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WO2025148196A1 - Use of microalgae extract for promoting absorption and permeation through blood-brain barrier of fatty acid and composition thereof - Google Patents

Use of microalgae extract for promoting absorption and permeation through blood-brain barrier of fatty acid and composition thereof

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Publication number
WO2025148196A1
WO2025148196A1 PCT/CN2024/090840 CN2024090840W WO2025148196A1 WO 2025148196 A1 WO2025148196 A1 WO 2025148196A1 CN 2024090840 W CN2024090840 W CN 2024090840W WO 2025148196 A1 WO2025148196 A1 WO 2025148196A1
Authority
WO
WIPO (PCT)
Prior art keywords
fatty acids
microalgae extract
acid
microalgae
extract
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
PCT/CN2024/090840
Other languages
French (fr)
Chinese (zh)
Inventor
张颖
俞威
刘海翔
李永鑫
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Xiaozao Technology Anji Co Ltd
Original Assignee
Xiaozao Technology Anji Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Xiaozao Technology Anji Co Ltd filed Critical Xiaozao Technology Anji Co Ltd
Publication of WO2025148196A1 publication Critical patent/WO2025148196A1/en
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

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Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/02Algae
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23LFOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/185Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19Carboxylic acids, e.g. valproic acid
    • A61K31/20Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/185Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19Carboxylic acids, e.g. valproic acid
    • A61K31/20Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
    • A61K31/201Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids having one or two double bonds, e.g. oleic, linoleic acids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/185Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19Carboxylic acids, e.g. valproic acid
    • A61K31/20Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
    • A61K31/202Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids having three or more double bonds, e.g. linolenic
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66Microorganisms or materials therefrom
    • A61K35/74Bacteria
    • A61K35/748Cyanobacteria, i.e. blue-green bacteria or blue-green algae, e.g. spirulina
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/02Algae
    • A61K36/04Rhodophycota or rhodophyta (red algae), e.g. Porphyra
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/02Algae
    • A61K36/05Chlorophycota or chlorophyta (green algae), e.g. Chlorella
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/14Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/22Anxiolytics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/24Antidepressants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/28Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00Drugs for disorders of the senses
    • A61P27/02Ophthalmic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00Drugs for disorders of the senses
    • A61P27/02Ophthalmic agents
    • A61P27/10Ophthalmic agents for accommodation disorders, e.g. myopia
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/04Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/10Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/12Antihypertensives
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23VINDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00Food compositions, function of food ingredients or processes for food or foodstuffs

Definitions

  • the present disclosure relates to the field of biomedicine industry, and specifically to an application of a microalgae extract and a composition thereof for promoting fatty acid absorption and crossing the blood-brain barrier.
  • the blood-brain barrier is a highly selective barrier located between the endothelial cells of brain blood vessels that controls the entry of substances from the blood into brain tissue. This barrier is essential for protecting the brain from harmful substances, but it also restricts the entry of certain beneficial substances (such as essential fatty acids) into the brain.
  • Essential fatty acids are essential for brain development and function.
  • DHA docosahexaenoic acid
  • studies have shown that DHA plays a significant role in the development of children's brains and the maintenance of adult brain function. Adequate DHA levels help reduce cognitive decline and reduce the risk of neurodegenerative diseases.
  • the brain since the brain itself cannot synthesize new DHA, it means that the brain must absorb DHA from the blood through the blood-brain barrier. The efficiency of DHA crossing the BBB is low, and its concentration in the brain is often limited.
  • the commonly used method to increase the fatty acid content in the human body is to provide the user with a preparation containing fatty acids to increase the fatty acid content in the user's body.
  • the body's own absorption rate of fatty acids is often not high, and only a small part of the fatty acids in the preparation may enter the human body.
  • the present disclosure is made in view of the above-mentioned prior art conditions, and its purpose is to provide a microalgae extract and application of a composition thereof that can promote fatty acid absorption and cross the blood-brain barrier.
  • the first aspect of the present disclosure provides a use of a microalgae extract in promoting fatty acid absorption and/or fatty acid crossing the blood-brain barrier, wherein the microalgae extract contains polar lipids, the polar lipids account for 30% to 99.9% of the microalgae extract, and the fatty acids are fatty acids that are not native to the microalgae extract.
  • microalgae extracts can promote fatty acid absorption and promote fatty acids to cross the blood-brain barrier, wherein polar lipids in microalgae extracts play an important role in helping fatty acids cross the blood-brain barrier (BBB).
  • BBB blood-brain barrier
  • polar lipids may be by increasing the solubility of fatty acids and improving their transport efficiency in the blood, and promoting fatty acids and polar lipids to synthesize hemolytic polar lipids in the body, thereby enhancing the transmembrane transport of fatty acids.
  • a microalgae extract for use in promoting fatty acid absorption and crossing the blood-brain barrier.
  • the microalgae extract of the present disclosure in combination with fatty acids, it can help promote the user's absorption of fatty acids, especially increase the fatty acid content in the heart and brain.
  • the microalgae extract contains phospholipids, glycolipids and/or betaine esters.
  • the microalgae extract is rich in phospholipids, glycolipids and/or betaine esters, wherein some of the phospholipids and betaine esters are lysophospholipids and lysobetaine esters, and most of the lysophospholipids and lysobetaine esters can bind to the active transport protein Mfsd2a on vascular cells and be directly transported, thereby helping to improve the absorption of fatty acids and the efficiency of fatty acids crossing the blood-brain barrier; other phospholipids and betaine esters can be converted into lysophospholipids and lysobetaine esters in the small intestine and/or liver and then transported and absorbed.
  • the microalgae extract is physically mixed with a raw material containing fatty acids or lipid derivatives containing fatty acids and then used, and the mass ratio of the microalgae extract to the fatty acids in the raw material is (1-50):(1-50), and the fatty acids are any one or more of palmitic acid (C16:0), palmitoleic acid (C16:1), stearic acid (C18:0), oleic acid (C18:1n9c), linoleic acid (C18:2n6c), ⁇ -linolenic acid (C18:3n3), arachidonic acid (C20:4n6), eicosapentaenoic acid (C20:5n3), docosahexaenoic acid (C22:6n3) and docosapentaenoic acid (C22:5n6).
  • the fatty acids are any one or more of palmitic acid (C16:0), palmitoleic acid
  • the microalgae extract and the raw material containing fatty acids or lipid derivatives are physically mixed, they reach the small intestine and/or liver through digestion and absorption.
  • the fatty acids or lipid derivatives in the raw materials are assembled into lysophospholipids and lysobetaine esters in the small intestine and/or liver, and can be transported and absorbed by the brain.
  • the scheme of using after physical mixing can simplify the process, improve preparation efficiency and reduce costs, and does not require the addition of additional process additives, which can reduce the risk of solvent residues. Therefore, the microalgae extract can promote the absorption of fatty acids and cross the blood-brain barrier to promote the absorption of fatty acids or lipid derivatives by users.
  • the microalgae extract is physically mixed with a raw material containing fatty acids or lipid derivatives containing fatty acids and then used, the mass ratio of the microalgae extract to the fatty acids in the raw material is (1 to 50): (1 to 50), and the lipid derivative is selected from any one or more of glyceride fatty acids, ethyl ester fatty acids, phospholipid fatty acids, glycolipid fatty acids, sterol ester fatty acids and/or sphingolipid fatty acids.
  • the microalgae extract and the raw material containing fatty acids or lipid derivatives are physically mixed, they reach the small intestine and/or liver through digestion and absorption.
  • the fatty acids or lipid derivatives in the raw materials are assembled into lysophospholipids and lysobetaine esters in the small intestine and/or liver, and can be transported and absorbed by the brain.
  • the scheme of using after physical mixing can simplify the process, improve preparation efficiency and reduce costs, and does not require the addition of additional process additives, which can reduce the risk of solvent residues. Therefore, the microalgae extract can promote the absorption of fatty acids and cross the blood-brain barrier to promote the absorption of fatty acids or lipid derivatives by users.
  • the microalgae extract is from blue algae, green algae or red algae.
  • the microalgae extract is from any one or more of Nannochloropsis, Heteroglea, Phaeochromis triangularis, Nitzschia crescentica, Haematococcus pluvialis, Euglena, Spirulina, Nostoc sphericalensis, Chlorella, Dunaliella and Chlamydomonas reinhardtii.
  • the second aspect of the present disclosure provides an application of a microalgae extract in increasing the fatty acid content in the heart, characterized in that the microalgae extract contains polar lipids, the polar lipids account for 30% to 99.9% of the microalgae extract, and the fatty acids are fatty acids that are not inherent in the microalgae extract.
  • the polar lipids in the microalgae extract play an important role in helping fatty acid absorption and promoting fatty acids to cross the blood-brain barrier, and can help increase the fatty acid content in the heart.
  • an application of a microalgae extract in increasing the fatty acid content in the heart can be provided.
  • the microalgae extract contains phospholipids, glycolipids and/or betaine esters.
  • the microalgae extract is physically mixed with a raw material containing fatty acids or lipid derivatives containing fatty acids and then used, and the mass ratio of the microalgae extract to the fatty acids in the raw material is (1-50):(1-50), and the fatty acids are any one or more of palmitic acid (C16:0), palmitoleic acid (C16:1), stearic acid (C18:0), oleic acid (C18:1n9c), linoleic acid (C18:2n6c), ⁇ -linolenic acid (C18:3n3), arachidonic acid (C20:4n6), eicosapentaenoic acid (C20:5n3), docosahexaenoic acid (C22:6n3) and docosapentaenoic acid (C22:5n6).
  • the fatty acids are any one or more of palmitic acid (C16:0), palmitoleic acid
  • the microalgae extract is physically mixed with a raw material containing fatty acids or lipid derivatives containing fatty acids and then used, the mass ratio of the microalgae extract to the fatty acids in the raw material is (1 to 50): (1 to 50), and the lipid derivative is selected from any one or more of glyceride fatty acids, ethyl ester fatty acids, phospholipid fatty acids, glycolipid fatty acids, sterol ester fatty acids and/or sphingolipid fatty acids.
  • the microalgae extract is from blue algae, green algae or red algae.
  • the microalgae extract is from any one or more of Nannochloropsis, Heteroglea, Phaeochromis triangularis, Nitzschia crescentica, Haematococcus pluvialis, Euglena, Spirulina, Nostoc sphericalensis, Chlorella, Dunaliella and Chlamydomonas reinhardtii.
  • the third aspect of the present disclosure provides an application of a microalgae extract in increasing the fatty acid content in the brain, characterized in that the microalgae extract contains polar lipids, the polar lipids account for 30% to 99.9% of the microalgae extract, and the fatty acids are fatty acids that are not inherent in the microalgae extract.
  • the polar lipids in the microalgae extract play an important role in helping fatty acid absorption and promoting fatty acids to cross the blood-brain barrier, and can help increase the fatty acid content in the brain.
  • an application of a microalgae extract in increasing the fatty acid content in the brain can be provided.
  • the microalgae extract contains phospholipids, glycolipids and/or betaine esters.
  • the microalgae extract is physically mixed with a raw material containing fatty acids or lipid derivatives containing fatty acids and then used, and the mass ratio of the microalgae extract to the fatty acids in the raw material is (1-50):(1-50), and the fatty acids are any one or more of palmitic acid (C16:0), palmitoleic acid (C16:1), stearic acid (C18:0), oleic acid (C18:1n9c), linoleic acid (C18:2n6c), ⁇ -linolenic acid (C18:3n3), arachidonic acid (C20:4n6), eicosapentaenoic acid (C20:5n3), docosahexaenoic acid (C22:6n3) and docosapentaenoic acid (C22:5n6).
  • the fatty acids are any one or more of palmitic acid (C16:0), palmitoleic acid
  • the microalgae extract is physically mixed with a raw material containing fatty acids or lipid derivatives containing fatty acids and then used, the mass ratio of the microalgae extract to the fatty acids in the raw material is (1 to 50): (1 to 50), and the lipid derivative is selected from any one or more of glyceride fatty acids, ethyl ester fatty acids, phospholipid fatty acids, glycolipid fatty acids, sterol ester fatty acids and/or sphingolipid fatty acids.
  • the microalgae extract is from blue algae, green algae or red algae.
  • the microalgae extract is from any one or more of Nannochloropsis, Heteroglea, Phaeochromis triangularis, Nitzschia crescentica, Haematococcus pluvialis, Euglena, Spirulina, Nostoc sphericalensis, Chlorella, Dunaliella and Chlamydomonas reinhardtii.
  • the fourth aspect of the present disclosure provides a composition comprising a microalgae extract and fatty acids not contained in the microalgae extract, wherein the microalgae extract contains polar lipids, and the polar lipids account for 30% to 99.9% of the microalgae extract.
  • the microalgae extract containing polar lipids can promote fatty acid absorption and cross the blood-brain barrier, so the composition containing the microalgae extract and fatty acids can have a strong absorption rate and can have a better effect when used, especially, it can significantly increase the content of total fatty acids and target fatty acids in the brain and heart.
  • the microalgae extract contains phospholipids, glycolipids and/or betaine esters.
  • the microalgae extract is physically mixed with a raw material containing fatty acids or lipid derivatives containing fatty acids and then used, and the mass ratio of the microalgae extract to the fatty acids in the raw material is (1 to 50): (1 to 50), and the lipid derivative is selected from any one or more of glyceride fatty acids, ethyl ester fatty acids, phospholipid fatty acids, glycolipid fatty acids, sterol ester fatty acids and/or sphingolipid fatty acids.
  • the microalgae extract is from blue algae, green algae or red algae.
  • the microalgae extract is from any one or more of Nannochloropsis, Heteroglea, Phaeochromis triangularis, Nitzschia crescentus, Haematococcus pluvialis, Euglena, Spirulina, Nostoc sphericalensis, Chlorella, Dunaliella and Chlamydomonas reinhardtii.
  • the composition is food, medicine, health product, animal nutrition or veterinary medicine, and the composition also contains auxiliary materials permitted for use by pharmacy, ordinary food, health food or special medical food regulations.
  • the composition of the fourth aspect of the present disclosure is used in the preparation of a preparation for improving brain function and/or improving eye function.
  • the microalgae extract in the composition can promote the absorption of fatty acids by the human body, thereby helping to improve brain function and improve eye function.
  • the preparation for improving brain function includes any one or more of the preparations for improving cognitive dysfunction, alleviating neurodegenerative lesions, alleviating attention deficit hyperactivity disorder, alleviating depression, alleviating anxiety, alleviating brain inflammation, developing intelligence in young children, improving Alzheimer's disease and related symptoms, and improving depression.
  • the microalgae extract in the composition can promote the absorption of fatty acids by the human body, thereby being able to help improve cognitive dysfunction, alleviating neurodegenerative lesions, alleviating attention deficit hyperactivity disorder, alleviating depression, alleviating anxiety, alleviating brain inflammation, developing intelligence in young children, improving Alzheimer's disease and related symptoms, and improving depression.
  • the preparation for improving eye function includes any one or more of preparations for alleviating dry eye, reducing retinopathy, reducing corneal problems, alleviating age-related macular degeneration, and preventing and treating children's vision development problems.
  • the microalgae extract in the composition can promote the absorption of fatty acids by the human body, thereby being able to help alleviate dry eye, reduce retinopathy, reduce corneal problems, alleviate age-related macular degeneration, and prevent and treat children's vision development problems.
  • FIG. 1 is a schematic diagram showing a method for extracting a microalgae extract according to an example of the present disclosure.
  • FIG. 2 is a volcano plot showing the proteomic and bioinformatics analysis of Example 1 and a blank group according to the examples of the present disclosure.
  • FIG. 3 is a heat map showing the proteomic and bioinformatics analysis of Example 1 and a blank group according to the examples of the present disclosure.
  • FIG. 4 is a schematic diagram showing pathways identified by GO enrichment analysis of proteomics and bioinformatics analysis of Example 1 and a blank group according to the examples of the present disclosure.
  • the present disclosure provides an application of a microalgae extract in promoting fatty acids to cross the blood-brain barrier.
  • the microalgae extract can promote fatty acids to cross the blood-brain barrier. Therefore, an application of a microalgae extract in promoting fatty acids to cross the blood-brain barrier can be provided.
  • the microalgae extract of the present disclosure in combination with fatty acids, it can help to increase the fatty acid content in the brain.
  • the present disclosure can also provide an application of a microalgae extract in the preparation of a preparation that promotes fatty acids to cross the blood-brain barrier.
  • the microalgae extract can also be referred to as an algae extract.
  • the present disclosure also provides an application of a microalgae extract in promoting fatty acid absorption.
  • the microalgae extract can promote fatty acid absorption, and therefore, an application of a microalgae extract in promoting fatty acid absorption can be provided.
  • an application of a microalgae extract in promoting fatty acid absorption can be provided.
  • the present disclosure can also provide an application of a microalgae extract in the preparation of a preparation for promoting fatty acid absorption.
  • "promoting fatty acid absorption” means promoting the user to absorb fatty acids.
  • the present disclosure also provides an application of a microalgae extract in increasing the fatty acid content in the brain.
  • the microalgae extract can promote fatty acid absorption and promote fatty acids to cross the blood-brain barrier, which can help increase the fatty acid content in the heart. Therefore, an application of a microalgae extract in increasing the fatty acid content in the heart can be provided.
  • the present disclosure can also provide an application of a microalgae extract in preparing a preparation for increasing the fatty acid content in the heart.
  • the present disclosure also provides an application of a microalgae extract in increasing the fatty acid content in the brain.
  • the microalgae extract can promote fatty acid absorption and promote fatty acids to cross the blood-brain barrier, which can help increase the fatty acid content in the brain. Therefore, an application of a microalgae extract in increasing the fatty acid content in the brain can be provided.
  • the present disclosure can also provide an application of a microalgae extract in preparing a preparation for increasing the fatty acid content in the brain.
  • the present disclosure also provides a composition, which includes microalgae extracts and fatty acids that are naturally present in non-microalgae extracts (hereinafter referred to as non-natural fatty acids).
  • non-natural fatty acids fatty acids that are naturally present in non-microalgae extracts
  • the composition containing microalgae extracts and fatty acids can have a strong absorption rate and can have a better effect when used. In particular, it can significantly increase the content of total fatty acids and target fatty acids in the brain and heart.
  • the composition has a strong absorption rate means that when the composition is applied to the user, the user has a good absorption efficiency of the composition.
  • the present disclosure also provides a microalgae extract that promotes fatty acids to cross the blood-brain barrier.
  • the microalgae extract may contain polar lipids.
  • the polar lipids in the microalgae extract play an important role in helping fatty acids cross the blood-brain barrier (BBB), thereby providing a microalgae extract that can promote fatty acids to cross the blood-brain barrier.
  • BBB blood-brain barrier
  • the microalgae extract may contain polar lipids.
  • the microalgae extract can promote the absorption of fatty acids and cross the blood-brain barrier, wherein polar lipids play an important role in helping fatty acids cross the blood-brain barrier (BBB).
  • BBB blood-brain barrier
  • polar lipids may be by increasing the solubility of fatty acids and improving their transport efficiency in the blood, and promoting the synthesis of lysotropic polar lipids by fatty acids and polar lipids in the body, thereby enhancing the transmembrane transport of fatty acids.
  • fatty acid refers not only to fatty acid in the general sense, but also to other substances containing fatty acid groups.
  • fatty acid can be unmodified free fatty acid, modified fatty acid, and fatty acid connected to its lipid structure.
  • fatty acid of the present disclosure can also include fatty acid connected to triglyceride or polar lipid.
  • the microalgae extract may contain any one or more of DGTS: diacylglycerol trimethyl homoserine, LDGTS: lysodiacylglycerol trimethyl homoserine, Cer: ceramide, MGDG: monogalactosyl diacylglycerol, DGDG: digalactosyl diacylglycerol, SQDG: thioisosorhamnosyl diacylglycerol, DGGA: diacylglycerol glucuronic acid, CE: cholesterol ester, CL: cardiolipin, LPA: lysophosphatidic acid, LPE: lysophosphatidylethanolamine, LPG: lysophosphatidylglycerol, LPC: lysophosphatidylcholine, LPI: lysophosphatidylinositol, PE: phosphatidylethanolamine, PG: phosphatidylglycerol
  • the microalgae extract may contain any one or more of FFA: free fatty acids, MG: monoglycerides, DG: diglycerides, and TG: triglycerides.
  • the microalgae extract may contain phospholipids, glycolipids and/or betaine esters.
  • the microalgae extract is rich in phospholipids, glycolipids and/or betaine esters, wherein some of the phospholipids and betaine esters are lysophospholipids and lysobetaine esters, most of which can bind to the active transport protein Mfsd2a on vascular cells and be directly transported, thereby helping to improve the absorption of fatty acids and the efficiency of fatty acids crossing the blood-brain barrier; other phospholipids and betaine esters can be converted into lysophospholipids and lysobetaine esters in the small intestine and/or liver and then transported and absorbed.
  • the phospholipids may include lysophospholipids, thereby facilitating fatty acid absorption and crossing the blood-brain barrier.
  • the betaine esters may include lysobetaine esters, thereby facilitating fatty acid absorption and crossing the blood-brain barrier.
  • polar lipids may include phospholipids, glycolipids and/or betaine esters.
  • a portion of phospholipids and betaine esters may be lysophospholipids and lysobetaine esters.
  • the microalgae extract is rich in lysophospholipids and lysobetaine esters, most of which can bind to the active transport protein Mfsd2a on vascular cells and be directly transported, thereby helping to improve the efficiency of fatty acids crossing the blood-brain barrier; other phospholipids and betaine esters can be converted into lysophospholipids and lysobetaine esters in the small intestine and/or liver and then transported and absorbed.
  • the microalgae extract may contain lysophospholipids and lysobetaine esters.
  • the molecules transported by the active transporter Mfsd2a on vascular cells must have two structural characteristics: one is to have a polar head containing both positively charged groups and negatively charged groups, and the other is to have a non-polar long chain of at least 14 carbons. Lysophospholipids and lysobetaine esters in the microalgae extracts meet this structural feature.
  • the mixed micelles formed by lysophospholipids and lysobetaine esters have a smaller diameter, so compared with other emulsifiers, they can further increase the contact area of lipase and improve digestibility. At the same time, the nutrients in the mixed micelles are also more easily absorbed by the small intestine, thereby optimizing the absorption efficiency of nutrients.
  • composition containing microalgae extract and fatty acid provided by the present disclosure can also be used for Alzheimer's disease indication research. Alzheimer's disease and its related symptoms can be improved.
  • present disclosure also provides a use of a microalgae extract in preparing a preparation for improving Alzheimer's disease and its related symptoms.
  • composition containing the microalgae extract and fatty acids provided by the present invention can also provide sports nutrition, promote the absorption of DHA by the athlete's brain and improve sports performance.
  • the present disclosure also provides a method for preparing a composition, comprising the following steps: physically mixing fatty acids and microalgae extracts to obtain a composition.
  • the fatty acids are fatty acids that are not contained in the microalgae extracts.
  • the microalgae extracts disclosed in the present disclosure have the effect of promoting fatty acids to cross the blood-brain barrier, and only physically mixing the fatty acids and microalgae extracts can allow the composition to automatically synthesize hemolytic polar lipids after entering the small intestine and/or liver and other parts. Therefore, the present disclosure can provide a method for preparing a composition with a simple synthesis process, which does not require the addition of additional process additives and can reduce the risk of solvent residues.
  • Example 1 Using corn oil as a solvent, the microalgae extract and the raw material containing 70% DHA were physically mixed to obtain the composition of Example 1, wherein the mass ratio of the microalgae extract to the raw material containing 70% DHA was 1:2.
  • the raw material containing 70% DHA was a commercially available refined microalgae oil raw material ( DHA refined microalgae oil, Xiaozao Technology (Anji) Co., Ltd.
  • Corn oil was used as a solvent, and microalgae extract was added, wherein the mass of the added microalgae extract was the same as that in Example 2.
  • Corn oil is used as a solvent, and phosphatidylserine and a raw material containing 70% DHA are added and physically mixed, wherein the mass ratio of phosphatidylserine to the raw material containing 70% DHA is 1:1.
  • Proteolysis and labeling According to the protein concentration, take 50 ⁇ g protein and add DTT to a final concentration of 5mM, incubate at 55°C for 30 minutes, then add iodoacetamide to 10mM at room temperature and protect from light for 15 minutes. Add 6 times acetone and store at -20°C for more than four hours, then collect the precipitate by centrifugation at 8000 ⁇ g for 10 minutes. The precipitate is re-dissolved with 200mM TEAB, and 1/50 mass of 1mg/mL Trypsin-TPCK is added and digested at 37°C overnight. After enzymatic hydrolysis, the sample is lyophilized, and then 100mM TEAB is added for TMT labeling. Finally, 5% hydroxylamine is added to terminate the reaction and lyophilized for storage.
  • Liquid chromatography separation Agilent 1100HPLC and Zorbax Extend-C18 narrow-bore columns were used to separate the samples. According to the set gradient elution conditions, the samples were collected into centrifuge tubes from 8 to 54 minutes and stored in the freezer.
  • LC-MS analysis Peptide separation was performed using an EASY-nLC 1200 system and subsequent analysis was performed using a Q Exactive HF mass spectrometer. The resolution and maximum injection time for primary MS and MS/MS were set to scan and perform data-dependent analysis on the selected peptides.
  • Example 1 and Example 2 can significantly increase the content of total fatty acids and several important fatty acids in brain tissue, such as palmitic acid (C16:0), stearic acid (C18:0), oleic acid (C18:1n9c), docosahexaenoic acid (C22:6n3, DHA), and arachidonic acid (C20:4n6).
  • This shows that mixing the microalgae extract with the raw material containing fatty acids can promote the passage of fatty acids through the blood-brain barrier and significantly increase the total fatty acids and target fatty acid content in the brain.
  • Example 1 Compared with Comparative Example 4, Example 1 also has significant differences in increasing the fatty acid content in brain tissue, especially DHA, indicating that the polar lipids contained in the microalgae extract have a better effect on DHA crossing the blood-brain barrier than the phospholipids in krill oil. This may be because the microalgae extract contains more hemolytic polar lipid components, while the polar lipids mainly contained in krill oil are phosphatidylcholine (PC). The EPA and DHA in the krill oil are located at the SN2 position of phosphatidylcholine (PC).
  • PC phosphatidylcholine
  • lysopolar lipids can be transported without the need for phospholipase A2 (PLA2) to convert them into LPC, and are therefore more likely to cross the blood-brain barrier by binding to the active transporter Mfsd2a.
  • PHA2 phospholipase A2
  • Example 1 has a more significant effect on increasing the total fatty acids and target fatty acids in brain tissue than Example 2.
  • the ratio of microalgae extract to the raw material containing 70% DHA is 0.5:1
  • the increase in fatty acid content in the mouse brain, especially DHA is more significant than when the ratio is 1:1. This shows that when crossing the blood-brain barrier, the more the amount of carrier, the better the effect.
  • the microalgae extract can promote the absorption of fatty acids, and can promote various essential fatty acids to cross the blood-brain barrier in an approximately equivalent manner, and keep the increase ratio of these fatty acids consistent, without changing the composition of brain lipids, and help maintain the homeostasis of brain lipids.
  • the composition containing microalgae extract and fatty acids has the potential to increase the content of various fatty acids and total fatty acids in the heart.
  • the present invention can provide an application of a microalgae extract and a composition thereof that can promote fatty acid absorption and crossing the blood-brain barrier.
  • a microalgae extract disclosed in the present invention in combination with fatty acids, it can help promote the user's absorption of fatty acids, especially increase the fatty acid content in the heart and brain.

