured fat. While meeting the energy and nutritional supply, achieving the maximum goal of the functional role of fatty acids is the most reasonable solution for medical nutrition and also the key technology in synthetic biology.

[0089] In some embodiment solutions, the third antioxidant satisfies one or more of the following conditions:

[0090] (1) The third antioxidant includes ascorbyl palmitate, astaxanthin oil, or a combination thereof; and,

[0091] (2) The dosage of the third antioxidant is 0.2 wt‰ - 3 wt‰ (such as 0.2 wt‰, 0.4 wt‰, 0.6 wt‰, 0.8 wt‰, 1 wt‰, 1.2 wt‰, 1.4 wt‰, 1.6 wt‰, 1.8 wt‰, 2 wt‰, 2.2 wt‰, 2.4 wt‰, 2.6 wt‰, 2.8 wt‰, 3 wt‰) of the weight of the third structured fat.

[0092] In some embodiments, the third structured fat satisfies one or more of the following conditions:

[0093] 1) The third lipase is an immobilized lipase; optionally, the third lipase is one or more of IMNE-100 immobilized lipase, Novozym immobilized lipase 435, and NS400190 immobilized lipase; and,

[0094] 2) The dosage of the third lipase is 3 wt% - 5 wt% (such as 3 wt%, 3.1 wt%, 3.2 wt%, 3.3 wt%, 3.4 wt%, 3.5 wt%, 3.6 wt%, 3.7 wt%, 3.8 wt%, 3.9 wt%, 4 wt%, 4.1 wt%, 4.2 wt%, 4.3 wt%, 4.4 wt%, 4.5 wt%, 4.6 wt%, 4.7 wt%, 4.8 wt%, 4.9 wt%, 5 wt%) of the total weight of the first structured fat, the second structured fat, and the borage seed oil.

[0095] In some embodiments, the first structured fat satisfies one or more of the following conditions:

[0096] (Ⅰ) The first antioxidant is astaxanthin oil; and,

[0097] (Ⅱ) The dosage of the first antioxidant is 0.2 wt‰ - 1.5 wt‰ (such as 0.2 wt‰, 0.3 wt‰, 0.4 wt‰, 0.5 wt‰, 0.6 wt‰, 0.7 wt‰, 0.8 wt‰, 0.9 wt‰, 1 wt‰, 1.1 wt‰, 1.2 wt‰, 1.3 wt‰, 1.4 wt‰, 1.5 wt‰) of the total weight of the ethyl ester type fish oil and the first glycerol;

[0098] (Ⅲ) The first lipase is an immobilized lipase; optionally, the first lipase is one or more of Novozym immobilized enzyme 435 and IMNE-100 immobilized lipase; and,

[0099] (Ⅳ) The dosage of the first lipase is 3 wt% - 5 wt% (such as 3 wt%, 3.1 wt%, 3.2 wt%, 3.3 wt%, 3.4 wt%, 3.5 wt%, 3.6 wt%, 3.7 wt%, 3.8 wt%, 3.9 wt%, 4 wt%, 4.1 wt%, 4.2 wt%, 4.3 wt%, 4.4 wt%, 4.5 wt%, 4.6 wt%, 4.7 wt%, 4.8 wt%, 4.9 wt%, 5 wt%) of the total weight of the ethyl ester type fish oil and the glycerol.

[0100] In some embodiments, the second structured fat satisfies one or more of the following conditions:

[0101] Ⅰ) The second lipase is an immobilized lipase; optionally, the second lipase is NS400190;

[0102] Ⅱ) The dosage of the second lipase is 3 wt% - 5 wt% of the total weight of the polyunsaturated fatty acid and the second glycerol; and,

[0103] Ⅲ) The polyunsaturated fatty acid is selected from two or more of almond oil, Acer truncatum Bunge seed oil, Xanthoceras sorbifolia Bunge oil, pine seed oil, evening primrose oil and blackcurrant oil.

[0104] In some embodiments, the polyunsaturated fatty acid is selected from two or three of almond oil, Acer truncatum Bunge seed oil, Xanthoceras sorbifolia Bunge oil, pine seed oil, evening primrose oil and blackcurrant oil.

[0105] In the second aspect of the embodiments of the present application, there is provided a method for preparing the stereostructured lipid, and the preparation method includes the following steps:

[0106] Preparing the first structured fat with the ethyl ester type fish oil, the first glycerol, the first lipase and the first antioxidant;

[0107] Preparing the second structured fat with the polyunsaturated fatty acid, the second glycerol, water and the second lipase;

[0108] Preparing the third structured fat with the first structured fat, the second structured fat, borage oil and the third lipase; and,

[0109] Mixing the third structured fat and the third antioxidant to prepare the stereostructured lipid.

[0110] In some embodiments of the present application, the preparation method satisfies one or more of the following conditions:

[0111] (A) In the process of preparing the first structured fat, the conditions for the transesterification reaction involving the first lipase include: a vacuum degree of 50 Pa - 200 Pa (such as 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200 Pa), a temperature of 55°C - 65°C (such as 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65°C), and a time of 22 h - 24 h (such as 22, 23, 24 h);

[0112] (B) In the process of preparing the second structured fat, the conditions for the transesterification reaction involving the second lipase include: normal pressure, a temperature of 55°C - 65°C (such as 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65°C), and a time of 5 h - 24 h (such as 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 h);

[0113] (C) In the process of preparing the third structured fat, the conditions for the transesterification reaction involving the third lipase include: a vacuum degree of 50 Pa - 200 Pa (such as 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65°C), a temperature of 55°C - 65°C (such as 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65°C), and a time of 3 h - 24 h (such as 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 h); and

[0114] (D) The third structured fat is treated with absolute ethanol and then mixed with the third antioxidant; the absolute ethanol treatment satisfies one or more of the following conditions:

[0115] D1) The volume ratio of the third structured fat to the absolute ethanol is 1:(0.5 - 1.5) (such as 1:0.5, 1:0.6, 1:0.7, 1:0.8, 1:0.9, 1:1, 1:1.2, 1:1.3, 1:1.4, 1:1.5); and,

[0116] D2) Normal pressure, a temperature higher than 65°C (such as 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85°C), and a time of 8 h - 11 h (such as 8, 9, 10, 11 h); further, the temperature of the thermal reaction is 68°C - 75°C.

[0117] In the third aspect of the embodiments of the present application, a three-dimensional structured lipid composition is provided, comprising:

[0118] the three-dimensional structured lipid; and,

[0119] excipients acceptable in food science or pharmacy.

[0120] In some embodiment schemes, the three-dimensional structured lipid composition is a beverage powder; optionally, the excipients include one or more of isomaltooligosaccharide, maltodextrin, sodium caseinate, sodium stearoyl lactate, sodium citrate, sodium L-ascorbate, and yeast β-glucan.

[0121] In some embodiment schemes, the three-dimensional structured lipid composition is a capsule; optionally, the capsule is a capsule-in-capsule, and the chip of the capsule-in-capsule includes the three-dimensional structured lipid; further optionally, the chip of the capsule-in-capsule further includes one or more of earthworm protein peptide, sea cucumber peptide, marine fish protein, collagen peptide, wheat oligopeptide, and γ-aminobutyric acid; optionally, the excipients include a thickening agent and a structural oil used for making tablets; further optionally, the thickening agent includes a capsule-in-capsule prepared from one or more of yeast β-glucan, hydroxypropyl methylcellulose, resistant dextrin, glyceryl triacetate, magnesium stearate, titanium dioxide, aluminum lake of tartrazine, and aluminum lake of sunset yellow.

[0122] In some embodiment schemes, the three-dimensional structured lipid composition is a gel candy; optionally, the excipients include gelatin, sorbitol, glycerol, and water.

[0123] In some embodiment schemes, the three-dimensional structured lipid composition is in a liquid form.

[0124] In some embodiment schemes, the three-dimensional structured lipid composition is an emulsion; optionally, the excipients include an emulsifier; optionally, the particle size of the emulsion droplets in the emulsion is 100 nm - 2500 nm.