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Abstract

Provided is use of a microalgae extract for promoting the absorption and permeation through the blood-brain barrier of a fatty acid and a composition thereof. The microalgae extract comprises a polar lipid in a proportion of 30% to 99.9%. The fatty acid is a fatty acid contained in a non-microalgae extract. The provided use of the microalgae extract for promoting the absorption and permeation through the blood-brain barrier of a fatty acid and the composition thereof can, by means of the cooperation of the microalgae extract and the fatty acid, promote the absorption of the fatty acid in a user, and particularly, increase the content of the fatty acid in the heart and the brain.

Description

一种促进脂肪酸吸收及跨越血脑屏障的微藻提取物及其组合物的应用Application of a microalgae extract for promoting fatty acid absorption and crossing the blood-brain barrier and a composition thereof 技术领域Technical Field

本公开涉及生物医药产业领域,具体涉及一种促进脂肪酸吸收及跨越血脑屏障的微藻提取物及其组合物的应用。The present disclosure relates to the field of biomedicine industry, and specifically to an application of a microalgae extract and a composition thereof for promoting fatty acid absorption and crossing the blood-brain barrier.

背景技术Background Art

血脑屏障(BBB)是一种高度选择性的屏障,它位于脑血管内皮细胞之间,控制物质从血液进入脑组织。这个屏障对于保护脑部免受有害物质侵害至关重要,但同时也限制了某些有益物质(例如必需脂肪酸)进入大脑。The blood-brain barrier (BBB) is a highly selective barrier located between the endothelial cells of brain blood vessels that controls the entry of substances from the blood into brain tissue. This barrier is essential for protecting the brain from harmful substances, but it also restricts the entry of certain beneficial substances (such as essential fatty acids) into the brain.

必需脂肪酸(例如Omega-3和Omega-6脂肪酸)对于脑部发育和功能至关重要,以DHA(二十二碳六烯酸)为例,有研究表明,DHA对于儿童大脑发育和成人脑功能的维持具有显著作用,充足的DHA水平有助于减少认知退化和降低患神经退行性疾病的风险。但由于大脑本身不能合成新的DHA,这意味着大脑必须通过血脑屏障从血液中吸收DHA,而DHA跨BBB的效率较低,其在脑部的浓度往往受限。Essential fatty acids (such as Omega-3 and Omega-6 fatty acids) are essential for brain development and function. Taking DHA (docosahexaenoic acid) as an example, studies have shown that DHA plays a significant role in the development of children's brains and the maintenance of adult brain function. Adequate DHA levels help reduce cognitive decline and reduce the risk of neurodegenerative diseases. However, since the brain itself cannot synthesize new DHA, it means that the brain must absorb DHA from the blood through the blood-brain barrier. The efficiency of DHA crossing the BBB is low, and its concentration in the brain is often limited.

目前,常用的增加人体内脂肪酸含量的手段是向使用者提供含有脂肪酸的制剂从而来提高使用者体内的脂肪酸含量,但是,人体自身对脂肪酸的吸收率往往不高,制剂中的脂肪酸可能仅有少部分脂肪酸能进入人体。Currently, the commonly used method to increase the fatty acid content in the human body is to provide the user with a preparation containing fatty acids to increase the fatty acid content in the user's body. However, the body's own absorption rate of fatty acids is often not high, and only a small part of the fatty acids in the preparation may enter the human body.

发明内容Summary of the invention

本公开有鉴于上述现有技术的状况而完成,其目的在于提供一种可促进脂肪酸吸收及跨越血脑屏障的微藻提取物及其组合物的应用。The present disclosure is made in view of the above-mentioned prior art conditions, and its purpose is to provide a microalgae extract and application of a composition thereof that can promote fatty acid absorption and cross the blood-brain barrier.

为此,本公开的第一方面提供一种微藻提取物在促进脂肪酸吸收和/或脂肪酸跨越血脑屏障中的应用,所述微藻提取物含有极性脂,所述极性脂在所述微藻提取物中占比为30%至99.9%,所述脂肪酸为非所述微藻提取物中自带的脂肪酸。To this end, the first aspect of the present disclosure provides a use of a microalgae extract in promoting fatty acid absorption and/or fatty acid crossing the blood-brain barrier, wherein the microalgae extract contains polar lipids, the polar lipids account for 30% to 99.9% of the microalgae extract, and the fatty acids are fatty acids that are not native to the microalgae extract.

在本公开的第一方面中,验证了微藻提取物可促进脂肪酸吸收和促进脂肪酸跨越血脑屏障,其中,微藻提取物中的极性脂在帮助脂肪酸跨越血脑屏障(BBB)中发挥着重要作用,申请人在研究中发现,极性脂可能是通过增加脂肪酸的溶解性和改善其在血液中的运输效率,并促进脂肪酸与极性脂在体内合成溶血极性脂质,从而增强脂肪酸的跨膜运输。由此,能够提供一种微藻提取物在促进脂肪酸吸收及跨越血脑屏障中的应用。通过将本公开的微藻提取物与脂肪酸配合使用,能够有助于促进使用者吸收脂肪酸,特别是提高心脏和大脑中的脂肪酸含量。In the first aspect of the present disclosure, it is verified that microalgae extracts can promote fatty acid absorption and promote fatty acids to cross the blood-brain barrier, wherein polar lipids in microalgae extracts play an important role in helping fatty acids cross the blood-brain barrier (BBB). The applicant has found in the study that polar lipids may be by increasing the solubility of fatty acids and improving their transport efficiency in the blood, and promoting fatty acids and polar lipids to synthesize hemolytic polar lipids in the body, thereby enhancing the transmembrane transport of fatty acids. Thus, it is possible to provide a microalgae extract for use in promoting fatty acid absorption and crossing the blood-brain barrier. By using the microalgae extract of the present disclosure in combination with fatty acids, it can help promote the user's absorption of fatty acids, especially increase the fatty acid content in the heart and brain.

在本公开的第一方面的应用中,可选地,所述微藻提取物含有磷脂、糖脂和/或甜菜碱酯。在这种情况下,微藻提取物含有丰富的磷脂、糖脂和/或甜菜碱酯,其中磷脂和甜菜碱酯中部分是溶血磷脂和溶血甜菜碱酯,大部分的溶血磷脂和溶血甜菜碱酯能够与血管细胞上的主动转运蛋白Mfsd2a结合而直接被转运,从而有助于提高脂肪酸吸收和脂肪酸跨越血脑屏障的效率;其他的磷脂和甜菜碱酯能够在小肠和/或肝脏等部位转化成溶血磷脂和溶血甜菜碱酯再被转运吸收。In the application of the first aspect of the present disclosure, optionally, the microalgae extract contains phospholipids, glycolipids and/or betaine esters. In this case, the microalgae extract is rich in phospholipids, glycolipids and/or betaine esters, wherein some of the phospholipids and betaine esters are lysophospholipids and lysobetaine esters, and most of the lysophospholipids and lysobetaine esters can bind to the active transport protein Mfsd2a on vascular cells and be directly transported, thereby helping to improve the absorption of fatty acids and the efficiency of fatty acids crossing the blood-brain barrier; other phospholipids and betaine esters can be converted into lysophospholipids and lysobetaine esters in the small intestine and/or liver and then transported and absorbed.

在本公开的第一方面的应用中,可选地,所述微藻提取物与含脂肪酸或含脂肪酸的脂质衍生物的原料物理混合后使用,微藻提取物与所述原料中的脂肪酸的质量比为(1~50):(1~50),所述脂肪酸为棕榈酸(C16:0)、棕榈油酸(C16:1)、硬脂酸(C18:0)、油酸(C18:1n9c)、亚油酸(C18:2n6c)、α-亚麻酸(C18:3n3)、花生四烯酸(C20:4n6)、二十碳五烯酸(C20:5n3)、二十二碳六烯酸(C22:6n3)和二十二碳五烯酸(C22:5n6)中的任意一种或多种。在这种情况下,微藻提取物与含脂肪酸或脂质衍生物的原料经过物理混合后,通过消化吸收到达小肠和/或肝脏等部位,原料中的脂肪酸或脂质衍生物被在小肠和/或肝脏等部位被组装到溶血磷脂和溶血甜菜碱酯上,即可被大脑转运吸收;相较于需要在体外先化学合成溶血极性脂质后使用的方案或现有技术中对脂肪酸进行化学修饰的方案来说,物理混合后使用的方案能够简化工艺,提高制备效率且能够降低成本,而且不需要额外添加工艺助剂,能够降低溶剂残留的风险;由此,能够利用微藻提取物可促进脂肪酸吸收和跨越血脑屏障的功效促进脂肪酸或脂质衍生物被使用者吸收。In the application of the first aspect of the present disclosure, optionally, the microalgae extract is physically mixed with a raw material containing fatty acids or lipid derivatives containing fatty acids and then used, and the mass ratio of the microalgae extract to the fatty acids in the raw material is (1-50):(1-50), and the fatty acids are any one or more of palmitic acid (C16:0), palmitoleic acid (C16:1), stearic acid (C18:0), oleic acid (C18:1n9c), linoleic acid (C18:2n6c), α-linolenic acid (C18:3n3), arachidonic acid (C20:4n6), eicosapentaenoic acid (C20:5n3), docosahexaenoic acid (C22:6n3) and docosapentaenoic acid (C22:5n6). In this case, after the microalgae extract and the raw material containing fatty acids or lipid derivatives are physically mixed, they reach the small intestine and/or liver through digestion and absorption. The fatty acids or lipid derivatives in the raw materials are assembled into lysophospholipids and lysobetaine esters in the small intestine and/or liver, and can be transported and absorbed by the brain. Compared with the scheme that requires chemical synthesis of lysopolar lipids in vitro before use or the scheme of chemically modifying fatty acids in the prior art, the scheme of using after physical mixing can simplify the process, improve preparation efficiency and reduce costs, and does not require the addition of additional process additives, which can reduce the risk of solvent residues. Therefore, the microalgae extract can promote the absorption of fatty acids and cross the blood-brain barrier to promote the absorption of fatty acids or lipid derivatives by users.

在本公开的第一方面的应用中,可选地,所述微藻提取物与含脂肪酸或含脂肪酸的脂质衍生物的原料物理混合后使用,微藻提取物与所述原料中的脂肪酸的质量比为(1~50):(1~50),所述脂质衍生物选自甘油酯型脂肪酸、乙酯型脂肪酸、磷脂型脂肪酸、糖脂型脂肪酸、固醇酯型脂肪酸和/或鞘脂型脂肪酸中的任意一种或多种。在这种情况下,微藻提取物与含脂肪酸或脂质衍生物的原料经过物理混合后,通过消化吸收到达小肠和/或肝脏等部位,原料中的脂肪酸或脂质衍生物被在小肠和/或肝脏等部位被组装到溶血磷脂和溶血甜菜碱酯上,即可被大脑转运吸收;相较于需要在体外先化学合成溶血极性脂质后使用的方案或现有技术中对脂肪酸进行化学修饰的方案来说,物理混合后使用的方案能够简化工艺,提高制备效率且能够降低成本,而且不需要额外添加工艺助剂,能够降低溶剂残留的风险;由此,能够利用微藻提取物可促进脂肪酸吸收和跨越血脑屏障的功效促进脂肪酸或脂质衍生物被使用者吸收。In the application of the first aspect of the present disclosure, optionally, the microalgae extract is physically mixed with a raw material containing fatty acids or lipid derivatives containing fatty acids and then used, the mass ratio of the microalgae extract to the fatty acids in the raw material is (1 to 50): (1 to 50), and the lipid derivative is selected from any one or more of glyceride fatty acids, ethyl ester fatty acids, phospholipid fatty acids, glycolipid fatty acids, sterol ester fatty acids and/or sphingolipid fatty acids. In this case, after the microalgae extract and the raw material containing fatty acids or lipid derivatives are physically mixed, they reach the small intestine and/or liver through digestion and absorption. The fatty acids or lipid derivatives in the raw materials are assembled into lysophospholipids and lysobetaine esters in the small intestine and/or liver, and can be transported and absorbed by the brain. Compared with the scheme that requires chemical synthesis of lysopolar lipids in vitro before use or the scheme of chemically modifying fatty acids in the prior art, the scheme of using after physical mixing can simplify the process, improve preparation efficiency and reduce costs, and does not require the addition of additional process additives, which can reduce the risk of solvent residues. Therefore, the microalgae extract can promote the absorption of fatty acids and cross the blood-brain barrier to promote the absorption of fatty acids or lipid derivatives by users.

在本公开的第一方面的应用中,可选地,所述微藻提取物来自于蓝藻、绿藻或红藻。In the application of the first aspect of the present disclosure, optionally, the microalgae extract is from blue algae, green algae or red algae.

在本公开的第一方面的应用中,可选地,所述微藻提取物来自于拟微球藻、异胶藻、三角褐指藻、新月菱形藻、雨生红球藻、裸藻、螺旋藻、球状念珠藻、小球藻、盐藻和莱茵衣藻中的任意一种或多种。In the application of the first aspect of the present disclosure, optionally, the microalgae extract is from any one or more of Nannochloropsis, Heteroglea, Phaeochromis triangularis, Nitzschia crescentica, Haematococcus pluvialis, Euglena, Spirulina, Nostoc sphericalensis, Chlorella, Dunaliella and Chlamydomonas reinhardtii.

本公开的第二方面提供一种微藻提取物在提高心脏中脂肪酸含量上的应用,其特征在于,所述微藻提取物含有极性脂,所述极性脂在所述微藻提取物中占比为30%至99.9%,所述脂肪酸为非所述微藻提取物中自带的脂肪酸。在本公开的第二方面中,微藻提取物中的极性脂在帮助脂肪酸吸收和促进脂肪酸跨越血脑屏障中发挥着重要作用,能够有助于提高心脏中脂肪酸含量,由此,能够提供一种微藻提取物在提高心脏中脂肪酸含量上的应用。The second aspect of the present disclosure provides an application of a microalgae extract in increasing the fatty acid content in the heart, characterized in that the microalgae extract contains polar lipids, the polar lipids account for 30% to 99.9% of the microalgae extract, and the fatty acids are fatty acids that are not inherent in the microalgae extract. In the second aspect of the present disclosure, the polar lipids in the microalgae extract play an important role in helping fatty acid absorption and promoting fatty acids to cross the blood-brain barrier, and can help increase the fatty acid content in the heart. Thus, an application of a microalgae extract in increasing the fatty acid content in the heart can be provided.

在本公开的第二方面的应用中,可选地,所述微藻提取物含有磷脂、糖脂和/或甜菜碱酯。In the application of the second aspect of the present disclosure, optionally, the microalgae extract contains phospholipids, glycolipids and/or betaine esters.

在本公开的第二方面的应用中,可选地,所述微藻提取物与含脂肪酸或含脂肪酸的脂质衍生物的原料物理混合后使用,微藻提取物与所述原料中的脂肪酸的质量比为(1~50):(1~50),所述脂肪酸为棕榈酸(C16:0)、棕榈油酸(C16:1)、硬脂酸(C18:0)、油酸(C18:1n9c)、亚油酸(C18:2n6c)、α-亚麻酸(C18:3n3)、花生四烯酸(C20:4n6)、二十碳五烯酸(C20:5n3)、二十二碳六烯酸(C22:6n3)和二十二碳五烯酸(C22:5n6)中的任意一种或多种。In the application of the second aspect of the present disclosure, optionally, the microalgae extract is physically mixed with a raw material containing fatty acids or lipid derivatives containing fatty acids and then used, and the mass ratio of the microalgae extract to the fatty acids in the raw material is (1-50):(1-50), and the fatty acids are any one or more of palmitic acid (C16:0), palmitoleic acid (C16:1), stearic acid (C18:0), oleic acid (C18:1n9c), linoleic acid (C18:2n6c), α-linolenic acid (C18:3n3), arachidonic acid (C20:4n6), eicosapentaenoic acid (C20:5n3), docosahexaenoic acid (C22:6n3) and docosapentaenoic acid (C22:5n6).

在本公开的第二方面的应用中,可选地,所述微藻提取物与含脂肪酸或含脂肪酸的脂质衍生物的原料物理混合后使用,微藻提取物与所述原料中的脂肪酸的质量比为(1~50):(1~50),所述脂质衍生物选自甘油酯型脂肪酸、乙酯型脂肪酸、磷脂型脂肪酸、糖脂型脂肪酸、固醇酯型脂肪酸和/或鞘脂型脂肪酸中的任意一种或多种。 In the application of the second aspect of the present disclosure, optionally, the microalgae extract is physically mixed with a raw material containing fatty acids or lipid derivatives containing fatty acids and then used, the mass ratio of the microalgae extract to the fatty acids in the raw material is (1 to 50): (1 to 50), and the lipid derivative is selected from any one or more of glyceride fatty acids, ethyl ester fatty acids, phospholipid fatty acids, glycolipid fatty acids, sterol ester fatty acids and/or sphingolipid fatty acids.

在本公开的第二方面的应用中,可选地,所述微藻提取物来自于蓝藻、绿藻或红藻。In the application of the second aspect of the present disclosure, optionally, the microalgae extract is from blue algae, green algae or red algae.

在本公开的第二方面的应用中,可选地,所述微藻提取物来自于拟微球藻、异胶藻、三角褐指藻、新月菱形藻、雨生红球藻、裸藻、螺旋藻、球状念珠藻、小球藻、盐藻和莱茵衣藻中的任意一种或多种。In the application of the second aspect of the present disclosure, optionally, the microalgae extract is from any one or more of Nannochloropsis, Heteroglea, Phaeochromis triangularis, Nitzschia crescentica, Haematococcus pluvialis, Euglena, Spirulina, Nostoc sphericalensis, Chlorella, Dunaliella and Chlamydomonas reinhardtii.

本公开的第三方面提供一种微藻提取物在提高大脑中脂肪酸含量上的应用,其特征在于,所述微藻提取物含有极性脂,所述极性脂在所述微藻提取物中占比为30%至99.9%,所述脂肪酸为非所述微藻提取物中自带的脂肪酸。在本公开的第三方面中,微藻提取物中的极性脂在帮助脂肪酸吸收和促进脂肪酸跨越血脑屏障中发挥着重要作用,能够有助于提高大脑中脂肪酸含量,由此,能够提供一种微藻提取物在提高大脑中脂肪酸含量上的应用。The third aspect of the present disclosure provides an application of a microalgae extract in increasing the fatty acid content in the brain, characterized in that the microalgae extract contains polar lipids, the polar lipids account for 30% to 99.9% of the microalgae extract, and the fatty acids are fatty acids that are not inherent in the microalgae extract. In the third aspect of the present disclosure, the polar lipids in the microalgae extract play an important role in helping fatty acid absorption and promoting fatty acids to cross the blood-brain barrier, and can help increase the fatty acid content in the brain. Thus, an application of a microalgae extract in increasing the fatty acid content in the brain can be provided.

在本公开的第三方面的应用中,可选地,所述微藻提取物含有磷脂、糖脂和/或甜菜碱酯。In the application of the third aspect of the present disclosure, optionally, the microalgae extract contains phospholipids, glycolipids and/or betaine esters.

在本公开的第三方面的应用中,可选地,所述微藻提取物与含脂肪酸或含脂肪酸的脂质衍生物的原料物理混合后使用,微藻提取物与所述原料中的脂肪酸的质量比为(1~50):(1~50),所述脂肪酸为棕榈酸(C16:0)、棕榈油酸(C16:1)、硬脂酸(C18:0)、油酸(C18:1n9c)、亚油酸(C18:2n6c)、α-亚麻酸(C18:3n3)、花生四烯酸(C20:4n6)、二十碳五烯酸(C20:5n3)、二十二碳六烯酸(C22:6n3)和二十二碳五烯酸(C22:5n6)中的任意一种或多种。In the application of the third aspect of the present disclosure, optionally, the microalgae extract is physically mixed with a raw material containing fatty acids or lipid derivatives containing fatty acids and then used, and the mass ratio of the microalgae extract to the fatty acids in the raw material is (1-50):(1-50), and the fatty acids are any one or more of palmitic acid (C16:0), palmitoleic acid (C16:1), stearic acid (C18:0), oleic acid (C18:1n9c), linoleic acid (C18:2n6c), α-linolenic acid (C18:3n3), arachidonic acid (C20:4n6), eicosapentaenoic acid (C20:5n3), docosahexaenoic acid (C22:6n3) and docosapentaenoic acid (C22:5n6).

在本公开的第三方面的应用中,可选地,所述微藻提取物与含脂肪酸或含脂肪酸的脂质衍生物的原料物理混合后使用,微藻提取物与所述原料中的脂肪酸的质量比为(1~50):(1~50),所述脂质衍生物选自甘油酯型脂肪酸、乙酯型脂肪酸、磷脂型脂肪酸、糖脂型脂肪酸、固醇酯型脂肪酸和/或鞘脂型脂肪酸中的任意一种或多种。In the application of the third aspect of the present disclosure, optionally, the microalgae extract is physically mixed with a raw material containing fatty acids or lipid derivatives containing fatty acids and then used, the mass ratio of the microalgae extract to the fatty acids in the raw material is (1 to 50): (1 to 50), and the lipid derivative is selected from any one or more of glyceride fatty acids, ethyl ester fatty acids, phospholipid fatty acids, glycolipid fatty acids, sterol ester fatty acids and/or sphingolipid fatty acids.

在本公开的第三方面的应用中,可选地,所述微藻提取物来自于蓝藻、绿藻或红藻。In the application of the third aspect of the present disclosure, optionally, the microalgae extract is from blue algae, green algae or red algae.

在本公开的第三方面的应用中,可选地,所述微藻提取物来自于拟微球藻、异胶藻、三角褐指藻、新月菱形藻、雨生红球藻、裸藻、螺旋藻、球状念珠藻、小球藻、盐藻和莱茵衣藻中的任意一种或多种。In the application of the third aspect of the present disclosure, optionally, the microalgae extract is from any one or more of Nannochloropsis, Heteroglea, Phaeochromis triangularis, Nitzschia crescentica, Haematococcus pluvialis, Euglena, Spirulina, Nostoc sphericalensis, Chlorella, Dunaliella and Chlamydomonas reinhardtii.

本公开的第四方面提供一种组合物,包含微藻提取物、以及非所述微藻提取物中自带的脂肪酸,所述微藻提取物含有极性脂,所述极性脂在所述微藻提取物中占比为30%至99.9%。在本公开的第三方面中,含有极性脂的微藻提取物可促进脂肪酸吸收和跨越血脑屏障,因此,含有微藻提取物与脂肪酸的组合物能够具有较强的吸收率,使用时能够起到更好的效果,特别地,能显著提高大脑和心脏中总脂肪酸和目标脂肪酸的含量。The fourth aspect of the present disclosure provides a composition comprising a microalgae extract and fatty acids not contained in the microalgae extract, wherein the microalgae extract contains polar lipids, and the polar lipids account for 30% to 99.9% of the microalgae extract. In the third aspect of the present disclosure, the microalgae extract containing polar lipids can promote fatty acid absorption and cross the blood-brain barrier, so the composition containing the microalgae extract and fatty acids can have a strong absorption rate and can have a better effect when used, especially, it can significantly increase the content of total fatty acids and target fatty acids in the brain and heart.

在本公开的第四方面的组合物中,可选地,所述微藻提取物含有磷脂、糖脂和/或甜菜碱酯。In the composition of the fourth aspect of the present disclosure, optionally, the microalgae extract contains phospholipids, glycolipids and/or betaine esters.

在本公开的第四方面的组合物中,可选地,所述微藻提取物与含脂肪酸或含脂肪酸的脂质衍生物的原料物理混合后使用,微藻提取物与所述原料中的脂肪酸的质量比为(1~50):(1~50),所述脂肪酸为棕榈酸(C16:0)、棕榈油酸(C16:1)、硬脂酸(C18:0)、油酸(C18:1n9c)、亚油酸(C18:2n6c)、α-亚麻酸(C18:3n3)、花生四烯酸(C20:4n6)、二十碳五烯酸(C20:5n3)、二十二碳六烯酸(C22:6n3)和二十二碳五烯酸(C22:5n6)中的任意一种或多种。In the composition of the fourth aspect of the present disclosure, optionally, the microalgae extract is physically mixed with a raw material containing fatty acids or lipid derivatives containing fatty acids and then used, and the mass ratio of the microalgae extract to the fatty acids in the raw material is (1-50):(1-50), and the fatty acids are any one or more of palmitic acid (C16:0), palmitoleic acid (C16:1), stearic acid (C18:0), oleic acid (C18:1n9c), linoleic acid (C18:2n6c), α-linolenic acid (C18:3n3), arachidonic acid (C20:4n6), eicosapentaenoic acid (C20:5n3), docosahexaenoic acid (C22:6n3) and docosapentaenoic acid (C22:5n6).

在本公开的第四方面的组合物中,可选地,所述微藻提取物与含脂肪酸或含脂肪酸的脂质衍生物的原料物理混合后使用,微藻提取物与所述原料中的脂肪酸的质量比为(1~50):(1~50),所述脂质衍生物选自甘油酯型脂肪酸、乙酯型脂肪酸、磷脂型脂肪酸、糖脂型脂肪酸、固醇酯型脂肪酸和/或鞘脂型脂肪酸中的任意一种或多种。In the composition of the fourth aspect of the present disclosure, optionally, the microalgae extract is physically mixed with a raw material containing fatty acids or lipid derivatives containing fatty acids and then used, and the mass ratio of the microalgae extract to the fatty acids in the raw material is (1 to 50): (1 to 50), and the lipid derivative is selected from any one or more of glyceride fatty acids, ethyl ester fatty acids, phospholipid fatty acids, glycolipid fatty acids, sterol ester fatty acids and/or sphingolipid fatty acids.

在本公开的第四方面的组合物中,可选地,所述微藻提取物来自于蓝藻、绿藻或红藻。In the composition of the fourth aspect of the present disclosure, optionally, the microalgae extract is from blue algae, green algae or red algae.

在本公开的第四方面的组合物中,可选地,所述微藻提取物来自于拟微球藻、异胶藻、三角褐指藻、新月菱形藻、雨生红球藻、裸藻、螺旋藻、球状念珠藻、小球藻、盐藻和莱茵衣藻中的任意一种或多种。In the composition of the fourth aspect of the present disclosure, optionally, the microalgae extract is from any one or more of Nannochloropsis, Heteroglea, Phaeochromis triangularis, Nitzschia crescentus, Haematococcus pluvialis, Euglena, Spirulina, Nostoc sphericalensis, Chlorella, Dunaliella and Chlamydomonas reinhardtii.

在本公开的第四方面的组合物中,可选地,所述组合物是食品、药品、保健品、动物营养或兽药,所述组合物还含有药剂学、普通食品、保健食品或特殊医学食品法规允许使用的辅料。In the composition of the fourth aspect of the present disclosure, optionally, the composition is food, medicine, health product, animal nutrition or veterinary medicine, and the composition also contains auxiliary materials permitted for use by pharmacy, ordinary food, health food or special medical food regulations.

在本公开的第四方面的组合物中,可选地,所述组合物应用于制备改善大脑功能和/或改善眼部功能的制剂中。在这种情况下,组合物中微藻提取物能够促进脂肪酸被人体吸收,从而能够有助于改善大脑功能和改善眼部功能。In the composition of the fourth aspect of the present disclosure, optionally, the composition is used in the preparation of a preparation for improving brain function and/or improving eye function. In this case, the microalgae extract in the composition can promote the absorption of fatty acids by the human body, thereby helping to improve brain function and improve eye function.

在本公开的第四方面的组合物中,可选地,所述改善大脑功能的制剂包括改善认知功能障碍、缓解神经退行性病变、减轻注意力缺陷多动障碍、缓解抑郁症、减轻焦虑症、减轻大脑炎症、青少儿智力开发、改善阿尔兹海默症及其相关症状、和改善抑郁症的制剂中的任意一种或多种。在这种情况下,组合物中微藻提取物能够促进脂肪酸被人体吸收,从而能够有助于改善认知功能障碍、缓解神经退行性病变、减轻注意力缺陷多动障碍、缓解抑郁症、减轻焦虑症、减轻大脑炎症、青少儿智力开发、改善阿尔兹海默症及其相关症状和改善抑郁症。In the composition of the fourth aspect of the present disclosure, optionally, the preparation for improving brain function includes any one or more of the preparations for improving cognitive dysfunction, alleviating neurodegenerative lesions, alleviating attention deficit hyperactivity disorder, alleviating depression, alleviating anxiety, alleviating brain inflammation, developing intelligence in young children, improving Alzheimer's disease and related symptoms, and improving depression. In this case, the microalgae extract in the composition can promote the absorption of fatty acids by the human body, thereby being able to help improve cognitive dysfunction, alleviating neurodegenerative lesions, alleviating attention deficit hyperactivity disorder, alleviating depression, alleviating anxiety, alleviating brain inflammation, developing intelligence in young children, improving Alzheimer's disease and related symptoms, and improving depression.

在本公开的第四方面的组合物中,可选地,所述改善眼部功能的制剂包括减轻干眼症、减少视网膜病变、减少角膜问题、减轻年龄相关性黄斑变性、和防治儿童视力发育问题的制剂中的任意一种或多种。在这种情况下,组合物中微藻提取物能够促进脂肪酸被人体吸收,从而能够有助于减轻干眼症、减少视网膜病变、减少角膜问题、减轻年龄相关性黄斑变性和防治儿童视力发育问题。In the composition of the fourth aspect of the present disclosure, optionally, the preparation for improving eye function includes any one or more of preparations for alleviating dry eye, reducing retinopathy, reducing corneal problems, alleviating age-related macular degeneration, and preventing and treating children's vision development problems. In this case, the microalgae extract in the composition can promote the absorption of fatty acids by the human body, thereby being able to help alleviate dry eye, reduce retinopathy, reduce corneal problems, alleviate age-related macular degeneration, and prevent and treat children's vision development problems.