[0125] In the fourth aspect of the embodiments of the present application, a preparation method of the three-dimensional structured lipid composition is provided, and the preparation method comprises the following steps:

[0126] Providing the three-dimensional structured lipid, or preparing a three-dimensional structured lipid according to the preparation method; and,

[0127] Preparing a three-dimensional structured lipid composition with the three-dimensional structured lipid and the excipients.

[0128] The purpose of preparing the second structured lipid in the embodiments of the present application is to first prepare a structured lipid that meets the reaction conditions because the ratio of functional characteristic vegetable oil should not be too large, reduce the reaction time of the third structured lipid, and lower the large-scale production cost.

[0129] In the embodiments of the present application, after each transesterification reaction is completed, the immobilized lipase has a process of precisely filtering the lipase and independently recycling the reactor equipment for repeated reactions. In the process of adding glycerol, there is a process of separating excess glycerol together with the lipase.

[0130] In the embodiments of the present application, in ethyl ester type fish oil, the total content of EPA and DHA is 60 wt% - 99 wt%.

[0131] In the embodiments of the present application, the purity of glycerol is 99%.

[0132] In the embodiments of the present application, the content of astaxanthin in astaxanthin oil is 5 wt% - 10 wt%.

[0133] In the embodiments of the present application, when the third structural fat is mixed and reacted with absolute ethanol, it is mainly to passivate the enzyme activity and inactivate the enzyme to avoid losses caused by high temperature to the antioxidant effects of astaxanthin and the like.

[0134] In the embodiments of the present application, in the transesterification reaction involving lipase, the reactor is selected from a reactor with a closed container lipase collection device or an ultrasonic reactor.

[0135] In the embodiments of the present application, the characteristics of the Sn-2 position fatty acid are as follows: containing C16:0 OPO (8 - 15 wt%), C18:0 (5 - 8 wt%), C18:1 (20 - 28 wt%), C18:2 (20 - 25 wt%), C20:5 EPA (8 - 20 wt%), C22:6 DHA (5 - 15 wt%), C18:3 r-linolenic acid (6 - 15 wt%), C24:1 nervonic acid (0.5 - 1.2 wt%), EPA / DHA, r-linolenic acid, oemga-3 (17 - 35 wt%), omega-6 (20 - 35 wt%), omega-9 (20 - 35 wt%), fatty acid triglycerides reacting with glycerol 55 - 65 wt%, diglycerides 25 - 30 wt%, monoglycerides 7 - 10 wt%, and the total amount of sn-2 position monoglycerides 95 - 100 wt%.

[0136] The embodiments of the present invention will be described in detail below. It should be understood that these embodiments are only used to illustrate the present invention and not to limit the scope of the present invention. For the experimental methods without specific conditions in the following embodiments, preference is given to the guidance given in the present invention, and it can also be carried out according to the experimental manuals or conventional conditions in the art, or according to the conditions recommended by the manufacturers, or referring to the experimental methods known in the art.

[0137] In the following specific embodiments, regarding the measurement parameters of raw material components, unless otherwise specified, there may be slight deviations within the weighing accuracy range. Regarding temperature and time parameters, acceptable deviations caused by instrument testing accuracy or operation accuracy are allowed.

[0138] The raw materials include:

[0139] Ethyl ester type fish oil: Jiangsu Wiscom Food Technology Development Co., Ltd., Sichuan Xinmeijia Biopharmaceutical Co., Ltd., Shandong Yuwang Pharmaceutical Co., Ltd.

[0140] Glycerol: Daoqin Biotechnology (Shanghai) Co., Ltd.

[0141] IMNE-100 immobilized lipase: Weifang Kangdien Biotechnology Co., Ltd., Beijing Gaoruisen Technology Development Co., Ltd.

[0142] Astaxanthin oil: Shanghai Yuncaikinco Biotechnology Co., Ltd.

[0143] Apricot kernel oil: Xinglin Chunxiao Chengde Biotechnology Co., Ltd.

[0144] Xanthoceras sorbifolia Bunge oil: Liaoning Wenguan Industrial Development Co., Ltd.

[0145] NS400190 immobilized lipase: Beijing Gaoruisen Technology Development Co., Ltd., Weifang Kangdien Biotechnology Co., Ltd.

[0146] Pine seed oil: Heze Zhonghe Jianyuan Biotechnology Co., Ltd.

[0147] Acer truncatum Bunge seed oil: Inner Mongolia Jingele Food Co., Ltd.

[0148] Evening primrose oil: Liaoning Jiashi Health Vegetable Oil Development Co., Ltd., Heze Zhonghe Jianyuan Biotechnology Co., Ltd.

[0149] Borage seed oil: Liaoning Jiashi Health Vegetable Oil Development Co., Ltd.

[0150] Ascorbyl palmitate: Huizhou Kangweijian Biotechnology Co., Ltd.

[0151] The determination of glycerides is based on the European Pharmacopoeia 1352 standard, and the determination of sn-2 monoglyceride is based on GB / T24894-2010.

[0152] Example 1

[0153] (1) Add 90 parts of ethyl ester type fish oil (the sum of EPA and DHA content is greater than 70 wt%; EPA: eicosapentaenoic acid; docosahexaenoic acid), 10 parts of glycerol, and IMNE-100 immobilized lipase (the addition amount is 3.5 wt% of the total weight of ethyl ester type fish oil and glycerol). React under the conditions of 100 Pa vacuum and 65 °C for 24 hours, then filter carefully. Add astaxanthin oil (the purity of astaxanthin is 5 wt%, and the addition amount of astaxanthin oil is 1.2 wt‰ of the total weight of ethyl ester type fish oil and glycerol) and mix evenly to obtain the first structured fat. The first structured fat meets the following conditions: the triglyceride content is 60 wt%, the diglyceride content is 29 wt%, the monoglyceride content is 8 wt%; the fatty acid content at the sn-2 position is 99 wt%.

[0154] (2) Add NS400190 immobilized lipase (the addition amount is 3.5 wt% of the total weight of almond oil, Xanthoceras sorbifolia oil and glycerol) to 4.8 parts of almond oil, 4.8 parts of Xanthoceras sorbifolia oil, 0.2 parts of water (add water first and then glycerol) and 0.4 parts of glycerol. React under the conditions of normal pressure and 65 °C for 9 hours, then evacuate the water under vacuum to obtain the second structured fat with a triglyceride content of 63 wt%, a diglyceride content of 36 wt%, a monoglyceride content of 1 wt%, and a fatty acid content at the sn-2 position of 97 wt%.

[0155] (3) Add 3 parts of the first structured fat, 2 parts of the second structured fat, 5 parts of borage oil and IMNE-100 immobilized lipase (the addition amount is 3.5 wt% of the total weight of the first structured fat, the second structured fat and borage oil). React under the conditions of 150 Pa vacuum and 60 °C for 24 hours to obtain the third structured fat. The triglyceride content of the third structured fat is greater than 60 wt%, the diglyceride content is greater than 29 wt%, the monoglyceride content is less than 10 wt%, and the fatty acid content at the sn-2 position is 97 wt%.

[0156] (4) Mix the third structured fat with absolute ethanol at a ratio of 1:1 (v:v), heat to 70 °C, stir at normal pressure for 5 hours, stop stirring, keep warm for 6 hours, evacuate ethanol under vacuum, add astaxanthin oil (the purity of astaxanthin is 10 wt%, and the addition amount of astaxanthin oil is 2 wt‰ of the weight of the third structured fat), and filter carefully to obtain the stereostructured lipid.

[0157] Press soft capsule gel candies, with a net content of 1.2 grams of stereostructured lipid per soft capsule gel candy, and 4 capsules per day. It is applicable for 3 - 4 months for the disappearance of symptoms of low high-density lipoprotein, the disappearance of hyperlipidemia, the increase in carotid blood flow velocity, the decrease in resistance, the thickening of the inner diameter of blood vessels, and the improvement of the clarity of the inner wall of the cardiovascular and cerebrovascular system.

[0158] The core material of the soft capsule gel candy is a structured lipid and earthworm protein peptide, and the weight ratio of the two is 23:1. The rubber skin includes gelatin, sorbitol, glycerol and water. Among them, the contents of gelatin, sorbitol and glycerol in the outer skin are 79.7wt%, 8.5wt%, 8wt% and 3.8wt% respectively.