在本公开的第四方面的组合物中,可选地,所述组合物应用于制备预防高血压、预防冠心病、减缓心力衰竭进展、减缓动脉粥样硬化的进展、促进心肌梗死后的康复、和/或促进心肌再生和心脏功能的恢复的制剂中。在这种情况下,组合物中微藻提取物能够促进脂肪酸被人体吸收,从而能够有助于预防高血压、预防冠心病、减缓心力衰竭进展、减缓动脉粥样硬化的进展、促进心肌梗死后的康复和促进心肌再生和心脏功能的恢复。In the composition of the fourth aspect of the present disclosure, optionally, the composition is used to prepare a preparation for preventing hypertension, preventing coronary heart disease, slowing the progression of heart failure, slowing the progression of atherosclerosis, promoting recovery after myocardial infarction, and/or promoting myocardial regeneration and recovery of cardiac function. In this case, the microalgae extract in the composition can promote the absorption of fatty acids by the human body, thereby being able to help prevent hypertension, prevent coronary heart disease, slow the progression of heart failure, slow the progression of atherosclerosis, promote recovery after myocardial infarction, and promote myocardial regeneration and recovery of cardiac function.

在本公开的第四方面的组合物中,可选地,所述组合物应用于制备增强大脑细胞生长调节、提高认知功能、促进营养补充、抑制炎症和/或抑制细胞凋亡的制剂中。在这种情况下,组合物中微藻提取物能够促进脂肪酸被人体吸收,从而能够有助于增强大脑细胞生长调节、提高认知功能、促进营养补充、抑制炎症和抑制细胞凋亡。In the composition of the fourth aspect of the present disclosure, optionally, the composition is used to prepare a preparation for enhancing brain cell growth regulation, improving cognitive function, promoting nutritional supplementation, inhibiting inflammation and/or inhibiting cell apoptosis. In this case, the microalgae extract in the composition can promote the absorption of fatty acids by the human body, thereby helping to enhance brain cell growth regulation, improve cognitive function, promote nutritional supplementation, inhibit inflammation and inhibit cell apoptosis.

根据本公开,能够提供一种可促进脂肪酸吸收及跨越血脑屏障的微藻提取物及其组合物的应用,通过将本公开的微藻提取物与脂肪酸配合使用,能够有助于促进使用者吸收脂肪酸,特别是提高心脏和大脑中的脂肪酸含量。According to the present disclosure, a microalgae extract and a composition thereof that can promote fatty acid absorption and crossing the blood-brain barrier can be provided. By using the microalgae extract of the present disclosure in combination with fatty acids, it can help promote the user's absorption of fatty acids, especially increase the fatty acid content in the heart and brain.

附图说明BRIEF DESCRIPTION OF THE DRAWINGS

图1是示出了本公开示例所涉及的微藻提取物的提取方法的示意图。FIG. 1 is a schematic diagram showing a method for extracting a microalgae extract according to an example of the present disclosure.

图2是示出了本公开示例所涉及的实施例1和空白组的蛋白质组学及生物信息学分析的火山图。FIG. 2 is a volcano plot showing the proteomic and bioinformatics analysis of Example 1 and a blank group according to the examples of the present disclosure.

图3是示出了本公开示例所涉及的实施例1和空白组的蛋白质组学及生物信息学分析的热图。 FIG. 3 is a heat map showing the proteomic and bioinformatics analysis of Example 1 and a blank group according to the examples of the present disclosure.

图4是示出了本公开示例所涉及的实施例1和空白组的蛋白质组学及生物信息学分析的通过GO富集分析识别出的途径的示意图。FIG. 4 is a schematic diagram showing pathways identified by GO enrichment analysis of proteomics and bioinformatics analysis of Example 1 and a blank group according to the examples of the present disclosure.

具体实施方式DETAILED DESCRIPTION

以下,参考附图,详细地说明本公开的优选实施方式。Hereinafter, preferred embodiments of the present disclosure will be described in detail with reference to the accompanying drawings.

本公开的提供一种微藻提取物在促进脂肪酸跨越血脑屏障中的应用。在本公开中,验证了微藻提取物可促进脂肪酸跨越血脑屏障,因此,能够提供一种微藻提取物在促进脂肪酸跨越血脑屏障中的应用。通过将本公开的微藻提取物与脂肪酸配合使用,能够有助于提高大脑中的脂肪酸含量。本公开还能够提供一种微藻提取物在制备促进脂肪酸跨越血脑屏障的制剂中的应用。在本公开中,微藻提取物也可以称为藻类提取物。The present disclosure provides an application of a microalgae extract in promoting fatty acids to cross the blood-brain barrier. In the present disclosure, it is verified that the microalgae extract can promote fatty acids to cross the blood-brain barrier. Therefore, an application of a microalgae extract in promoting fatty acids to cross the blood-brain barrier can be provided. By using the microalgae extract of the present disclosure in combination with fatty acids, it can help to increase the fatty acid content in the brain. The present disclosure can also provide an application of a microalgae extract in the preparation of a preparation that promotes fatty acids to cross the blood-brain barrier. In the present disclosure, the microalgae extract can also be referred to as an algae extract.

本公开还提供一种微藻提取物在促进脂肪酸吸收中的应用。在本公开中,验证了微藻提取物可促进脂肪酸吸收,因此,能够提供一种微藻提取物在促进脂肪酸吸收中的应用。通过将本公开的微藻提取物与脂肪酸配合使用,能够有助于促进脂肪酸吸收。本公开还能够提供一种微藻提取物在制备促进脂肪酸吸收的制剂中的应用。在本公开中,“促进脂肪酸吸收”是指促进使用者吸收脂肪酸。The present disclosure also provides an application of a microalgae extract in promoting fatty acid absorption. In the present disclosure, it is verified that the microalgae extract can promote fatty acid absorption, and therefore, an application of a microalgae extract in promoting fatty acid absorption can be provided. By using the microalgae extract of the present disclosure in combination with fatty acids, it can help promote fatty acid absorption. The present disclosure can also provide an application of a microalgae extract in the preparation of a preparation for promoting fatty acid absorption. In the present disclosure, "promoting fatty acid absorption" means promoting the user to absorb fatty acids.

本公开还提供一种微藻提取物在提高大脑中脂肪酸含量上的应用。在本公开中,验证了微藻提取物可促进脂肪酸吸收和促进脂肪酸跨越血脑屏障,能够有助于提高心脏中脂肪酸含量,因此,能够提供一种微藻提取物在提高心脏中脂肪酸含量上的应用。另外,本公开还能够提供一种微藻提取物在制备提高心脏中脂肪酸含量的制剂上的应用。The present disclosure also provides an application of a microalgae extract in increasing the fatty acid content in the brain. In the present disclosure, it is verified that the microalgae extract can promote fatty acid absorption and promote fatty acids to cross the blood-brain barrier, which can help increase the fatty acid content in the heart. Therefore, an application of a microalgae extract in increasing the fatty acid content in the heart can be provided. In addition, the present disclosure can also provide an application of a microalgae extract in preparing a preparation for increasing the fatty acid content in the heart.

本公开还提供一种微藻提取物在提高大脑中脂肪酸含量上的应用。在本公开中,验证了微藻提取物可促进脂肪酸吸收和促进脂肪酸跨越血脑屏障,能够有助于提高大脑中脂肪酸含量,因此,能够提供一种微藻提取物在提高大脑中脂肪酸含量上的应用。另外,本公开还能够提供一种微藻提取物在制备提高大脑中脂肪酸含量的制剂上的应用。The present disclosure also provides an application of a microalgae extract in increasing the fatty acid content in the brain. In the present disclosure, it is verified that the microalgae extract can promote fatty acid absorption and promote fatty acids to cross the blood-brain barrier, which can help increase the fatty acid content in the brain. Therefore, an application of a microalgae extract in increasing the fatty acid content in the brain can be provided. In addition, the present disclosure can also provide an application of a microalgae extract in preparing a preparation for increasing the fatty acid content in the brain.

本公开还提供一种组合物,组合物包括微藻提取物和非微藻提取物中自带的脂肪酸(后续简称为非自带脂肪酸)。在本公开中,验证了微藻提取物可促进脂肪酸吸收和促进脂肪酸跨越血脑屏障,因此,含有微藻提取物与脂肪酸的组合物能够具有较强的吸收率,使用时能够起到更好的效果,特别地,能显著提高大脑和心脏中总脂肪酸和目标脂肪酸的含量。在本公开中,“组合物具有较强的吸收率”是指当组合物被施用于使用者时,使用者对组合物具有良好的吸收效率。The present disclosure also provides a composition, which includes microalgae extracts and fatty acids that are naturally present in non-microalgae extracts (hereinafter referred to as non-natural fatty acids). In the present disclosure, it is verified that microalgae extracts can promote fatty acid absorption and promote fatty acids to cross the blood-brain barrier. Therefore, the composition containing microalgae extracts and fatty acids can have a strong absorption rate and can have a better effect when used. In particular, it can significantly increase the content of total fatty acids and target fatty acids in the brain and heart. In the present disclosure, "the composition has a strong absorption rate" means that when the composition is applied to the user, the user has a good absorption efficiency of the composition.

本公开还提供一种促进脂肪酸跨越血脑屏障的微藻提取物。其中,微藻提取物可以含有极性脂。微藻提取物中的极性脂在帮助脂肪酸跨越血脑屏障(BBB)中发挥着重要作用,由此,能够提供一种可促进脂肪酸跨越血脑屏障的微藻提取物。The present disclosure also provides a microalgae extract that promotes fatty acids to cross the blood-brain barrier. The microalgae extract may contain polar lipids. The polar lipids in the microalgae extract play an important role in helping fatty acids cross the blood-brain barrier (BBB), thereby providing a microalgae extract that can promote fatty acids to cross the blood-brain barrier.

目前,常用手段是将从藻类中提取出来的富含脂肪酸(例如EPA)的藻油作为一种脂肪酸补充剂进行使用。但在本发明中,申请人发现微藻提取物可以作为促进脂肪酸吸收的促进剂与其他脂肪酸(即非自带脂肪酸,也可以称为外源脂肪酸)复配使用,本发明中使用天然来源的微藻提取物与脂肪酸复配为使用者更安全有效地吸收脂肪酸提供了一种新的解决方案。At present, the common method is to use algae oil rich in fatty acids (such as EPA) extracted from algae as a fatty acid supplement. However, in the present invention, the applicant has found that microalgae extracts can be used as a promoter to promote the absorption of fatty acids in combination with other fatty acids (i.e., non-self-contained fatty acids, also known as exogenous fatty acids). The use of microalgae extracts from natural sources in combination with fatty acids in the present invention provides a new solution for users to absorb fatty acids more safely and effectively.

以下,对本公开涉及的微藻提取物及其组合物的应用进行详细描述。Hereinafter, the application of the microalgae extract and the composition thereof involved in the present disclosure will be described in detail.

在本公开中,微藻提取物可以含有极性脂。在本公开中,验证了微藻提取物可促进脂肪酸吸收及跨越血脑屏障,其中,极性脂在帮助脂肪酸跨越血脑屏障(BBB)中发挥着重要作用,申请人在研究中发现,极性脂可能是通过增加脂肪酸的溶解性和改善其在血液中的运输效率,并促进脂肪酸与极性脂在体内合成溶血极性脂质,从而增强脂肪酸的跨膜运输。由此,能够提供一种微藻提取物在促进脂肪酸吸收及跨越血脑屏障中的应用。通过将本公开的微藻提取物与脂肪酸配合使用,能够有助于促进使用者吸收脂肪酸,特别是提高心脏和大脑中的脂肪酸含量。在一些示例中,微藻提取物可以含有脂类物质。其中,脂类物质可以具有极性脂。In the present disclosure, the microalgae extract may contain polar lipids. In the present disclosure, it is verified that the microalgae extract can promote the absorption of fatty acids and cross the blood-brain barrier, wherein polar lipids play an important role in helping fatty acids cross the blood-brain barrier (BBB). The applicant found in the study that polar lipids may be by increasing the solubility of fatty acids and improving their transport efficiency in the blood, and promoting the synthesis of lysotropic polar lipids by fatty acids and polar lipids in the body, thereby enhancing the transmembrane transport of fatty acids. Thus, it is possible to provide a microalgae extract for use in promoting the absorption of fatty acids and crossing the blood-brain barrier. By using the microalgae extract of the present disclosure in combination with fatty acids, it can help promote the user's absorption of fatty acids, especially increase the fatty acid content in the heart and brain. In some examples, the microalgae extract may contain lipid substances. Among them, the lipid substance may have polar lipids.

在本公开中,极性脂是一类含有极性基团的脂质分子。这些极性基团使得极性脂在水中具有一定的溶解性或亲水性,而其疏水性的脂肪酸链则使其在非极性环境中具有亲脂性。极性脂通常由两部分组成:一个或多个长链脂肪酸(疏水部分)和含有极性基团的头部(亲水部分)。当甘油酯型极性脂SN1或SN2位的1个脂肪酸被切除,即可得到溶血极性脂。In the present disclosure, polar lipids are a class of lipid molecules containing polar groups. These polar groups make polar lipids have a certain solubility or hydrophilicity in water, while their hydrophobic fatty acid chains make them lipophilic in non-polar environments. Polar lipids are usually composed of two parts: one or more long-chain fatty acids (hydrophobic part) and a head containing polar groups (hydrophilic part). When a fatty acid at the SN1 or SN2 position of a glyceride-type polar lipid is removed, a hemolytic polar lipid can be obtained.

在本公开中,脂肪酸不仅指代通用意义上的脂肪酸,也可以指代其他含有脂肪酸基团的物质。例如,脂肪酸可以为未经修饰的游离脂肪酸、经过修饰的脂肪酸、以及连接在其脂质结构上的脂肪酸。例如,本公开的脂肪酸也可以包括连接在甘油三酯或者极性脂上的脂肪酸。 In the present disclosure, fatty acid refers not only to fatty acid in the general sense, but also to other substances containing fatty acid groups. For example, fatty acid can be unmodified free fatty acid, modified fatty acid, and fatty acid connected to its lipid structure. For example, fatty acid of the present disclosure can also include fatty acid connected to triglyceride or polar lipid.

在一些示例中,微藻提取物可以含有DGTS:二酰甘油三甲基高丝氨酸、LDGTS:溶血二酰甘油三甲基高丝氨酸、Cer:神经酰胺、MGDG:单半乳糖二酰甘油酯、DGDG:双半乳糖基二酰甘油酯、SQDG:硫代异鼠李糖甘油二酯,DGGA:二酰基甘油葡糖醛酸、CE:胆固醇脂、CL:心磷脂、LPA:溶血磷脂酸、LPE:溶血磷脂酰乙醇胺、LPG:溶血磷脂酰甘油、LPC:溶血磷脂酰胆碱、LPI:溶血磷脂酰肌醇、PE:磷脂酰乙醇胺、PG:磷脂酰甘油、PI:磷脂酰肌醇、PC:磷脂酰胆碱、以及PI-Cer:肌醇磷酰神经酰胺中的任意一种或多种。在这种情况下,这些成分都是极性脂,能够有助于促使脂肪酸跨越血脑屏障。In some examples, the microalgae extract may contain any one or more of DGTS: diacylglycerol trimethyl homoserine, LDGTS: lysodiacylglycerol trimethyl homoserine, Cer: ceramide, MGDG: monogalactosyl diacylglycerol, DGDG: digalactosyl diacylglycerol, SQDG: thioisosorhamnosyl diacylglycerol, DGGA: diacylglycerol glucuronic acid, CE: cholesterol ester, CL: cardiolipin, LPA: lysophosphatidic acid, LPE: lysophosphatidylethanolamine, LPG: lysophosphatidylglycerol, LPC: lysophosphatidylcholine, LPI: lysophosphatidylinositol, PE: phosphatidylethanolamine, PG: phosphatidylglycerol, PI: phosphatidylinositol, PC: phosphatidylcholine, and PI-Cer: inositolphosphoceramide. In this case, these components are polar lipids that can help promote fatty acids to cross the blood-brain barrier.

在一些示例中,微藻提取物可以含有FFA:游离脂肪酸、MG:甘油一脂、DG:甘油二酯和TG:甘油三脂中的任意一种或多种。In some examples, the microalgae extract may contain any one or more of FFA: free fatty acids, MG: monoglycerides, DG: diglycerides, and TG: triglycerides.

在一些示例中,微藻提取物可以含有磷脂、糖脂和/或甜菜碱酯。在这种情况下,微藻提取物含有丰富的磷脂、糖脂和/或甜菜碱酯,其中磷脂和甜菜碱酯中部分是溶血磷脂和溶血甜菜碱酯,大部分的溶血磷脂和溶血甜菜碱酯能够与血管细胞上的主动转运蛋白Mfsd2a结合而直接被转运,从而有助于提高脂肪酸吸收和脂肪酸跨越血脑屏障的效率;其他的磷脂和甜菜碱酯能够在小肠和/或肝脏等部位转化成溶血磷脂和溶血甜菜碱酯再被转运吸收。In some examples, the microalgae extract may contain phospholipids, glycolipids and/or betaine esters. In this case, the microalgae extract is rich in phospholipids, glycolipids and/or betaine esters, wherein some of the phospholipids and betaine esters are lysophospholipids and lysobetaine esters, most of which can bind to the active transport protein Mfsd2a on vascular cells and be directly transported, thereby helping to improve the absorption of fatty acids and the efficiency of fatty acids crossing the blood-brain barrier; other phospholipids and betaine esters can be converted into lysophospholipids and lysobetaine esters in the small intestine and/or liver and then transported and absorbed.

在一些示例中,磷脂可以包括溶血磷脂。由此,能够有助于促使脂肪酸吸收和跨越血脑屏障。在一些示例中,甜菜碱酯可以包括溶血甜菜碱酯。由此,能够有助于促使脂肪酸吸收和跨越血脑屏障。In some examples, the phospholipids may include lysophospholipids, thereby facilitating fatty acid absorption and crossing the blood-brain barrier. In some examples, the betaine esters may include lysobetaine esters, thereby facilitating fatty acid absorption and crossing the blood-brain barrier.

在一些示例中,极性脂可以包括磷脂、糖脂和/或甜菜碱酯。其中,一部分磷脂和甜菜碱酯可以为溶血磷脂和溶血甜菜碱酯。在这种情况下,微藻提取物含有丰富的溶血磷脂和溶血甜菜碱酯,大部分溶血磷脂和溶血甜菜碱酯能够与血管细胞上的主动转运蛋白Mfsd2a结合而直接被转运,从而有助于提高脂肪酸跨越血脑屏障的效率;其他的磷脂和甜菜碱酯能够在小肠和/或肝脏等部位转化成溶血磷脂和溶血甜菜碱酯再被转运吸收。In some examples, polar lipids may include phospholipids, glycolipids and/or betaine esters. Among them, a portion of phospholipids and betaine esters may be lysophospholipids and lysobetaine esters. In this case, the microalgae extract is rich in lysophospholipids and lysobetaine esters, most of which can bind to the active transport protein Mfsd2a on vascular cells and be directly transported, thereby helping to improve the efficiency of fatty acids crossing the blood-brain barrier; other phospholipids and betaine esters can be converted into lysophospholipids and lysobetaine esters in the small intestine and/or liver and then transported and absorbed.

在一些示例中,优选地,微藻提取物可以含有溶血磷脂和溶血甜菜碱酯。血管细胞上主动转运蛋白Mfsd2a转运的分子必须具备两个结构特点:一是要有一个同时含有正电荷基团和负电荷基团的极性头部,二是要有一条长度至少达到14个碳的非极性长链。微藻提取物中溶血磷脂和溶血甜菜碱酯都符合这个结构特点。本公开中含有丰富的溶血磷脂和溶血甜菜碱酯的微藻提取物中的大部分溶血磷脂和溶血甜菜碱酯能够直接被转运,其他磷脂和甜菜碱酯能够在小肠和/或肝脏等部位转化成溶血磷脂和溶血甜菜碱酯再被转运吸收。含有脂肪酸的原料与微藻提取物经过物理混合后,通过消化吸收到达小肠和/或肝脏等部位,在小肠和/或肝脏等部位被组装到溶血磷脂和溶血甜菜碱酯上,即可被大脑转运吸收。In some examples, preferably, the microalgae extract may contain lysophospholipids and lysobetaine esters. The molecules transported by the active transporter Mfsd2a on vascular cells must have two structural characteristics: one is to have a polar head containing both positively charged groups and negatively charged groups, and the other is to have a non-polar long chain of at least 14 carbons. Lysophospholipids and lysobetaine esters in the microalgae extracts meet this structural feature. Most of the lysophospholipids and lysobetaine esters in the microalgae extracts rich in lysophospholipids and lysobetaine esters disclosed in the present invention can be directly transported, and other phospholipids and betaine esters can be converted into lysophospholipids and lysobetaine esters in the small intestine and/or liver and then transported and absorbed. After the raw material containing fatty acids is physically mixed with the microalgae extract, it reaches the small intestine and/or liver through digestion and absorption, and is assembled on lysophospholipids and lysobetaine esters in the small intestine and/or liver, and can be transported and absorbed by the brain.

此外,溶血磷脂作为细胞膜的关键组成部分,对于脂肪酸吸收和穿越细胞膜至关重要,它们还参与脂蛋白的形成,这是体内脂肪酸运输的重要机制。这种机制不仅提高了脂肪酸在体内的生物利用率,尤其是在大脑中的利用率,还对维护大脑健康和功能,特别是在神经保护和认知功能方面,具有显著的重要性。In addition, as key components of cell membranes, lysophospholipids are essential for fatty acid absorption and translocation across cell membranes, and they are also involved in the formation of lipoproteins, which is an important mechanism for fatty acid transport in the body. This mechanism not only improves the bioavailability of fatty acids in the body, especially in the brain, but also has significant importance in maintaining brain health and function, especially in neuroprotection and cognitive function.

脂肪酸在生物体中的转运机理如下:一般情况下,非极性脂型脂肪酸(如甘油三酯等)在肠道中被胰脂酶和其他消化酶(如肠道脂肪酶)水解成游离脂肪酸和甘油。水解产生的游离脂肪酸和甘油被肠上皮细胞吸收后,在内质网中重新酯化形成甘油三酯。新合成的甘油三酯与胆固醇、脂蛋白和其他脂类结合形成胆固醇酯,生成乳糜微粒,通过淋巴系统运输,绕过门静脉系统直接进入血循环。在大脑、肝脏、心脏等脂质代谢活跃的地方,这些甘油三酯上的脂肪酸,尤其是不饱和脂肪酸可能通过Lands循环的磷脂重塑途径,被连接到磷脂等极性脂质上,再通过磷脂酶等生成溶血磷脂,继而被转运到大脑中。磷脂和甜菜碱酯等极性脂型脂肪酸在小肠被磷脂酶转化成游离脂肪酸和溶血极性脂后被小肠细胞吸收。溶血磷脂和溶血甜菜碱酯可以直接被小肠细胞吸收。当甘油三酯型脂肪酸和含有磷脂和/或甜菜碱酯等的极性脂被混合摄入后,因为同时在小肠内被消化吸收,在脂质的重组过程中,可以为甘油三酯来源的脂肪酸提供更多的连接到磷脂或甜菜碱酯等极性脂上的机会。进而提高这些脂肪酸以溶血极性脂被转运到大脑中的机率。The transport mechanism of fatty acids in organisms is as follows: In general, non-polar lipid fatty acids (such as triglycerides) are hydrolyzed into free fatty acids and glycerol by pancreatic lipase and other digestive enzymes (such as intestinal lipase) in the intestine. The free fatty acids and glycerol produced by hydrolysis are absorbed by intestinal epithelial cells and re-esterified in the endoplasmic reticulum to form triglycerides. Newly synthesized triglycerides combine with cholesterol, lipoproteins and other lipids to form cholesterol esters, generate chylomicrons, and are transported through the lymphatic system, bypassing the portal vein system and directly entering the blood circulation. In places where lipid metabolism is active, such as the brain, liver, and heart, the fatty acids on these triglycerides, especially unsaturated fatty acids, may be connected to polar lipids such as phospholipids through the phospholipid remodeling pathway of the Lands cycle, and then lysophospholipids are generated by phospholipases and other methods, and then transported to the brain. Polar lipid fatty acids such as phospholipids and betaine esters are converted into free fatty acids and lysopolar lipids by phospholipases in the small intestine and absorbed by small intestinal cells. Lysophospholipids and lysobetaine esters can be directly absorbed by small intestinal cells. When triglyceride fatty acids and polar lipids containing phospholipids and/or betaine esters are mixed and ingested, they are digested and absorbed in the small intestine at the same time. During the lipid reorganization process, triglyceride-derived fatty acids can be provided with more opportunities to connect to polar lipids such as phospholipids or betaine esters, thereby increasing the probability of these fatty acids being transported to the brain as lysotropic polar lipids.

微藻提取物在促进脂肪酸消化吸收方面作用及优势如下:The effects and advantages of microalgae extract in promoting fatty acid digestion and absorption are as follows:

(1)乳化脂类:溶血磷脂和溶血甜菜碱酯作为乳化剂,可以将含有脂肪酸的脂类物质在水中形成乳状混合物,使其亲水化。这个过程被称为乳化,类似于肥皂洗涤油脂的原理。通过乳化,大块脂肪被撬开成一颗颗小油滴,增大了与消化酶接触的表面积,有利于脂肪酶的作用。(1) Emulsified lipids: Lysophospholipids and lysobetaine esters act as emulsifiers to form an emulsified mixture of lipid substances containing fatty acids in water, making them hydrophilic. This process is called emulsification, which is similar to the principle of soap washing grease. Through emulsification, large pieces of fat are pried apart into small oil droplets, increasing the surface area in contact with digestive enzymes and facilitating the action of lipase.

(2)提高消化率:乳化后的脂类更易受消化酶的作用,从而提高了脂类的消化率。这是因为乳化后的脂肪形成了大量小油滴,使脂肪酶更容易进入并分解脂肪。 (2) Improve digestibility: Emulsified lipids are more susceptible to digestive enzymes, thereby improving the digestibility of lipids. This is because the emulsified fat forms a large number of small oil droplets, making it easier for lipase to enter and decompose the fat.

(3)形成混合微团:溶血磷脂和溶血甜菜碱酯与胆盐结合后,可以形成混合微团,是水溶性的小球,携带着脂类的消化产物以及其他脂溶性营养物质。这些混合微团有助于将消化产物运送到小肠微绒毛附近,使其更容易被吸收。(3) Formation of mixed micelles: Lysophospholipids and lysobetaine esters can form mixed micelles after combining with bile salts. These are water-soluble globules that carry the digestion products of lipids and other fat-soluble nutrients. These mixed micelles help transport the digestion products to the vicinity of the microvilli in the small intestine, making them easier to absorb.

(4)优化吸收:溶血磷脂和溶血甜菜碱酯形成的混合微团具有较小的直径,因此相比于其他乳化剂,能够进一步增大脂肪酶的接触面积,提高消化率。同时,混合微团中的营养物质也更容易被小肠吸收,从而优化了营养物质的吸收效率。(4) Optimizing absorption: The mixed micelles formed by lysophospholipids and lysobetaine esters have a smaller diameter, so compared with other emulsifiers, they can further increase the contact area of lipase and improve digestibility. At the same time, the nutrients in the mixed micelles are also more easily absorbed by the small intestine, thereby optimizing the absorption efficiency of nutrients.

在一些示例中,优选地,微藻提取物可以含有溶血磷脂酰胆碱(LPC)、溶血磷脂酰乙醇胺(LPE)和溶血甜菜碱酯(LDGTS)。由此,能够有助于促进脂肪酸吸收和促使脂肪酸跨越血脑屏障。In some examples, preferably, the microalgae extract may contain lysophosphatidylcholine (LPC), lysophosphatidylethanolamine (LPE) and lysobetaine ester (LDGTS), thereby helping to promote fatty acid absorption and facilitate fatty acids to cross the blood-brain barrier.

在一些示例中,微藻提取物可以来自于单细胞微藻。在一些示例中,单细胞微藻可以为蓝藻、绿藻或红藻等。在一些示例中,微藻提取物可以来自于拟微球藻、异胶藻、三角褐指藻、新月菱形藻、雨生红球藻、裸藻、螺旋藻、球状念珠藻、小球藻、盐藻和莱茵衣藻中的任意一种或多种。在一些示例中,优选地,单细胞微藻可以为拟微球藻。也就是说,在一些示例中,优选地,微藻提取物可以来源于拟微球藻(Nannochloropsis sp.)。拟微球藻又称微拟球藻或微绿球藻,是一种分布广泛的海水藻类,细胞大量积累Omega-3型多不饱和脂肪酸,且拟微球藻中含有丰富的天然极性脂,具有特殊的健康功效和极高的生物利用率。在这种情况下,来源于拟微球藻的微藻提取物中含有丰富的天然极性脂,能够帮助脂肪酸吸收和跨越血脑屏障。另外,拟微球藻是一种新食品原料,微藻提取物来源于新食品原料,具有较高的营养及药用价值,且具有较高的生物安全性,长期食用没有明显的毒副作用。In some examples, the microalgae extract may come from unicellular microalgae. In some examples, the unicellular microalgae may be cyanobacteria, green algae or red algae, etc. In some examples, the microalgae extract may come from any one or more of Nannochloropsis sp., Heterocystis sp., Triangular Phaeodactylum sp., Crescent Nitzschia sp., Haematococcus pluvialis, Euglena sp., Spirulina sp., Globular Nostoc sp., Chlorella sp., Dunaliella sp. and Chlamydomonas sp. In some examples, preferably, the unicellular microalgae may be Nannochloropsis sp. That is, in some examples, preferably, the microalgae extract may come from Nannochloropsis sp. Nannochloropsis sp., also known as Microchloropsis sp. or Microchloropsis sp., is a widely distributed marine algae, and the cells accumulate a large amount of Omega-3 polyunsaturated fatty acids, and Nannochloropsis sp. is rich in natural polar lipids, which have special health benefits and extremely high bioavailability. In this case, the microalgae extract derived from Nannochloropsis sp. contains rich natural polar lipids, which can help fatty acids absorb and cross the blood-brain barrier. In addition, Microchloropsis spp. is a new food raw material. Microalgae extracts are derived from new food raw materials, have high nutritional and medicinal value, and have high biosafety. Long-term consumption has no obvious toxic side effects.

在一些示例中,微藻提取物也可以含有脂肪酸。拟微球藻的细胞中大量积累Omega-3型多不饱和脂肪酸,因此,从中提取的微藻提取物中也含有一定的脂肪酸,在这种情况下,微藻提取物自身也含有一定量的脂肪酸(可以称为自带脂肪酸),能够有助于增加大脑中脂肪酸的含量。In some examples, the microalgae extract may also contain fatty acids. Omega-3 polyunsaturated fatty acids are accumulated in large quantities in the cells of Nannochloropsis algae, so the microalgae extract extracted therefrom also contains certain fatty acids. In this case, the microalgae extract itself also contains a certain amount of fatty acids (which can be called self-contained fatty acids), which can help increase the fatty acid content in the brain.

在一些示例中,微藻提取物中的极性脂的含量可以为30%至99.9%。由此,能够有助于促进脂肪酸吸收和跨越血脑屏障。例如,极性脂在微藻提取物中的占比可以为30%、33%、35%、37%、40%、42%、45%、48%、50%、52%、55%、58%、60%、62%、65%、68%、70%、72%、75%、77%、78%、80%、82%、83%、84%、85%、86%、87%、88%、89%、90%、91%、92%、93%、94%、 95%、96%、97%、98%、99%、或99.9%。在一些示例中,优选地,极性脂在微藻提取物中的占比可以不小于70%。在一些示例中,优选地,极性脂在微藻提取物中的占比可以为70%至90%。由此,能够有助于提高促进脂肪酸吸收和跨越血脑屏障的效率。In some examples, the content of polar lipids in the microalgae extract can be 30% to 99.9%. This can help promote fatty acid absorption and cross the blood-brain barrier. For example, the proportion of polar lipids in the microalgae extract can be 30%, 33%, 35%, 37%, 40%, 42%, 45%, 48%, 50%, 52%, 55%, 58%, 60%, 62%, 65%, 68%, 70%, 72%, 75%, 77%, 78%, 80%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 99.9%. In some examples, preferably, the proportion of polar lipids in the microalgae extract may be no less than 70%. In some examples, preferably, the proportion of polar lipids in the microalgae extract may be 70% to 90%. Thus, it can help to improve the efficiency of promoting fatty acid absorption and crossing the blood-brain barrier.

在一些示例中,极性脂在微藻提取物的脂类物质中的占比可以为30%至100%。由此,能够有助于促进脂肪酸吸收和跨越血脑屏障。例如,极性脂在脂类物质中的占比可以为30%、33%、35%、37%、40%、42%、45%、48%、50%、52%、55%、58%、60%、62%、65%、68%、70%、72%、75%、77%、78%、80%、82%、83%、84%、85%、86%、87%、88%、89%、90%、91%、92%、93%、94%、95%、96%、97%、98%、99%、或100%。在一些示例中,优选地,极性脂在脂类物质中的占比可以为70%至90%。由此,能够有助于提高促进脂肪酸吸收和跨越血脑屏障的效率。In some examples, the proportion of polar lipids in the lipid substances of microalgae extracts can be 30% to 100%. Thus, it can help promote fatty acid absorption and cross the blood-brain barrier. For example, the proportion of polar lipids in lipid substances can be 30%, 33%, 35%, 37%, 40%, 42%, 45%, 48%, 50%, 52%, 55%, 58%, 60%, 62%, 65%, 68%, 70%, 72%, 75%, 77%, 78%, 80%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%. In some examples, preferably, the proportion of polar lipids in lipid substances can be 70% to 90%. This can help improve the efficiency of promoting fatty acid absorption and crossing the blood-brain barrier.

在一些示例中,在对藻类提取物进行应用时,可以基于不同的需求对藻类提取物进行稀释,或者直接调节藻类提取物中极性脂的含量。例如,在一些示例中,可以将藻类提取物中的极性脂的含量调节为30%-50%再进行应用。In some examples, when the algae extract is applied, the algae extract may be diluted based on different requirements, or the content of polar lipids in the algae extract may be directly adjusted. For example, in some examples, the content of polar lipids in the algae extract may be adjusted to 30%-50% before application.

在一些示例中,可以使用有机溶剂从藻类生物质中提取处微藻提取物。例如,在一些示例中,微藻提取物的提取方法可以为:使藻类生物质与乙醇接触,除去乙醇,获得微藻提取物。在一些示例中,藻类生物质可以为干藻。其中,干藻是指含水量为5wt%以下的藻。在一些示例中,干藻可以通过将藻类生物质絮凝、去絮凝、去盐和干燥而得到。在一些示例中,干藻可以为微拟球藻属的细胞壁完整的藻。In some examples, an organic solvent may be used to extract a microalgae extract from the algae biomass. For example, in some examples, the method for extracting the microalgae extract may be: contacting the algae biomass with ethanol, removing the ethanol, and obtaining the microalgae extract. In some examples, the algae biomass may be dry algae. Dry algae refers to algae with a water content of less than 5 wt%. In some examples, dry algae may be obtained by flocculating, deflocculating, desalting, and drying the algae biomass. In some examples, the dry algae may be algae with intact cell walls of the genus Nannochloropsis.

图1是示出了本公开示例所涉及的微藻提取物的提取方法的示意图。FIG. 1 is a schematic diagram showing a method for extracting a microalgae extract according to an example of the present disclosure.

在一些示例中,参见图1,微藻提取物的提取方法可以包括以下步骤:将藻类生物质絮凝、去絮凝、去盐和干燥,得到干藻(步骤S10);使干藻与乙醇接触,除去乙醇,获得微藻提取物(步骤S20)。在本公开中,微藻提取物是从天然藻类提取的,该方法的可持续性和环境友好性也是其重要优点,微藻强大的固碳能力可助力节能减排,推动“碳达峰,碳中和”。In some examples, referring to FIG. 1 , the extraction method of the microalgae extract may include the following steps: flocculating, deflocculating, desalting and drying the algae biomass to obtain dry algae (step S10); contacting the dry algae with ethanol, removing the ethanol, and obtaining the microalgae extract (step S20). In the present disclosure, the microalgae extract is extracted from natural algae. The sustainability and environmental friendliness of the method are also its important advantages. The powerful carbon fixation capacity of microalgae can help energy conservation and emission reduction, and promote "carbon peak and carbon neutrality".

在一些示例中,微藻提取物可以与脂肪酸混合后使用。其中,脂肪酸是非微藻提取物中自带的脂肪酸(非自带脂肪酸,也可以称为外源脂肪酸)。由此,能够利用微藻提取物可促进脂肪酸吸收和跨越血脑屏障的功效促进脂肪酸被使用者吸收。可以理解的是,在本公开中,“微藻提取物与脂肪酸混合后使用”并不局限与微藻提取物只能与游离脂肪酸混合使用,也可以包括将微藻提取物与含脂肪酸物质混合后使用的方案。比如,一般的含脂肪酸物质有藻油、鱼油和磷虾油等,可以将藻类提取物与这些含脂肪酸物质进行混合再进行使用。在这种情况下,通过本公开的藻类提取物能够促进这些含脂肪酸物质中的脂肪酸被使用者吸收。In some examples, the microalgae extract can be mixed with fatty acids before use. Wherein, the fatty acids are fatty acids that are not contained in the microalgae extract (non-contained fatty acids, also referred to as exogenous fatty acids). Thus, the microalgae extract can promote the absorption of fatty acids and the effect of crossing the blood-brain barrier to promote the absorption of fatty acids by the user. It is understandable that in the present disclosure, "the use of microalgae extract mixed with fatty acids" is not limited to the use of microalgae extracts that can only be mixed with free fatty acids, but can also include the use of microalgae extracts mixed with fatty acid-containing substances. For example, general fatty acid-containing substances include algae oil, fish oil, krill oil, etc., and algae extracts can be mixed with these fatty acid-containing substances and then used. In this case, the algae extracts disclosed in the present disclosure can promote the fatty acids in these fatty acid-containing substances to be absorbed by the user.

在一些示例中,微藻提取物与脂肪酸可以物理混合后使用。在这种情况下,脂肪酸与微藻提取物经过物理混合后,通过消化吸收到达小肠和/或肝脏等部位,在小肠和/或肝脏等部位被组装到溶血磷脂和溶血甜菜碱酯上,即可被大脑转运吸收,相较于需要在体外先化学合成溶血型脂肪酸后使用的方案或现有技术中对脂肪酸进行化学修饰的方案来说,物理混合后使用的方案能够简化工艺,提高制备效率且能够降低成本,而且不需要额外添加工艺助剂,能够降低溶剂残留的风险。也就是说,微藻提取物与脂肪酸在物理混合后,进入小肠和/或肝脏等部位后能够自动合成溶血极性脂质。In some examples, microalgae extracts and fatty acids can be used after physical mixing. In this case, after the fatty acids and microalgae extracts are physically mixed, they reach the small intestine and/or liver through digestion and absorption, and are assembled into lysophospholipids and lysobetaine esters in the small intestine and/or liver, and can be transported and absorbed by the brain. Compared with the scheme that requires chemical synthesis of lyso-type fatty acids in vitro before use or the scheme of chemical modification of fatty acids in the prior art, the scheme of using after physical mixing can simplify the process, improve preparation efficiency and reduce costs, and does not require additional process additives, which can reduce the risk of solvent residues. In other words, after the microalgae extract and fatty acids are physically mixed, they can automatically synthesize lyso-polar lipids after entering the small intestine and/or liver.