[0159] Example 2

[0160] (1) 90 parts of ethyl ester type fish oil (the sum of EPA and DHA contents is 70wt%, and the DHA content is 10wt%), 10 parts of glycerol, and IMNE-100 immobilized lipase (the addition amount is 4wt% of the total weight of ethyl ester type fish oil and glycerol) are reacted for 22 hours under the conditions of 100 Pa in vacuum and 60 °C in temperature, and then finely filtered. Astaxanthin oil (the purity of astaxanthin is 10wt%, and the addition amount is 1.2wt‰ of the total weight of ethyl ester type fish oil and glycerol) is added and mixed evenly to obtain the first structured fat. It is measured that the triglyceride content is 62wt%, the diglyceride content is 27wt%, the monoglyceride content is 9.5wt%, and the content of sn-2 position fatty acid is 98wt%.

[0161] (2) 4.8 parts of almond oil, 4.8 parts of Xanthoceras sorbifolia Bunge oil, 0.3 part of water (add water first and then glycerol), 0.4 part of glycerol and IMNE-100 immobilized lipase (the addition amount is 4wt% of the total weight of almond oil, Xanthoceras sorbifolia Bunge oil and glycerol) are reacted for 8 hours under the conditions of normal pressure and 60 °C in temperature, and then the water is evacuated in vacuum to obtain the second structured fat with a triglyceride content of 70wt%, a diglyceride content of 25wt%, a monoglyceride content of 5wt%, and a content of sn-2 position fatty acid of 97wt%.

[0162] (3) 3.5 parts of the first structured fat, 1 part of the second structured fat, 5.5 parts of borage oil, and IMNE-100 immobilized lipase (the addition amount is 4wt% of the total weight of the first structured fat, the second structured fat and borage oil) are reacted for 4.5 hours under the conditions of 100 Pa in vacuum and 65 °C in temperature, and then finely filtered to prepare the third structured fat. It is measured that the triglyceride content is 65wt%, the diglyceride content is 34wt%, the monoglyceride content is 1wt%, and the content of sn-2 position monoglyceride is 97wt%.

[0163] (4) The third structured fat is mixed with absolute ethanol at a ratio of 1:1 (v:v), heated to 70 °C, stirred and mixed at normal pressure for 3 hours, then the stirring is stopped, and it is kept warm for 5.5 hours. The absolute ethanol is evacuated in vacuum. Astaxanthin oil (the purity of astaxanthin is 5wt%, and the addition amount is 0.5wt‰ of the weight of the third structured fat) and ascorbyl palmitate (the addition amount is 0.2wt‰ of the weight of the third structured fat) are added, and then finely filtered to obtain the structured lipid.

[0164] Oil-pressed soft capsule gel candy. The net content of the three-dimensional structured lipid in each soft capsule gel candy is 0.85 grams. Take 6 capsules per day for 25 days, and the blood pressure of hypertension and hereditary low-high blood pressure can be reduced from 110 to 85, basically returning to the normal value.

[0165] The core material of the soft capsule gel candy is three-dimensional structured lipid and earthworm protein peptide, and the ratio of the two is 11:1.

[0166] The auxiliary material formula of the soft capsule gel candy is the same as that in Example 1.

[0167] Example 3

[0168] (1) Mix 90 parts of ethyl ester type fish oil (the total content of EPA and DHA is 80 wt%), 12 parts of glycerol, and IMNE-100 immobilized lipase (the addition amount is 5 wt% of the ethyl ester type fish oil) under the conditions of a vacuum of 150 Pa and a constant temperature of 65 °C for 24 hours. Then add astaxanthin oil (the purity of astaxanthin is 5 wt%, and the addition amount is 1.5 wt‰ of the total weight of the ethyl ester type fish oil and glycerol) and mix evenly to obtain the first structured fat, in which the triglyceride content is 55 wt%, the diglyceride content is 35 wt%, the monoglyceride content is 11.5 wt%, and the sn-2 position fatty acid content is 99 wt%.

[0169] (2) Mix 4.8 parts of pine seed oil, 4.8 parts of Acer truncatum Bunge seed oil, 0.3 parts of water (add water first and then glycerol), 0.4 parts of glycerol, and NS400190 immobilized lipase (the addition amount is 4.5 wt% of the total weight of pine seed oil, Acer truncatum Bunge seed oil, and glycerol) under normal pressure and at a temperature of 65 °C for 6 hours, and then vacuum-extract the water to obtain the second structured fat with a triglyceride content of 64 wt%, a diglyceride content of 35 wt%, a monoglyceride content of 1 wt%, and an Sn-2 position fatty acid content of 98 wt%.

[0170] (3) Mix 4 parts of the first structured fat, 1 part of the second structured fat, 5 parts of borage oil, and IMNE-100 immobilized lipase (the addition amount is 3.5 wt% of the total weight of the first structured fat, the second structured fat, and borage oil) under a vacuum of 100 Pa and at a temperature of 60 °C for 4 hours to obtain the third structured fat with a triglyceride content of 63 wt%, a diglyceride content of 33 wt%, a monoglyceride content of 4 wt%, and an sn-2 position fatty acid content of 98 wt%.

[0171] (4) Mix the third structured fat with absolute ethanol in a ratio of 1:1, stir for 4 hours under the conditions of a temperature of 70 °C and normal pressure, stop stirring, keep warm for 6 hours, and vacuum-extract the absolute ethanol to obtain the structured lipid. Add ascorbyl palmitate (the addition amount is 0.2 wt‰ of the weight of the third structured fat) and astaxanthin oil (the purity of astaxanthin is 5 wt%, and the addition amount is 0.5 wt‰ of the weight of the third structured fat), mix evenly and filter precisely to obtain the three-dimensional structured lipid.

[0172] For the oil-pressed soft capsule gel candy, the net content of the three-dimensional structured lipid in each soft capsule gel candy is 0.85 grams. Take 6 capsules per day and consume for 8 - 12 months. The stenosis of each lumen of the coronary aorta and branch arteries, which was originally 50 - 70%, is reduced to 30% or disappears.

[0173] The core material of the soft capsule gel candy is the three-dimensional structured lipid and earthworm protein peptide, and the weight ratio of the two is 7:1.

[0174] The auxiliary material formula of the soft capsule gel candy is the same as that in Example 1.

[0175] Example 4

[0176] (1) React 90 parts of ethyl ester type fish oil (the content of EPA and DHA is 85 wt%), 10 parts of glycerol, and Novozym 435 lipase (the addition amount is 3.5 wt% of the total weight of ethyl ester type fish oil and glycerol) under the conditions of a vacuum of 150 Pa and a constant temperature of 55 °C for 24 hours. Add astaxanthin oil (the purity of astaxanthin is 10 wt%, and the addition amount is 1.5 wt‰ of the weight of ethyl ester type fish oil) and mix evenly to obtain the first structured fat, in which the triglyceride content is 65 wt%, the diglyceride content is 31 wt%, the monoglyceride content is 4 wt%, and the sn-2 position fatty acid content is 97 wt%.

[0177] (2) React 4.5 parts of almond oil, 3.6 parts of evening primrose oil, 1.5 parts of Acer truncatum seed oil, 0.2 parts of water (add water first and then glycerol), 0.4 parts of glycerol, and IMNE-100 immobilized lipase (the addition amount is 4 wt% of the total weight of almond oil, evening primrose oil, Acer truncatum seed oil, and glycerol) under the conditions of normal pressure and a temperature of 63 °C for 7 hours, and vacuum-extract the water to obtain the second structured fat with a triglyceride content of 64 wt%, a diglyceride content of 29 wt%, a monoglyceride content of 7 wt%, and an sn-2 position fatty acid content of 99 wt%.

[0178] (3) Mix 3 parts of the first structured fat, 1 part of the second structured fat, 6 parts of borage seed oil, and IMNE-100 immobilized lipase (the addition amount is 5 wt% of the total weight of the first structured fat, the second structured fat, and borage seed oil), and react at 60 °C under a vacuum of 100 Pa for 3 hours to obtain a third structured fat with a triglyceride content of 66 wt%, a diglyceride content of 32 wt%, a monoglyceride content of 2 wt%, and an sn-2 position fatty acid content of 99 wt%.