以下,对肝脏中的脂肪酸置换过程进行说明:The following is an explanation of the fatty acid replacement process in the liver:

在肝脏中置换极性脂上的脂肪酸链通常涉及一系列酶促反应,这些反应使得极性脂分子中的脂肪酸链被移除、改变或重新酰化。以磷脂酰胆碱(PC)为例,这个过程主要包括以下几个步骤:The replacement of fatty acid chains on polar lipids in the liver usually involves a series of enzymatic reactions that remove, change or reacylate the fatty acid chains in polar lipid molecules. Taking phosphatidylcholine (PC) as an example, this process mainly includes the following steps:

(1)脂肪酸链的去酰化:首先,磷脂酶(如磷脂酶Phospholipase A2,PLA2)会作用于PC,从而去除其脂肪酸链之一。这通常发生在磷脂分子的SN2位置。剩下的分子就是溶血磷脂酰胆碱(LPC)。(1) Deacylation of fatty acid chains: First, phospholipases (such as phospholipase A2, PLA2) act on PC to remove one of its fatty acid chains. This usually occurs at the SN2 position of the phospholipid molecule. The remaining molecule is lysophosphatidylcholine (LPC).

(2)脂肪酸链的交换:随后,溶血磷脂酰胆碱酰基转移酶(LPCAT)可以催化新的脂肪酸链与去酰化的磷脂分子结合,从而产生一个新的PC分子。这个过程中,可以选择不同类型的脂肪酸作为新链。(2) Exchange of fatty acid chains: Subsequently, lysophosphatidylcholine acyltransferase (LPCAT) can catalyze the binding of new fatty acid chains to the deacylated phospholipid molecules, thereby generating a new PC molecule. In this process, different types of fatty acids can be selected as new chains.

(3)重新酰化:在脂肪酸链被移除之后,另一个脂肪酸可以通过酰化酶如酰基转移酶的作用被添加到磷脂分子上。这一步是选择性的,取决于哪种脂肪酸可用并被酶识别。(3) Reacylation: After the fatty acid chain has been removed, another fatty acid can be added to the phospholipid molecule by the action of an acylase such as an acyltransferase. This step is selective, depending on which fatty acid is available and recognized by the enzyme.

在一些示例中,微藻提取物可以与含脂肪酸的原料物理混合后使用。在一些示例中,脂肪酸可以为棕榈酸(C16:0)、棕榈油酸(C16:1)、硬脂酸(C18:0)、油酸(C18:1n9c)、亚油酸(C18:2n6c)、α-亚麻酸(C18:3n3)、花生四烯酸(C20:4n6)、二十碳五烯酸(C20:5n3)、二十二碳六烯酸(C22:6n3)和二十二碳五烯酸(C22:5n6)中的任意一种或多种。 In some examples, the microalgae extract can be used after being physically mixed with a raw material containing fatty acids. In some examples, the fatty acids can be any one or more of palmitic acid (C16:0), palmitoleic acid (C16:1), stearic acid (C18:0), oleic acid (C18:1n9c), linoleic acid (C18:2n6c), α-linolenic acid (C18:3n3), arachidonic acid (C20:4n6), eicosapentaenoic acid (C20:5n3), docosahexaenoic acid (C22:6n3), and docosapentaenoic acid (C22:5n6).

在一些示例中,微藻提取物可以与含脂肪酸的脂质衍生物(可以简称为脂质衍生物)的原料物理混合后使用。在一些示例中,脂质衍生物可以选自甘油酯型脂肪酸、乙酯型脂肪酸、磷脂型脂肪酸、糖脂型脂肪酸、固醇酯型脂肪酸和/或鞘脂型脂肪酸中的任意一种或多种。在一些示例中,脂质衍生物可以是甘油酯(甘油一酯、甘油二酯、甘油三酯)、乙酯、磷脂、糖脂、胆固醇酯、神经酰胺和脂肪醇酯中的任意一种或多种。在一些示例中,脂质衍生物可以是其他含脂肪酸的脂质衍生物。In some examples, the microalgae extract can be used after physical mixing with the raw materials of lipid derivatives containing fatty acids (which can be referred to as lipid derivatives). In some examples, the lipid derivatives can be selected from any one or more of glyceride fatty acids, ethyl ester fatty acids, phospholipid fatty acids, glycolipid fatty acids, sterol ester fatty acids and/or sphingolipid fatty acids. In some examples, the lipid derivatives can be any one or more of glycerides (monoglycerides, diglycerides, triglycerides), ethyl esters, phospholipids, glycolipids, cholesterol esters, ceramides and fatty alcohol esters. In some examples, the lipid derivatives can be other lipid derivatives containing fatty acids.

在一些示例中,微藻提取物与含脂肪酸或含脂肪酸的脂质衍生物的原料物理混合后使用。在这种情况下,微藻提取物与含脂肪酸或脂质衍生物的原料经过物理混合后,通过消化吸收到达小肠和/或肝脏等部位,原料中的脂肪酸或脂质衍生物被在小肠和/或肝脏等部位被组装到溶血磷脂和溶血甜菜碱酯上,即可被大脑转运吸收;相较于需要在体外先化学合成溶血极性脂质后使用的方案或现有技术中对脂肪酸进行化学修饰的方案来说,物理混合后使用的方案能够简化工艺,提高制备效率且能够降低成本,而且不需要额外添加工艺助剂,能够降低溶剂残留的风险;由此,能够利用微藻提取物可促进脂肪酸吸收和跨越血脑屏障的功效促进脂肪酸或脂质衍生物被使用者吸收。In some examples, microalgae extracts are physically mixed with raw materials containing fatty acids or lipid derivatives of fatty acids before use. In this case, after the microalgae extracts are physically mixed with raw materials containing fatty acids or lipid derivatives, they reach the small intestine and/or liver through digestion and absorption. The fatty acids or lipid derivatives in the raw materials are assembled into lysophospholipids and lysobetaine esters in the small intestine and/or liver, and can be transported and absorbed by the brain; compared with the scheme that requires chemical synthesis of lysopolar lipids in vitro before use or the scheme of chemical modification of fatty acids in the prior art, the scheme of using after physical mixing can simplify the process, improve preparation efficiency and reduce costs, and does not require additional process additives, which can reduce the risk of solvent residues; thus, the microalgae extract can promote the absorption of fatty acids and cross the blood-brain barrier to promote the absorption of fatty acids or lipid derivatives by users.

在一些示例中,微藻提取物与脂肪酸的质量比可以为(1~50):(1~50)。在一些示例中,微藻提取物与含脂肪酸或含脂肪酸的脂质衍生物的原料中的脂肪酸的质量比为(1~50):(1~50)。由此,能够有助于促进脂肪酸跨越血脑屏障。例如,微藻提取物与脂肪酸的质量比可以为1:1、1:2、1:3、1:4、1:5、1:6、1:7、1:8、1:9、1:10、1:11、1:12、1:13、1:14、1:15、1:16、1:17、1:18、1:19、1:20、1:21、1:22、1:23、1:24、1:25、1:26、1:27、1:28、1:29、1:30、1:31、1:32、1:33、1:34、1:35、1:36、1:37、1:38、1:39、1:40、1:41、1:42、1:43、1:44、1:45、1:46、1:47、1:48、1:49、1:50、50:1、49:1、48:1、47:1、46:1、45:1、44:1、43:1、42:1、41:1、40:1、39:1、38:1、37:1、36:1、35:1、34:1、33:1、32:1、31:1、30:1、29:1、28:1、27:1、26:1、25:1、24:1、23:1、22:1、21:1、20:1、19:1、18:1、17:1、16:1、15:1、14:1、13:1、12:1、11:1、10:1、9:1、8:1、7:1、6:1、5:1、4:1、3:1、2:1、或1:1。如前所述,脂肪酸可以包括含脂肪酸物质的含义,当微藻提取物与含脂肪酸物质一起使用时,微藻提取物与含脂肪酸物质的比例可以与微藻提取物与脂肪酸的比例一致。换言之,在一些示例中,微藻提取物与含脂肪酸物质的质量比可以为(1~50):(1~50)。In some examples, the mass ratio of the microalgae extract to the fatty acid can be (1-50):(1-50). In some examples, the mass ratio of the microalgae extract to the fatty acid in the raw material containing fatty acids or fatty acid-containing lipid derivatives is (1-50):(1-50). This can help promote fatty acids to cross the blood-brain barrier. For example, the mass ratio of microalgae extract to fatty acids can be 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:11, 1:12, 1:13, 1:14, 1:15, 1:16, 1:17, 1:18, 1:19, 1:20, 1:21, 1:22, 1:23, 1:24, 1:25, 1:26, 1:27, 1:28, 1:29, 1:30, 1:31, 1:32, 1:33, 1:34, 1:35, 1:36, 1:37, 1:38, 1:39, 1:40, 1:41, 1:42, 1:43, 1:44, 1:45, 1:46, 1:47, 1:48, 1:49, 1:50 :49, 1:50, 50:1, 49:1, 48:1, 47:1, 46:1, 45:1, 44:1, 43:1, 42:1, 41:1, 40:1, 39:1, 38:1, 37:1, 36:1, 35:1, 34:1, 33:1, 32:1, 31:1, 30:1, 29:1, 28:1, 2 7:1, 26:1, 25:1, 24:1, 23:1, 22:1, 21:1, 20:1, 19:1, 18:1, 17:1, 16:1, 15:1, 14:1, 13:1, 12:1, 11:1, 10:1, 9:1, 8:1, 7:1, 6:1, 5:1, 4:1, 3:1, 2:1, or 1:1. As mentioned above, fatty acids can include the meaning of fatty acid-containing substances. When the microalgae extract is used together with the fatty acid-containing substance, the ratio of the microalgae extract to the fatty acid-containing substance can be consistent with the ratio of the microalgae extract to the fatty acid. In other words, in some examples, the mass ratio of the microalgae extract to the fatty acid-containing substance can be (1-50): (1-50).

在一些示例中,优选地,微藻提取物与脂肪酸的质量比可以为(1~5):(1~5)。例如,微藻提取物与脂肪酸的质量比可以为1:1、1:1.5、1:2、1:2.5、1:3、1:3.5、1:4、1:4.5、1:5、5:1、4.5:1、4:1、3.5:1、3:1、2.5:1、2:1、或1.5:1。由此,能够有助于促进脂肪酸跨越血脑屏障。在一些示例中,优选地,微藻提取物与含脂肪酸物质的质量比可以为(1~5):(1~5)。In some examples, preferably, the mass ratio of microalgae extract to fatty acid can be (1-5): (1-5). For example, the mass ratio of microalgae extract to fatty acid can be 1:1, 1:1.5, 1:2, 1:2.5, 1:3, 1:3.5, 1:4, 1:4.5, 1:5, 5:1, 4.5:1, 4:1, 3.5:1, 3:1, 2.5:1, 2:1, or 1.5:1. Thus, it can help promote fatty acids to cross the blood-brain barrier. In some examples, preferably, the mass ratio of microalgae extract to fatty acid-containing substance can be (1-5): (1-5).

在一些示例中,微藻提取物也可以与脂肪酸化学合成溶血极性脂质后使用。在这种情况下,溶血极性脂质能够与血管细胞上的主动转运蛋白Mfsd2a结合而被转运。在一些示例中,可以在体外将脂肪酸化学合成溶血极性脂质后再使用。In some examples, the microalgae extract can also be used after chemically synthesizing lysotropic polar lipids with fatty acids. In this case, the lysotropic polar lipids can be transported by binding to the active transport protein Mfsd2a on vascular cells. In some examples, fatty acids can be chemically synthesized into lysotropic polar lipids in vitro before use.

在一些示例中,非自带脂肪酸可以为对人体具有有益效果的脂肪酸。例如,脂肪酸可以为人体大脑及视网膜所需的脂肪酸。在一些示例中,脂肪酸可以包括但不限于棕榈酸、油酸、亚油酸、α-亚麻酸(ALA)、花生四烯酸(ARA)、二十碳五烯酸(EPA)、二十二碳六稀酸(DHA)以及神经酸。In some examples, the non-self-contained fatty acid can be a fatty acid that has a beneficial effect on the human body. For example, the fatty acid can be a fatty acid required by the human brain and retina. In some examples, the fatty acid can include but is not limited to palmitic acid, oleic acid, linoleic acid, α-linolenic acid (ALA), arachidonic acid (ARA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and nervonic acid.

如前所述,在本公开中,组合物可以包括微藻提取物和非自带脂肪酸。在一些示例中,优选地,组合物中的脂肪酸与微藻提取物物理混合。在本公开中,微藻提取物与脂肪酸物理混合即可使组合物进入小肠和/或肝脏等部位后能够自动合成溶血极性脂质,因此,组合物的合成工艺简单,且不需要额外添加工艺助剂,能够降低溶剂残留的风险。As mentioned above, in the present disclosure, the composition may include microalgae extracts and non-self-contained fatty acids. In some examples, preferably, the fatty acids in the composition are physically mixed with the microalgae extracts. In the present disclosure, the physical mixing of the microalgae extracts and the fatty acids can enable the composition to automatically synthesize hemolytic polar lipids after entering the small intestine and/or liver, etc. Therefore, the synthesis process of the composition is simple, and no additional process additives are required, which can reduce the risk of solvent residues.

在一些示例中,组合物可以通过内服的方式使用。例如,在一些示例中,组合物可以通过口服的方式进入人体。In some examples, the composition can be used orally. For example, in some examples, the composition can be taken orally into the human body.

在一些示例中,组合物中的脂肪酸与微藻提取物也可以在体外化学合成为溶血型脂肪酸再使用。In some examples, the fatty acids and microalgae extracts in the composition can also be chemically synthesized in vitro into lyso-type fatty acids for reuse.

在一些示例中,组合物可以是食品、药品、保健品、动物营养或兽药。在本公开中,组合物也可以称为制剂。在一些示例中,优选地,食品为功能食品。在一些示例中,食品可以包括饼干、糖果、糕点和饮料。在一些示例中,优选地,药品的剂型为口服液、颗粒剂、片剂、胶囊剂、粉剂、散剂、丸剂、溶液剂、糖浆剂、煎膏剂、贴剂、凝胶剂、乳膏剂或喷雾剂。由此,能够有利于保存和使用。In some examples, the composition can be food, medicine, health care product, animal nutrition or veterinary medicine. In the present disclosure, the composition can also be referred to as a preparation. In some examples, preferably, the food is a functional food. In some examples, the food can include biscuits, candies, cakes and beverages. In some examples, preferably, the dosage form of the medicine is an oral liquid, granules, tablets, capsules, powders, powders, pills, solutions, syrups, decoctions, patches, gels, creams or sprays. Thus, it can be beneficial to storage and use.

在一些示例中,组合物可以含有其他功能助剂。在一些示例中,组合物还可以含有药剂学、普通食品、保健食品或特殊医学食品法规允许使用的辅料。例如,组合物可以含有稀释剂、增稠剂、抗氧化剂、维生素等辅料。 In some examples, the composition may contain other functional additives. In some examples, the composition may also contain auxiliary materials permitted for use by pharmacy, ordinary food, health food or special medical food regulations. For example, the composition may contain auxiliary materials such as diluents, thickeners, antioxidants, vitamins, etc.

在一些示例中,组合物可以应用于制备改善大脑功能和/或改善眼部功能的制剂中。在这种情况下,组合物中微藻提取物能够促进脂肪酸被人体吸收,从而能够有助于改善大脑功能和改善眼部功能。In some examples, the composition can be used to prepare a preparation for improving brain function and/or improving eye function. In this case, the microalgae extract in the composition can promote the absorption of fatty acids by the human body, thereby helping to improve brain function and eye function.

在一些示例中,改善大脑功能的制剂可以包括改善认知功能障碍、缓解神经退行性病变、减轻注意力缺陷多动障碍、缓解抑郁症、减轻焦虑症、减轻大脑炎症、青少儿智力开发、改善阿尔兹海默症及其相关症状、和改善抑郁症的制剂中的任意一种或多种。在这种情况下,组合物中微藻提取物能够促进脂肪酸被人体吸收,从而能够有助于改善认知功能障碍、缓解神经退行性病变、减轻注意力缺陷多动障碍、缓解抑郁症、减轻焦虑症、减轻大脑炎症、青少儿智力开发、改善阿尔兹海默症及其相关症状和改善抑郁症。In some examples, the preparation for improving brain function may include any one or more of the preparations for improving cognitive dysfunction, alleviating neurodegenerative lesions, alleviating attention deficit hyperactivity disorder, alleviating depression, alleviating anxiety, alleviating brain inflammation, developing intelligence in young children, improving Alzheimer's disease and its related symptoms, and improving depression. In this case, the microalgae extract in the composition can promote the absorption of fatty acids by the human body, thereby being able to help improve cognitive dysfunction, alleviating neurodegenerative lesions, alleviating attention deficit hyperactivity disorder, alleviating depression, alleviating anxiety, alleviating brain inflammation, developing intelligence in young children, improving Alzheimer's disease and its related symptoms, and improving depression.

在一些示例中,改善眼部功能的制剂包括减轻干眼症、减少视网膜病变、减少角膜问题、减轻年龄相关性黄斑变性、和防治儿童视力发育问题的制剂中的任意一种或多种。在这种情况下,组合物中微藻提取物能够促进脂肪酸被人体吸收,从而能够有助于减轻干眼症、减少视网膜病变、减少角膜问题、减轻年龄相关性黄斑变性和防治儿童视力发育问题。In some examples, the preparation for improving eye function includes any one or more of the preparations for alleviating dry eye, reducing retinopathy, reducing corneal problems, alleviating age-related macular degeneration, and preventing and treating children's vision development problems. In this case, the microalgae extract in the composition can promote the absorption of fatty acids by the human body, thereby being able to help alleviate dry eye, reduce retinopathy, reduce corneal problems, alleviate age-related macular degeneration, and prevent and treat children's vision development problems.

因此,本公开还能够提供一种组合物在制备改善认知功能障碍、缓解神经退行性病变、减轻注意力缺陷多动障碍、缓解抑郁症、减轻焦虑症、减轻大脑炎症、减轻干眼症、减轻年龄相关性黄斑变性、防治儿童视力发育问题、减少视网膜病变、减少角膜问题、青少儿智力开发、改善阿尔兹海默症及其相关症状和/或改善抑郁症的制剂中的应用。另外,本公开还能够提供一种组合物在改善认知功能障碍、缓解神经退行性病变、减轻注意力缺陷多动障碍、缓解抑郁症、减轻焦虑症、减轻大脑炎症、减轻干眼症、减轻年龄相关性黄斑变性、防治儿童视力发育问题、减少视网膜病变、减少角膜问题、青少儿智力开发、改善阿尔兹海默症及其相关症状和/或改善抑郁症中的应用。Therefore, the present disclosure can also provide a composition for use in the preparation of a preparation for improving cognitive dysfunction, alleviating neurodegenerative lesions, alleviating attention deficit hyperactivity disorder, alleviating depression, alleviating anxiety, alleviating brain inflammation, alleviating dry eye syndrome, alleviating age-related macular degeneration, preventing and treating children's visual development problems, reducing retinopathy, reducing corneal problems, intellectual development of young children, improving Alzheimer's disease and related symptoms and/or improving depression. In addition, the present disclosure can also provide a composition for use in improving cognitive dysfunction, alleviating neurodegenerative lesions, alleviating attention deficit hyperactivity disorder, alleviating depression, alleviating anxiety, alleviating brain inflammation, alleviating dry eye syndrome, alleviating age-related macular degeneration, preventing and treating children's visual development problems, reducing retinopathy, reducing corneal problems, intellectual development of young children, improving Alzheimer's disease and related symptoms and/or improving depression.