[0179] (4) Mix the third structured fat and absolute ethanol in a ratio of 1:1 (v:v), stir at 70 °C under normal pressure for 4 hours, stop stirring, keep warm for 5.5 hours, and vacuum-extract the absolute ethanol to obtain the structured lipid. Astaxanthin oil (the purity of astaxanthin is 10 wt%, and the addition amount is 0.5 wt‰ of the weight of the third structured fat), mix evenly and filter precisely to obtain the three-dimensional structured lipid. The inspection report is shown in Figure 1 .

[0180] Press soft capsule gel candies. The net content of the three-dimensional structured lipid in each soft capsule gel candy is 0.85 grams, and 9 capsules are taken every day. It can regulate immunity, antioxidant, anti-inflammatory, and improve the side effects of tumor radiotherapy and chemotherapy.

[0181] The core material of the soft capsule gel candy is three-dimensional structured lipid, r-aminobutyric acid (GABA), and sea cucumber peptide, and the weight ratio of the three is 22:1:1.

[0182] The auxiliary material formula of the soft capsule gel candy is the same as that in Example 1.

[0183] Example 5

[0184] (1) Mix 90 parts of ethyl ester type fish oil (the content of EPA and DHA is 90 wt%), 10 parts of glycerol, and IMNE-100 immobilized lipase (the addition amount is 3.5 wt% of the total weight of ethyl ester type fish oil and glycerol), and react at 55 °C under a vacuum of 200 Pa for 24 hours. Add astaxanthin oil (where the purity of astaxanthin is 5 wt%, and the addition amount is 1.5 wt‰ of the total weight of ethyl ester type fish oil and glycerol), mix evenly to obtain the first structured fat, where the triglyceride content is 65 wt%, the diglyceride content is 31 wt%, the monoglyceride content is 4 wt%, and the sn-2 position fatty acid content is 98 wt%.

[0185] (2) Add 5 parts of almond oil, 3.1 parts of evening primrose oil, 1.5 parts of Acer truncatum Bunge seed oil, 0.2 parts of water (add water first and then glycerol), 0.4 parts of glycerol, and NS400190 immobilized lipase (the addition amount is 4 wt% of the total weight of almond oil, evening primrose oil, Acer truncatum Bunge seed oil, and glycerol). React under normal pressure at a temperature of 60 °C for 5.5 hours, and remove water by vacuum pumping to obtain a second-structured fat with a diglyceride content of 28 wt%, a monoglyceride content of 5 wt%, and an sn-2 fatty acid content of 98 wt%.

[0186] (3) Add 4 parts of the first-structured fat, 1 part of the second-structured fat, 5 parts of borage oil, and IMNE-100 immobilized lipase (the addition amount is 5 wt% of the first-structured fat, the second-structured fat, and borage oil). React under a vacuum of 150 Pa at 60 °C for 3 hours to obtain a third-structured fat with a triglyceride content of 61 wt%, a diglyceride content of 32 wt%, a monoglyceride content of 7 wt%, and an sn-2 fatty acid content of 98 wt%.

[0187] (4) Mix the third-structured fat with absolute ethanol at a ratio of 1:1 (v:v) at 70 °C, stir under the conditions of a temperature of 70 °C and normal pressure for 4 hours, stop stirring, keep warm for 6 hours, and remove absolute ethanol by vacuum pumping to obtain a structured lipid. Add astaxanthin oil (the purity of astaxanthin is 10 wt%, and the addition amount is 0.5 wt‰ of the weight of the third-structured fat), mix evenly and filter precisely to obtain a three-dimensional structured lipid.

[0188] The three-dimensional structured lipid is made into a soft capsule gel candy with a sea cucumber peptide tablet in the capsule within a capsule. Swallow 9 - 12 tablets per day to prevent the generation or continued spread of cachexia and muscle atrophy.

[0189] The core material of the soft capsule gel candy is a three-dimensional structured lipid and sea cucumber peptide, and their weight ratio is 11:1. The formula of the rubber skin is the same as that in Example 1.

[0190] Example 6

[0191] (1) Add 90 parts of ethyl ester type fish oil (the sum of EPA and DHA contents is 90 wt%), 10 parts of glycerol, and Novozym 435 immobilized lipase (the addition amount is 3.5 wt% of the total weight of ethyl ester type fish oil and glycerol). React under a vacuum of 150 Pa at a temperature of 65 °C for 23 hours, filter precisely and add astaxanthin oil (the purity of astaxanthin is 10 wt%, and the addition amount is 1.2 wt‰ of the total weight of ethyl ester type fish oil and glycerol), mix evenly to obtain the first-structured fat, and measure that the triglyceride content is 55 wt%, the diglyceride content is 33 wt%, the monoglyceride content is 9 wt%, and the sn-2 fatty acid content is 97 wt%.

[0192] (2) Add 6 parts of almond oil, 3.7 parts of Xanthoceras sorbifolia oil, 0.2 part of water (add water first and then glycerol), 0.3 part of glycerol, and IMNE-100 immobilized lipase (the addition amount is 4.5 wt% of the total weight of almond oil, Xanthoceras sorbifolia oil, and glycerol). React at a temperature of 60 °C under normal pressure for 6.5 hours, and vacuum extract the water to obtain a second structured lipid with a triglyceride content of 65 wt%, a diglyceride content of 29 wt%, a monoglyceride content of 6 wt%, and an sn-2 position fatty acid content of 98 wt%.

[0193] (3) Add 3.5 parts of the first structured lipid, 1 part of the second structured lipid, 5.5 parts of borage seed oil, and IMNE-100 immobilized lipase (the addition amount is 3 wt% of the total weight of the first structured lipid, the first structured lipid, and borage seed oil). React under a vacuum of 120 Pa and a temperature of 60 °C for 5 hours, and then filter precisely to obtain the third structured fat. The measured triglyceride content is 66 wt%, the diglyceride content is 31 wt%, the monoglyceride content is 3 wt%, and the sn-2 position monoglyceride content is 98 wt%.

[0194] (4) Mix the third structured fat with absolute ethanol at a ratio of 1:1 (v:v), heat it to 70 °C, under normal pressure, stir and mix for 4 hours, keep warm for 5.5 hours, vacuum extract the ethanol, add astaxanthin oil (astaxanthin purity is 10 wt%, the addition amount is 0.2 wt‰ of the weight of the third structured fat), and ascorbyl palmitate (the addition amount is 0.2 wt‰ of the weight of the third structured fat), and then filter precisely to obtain the stereostructured lipid.

[0195] Press soft capsule gel candies, with a net content of 0.85 grams of stereostructured lipid in each soft capsule gel candy, and 9 - 12 candies per day. The formula of the rubber skin is the same as that in Example 1. The white blood cells of lung cancer, colorectal cancer, and gastric cancer chemotherapy patients are maintained in basic balance.

[0196] The core material of the soft capsule gel candy is stereostructured lipid and γ-aminobutyric acid (GABA), and the weight ratio of the two is 23:1.

[0197] Example 7

[0198] (1) Add 90 parts of ethyl ester type fish oil (the sum of EPA and DHA contents is 70 wt%), 10 parts of glycerol, and Novozym 435 immobilized lipase (the addition amount is 3.5 wt% of the total weight of ethyl ester type fish oil and glycerol). React under a vacuum of 150 Pa and a temperature of 65 °C for 23 hours, and then filter precisely and add astaxanthin oil (where the purity of astaxanthin is 10 wt%, the addition amount is 1.2 wt‰ of the total weight of ethyl ester type fish oil and glycerol), mix evenly to obtain the first structured fat. The measured triglyceride content is 55 wt%, the diglyceride content is 33 wt%, the monoglyceride content is 9 wt%, and the sn-2 position fatty acid content is 97 wt%.

[0199] (2) Add 6 parts of almond oil, 3.7 parts of Xanthoceras sorbifolia oil, 0.2 parts of water (add water first and then glycerol), 0.3 parts of glycerol, and IMNE-100 immobilized lipase (the addition amount is 4.5 wt% of the total weight of almond oil, Xanthoceras sorbifolia oil, and glycerol). React at a temperature of 60 °C under normal pressure for 6.5 hours, and vacuum-extract water to obtain a second structured lipid with a triglyceride content of 65 wt%, a diglyceride content of 29 wt%, a monoglyceride content of 6 wt%, and an sn-2 position fatty acid content of 98 wt%.

[0200] (3) Add 3.5 parts of the first structured lipid, 1 part of the second structured lipid, 5.5 parts of borage oil, and IMNE-100 immobilized lipase (the addition amount is 3 wt% of the total weight of the first structured lipid, the second structured lipid, and borage oil). React under a vacuum of 120 Pa and a temperature of 60 °C for 5 hours, and then filter precisely to obtain a third structured fat. The measured triglyceride content is 64 wt%, the diglyceride content is 30 wt%, the monoglyceride content is 6 wt%, and the sn-2 position monoglyceride content is 98 wt%.

[0201] (4) Mix the third structured fat with absolute ethanol at a ratio of 1:1 (v:v), heat to 70 °C, stir and mix under normal pressure for 4 hours, keep warm for 5.5 hours, vacuum-extract ethanol, add astaxanthin oil (astaxanthin purity is 10 wt%, and the addition amount is 0.2 wt‰ of the weight of the third structured fat), and ascorbyl palmitate (the addition amount is 0.2 wt‰ of the weight of the third structured fat), and then filter precisely to obtain a stereostructured lipid.

[0202] Press soft capsule gel candies. The net content of the stereostructured lipid in each soft capsule gel candy is 0.85 grams. Take 9 candies per day, 3 candies each time, 3 times a day. The formula of the rubber skin is the same as that in Example 1.

[0203] Limited by the difference between the ethical goal and the actual recruitment direction, 2 clinical effects of Example 7 are obtained.

[0204] Show good effects in the following clinical studies:

[0205] 1. Clinical effect conclusion for lung cancer: By long-term supplementing the stereostructured lipid composition (i.e., soft capsule gel candies), lung cancer patients can improve their immune status, especially the effects on complement C3, IgG level, CD4, and CD4 / CD8. In addition, it can also reduce the triglyceride level in lung cancer patients, increase folic acid, and the mean corpuscular hemoglobin concentration. Therefore, the stereostructured lipid composition can be used as a supplement to improve the immune and nutritional status of lung cancer patients.

[0206] 2. Clinical Effect Conclusion of Mild Hyperlipidemia: In the population with mild hyperlipidemia, supplementing the stereostructured lipid composition has no adverse effects on liver and kidney functions, can improve blood lipid and inflammation levels, and play a role in reducing the risk of atherosclerotic cardiovascular diseases. It is confirmed that on the basis of a low-salt and low-fat diet and exercise intervention, supplementing the stereostructured lipid composition rich in sn-2-monoacylglycerol and Omega-3 PUFA can significantly improve the levels of TG, LDL-C, non-HDL-C and hs-CRP / HDL-C in patients with mild hyperlipidemia, and has no adverse effects on liver and kidney functions. Its mechanism of action may involve multiple pathways such as lipid hydrolysis regulation, enhanced fatty acid oxidation and inhibition of inflammatory pathways. This composition provides a safe and effective auxiliary intervention strategy for early blood lipid management and has potential clinical value in reducing the risk of atherosclerosis.

[0207] The method and results of verifying the effects of the stereostructured lipid in two directions simultaneously in this embodiment are as follows.

[0208] Effect Verification: Clinical Effect Verification Study on Patients with Mild Hyperlipidemia or Lung Cancer

[0209] I. Research Overview

[0210] In this study, functional fatty acids such as EPA, DHA, nervonic acid, γ-linolenic acid, etc. were used to synthesize sn-2-monoacylglycerol by biocatalytic technology to form the novel stereostructured lipid composition of Example 7. This project orally supplements this novel stereostructured lipid composition to patients with mild dyslipidemia or lung cancer, observes its clinical effects on improving blood lipids, regulating immunity, antioxidant, and anti-inflammatory effects, and has important significance for preventing and treating the occurrence and development of atherosclerotic cardiovascular diseases, combating chronic inflammatory diseases, and improving the quality of life of cancer patients.

[0211] II. Research Objectives and Significance

[0212] (1) Observe the effects of supplementing the stereostructured lipid composition on the blood lipid levels of the population with mild hyperlipidemia, and simultaneously evaluate the health effects on blood pressure, body fat, inflammation, antioxidant indexes, arteriosclerosis index (AI), carotid intima-media thickness (IMT), plaque score, etc.

[0213] (2) Observe the effects of supplementing the stereostructured lipid composition on inflammation, immune function, chemotherapy adverse reactions, antioxidant capacity and quality of life of lung cancer patients.

[0214] (3) Confirm that long-term supplementation of the stereostructured lipid composition has the effects of improving blood lipid levels, reducing the risks related to carotid atherosclerosis, improving the immunity of cancer patients and improving the quality of life.

[0215] III. Main Research Contents

[0216] Using a randomized controlled study method, subjects with mild hyperlipidemia and newly diagnosed lung cancer were recruited respectively, and those who met the inclusion and exclusion criteria and voluntarily signed the informed consent form.

[0217] (1) Eighty patients with mild hyperlipidemia were randomly divided into two groups: the structured lipid composition group and the control group (conventional treatment group), with a duration of 3 months. During this period, drugs that affect blood lipid metabolism were avoided. Before and at the end of the intervention, the changes in blood lipids, blood pressure, waist circumference, BMI, serum inflammatory indicators, antioxidant indicators (such as serum superoxide dismutase, glutathione peroxidase, malondialdehyde, etc.), atherosclerosis index (AI), carotid intima-media thickness (IMT), and plaque score were observed in each group after long-term intervention in the hyperlipidemic population. Alternatively, sixty patients with mild hyperlipidemia were not grouped, and a before-and-after control study was conducted. The intervention lasted for 2 months. During this period, drugs that affect blood lipid metabolism were avoided. Before and at the end of the intervention, the blood pressure, waist circumference, blood pressure, and blood lipids of the patients with mild hyperlipidemia (i.e., the subjects) were measured.

[0218] (2) Ninety-two patients with lung cancer were randomly divided into two groups: the structured lipid composition group and the control group (conventional treatment group), with a duration of 3 months. Before and at the end of the intervention, the effects of the structured lipid composition on inflammation, immune function, chemotherapy adverse reactions, antioxidant capacity, and quality of life in lung cancer patients were observed.

[0219] IV. Key Issues to be Solved

[0220] After the randomized controlled intervention experiment, determining the effects of the structured lipid composition on improving blood lipid levels, reducing atherosclerosis-related risks, carotid intima-media thickness (IMT), plaque score indicators, and improving the inflammatory level, enhancing immunity, and quality of life in lung cancer patients is the key issue to be solved in this study.

[0221] V. Proposed Research Methods, Steps, and Technical Routes

[0222] 1. Research method: Randomized controlled study method

[0223] 2. Research steps:

[0224] 2.1 Intervention study on patients with mild hyperlipidemia

[0225] (1) Recruitment of subjects with mild hyperlipidemia:

[0226] Patients with mild hyperlipidemia who were examined or treated in the outpatient department of the General Hospital of the Chinese People's Liberation Army and met the clinical diagnostic criteria for mild hyperlipidemia according to the definition of the "Guidelines for the Prevention and Treatment of Dyslipidemia in Adults in China in 2016", that is, hypertriglyceridemia (1.7mmol / L≤TG<2.3mmol / L), hypercholesterolemia (5.2mmol / L≤TC<6.2mmol / L), high low-density lipoprotein cholesterol (3.4mmol / L≤LDL-C<4.1mmol / L) or mixed hyperlipidemia Hyperlipidemia (1.7mmol / L≤TG<2.3mmol / L and 5.2mmol / L≤TC<6.2mmol / L, or 1.7mmol / L≤TG<2.3mmol / L and 3.4mmol / L≤LDL-C<4.1mmol / L, or 1.7mmol / L≤TG<2.3mmol / L and 5.2mmol / L≤TC<6.2mmol / L and 3.4mmol / L≤LDL-C<4.1mmol / L).