与大脑健康紧密相关的脂肪酸主要是Omega-3和Omega-6脂肪酸,尤其是Omega-3脂肪酸中的EPA和DHA。这些脂肪酸在维持神经细胞膜的结构和功能、促进儿童大脑发育、提高认知功能、以及抗炎方面发挥关键作用。特别值得注意的是,DHA不仅对大脑健康至关重要,还是视网膜细胞的重要组成部分,对于维护视力和预防年龄相关的眼部疾病(如黄斑变性)具有重要作用。Omega-3脂肪酸对于情绪调节和神经保护也特别重要,有助于改善抑郁和焦虑症状,并可能防止神经退行性疾病。Omega-6脂肪酸,例如花生四烯酸(AA),也对大脑和视力健康至关重要,是神经细胞膜和视网膜细胞的一个主要组成部分。The fatty acids closely related to brain health are mainly Omega-3 and Omega-6 fatty acids, especially EPA and DHA in Omega-3 fatty acids. These fatty acids play a key role in maintaining the structure and function of nerve cell membranes, promoting brain development in children, improving cognitive function, and anti-inflammation. It is particularly noteworthy that DHA is not only essential for brain health, but also an important component of retinal cells, playing an important role in maintaining vision and preventing age-related eye diseases (such as macular degeneration). Omega-3 fatty acids are also particularly important for mood regulation and neuroprotection, helping to improve symptoms of depression and anxiety, and may prevent neurodegenerative diseases. Omega-6 fatty acids, such as arachidonic acid (AA), are also essential for brain and vision health and are a major component of nerve cell membranes and retinal cells.

因此,在本公开中,组合物中的微藻提取物能够促使脂肪酸吸收和跨越血脑屏障,脂肪酸进入使用者体内后能够产生诸多有益效果,因此,能够将组合物应用在制备多方面功效的制剂中。Therefore, in the present disclosure, the microalgae extract in the composition can promote the absorption of fatty acids and cross the blood-brain barrier. After the fatty acids enter the user's body, they can produce many beneficial effects. Therefore, the composition can be used in the preparation of preparations with multiple functions.

在一些示例中,如前所述,微藻提取物本身也可以含有一定量的脂肪酸,能够有助于增加大脑中脂肪酸的含量。因此,将组合物应用在制备多方面功效的制剂中除了微藻提取物对脂肪酸吸收和跨越血脑屏障的促进作用,微藻提取物本身也能够起到一些协同作用。In some examples, as mentioned above, the microalgae extract itself may also contain a certain amount of fatty acids, which can help increase the content of fatty acids in the brain. Therefore, in addition to the promotion of the microalgae extract on fatty acid absorption and crossing the blood-brain barrier, the microalgae extract itself can also play some synergistic roles in the preparation of a multi-functional preparation.

在一些示例中,组合物可以应用于制备预防高血压、预防冠心病、减缓心力衰竭进展、减缓动脉粥样硬化的进展、促进心肌梗死后的康复、和/或促进心肌再生和心脏功能的恢复的制剂中。在这种情况下,组合物中微藻提取物能够促进脂肪酸被人体吸收,从而能够有助于预防高血压、预防冠心病、减缓心力衰竭进展、减缓动脉粥样硬化的进展、促进心肌梗死后的康复和促进心肌再生和心脏功能的恢复。In some examples, the composition can be used to prepare a preparation for preventing hypertension, preventing coronary heart disease, slowing the progression of heart failure, slowing the progression of atherosclerosis, promoting recovery after myocardial infarction, and/or promoting myocardial regeneration and recovery of cardiac function. In this case, the microalgae extract in the composition can promote the absorption of fatty acids by the human body, thereby helping to prevent hypertension, prevent coronary heart disease, slow the progression of heart failure, slow the progression of atherosclerosis, promote recovery after myocardial infarction, and promote myocardial regeneration and recovery of cardiac function.

因此,本公开还能够提供一种组合物在制备预防高血压、预防冠心病、减缓心力衰竭进展、减缓动脉粥样硬化的进展、促进心肌梗死后的康复、和/或促进心肌再生和心脏功能的恢复的制剂中的应用。另外,本公开还能够提供一种组合物在预防高血压、预防冠心病、减缓心力衰竭进展、减缓动脉粥样硬化的进展、促进心肌梗死后的康复、和/或促进心肌再生和心脏功能的恢复中的应用。Therefore, the present disclosure can also provide a composition for use in the preparation of a preparation for preventing hypertension, preventing coronary heart disease, slowing the progression of heart failure, slowing the progression of atherosclerosis, promoting recovery after myocardial infarction, and/or promoting myocardial regeneration and recovery of cardiac function. In addition, the present disclosure can also provide a composition for use in preventing hypertension, preventing coronary heart disease, slowing the progression of heart failure, slowing the progression of atherosclerosis, promoting recovery after myocardial infarction, and/or promoting myocardial regeneration and recovery of cardiac function.

在一些示例中,组合物可以应用于制备增强大脑细胞生长调节、提高认知功能、促进营养补充、抑制炎症和/或抑制细胞凋亡的制剂中。在这种情况下,组合物中微藻提取物能够促进脂肪酸被人体吸收,从而能够有助于增强大脑细胞生长调节、提高认知功能、促进营养补充、抑制炎症和抑制细胞凋亡。In some examples, the composition can be used to prepare a preparation that enhances brain cell growth regulation, improves cognitive function, promotes nutritional supplementation, inhibits inflammation and/or inhibits apoptosis. In this case, the microalgae extract in the composition can promote the absorption of fatty acids by the human body, thereby helping to enhance brain cell growth regulation, improve cognitive function, promote nutritional supplementation, inhibit inflammation and inhibit apoptosis.

因此,本公开还能够提供一种组合物在制备增强大脑细胞生长调节、提高认知功能、促进营养补充、抑制炎症和/或抑制细胞凋亡的制剂中的应用。另外,本公开还能够提供一种组合物在增强大脑细胞生长调节、提高认知功能、促进营养补充、抑制炎症和/或抑制细胞凋亡中的应用。Therefore, the present disclosure can also provide a composition for use in preparing a preparation for enhancing brain cell growth regulation, improving cognitive function, promoting nutritional supplementation, inhibiting inflammation and/or inhibiting cell apoptosis. In addition, the present disclosure can also provide a composition for use in enhancing brain cell growth regulation, improving cognitive function, promoting nutritional supplementation, inhibiting inflammation and/or inhibiting cell apoptosis.

在本公开的一些示例中,微藻提取物和组合物的应用可以为非诊断目的的应用。In some examples of the present disclosure, the use of microalgae extracts and compositions can be for non-diagnostic purposes.

在一些示例中,本发明提供的含有微藻提取物和脂肪酸的组合物有以下效果: In some examples, the composition containing microalgae extract and fatty acid provided by the present invention has the following effects:

(l)改善认知功能障碍,包括学习障碍和记忆力减退;(l) Improve cognitive dysfunction, including learning disabilities and memory loss;

(2)缓解神经退行性病变,包括阿尔茨海默症、帕金森症;(2) Alleviate neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease;

(3)减轻注意力缺陷多动障碍(ADHD);(3) Alleviate attention deficit hyperactivity disorder (ADHD);

(4)缓解抑郁症;(4) Relieve depression;

(5)减轻焦虑症;(5) Reduce anxiety;

(6)减轻大脑炎症;(6) Reduce brain inflammation;

(7)减轻干眼症;(7) Relieve dry eye syndrome;

(8)减轻年龄相关性黄斑变性(AMD);(8) Reduce age-related macular degeneration (AMD);

(9)防治儿童视力发育问题;(9) Prevent and treat children’s vision development problems;

(10)减少视网膜病变;(10) Reduce retinopathy;

(11)减少角膜问题;(11) Reduce corneal problems;

(12)青少儿智力开发。(12) Intellectual development of young people.

另外,在一些示例中,本发明提供的含有微藻提取物和脂肪酸的组合物有以下效果:In addition, in some examples, the composition containing microalgae extract and fatty acid provided by the present invention has the following effects:

(l)预防高血压;(l) Preventing hypertension;

(2)预防冠心病;(2) Prevent coronary heart disease;

(3)减缓心力衰竭进展;(3) Slow down the progression of heart failure;

(4)减缓动脉粥样硬化的进展;(4) Slow down the progression of atherosclerosis;

(5)有助于心肌梗死后的康复,促进心肌再生和心脏功能的恢复。(5) It helps in recovery after myocardial infarction and promotes myocardial regeneration and recovery of cardiac function.

此外,本公开提供的含有微藻提取物和脂肪酸的组合物还可以用于阿尔兹海默症适应症研究。可以改善阿尔兹海默症及其相关症状。换言之,本公开还提供一种微藻提取物在制备改善阿尔兹海默症及其相关症状的制剂中的应用。In addition, the composition containing microalgae extract and fatty acid provided by the present disclosure can also be used for Alzheimer's disease indication research. Alzheimer's disease and its related symptoms can be improved. In other words, the present disclosure also provides a use of a microalgae extract in preparing a preparation for improving Alzheimer's disease and its related symptoms.

此外,本发明提供的含有微藻提取物和脂肪酸的组合物还可以用于改善抑郁症。换言之,本发明还提供一种微藻提取物在制备改善抑郁症的制剂中的应用。In addition, the composition containing the microalgae extract and fatty acids provided by the present invention can also be used to improve depression. In other words, the present invention also provides a use of the microalgae extract in preparing a preparation for improving depression.

此外,本发明提供的含有微藻提取物和脂肪酸的组合物还可以提供运动营养,促进运动员大脑吸收DHA提高运动表现。In addition, the composition containing the microalgae extract and fatty acids provided by the present invention can also provide sports nutrition, promote the absorption of DHA by the athlete's brain and improve sports performance.

另外,本公开还提供一种组合物的制备方法,包括以下步骤:将脂肪酸与微藻提取物两者物理混合,得到组合物。其中,脂肪酸是非微藻提取物自带的脂肪酸。本公开的微藻提取物具有促进脂肪酸跨越血脑屏障的效果,且仅将脂肪酸与微藻提取物两者物理混合,即可使组合物进入小肠和/或肝脏等部位后能够自动合成溶血极性脂质,因此,本公开能够提供一种合成工艺简单的组合物的制备方法,不需要额外添加工艺助剂,能够降低溶剂残留的风险。In addition, the present disclosure also provides a method for preparing a composition, comprising the following steps: physically mixing fatty acids and microalgae extracts to obtain a composition. The fatty acids are fatty acids that are not contained in the microalgae extracts. The microalgae extracts disclosed in the present disclosure have the effect of promoting fatty acids to cross the blood-brain barrier, and only physically mixing the fatty acids and microalgae extracts can allow the composition to automatically synthesize hemolytic polar lipids after entering the small intestine and/or liver and other parts. Therefore, the present disclosure can provide a method for preparing a composition with a simple synthesis process, which does not require the addition of additional process additives and can reduce the risk of solvent residues.

综上所述,根据本公开,能够提供一种可促进脂肪酸吸收及跨越血脑屏障的微藻提取物及其组合物的应用。In summary, according to the present disclosure, a microalgae extract and a composition thereof that can promote fatty acid absorption and cross the blood-brain barrier can be provided.

本公开通过将微藻提取物与非自带脂肪酸配合使用,能够有助于促进使用者吸收脂肪酸,特别是提高心脏和大脑中的总脂肪酸和目标脂肪酸的含量。特别地,微藻提取物中的极性脂可促进脂肪酸吸收和跨越血脑屏障,因此对因缺乏特定脂肪酸而引起的大脑健康问题及疾病,可提供辅助治疗作用(即微藻提取物可以应用在制备促使脂肪酸进入大脑的制剂中)。The present disclosure can help promote the user's absorption of fatty acids, especially increase the content of total fatty acids and target fatty acids in the heart and brain, by using microalgae extracts in combination with non-self-contained fatty acids. In particular, the polar lipids in the microalgae extracts can promote fatty acid absorption and crossing the blood-brain barrier, thus providing auxiliary treatment for brain health problems and diseases caused by a lack of specific fatty acids (i.e., the microalgae extracts can be used in the preparation of preparations that promote the entry of fatty acids into the brain).

本公开中的微藻提取物来源于新食品原料,具有较高的营养及药用价值,长期食用没有明显的毒副作用。可用于开发用于大脑和眼部健康的产品,如缓解神经退行性病变、抑郁症、年龄相关性黄斑病变等疾病等,具有重要的实际应用意义。The microalgae extract disclosed in the present invention is derived from a new food raw material, has high nutritional and medicinal value, and has no obvious toxic side effects after long-term consumption. It can be used to develop products for brain and eye health, such as alleviating neurodegenerative diseases, depression, age-related macular degeneration, etc., and has important practical application significance.

为了进一步说明本公开,以下结合实施例对本公开提供的微藻提取物及其组合物的应用进行详细描述,并结合对比例对本公开实现的有益效果进行充分说明。In order to further illustrate the present disclosure, the application of the microalgae extract and the composition thereof provided by the present disclosure is described in detail below in conjunction with the examples, and the beneficial effects achieved by the present disclosure are fully illustrated in conjunction with the comparative examples.

本发明实施例采用的微藻提取物由小藻科技(安吉)有限公司制备提供,其余试剂为常规购买的原料试剂。其中微藻提取物的制备工艺如下:将拟微球藻絮凝、去絮凝、去盐和干燥得到干藻;使干藻与乙醇接触;除去乙醇,得到微藻提取物。微藻提取物中的极性脂的含量约80%-90%。The microalgae extract used in the embodiment of the present invention is prepared and provided by Xiaozao Technology (Anji) Co., Ltd., and the other reagents are conventionally purchased raw material reagents. The preparation process of the microalgae extract is as follows: flocculating, deflocculating, desalting and drying Pseudochlorophyll to obtain dry algae; contacting the dry algae with ethanol; removing the ethanol to obtain the microalgae extract. The content of polar lipids in the microalgae extract is about 80%-90%.

实施例1Example 1

以玉米油作为溶剂,将微藻提取物与含70%DHA的原料物理混合,得到实施例1的组合物,其中,微藻提取物与含70%DHA的原料的质量比为1:2。其中,含70%DHA的原料为市售的精炼微藻油原料(DHA精炼微藻油,小藻科技(安吉)有限公司)。Using corn oil as a solvent, the microalgae extract and the raw material containing 70% DHA were physically mixed to obtain the composition of Example 1, wherein the mass ratio of the microalgae extract to the raw material containing 70% DHA was 1:2. The raw material containing 70% DHA was a commercially available refined microalgae oil raw material ( DHA refined microalgae oil, Xiaozao Technology (Anji) Co., Ltd.

实施例2Example 2

以玉米油作为溶剂,将微藻提取物与含70%DHA的原料物理混合,得到实施例2的组合物,其中,微藻提取物与含70%DHA的原料的质量比为1:1。The microalgae extract and the raw material containing 70% DHA were physically mixed using corn oil as a solvent to obtain the composition of Example 2, wherein the mass ratio of the microalgae extract to the raw material containing 70% DHA was 1:1.

对比例1 Comparative Example 1

以玉米油作为溶剂,加入微藻提取物,其中,加入的微藻提取物的质量与实施例1中相同。Corn oil was used as a solvent, and microalgae extract was added, wherein the mass of the added microalgae extract was the same as that in Example 1.

对比例2Comparative Example 2

以玉米油作为溶剂,加入微藻提取物,其中,加入的微藻提取物的质量与实施例2中相同。Corn oil was used as a solvent, and microalgae extract was added, wherein the mass of the added microalgae extract was the same as that in Example 2.

对比例3Comparative Example 3

以玉米油作为溶剂,加入含70%DHA的原料(DHA精炼微藻油),加入的含70%DHA的原料质量与实施例1中含70%DHA的原料相同。Corn oil was used as solvent and raw materials containing 70% DHA ( DHA refined microalgae oil), the mass of the raw material containing 70% DHA added is the same as the raw material containing 70% DHA in Example 1.

对比例4Comparative Example 4

以玉米油作为溶剂,加入磷虾油。其中,磷虾油为市售产品(山东康境海洋生物工程有限公司南极磷虾油)。Corn oil was used as a solvent, and krill oil was added, wherein the krill oil was a commercially available product (Antarctic krill oil from Shandong Kangjing Marine Bioengineering Co., Ltd.).

对比例5Comparative Example 5

以玉米油作为溶剂,加入磷脂酰丝氨酸和含70%DHA的原料物理混合,其中,磷脂酰丝氨酸与含70%DHA的原料的质量比为1:1。Corn oil is used as a solvent, and phosphatidylserine and a raw material containing 70% DHA are added and physically mixed, wherein the mass ratio of phosphatidylserine to the raw material containing 70% DHA is 1:1.

功效验证实验Efficacy verification experiment

准备三月龄C57BL/6雄性小鼠共40只,随机分8组,每组5只,在SPF级鼠房饲养。小鼠在适应饲养环境1个月后通过灌胃方式进行物料饲喂。分别设空白对照组、实施例组1-2,对比例组1-5,每天每只灌胃受试物如表1所示。饲喂15天后进行组织器官取材。小鼠经异氟烷麻醉约30秒后,取脑置于1.5毫升聚乙烯管中,标记,并转移到干冰乙醇混合物中快速冷冻,随后移入-80摄氏度冰箱进行冷冻保存直至脂质提取。脂质提取按照如下步骤进行:将冷冻保存上述每管器官切出20-50毫克样本各置于新的聚乙烯管中,并加入800微升提前配置的比例为1:1的0.1N盐酸和乙醇混合液,将样本通过多通道研磨机(塞尔特型号为SRT-24)研磨1分钟,取出样本,呈现乳状。在试管中加入400微升三氯甲烷(氯仿),震动试管约30秒使其充分混合,将试管转移至离心机进行离心操作(5分钟,4摄氏度,18000xg)。随后取出试管,弃上清液,并风干残余液体,由此分离出的固体即为脂质,将其冷冻保存。A total of 40 three-month-old C57BL/6 male mice were prepared and randomly divided into 8 groups, 5 mice in each group, and raised in an SPF mouse house. After the mice adapted to the breeding environment for 1 month, they were fed by gavage. A blank control group, embodiment groups 1-2, and comparative groups 1-5 were set up respectively, and the test substances were gavaged every day as shown in Table 1. Tissue and organ sampling was performed after 15 days of feeding. After the mice were anesthetized with isoflurane for about 30 seconds, the brain was taken and placed in a 1.5 ml polyethylene tube, marked, and transferred to a dry ice ethanol mixture for rapid freezing, and then moved to a -80 degree Celsius refrigerator for cryopreservation until lipid extraction. Lipid extraction was carried out according to the following steps: 20-50 mg of samples were cut out of each tube of the above-mentioned organs for cryopreservation and placed in a new polyethylene tube, and 800 microliters of a 0.1N hydrochloric acid and ethanol mixture with a ratio of 1:1 in advance were added, and the samples were ground for 1 minute by a multi-channel grinder (Celter model SRT-24), and the samples were taken out and presented as milky. Add 400 microliters of chloroform to the test tube, shake the test tube for about 30 seconds to mix it thoroughly, and transfer the test tube to a centrifuge for centrifugation (5 minutes, 4 degrees Celsius, 18000xg). Then take out the test tube, discard the supernatant, and air-dry the residual liquid. The solid separated is lipid, which is frozen and stored.