[0227] A. Inclusion criteria:

[0228] (a) Patients with confirmed mild hyperlipidemia.

[0229] (b) Nationality: any nationality.

[0230] (c) Gender: male and female.

[0231] (d) Age: greater than or equal to 18 years old and less than 65 years old.

[0232] (e) Have communication and cognitive abilities and be able to take medication on a long-term basis.

[0233] (f) Voluntary participation in the trial.

[0234] B. Exclusion criteria:

[0235] (a) Patients who are currently receiving lipid-lowering medication.

[0236] (b) Hyperlipidemia caused by secondary causes, such as nephrotic syndrome, liver disease, hypothyroidism, renal failure, etc.

[0237] (c) Patients with severe diabetes, hypertriglyceridemia, cerebrovascular disease and other major diseases that require immediate treatment, heart disease, immune system disease, acute onset of chronic disease, infectious disease, or malignant tumor.

[0238] (d) Patients with severe primary diseases of the liver, kidney, hematopoietic system, or mental illness.

[0239] (e) Pregnant or breastfeeding women.

[0240] (f) Those with allergic constitution or allergic to the experimental drugs.

[0241] C. Criteria for Subjects to Withdraw from the Trial

[0242] (a) Any situation that meets the exclusion criteria occurs.

[0243] (b) Unable to participate in follow-up as required.

[0244] (c) Severe new-onset diseases or death.

[0245] (d) Voluntary withdrawal or loss to follow-up.

[0246] (e) If the researcher determines that the patient has not complied with the trial procedures or for safety considerations, the subject can be withdrawn.

[0247] (2) Sample Size Calculation

[0248] The sample size was calculated using the serum triglyceride level, total cholesterol level, and LDL-C level as the main outcome indicators, respectively. According to the literature (Zhao N, Wang L, Guo N. α-Linolenic acid increases the G0 / G1 switchgene 2mRNA expression in peripheral blood mononuclear cells from obese patients: a pilot study. Lipids Health Dis. 2016; 24; 15:36; and Karvonen HM, Aro A, Tapola NS, Salminen I, Uusitupa MI, Sarkkinen ES. Effect of alpha-linolenic acid-rich Camelina sativa oil on serum fatty acid composition and serum lipids in hypercholesterolemic subjects. Metabolism. 2002; 51(10):1253 - 60), using G*Power3.1.9.2 software (Heinrich-Heine University, Germany), with an effect size F value = 0.85, α = 0.05, Power(1-β) = 0.95, a total of n = 2, the sample size required for statistical significance (P < 0.05) was calculated to be 73 cases. Considering the situation of subject loss to follow-up, according to a 10% loss to follow-up rate, 80 subjects were planned to be recruited, with approximately 40 cases in each group.

[0249] (3) Random Grouping

[0250] This study adopted a single-center randomized controlled study method. Method for subject grouping: The random grouping method was used. Specifically, the data center generated random codes QZZ (the three-dimensional structured lipid composition was AZZ, and the control group was BZZ); Q(A, B) represented the intervention method (A represented the three-dimensional structured lipid composition group, and B represented the control group); ZZ represented the subject number starting from 01. Subjects in group A took three-dimensional structured lipid composition capsules (3 capsules each time, 3 times a day) on the basis of conventional low-salt and low-fat diet and exercise guidance, while the control group received conventional low-salt and low-fat diet and exercise guidance.

[0251] (4) Primary / secondary observation indicators of the study.

[0252] (a) Data collection time: Before the start of the experiment and at the end of the experiment.

[0253] (b) Case data and content:

[0254] Primary indicators:

[0255] Blood lipid levels: Triglyceride, cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol.

[0256] Atherosclerosis evaluation: Carotid intima-media thickness (IMT), plaque integral index.

[0257] Secondary observation indicators:

[0258] ① General conditions: Name, gender, age, height, waist circumference, weight, body mass index (BMI), blood pressure, past history.

[0259] ② Biochemical tests: Blood transaminase, creatinine, urea nitrogen, blood glucose, etc., which were completed by the clinical laboratory center of this unit.

[0260] ③ Determination of inflammatory factors: IL-6, C-reactive protein, IL-10, TNF-α, etc., which were completed by the clinical laboratory center of this unit.

[0261] ④ Calculation of atherosclerosis index (AI) [Atherosclerosis index (AI) = [total blood cholesterol (TC) - high-density lipoprotein (HDL)] ÷ high-density lipoprotein (HDL)].

[0262] (5) Safety and efficacy indicators.

[0263] Safety: The subjects of this study were patients with mild hyperlipidemia, and health foods were used for intervention without toxic or side effects, and safety monitoring was carried out. And all routine blood samplings during the sampling process were non-invasive operations without serious risks.

[0264] Validity indicators: Compare the changes in triglyceride, cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol levels, carotid intima-media thickness (IMT), and plaque score before and after the test.

[0265] (6) Technical route

[0266] See Figure 4 。

[0267] 2.2 Intervention study on lung cancer patients

[0268] (1) Lung cancer subjects:

[0269] 92 newly hospitalized lung cancer patients in the Department of Oncology, the First Medical Center of Chinese PLA General Hospital.

[0270] A. Inclusion criteria:

[0271] (a) Age ≥ 18 years old, of any ethnicity and gender.

[0272] (b) Confirmed as lung cancer patients by histopathological examination and scheduled to receive chemotherapy ≥ 3 times.

[0273] (c) Conscious, no serious disorders in major organs, and no metabolic diseases.

[0274] (d) Stable condition and capable of language communication.

[0275] (e) The patient and relatives can understand the purpose of the study and voluntarily participate in this study.

[0276] (f) Voluntarily join the trial.

[0277] B. Exclusion criteria:

[0278] (a) Suffering from chronic liver and kidney insufficiency, cirrhosis, hepatitis, etc.

[0279] (b) The patient already has an infection and fever.

[0280] (c) Those with unstable blood sugar control.

[0281] (d) Patients who are intolerant or allergic to the stereostructured lipid composition that may be used in this study.

[0282] (e) Any factors considered by the researcher as unsuitable for the study.

[0283] C. Criteria for subjects to withdraw from the trial

[0284] (a) Appearing any of the situations in the exclusion criteria.

[0285] (b) Unable to participate in the follow-up as required.

[0286] (c) Serious new-onset diseases or death.

[0287] (d) Voluntary withdrawal or loss to follow-up.

[0288] (e) If the researcher determines that the patient has not complied with the trial procedures or for safety reasons, the subject can be withdrawn.

[0289] (2) Sample size calculation

[0290] The sample size was calculated using the inflammatory level and immune function level as the main outcome indicators. According to the literature (Long H, Yang H, Lin Y, Situ D, Liu W. Fish oil-supplemented parenteral nutrition in patients following esophageal cancer surgery: effect on inflammation and immune function. Nutr Cancer. 2013;65(1):71-5), using G*Power 3.1.9.2 software (Heinrich-Heine University, Germany), with effect size F value = 0.8, α = 0.05, Power(1-β) = 0.90, a total of n = 2, the sample size required for statistical significance (P<0.05) was calculated to be 68 cases. Considering the situation of subject loss to follow-up, according to a 10% loss to follow-up rate, 80 subjects were planned to be recruited, approximately 40 in each group.

[0291] (3) Random grouping

[0292] This study used a single-center randomized controlled study method. The method of subject grouping: The method of random grouping was adopted. Specifically, the random codes QZZ (the stereostructured lipid composition is CZZ, and the control group is DZZ) were generated by the data center; Q(C, D) represents the intervention method (C represents the stereostructured lipid composition group, D represents the control group); ZZ represents the subject number starting from 01. Subjects in group C took stereostructured lipid composition capsules (3 capsules each time, 3 times a day) on the basis of regular nutritional guidance, and the control group was given regular nutritional guidance.

[0293] (4) Main / secondary observation indicators of the study.

[0294] (a) Time for data and information collection: Before the start of the experiment and at the end of the experiment.

[0295] (b) Case data and information content:

[0296] Main indicators:

[0297] Measurement of inflammatory factors: IL-6, C-reactive protein, IL-10, TNF-α, etc.

[0298] Immune indicators: lgA, lgE, lgG, etc.

[0299] Secondary observation indicators:

[0300] ① General conditions: name, gender, age, height, waist circumference, weight, body mass index (BMI), blood pressure, past medical history.

[0301] ② Biochemical tests: blood transaminases, creatinine, urea nitrogen, blood glucose, etc., completed by the Clinical Laboratory Center of our unit.

[0302] ③ Antioxidant indicators: SOD, GSH, MDA, completed by the Clinical Laboratory Center of our unit.

[0303] ④ Chemotherapy adverse reactions, quality of life scores.

[0304] ⑤ Nutrition-related indicators: folic acid, VB12, glycated hemoglobin, hemoglobin, mean corpuscular hemoglobin, etc.

[0305] (4) Safety and effectiveness indicators.

[0306] Safety: The research subjects of this study are newly admitted lung cancer patients in the oncology department. This intervention is a functional nutritional product without toxic or side effects, and nutritional guidance and management are provided. During the hospitalization period, the attending doctor conducts safety monitoring. And all routine blood samplings during the sampling process are non-invasive operations without serious risks.

[0307] Effectiveness indicators: Changes in inflammatory indicators and immune indicators before and after intervention.

[0308] (5) Technical route

[0309] See Figure 5 .

[0310] VI. Statistical Methods

[0311] 1. For population data, a database is established using Access, and the information of each selected patient is entered in a timely manner. The data exported from Access can be preliminarily processed by an Excel spreadsheet, and further statistical analysis is performed using SPSS 26.0.

[0312] 2. Data conforming to a normal distribution are expressed as mean ± standard deviation. Homogeneity of variance analysis is first performed between the two groups, and a t-test is used. Count data are expressed as frequencies, and a chi-square test is used. P < 0.05 indicates that the difference is statistically significant.

[0313] VII. Treatment Plans for Common Adverse Reactions / Severe Adverse Reactions

[0314] The blood samples collected in this study will be strictly operated in accordance with sterile requirements. The collection of samples may have some minor adverse reactions, including short-term pain, etc. There will be no serious adverse reactions.

[0315] 1. Report: Any adverse event must be taken seriously, carefully analyzed, and immediate measures must be taken to protect the safety of the subjects.

[0316] 2. Procedure: Keep detailed records and retest as needed, recording the persistence, outcome, disappearance, etc.

[0317] 3. Follow up on adverse events that have not been resolved and conduct observation and tracking until they are properly resolved or the situation stabilizes.

[0318] 4. Adverse event record form (Table 1)

[0319] Table 1. Adverse event record

[0320]

[0321]

[0322] VIII. Research Results on the Clinical Efficacy Verification of the Cubic-structured Lipid Composition in Patients with Mild Hyperlipidemia

[0323] 1 Research Methods

[0324] A pre- and post-intervention controlled study was conducted. Patients with mild hyperlipidemia who underwent physical examination or received treatment in the outpatient clinic of the General Hospital of the Chinese People's Liberation Army were included. After informed consent, the subjects took three-dimensional structured lipid composition capsules (functional fatty acids such as EPA, DHA, neuraminic acid, γ-linolenic acid, etc. were synthesized by biocatalytic technology to form Sn-2 monoglycerides to form a new three-dimensional structured lipid composition) (3 capsules each time, 3 times a day) on the basis of conventional low-salt and low-fat diet and exercise guidance. After taking it for 2 months, the changes in blood lipid levels (triglycerides, cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol) were observed.

[0325] 2 Research Results:

[0326] 2.1 General Condition of Subjects

[0327] A total of 60 subjects were included in this study. During the intervention period, 3 subjects did not take the medication as required and withdrew from the study, with a total dropout rate of 5.00%. Finally, 57 subjects completed the study (29 males and 28 females), aged 46.83±8.55 years old. The basic characteristics of the subjects are shown in the table below.

[0328] Table 2. Basic characteristics of the subjects

[0329] Indicators Before Intervention (n = 60) After Intervention (n = 57) t P Age 46.48±9.16 46.83±8.55 -0.13 0.901 Height (cm) 165.59±7.48 166.07±7.27 -0.18 0.856 Weight (kg) 70.47±13.21 72.00±13.34 -0.33 0.747 Waist Circumference (cm) 85.47±9.27 86.20±9.67 -0.22 0.829 Systolic Blood Pressure (mmHg) 123.35±14.23 122.73±14.51 0.12 0.904 Diastolic Blood Pressure (mmHg) 87.29±14.34 87.33±14.91 -0.01 0.994

[0330] 2.2 Changes in blood lipid levels

[0331] After 57 subjects supplemented with the stereostructured lipid composition for 2 months, it was found that their serum triglyceride (TG) levels were significantly reduced compared with those before the intervention, while the total cholesterol (TC) level, high-density lipoprotein cholesterol (HDL-C) level, and low-density lipoprotein cholesterol (LDL-C) level did not show significant decreases. See the following table.

[0332] Table 3. Effects on blood lipid levels after intervention

[0333] Indicators Before Intervention (n = 60) After Intervention (n = 57) t P TG (mmol / L) 2.25±2.09 1.89±1.22 -2.14 0.037 TC (mmol / L) 5.79±1.12 5.74±1.27 1.07 0.290 HDL-C (mmol / L) 1.29±0.32 1.23±0.39 0.60 0.553 LDL-C (mmol / L) 3.70±0.96 3.65±1.14 0.13 0.899

[0334] 3 Conclusions

[0335] By long-term supplementation with the stereostructured lipid composition, patients with mild hyperlipidemia can improve their blood lipid levels, especially triglyceride levels, and it can be used as a supplement to reduce the risk of cardiovascular and cerebrovascular diseases.

[0336] IX. Research on the Clinical Efficacy Verification of the Cubic-structured Lipid Composition in Patients with Lung Cancer

[0337] 1. Research methods

[0338] A randomized controlled study was conducted. Non-small cell lung cancer patients newly admitted to the Department of Oncology, the First Medical Center of Chinese PLA General Hospital were included. After obtaining informed consent, on the basis of routine nutritional guidance, the experimental group subjects took stereostructured lipid composition capsules (selecting functional fatty acids such as EPA, DHA, nervonic acid, γ-linolenic acid, etc. to synthesize Sn-2-monoacylglycerol by biocatalytic technology to form a new stereostructured lipid composition) (3 capsules each time, 3 times a day), and the control group was given routine nutritional guidance. After 3 months of administration, changes in inflammatory immune indexes and biochemical detection indexes were observed.

[0339] 2 Research results:

[0340] 2.1 General situation of the subjects

[0341] A total of 92 subjects were included in this study. During the intervention period, 3 subjects in the control group did not take the medicine as required and dropped out of the study, and the total dropout rate was 3.26%. Finally, 89 subjects completed the study. The basic characteristics of the subjects are shown in the following table.

[0342] Table 4. Basic characteristics of the subjects

[0343]

[0344] P*, comparison before and after within the group; P#, comparison between groups; T0, baseline time; T1, 3 months later.

[0345] 2.2 Changes in immune-inflammatory indicators

[0346] After 89 subjects supplemented with the stereostructured lipid composition for 3 months, it was found that the levels of complement C3, IgG, CD4, and CD4 / CD8 in the experimental group were significantly increased compared with those before the intervention, while there were no significant changes in the levels of IgA, IgM, Ig light chain KAP, C-reactive protein, IgE, Ig light chain LAM, and complement C4 (mg / dl). See the following table.

[0347] Table 5. Changes in immune-inflammatory indicators after the intervention

[0348]

[0349]

[0350] P*, comparison before and after within the group; P#, comparison between groups; T0, baseline time; T1, after 3 months.

[0351] 2.3 Changes in blood lipid levels

[0352] After 89 subjects supplemented with the stereostructured lipid composition for 3 months, it was found that the serum triglyceride (TG) level in the experimental group was significantly decreased compared with that before the intervention, and the high-density lipoprotein cholesterol (HDL-C) levels in both groups were significantly increased, while there were no significant changes in the total cholesterol (TC) level and low-density lipoprotein cholesterol (LDL-C) level. See the following table.

[0353] Table 6. Changes in blood lipid levels after the intervention

[0354]

[0355] P*, comparison before and after within the group; P#, comparison between groups; T0, baseline time; T1, after 3 months

[0356] 2.4 Changes in nutrition-related indicator levels

[0357] After 89 subjects supplemented with the stereostructured lipid composition for 3 months, it was found that the serum folic acid level in the experimental group was significantly increased compared with that before the intervention and that of the control group, and the mean corpuscular hemoglobin level in the experimental group was significantly increased compared with that before the intervention, while there were no significant changes in VB12, glycated hemoglobin, and hemoglobin. See the following table.

[0358] Table 7. Effects of nutrition-related indicators after the intervention

[0359]

[0360] 3 Conclusion

[0361] By long-term supplementation with the sterically structured lipid composition, lung cancer patients can improve their immune status, especially the effects on complement C3, IgG levels, CD4, and CD4 / CD8. In addition, it can also reduce the triglyceride levels in lung cancer patients and increase folic acid and mean corpuscular hemoglobin concentration. Therefore, the sterically structured lipid composition can be used as a supplement to improve the immune and nutritional status of lung cancer patients.

[0362] The technical features of the above-described embodiments and examples can be combined in any suitable manner. For the sake of brevity of description, not all possible combinations of the various technical features in the above-described embodiments and examples are described. However, as long as there is no contradiction in the combination of these technical features, it should be considered to be within the scope described in this specification.

[0363] The above-described examples only represent several embodiments of the present invention and are convenient for understanding the technical solutions of the present invention specifically and in detail, but should not be construed as a limitation on the protection scope of the invention patent. It should be noted that for those of ordinary skill in the art, without departing from the concept of the present invention, several modifications and improvements can still be made, and these all belong to the protection scope of the present invention. In addition, it should be understood that after reading the above teachings of the present invention, those skilled in the art can make various changes or modifications to the present invention, and the equivalent forms obtained also fall within the protection scope of this application. It should also be understood that the technical solutions obtained by those skilled in the art through logical analysis, reasoning, or limited experiments based on the technical solutions provided by the present invention are all within the protection scope of the appended claims of the present invention. Therefore, the protection scope of this invention patent should be determined by the content of the appended claims, and the specification and drawings can be used to explain the content of the claims.

Claims

1. A three-dimensional structured lipid, characterized in that, The three-dimensional structured lipid includes a third structured fat and a third antioxidant; By weight, The raw materials for preparing the third structured fat include 3 to 4 parts of a first structured fat, 1 to 2 parts of a second structured fat, 5 to 6 parts of borage seed oil, and a third lipase; The raw materials for preparing the second structured fat include 3 to 40 parts of polyunsaturated fatty acids, 0.2 to 4 parts of a second glycerol, 0.2 to 0.3 parts of water, and a second lipase; The raw materials for preparing the first structured fat include 90 parts of ethyl ester type fish oil, 9 to 13 parts of a first glycerol, a first lipase, and a first antioxidant.

2. The three-dimensional structured lipid according to claim 1, wherein The third antioxidant satisfies one or more of the following conditions: (1) The third antioxidant includes ascorbyl palmitate, astaxanthin oil, or a combination thereof; and, (2) The dosage of the third antioxidant is 0.2 wt‰ - 3 wt‰ of the weight of the third structured fat.

3. The three-dimensional structured lipid according to claim 1, wherein The third structured fat satisfies one or more of the following conditions: 1) The third lipase is an immobilized lipase; optionally, the third lipase is one or more of IMNE-100 immobilized lipase, Novozym immobilized lipase 435, and NS400190 immobilized lipase; and, 2) The dosage of the third lipase is 3 wt% - 5 wt% of the total weight of the first structured fat, the second structured fat, and the borage seed oil.

4. The structured lipid according to any one of claims 1 to 3, characterized in that, The first structured fat satisfies one or more of the following conditions: (Ⅰ) The first antioxidant is astaxanthin oil; and, (Ⅱ) The dosage of the first antioxidant is 0.2 wt‰ - 1.5 wt‰ of the total weight of the ethyl ester type fish oil and the first glycerol; (Ⅲ) The first lipase is an immobilized lipase; optionally, the first lipase is one or more of Novozym immobilized enzyme 435 and IMNE-100 immobilized lipase; and, (Ⅳ) The dosage of the first lipase is 3 wt% - 5 wt% of the total weight of the ethyl ester type fish oil and the glycerol.

5. The structured lipid according to any one of claims 1 to 3, characterized in that, The second structured fat satisfies one or more of the following conditions: Ⅰ) The second lipase is an immobilized lipase; optionally, the second lipase is NS400190; Ⅱ) The dosage of the second lipase is 3 wt% - 5 wt% of the total weight of the polyunsaturated fatty acids and the second glycerol; and, Ⅲ) The polyunsaturated fatty acids are selected from two or more of almond oil, Acer truncatum seed oil, Xanthoceras sorbifolium oil, pine seed oil, evening primrose oil, and blackcurrant oil.

6. The preparation method of the three-dimensional structured lipid according to any one of claims 1 to 5, characterized in that, The preparation method includes the following steps: Preparing the first structured fat with the ethyl ester type fish oil, the first glycerol, the first lipase, and the first antioxidant; Preparing the second structured fat with the polyunsaturated fatty acids, the second glycerol, the water, and the second lipase; Preparing the third structured fat with the first structured fat, the second structured fat, the borage seed oil, and the third lipase; And, Mixing the third structured fat and the third antioxidant to prepare the three-dimensional structured lipid.

7. The method for preparing the three-dimensional structured lipid according to claim 6, characterized in that, The preparation method satisfies one or more of the following conditions: (A) In the process of preparing the first structured fat, the conditions for the transesterification reaction involving the first lipase include: a vacuum degree of 50 Pa - 200 Pa, a temperature of 55°C - 65°C, and a time of 22 h - 24 h; (B) In the process of preparing the second structured fat, the conditions for the transesterification reaction involving the second lipase include: normal pressure, a temperature of 55°C - 65°C, and a time of 5 h - 24 h; (C) In the process of preparing the third structured fat, the conditions for the transesterification reaction involving the third lipase include: a vacuum degree of 50 Pa - 200 Pa, a temperature of 55°C - 65°C, and a time of 3 h - 24 h; and (D) The third structured fat is treated with absolute ethanol and then mixed with the third antioxidant; the absolute ethanol treatment satisfies one or more of the following conditions: D1) The volume ratio of the third structured fat to the absolute ethanol is 1:(0.5 - 1.5); and, D2) Normal pressure, a temperature higher than 65°C, and a time of 8 h - 11 h; further, the temperature of the thermal reaction is 68°C - 75°C.

8. A three-dimensional structured lipid composition, characterized in that, Comprising: The three-dimensional structured lipid according to any one of claims 1 to 5; and, Food-grade or pharmaceutically acceptable excipients.

9. The three-dimensional structured lipid composition according to claim 8, characterized in that, The three-dimensional structured lipid composition is in the form of a granule, a capsule, a gel candy, a fluid type, or an emulsion; Optionally, the capsule is a capsule within a capsule, and the chip of the capsule within a capsule comprises the three-dimensional structured lipid; further optionally, the chip of the capsule within a capsule further comprises one or more of earthworm protein peptide, sea cucumber peptide, marine fish protein peptide, wheat oligopeptide, collagen peptide, and γ-aminobutyric acid.

10. A method for preparing the three-dimensional structured lipid composition according to any one of claims 8 to 9, characterized in that, The preparation method comprises the following steps: Providing the three-dimensional structured lipid according to any one of claims 1 to 5, or preparing the three-dimensional structured lipid according to the preparation method according to any one of claims 6 to 7; and, Preparing a three-dimensional structured lipid composition with the three-dimensional structured lipid and the excipients.

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