表1.各实验组灌胃受试物
Table 1. Test substances administered orally in each experimental group

脂肪酸含量检测Fatty acid content detection

将试样置于105℃环境中烘烤约40min,待样品完全干燥后,取出并冷却至室温。将干燥后的试样称量记重,置于水解管中,加入0.25mL内标溶液(C11:0甲酯-甲醇溶液,2mg/mL)。往水解管中加入5mLNaOH-甲醇溶液(2%,W/V),充氮30s,加塞密封,置于80℃水浴环境中水解约40min。取出放冷,再往水解管中加入10mL硫酸-甲醇溶液(5%,W/V),充氮30s,加塞密封,置于沸水浴中反应约20min。取出放冷,往水解管中加入5mL正己烷,漩涡振荡1min,再加入15mL水,静置约5min。取上层正己烷溶液1mL过滤至进样小瓶中,通过气相色谱进样检测,记录各脂肪酸的峰面积。将已知浓度的脂肪酸甲酯混合标准溶液通过气相色谱进样检测,记录各脂肪酸的峰面积。通过对比标准曲线中不同浓度标品峰面积计算样品中脂肪酸含量。结果见表2。Place the sample in a 105℃ environment and bake for about 40 minutes. After the sample is completely dried, take it out and cool it to room temperature. Weigh the dried sample and place it in a hydrolysis tube. Add 0.25mL of internal standard solution (C11:0 methyl ester-methanol solution, 2mg/mL). Add 5mL of NaOH-methanol solution (2%, W/V) to the hydrolysis tube, fill it with nitrogen for 30s, seal it with a stopper, and place it in an 80℃ water bath for hydrolysis for about 40min. Take it out and let it cool. Then add 10mL of sulfuric acid-methanol solution (5%, W/V) to the hydrolysis tube, fill it with nitrogen for 30s, seal it with a stopper, and place it in a boiling water bath for reaction for about 20min. Take it out and let it cool. Add 5mL of n-hexane to the hydrolysis tube, vortex it for 1min, then add 15mL of water and let it stand for about 5min. Take 1mL of the upper n-hexane solution and filter it into an injection vial. Detect it by gas chromatography injection and record the peak area of each fatty acid. A mixed standard solution of fatty acid methyl esters with known concentrations was tested by gas chromatography injection, and the peak area of each fatty acid was recorded. The fatty acid content in the sample was calculated by comparing the peak areas of the standard samples with different concentrations in the standard curve. The results are shown in Table 2.

表2.实验组脑组织中各脂肪酸含量(%)

Table 2. Content of fatty acids in brain tissue of experimental groups (%)

注:空白组vs实施例和对比例,#为p<0.05;##为p<0.01;###为p<0.001,####为p<0.0001;Note: Blank group vs. Example and Comparative Example, # means p<0.05; ## means p<0.01; ### means p<0.001, #### means p<0.0001;

实施例1vs对比例,a为p<0.05;b为p<0.01;c为p<0.001;d为p<0.0001;Example 1 vs. Comparative Example, a is p<0.05; b is p<0.01; c is p<0.001; d is p<0.0001;

实施例2vs对比例,e为p<0.05;f为p<0.01;g为p<0.001;h为p<0.0001;Example 2 vs. Comparative Example, e is p<0.05; f is p<0.01; g is p<0.001; h is p<0.0001;

表2中的从统计学上看无显著差异的一些数据不是可以比较的对象。Some data in Table 2 that are not statistically significantly different are not comparable.

为了进一步验证微藻提取物在促脂肪酸吸收方面的功效,选择空白组和实施例1的小鼠测量了心脏中的脂肪酸含量,结果如表3所示。In order to further verify the efficacy of the microalgae extract in promoting fatty acid absorption, the blank group and mice in Example 1 were selected to measure the fatty acid content in the heart. The results are shown in Table 3.

表3实验组心脏组织中各脂肪酸含量(%)
Table 3 Fatty acid content in heart tissue of experimental group (%)

蛋白组学实验Proteomics experiments

蛋白提取与测定:从冷冻组织样品中取样,添加液氮后研磨,再置于1.5mL离心管中。加入裂解液、磷酸酶抑制剂和1mM PMSF,使用冷研仪在-35℃下研磨。研磨后的样本在4℃下以12000rpm离心10分钟,取上清液。使用BCA法测定蛋白浓度,蛋白溶液存于-80℃。Protein extraction and determination: Take samples from frozen tissue samples, add liquid nitrogen and grind them, then place them in 1.5mL centrifuge tubes. Add lysis buffer, phosphatase inhibitors and 1mM PMSF, and grind them at -35℃ using a cold grinder. Centrifuge the ground samples at 12000rpm for 10 minutes at 4℃, and take the supernatant. Use the BCA method to determine the protein concentration, and store the protein solution at -80℃.

蛋白酶解与标记:根据蛋白浓度,取50μg蛋白加入DTT至终浓度5mM,55℃孵育30分钟,随后在室温下加入碘乙酰胺至10mM,避光15分钟。加入6倍丙酮,-20℃保存超过四小时,再以8000×g离心10分钟收集沉淀。沉淀用200mM TEAB复溶,并加入1/50质量的1mg/mL Trypsin-TPCK,在37℃消化过夜。酶解后样品冻干,再加入100mM TEAB进行TMT标记,最后加入5%羟胺终止反应并冻干保存。Proteolysis and labeling: According to the protein concentration, take 50μg protein and add DTT to a final concentration of 5mM, incubate at 55℃ for 30 minutes, then add iodoacetamide to 10mM at room temperature and protect from light for 15 minutes. Add 6 times acetone and store at -20℃ for more than four hours, then collect the precipitate by centrifugation at 8000×g for 10 minutes. The precipitate is re-dissolved with 200mM TEAB, and 1/50 mass of 1mg/mL Trypsin-TPCK is added and digested at 37℃ overnight. After enzymatic hydrolysis, the sample is lyophilized, and then 100mM TEAB is added for TMT labeling. Finally, 5% hydroxylamine is added to terminate the reaction and lyophilized for storage.

液相色谱分离:使用Agilent 1100HPLC和Zorbax Extend-C18窄径柱对样品进行分离。根据设定的梯度洗脱条件,从8到54分钟内收集样品至离心管中,冷冻保存。 Liquid chromatography separation: Agilent 1100HPLC and Zorbax Extend-C18 narrow-bore columns were used to separate the samples. According to the set gradient elution conditions, the samples were collected into centrifuge tubes from 8 to 54 minutes and stored in the freezer.

液相色谱-质谱联用分析:使用EASY-nLC 1200系统进行肽段分离,之后通过Q Exactive HF质谱仪分析。设定一级MS和MS/MS的分辨率和最大注射时间,对选定的肽段进行扫描和数据依赖型分析。LC-MS analysis: Peptide separation was performed using an EASY-nLC 1200 system and subsequent analysis was performed using a Q Exactive HF mass spectrometer. The resolution and maximum injection time for primary MS and MS/MS were set to scan and perform data-dependent analysis on the selected peptides.

数据处理与功能分析:将质谱数据导入Proteome Discoverer软件进行处理。设置适当的质量容差和修饰,对差异蛋白进行统计和生物信息学分析,包括GO(Gene Ontology)和KEGG通路分析,及基于string数据库的蛋白质互作网络构建。蛋白组学结果如图2至图4、以及表4所示。图2是示出了本公开示例所涉及的实施例1和空白组的蛋白质组学及生物信息学分析的火山图;图3是示出了本公开示例所涉及的实施例1和空白组的蛋白质组学及生物信息学分析的热图;图4是示出了本公开示例所涉及的实施例1和空白组的蛋白质组学及生物信息学分析的通过GO富集分析识别出的途径的示意图。Data processing and functional analysis: The mass spectrometry data was imported into Proteome Discoverer software for processing. Appropriate mass tolerance and modification were set to perform statistical and bioinformatics analysis on the differential proteins, including GO (Gene Ontology) and KEGG pathway analysis, and protein interaction network construction based on the string database. The proteomics results are shown in Figures 2 to 4, and Table 4. Figure 2 is a volcano map showing the proteomics and bioinformatics analysis of Example 1 and a blank group involved in the examples of the present disclosure; Figure 3 is a heat map showing the proteomics and bioinformatics analysis of Example 1 and a blank group involved in the examples of the present disclosure; Figure 4 is a schematic diagram showing the pathways identified by GO enrichment analysis of the proteomics and bioinformatics analysis of Example 1 and a blank group involved in the examples of the present disclosure.

表4实施例1与空白组对比上调及下调信号通路及其效果

Table 4 Comparison of up-regulated and down-regulated signal pathways and their effects between Example 1 and the blank group

功效验证结果分析Efficacy verification results analysis

通过空白组和对比例3-5的结果可以发现,小鼠大脑皮层中DHA及其他脂肪酸的含量并没有显著差异。这表明仅通过补充DHA、磷虾油或与磷脂酰丝氨酸配合的DHA,无法有效增强DHA穿越血脑屏障。而实施例1和实施例2,特别是实施例1可显著增加脑组织中总脂肪酸和几类重要脂肪酸,如棕榈酸(C16:0)、硬脂酸(C18:0)、油酸(C18:1n9c)、二十二碳六烯酸(C22:6n3,DHA)、花生四烯酸(C20:4n6)的含量。这说明将微藻提取物与含脂肪酸的原料混合后,可促进脂肪酸通过血脑屏障,显著提高大脑中总脂肪酸和目标脂肪酸含量。It can be found from the results of the blank group and comparative examples 3-5 that there is no significant difference in the content of DHA and other fatty acids in the mouse cerebral cortex. This shows that only by supplementing DHA, krill oil or DHA in combination with phosphatidylserine, it is impossible to effectively enhance DHA to cross the blood-brain barrier. However, Example 1 and Example 2, especially Example 1, can significantly increase the content of total fatty acids and several important fatty acids in brain tissue, such as palmitic acid (C16:0), stearic acid (C18:0), oleic acid (C18:1n9c), docosahexaenoic acid (C22:6n3, DHA), and arachidonic acid (C20:4n6). This shows that mixing the microalgae extract with the raw material containing fatty acids can promote the passage of fatty acids through the blood-brain barrier and significantly increase the total fatty acids and target fatty acid content in the brain.

实施例1与对比例4比较,对于提高脑组织中的脂肪酸含量特别是DHA也有显著性差异,说明微藻提取物中所含有的极性脂比磷虾油中的磷脂对于DHA跨越血脑屏障有更好的效果。这可能是因为微藻提取物含有更多的溶血极性脂成分,而磷虾油主要含有的极性脂是磷脂酰胆碱(PC),磷虾油中的EPA和DHA位于磷脂酰胆碱(PC)的SN2位置,因此在消化过程中由胰腺磷脂酶A2作用变成游离脂肪酸DHA和EPA,无法生成输跨越血脑屏障所需的LPC-EPA或LPC-DHA。因此,食用磷虾油不会导致大脑中EPA和DHA的显著富集,只有用特异性针对SN1酯键的脂肪酶预处理磷虾油,才能生成LPC-EPA和LPC-DHA,使它们在大脑中的富集。而溶血极性脂与PC相比,不需要经过磷脂酶A2(PLA2)转化成LPC的步骤就可以被转运,因此更容易通过与主动转运蛋白Mfsd2a结合而跨越血脑屏障。Compared with Comparative Example 4, Example 1 also has significant differences in increasing the fatty acid content in brain tissue, especially DHA, indicating that the polar lipids contained in the microalgae extract have a better effect on DHA crossing the blood-brain barrier than the phospholipids in krill oil. This may be because the microalgae extract contains more hemolytic polar lipid components, while the polar lipids mainly contained in krill oil are phosphatidylcholine (PC). The EPA and DHA in the krill oil are located at the SN2 position of phosphatidylcholine (PC). Therefore, during the digestion process, they are converted into free fatty acids DHA and EPA by the action of pancreatic phospholipase A2, and LPC-EPA or LPC-DHA required for crossing the blood-brain barrier cannot be generated. Therefore, consuming krill oil will not lead to significant enrichment of EPA and DHA in the brain. Only by pretreating krill oil with a lipase specific for the SN1 ester bond can LPC-EPA and LPC-DHA be generated, so that they are enriched in the brain. Compared with PC, lysopolar lipids can be transported without the need for phospholipase A2 (PLA2) to convert them into LPC, and are therefore more likely to cross the blood-brain barrier by binding to the active transporter Mfsd2a.

对比空白组和对比例5,可以看到直接将磷脂酰丝氨酸和含70%DHA的原料物理混合的对比例5中脂肪酸含量相较于空白组不升反降,说明非化学键合的磷脂酰丝氨酸和脂肪酸直接物理混合的效果不佳。 Comparing the blank group and comparative example 5, it can be seen that the fatty acid content in comparative example 5, in which phosphatidylserine and a raw material containing 70% DHA are directly physically mixed, is decreased instead of increased compared with the blank group, indicating that the direct physical mixing of non-chemically bonded phosphatidylserine and fatty acids is not effective.

此外,实施例1比实施例2提高脑组织中总脂肪酸及目标脂肪酸的效果更显著,当微藻提取物与含70%DHA的原料的比例为0.5:1时,小鼠大脑中脂肪酸含量,尤其是DHA的提升,比比例为1:1时更为显著。这表明在穿越血脑屏障时,并非载体的量越多效果越好。In addition, Example 1 has a more significant effect on increasing the total fatty acids and target fatty acids in brain tissue than Example 2. When the ratio of microalgae extract to the raw material containing 70% DHA is 0.5:1, the increase in fatty acid content in the mouse brain, especially DHA, is more significant than when the ratio is 1:1. This shows that when crossing the blood-brain barrier, the more the amount of carrier, the better the effect.

另外,从表3中可以看到,实施例1与空白组相比,各脂肪酸及总脂肪酸的含量有增加的趋势,验证了组合物具有提高心脏中各脂肪酸及总脂肪酸的含量的潜在作用。由于实施例1在心脏中所提高的脂肪酸主要是不饱和脂肪酸,这对心脏的功能有以下的健康益处:(1)降低胆固醇水平:不饱和脂肪酸,特别是Omega-3脂肪酸,有助于降低LDL(低密度脂蛋白)胆固醇的水平,从而降低心脏疾病的风险。(2)抗炎作用:Omega-3脂肪酸在体内转化为抗炎物质,有助于减轻心血管系统的炎症反应。(3)降低血压:不饱和脂肪酸,尤其是Omega-3脂肪酸,已被证明可以有助于降低血压,从而减少心血管疾病的风险。(4)减少血栓形成:不饱和脂肪酸可以降低血液中的凝血性,减少血栓形成的风险。组合物在心脏方面的有益作用说明其在预防高血压、冠心病、心力衰竭、心肌梗塞等方面具有有益作用。In addition, it can be seen from Table 3 that compared with the blank group, the content of each fatty acid and the total fatty acid in Example 1 has an increasing trend, which verifies that the composition has the potential to increase the content of each fatty acid and the total fatty acid in the heart. Since the fatty acids increased in the heart in Example 1 are mainly unsaturated fatty acids, this has the following health benefits for the function of the heart: (1) Lowering cholesterol levels: Unsaturated fatty acids, especially Omega-3 fatty acids, help to lower the level of LDL (low-density lipoprotein) cholesterol, thereby reducing the risk of heart disease. (2) Anti-inflammatory effect: Omega-3 fatty acids are converted into anti-inflammatory substances in the body, which help to reduce the inflammatory response of the cardiovascular system. (3) Lowering blood pressure: Unsaturated fatty acids, especially Omega-3 fatty acids, have been shown to help lower blood pressure, thereby reducing the risk of cardiovascular disease. (4) Reducing thrombosis: Unsaturated fatty acids can reduce the coagulability in the blood and reduce the risk of thrombosis. The beneficial effects of the composition on the heart indicate that it has a beneficial effect in preventing hypertension, coronary heart disease, heart failure, myocardial infarction, etc.

蛋白组学结果分析Proteomics results analysis

实施例1因摄入微藻提取物和DHA混合物而在大脑中显示出较高水平的脂肪酸含量。为进一步分析大脑内蛋白质表达的变化,我们使用小鼠大脑样本对实施例1和空白组进行了蛋白质组学的比较分析。通过筛选大脑中表达水平差异的蛋白质发现,其中有3个蛋白质显著下调,11个蛋白质显著上调。图2和图3分别使用火山图和热图展示了这些蛋白质的相对差异。经过GO分析,发现这些蛋白质与图4所示的13条通路相关。通路活性的变化,无论是增加还是减少,均可见于表4。可以观察到,与空白组相比,实施例1不仅增加了某些跨膜转运通路的活性,还促进了细胞生长,减少了组织的炎症反应,并抑制了细胞凋亡。此外,表4还列出了从KEGG分析得到的增强的视黄醇代谢水平。总的来说,这些数据支持了微藻提取物和DHA混合物在改善脑部脂质代谢和促进脑健康方面的效果,主要包括增强细胞生长调节、提高认知功能、促进营养补充、抑制炎症、抑制细胞凋亡等。Example 1 showed a higher level of fatty acid content in the brain due to the intake of microalgae extract and DHA mixture. To further analyze the changes in protein expression in the brain, we used mouse brain samples to perform a comparative proteomic analysis of Example 1 and the blank group. By screening the proteins with different expression levels in the brain, it was found that 3 proteins were significantly downregulated and 11 proteins were significantly upregulated. Figures 2 and 3 use volcano maps and heat maps to show the relative differences of these proteins, respectively. After GO analysis, it was found that these proteins were associated with the 13 pathways shown in Figure 4. Changes in pathway activity, whether increased or decreased, can be seen in Table 4. It can be observed that compared with the blank group, Example 1 not only increased the activity of certain transmembrane transport pathways, but also promoted cell growth, reduced tissue inflammatory response, and inhibited cell apoptosis. In addition, Table 4 also lists the enhanced retinol metabolism levels obtained from KEGG analysis. In general, these data support the effects of microalgae extract and DHA mixture in improving brain lipid metabolism and promoting brain health, mainly including enhancing cell growth regulation, improving cognitive function, promoting nutritional supplementation, inhibiting inflammation, inhibiting cell apoptosis, etc.

从以上结果可以看出,微藻提取物能促进脂肪酸吸收,且能近似等效地促进各种必需脂肪酸穿越血脑屏障,并使这些脂肪酸的增加比例保持一致,不会改变大脑脂质的组成,有助于保持大脑脂质的稳态。另外,含有微藻提取物和脂肪酸的组合物具有提高心脏中各脂肪酸及总脂肪酸的含量的潜在作用。From the above results, it can be seen that the microalgae extract can promote the absorption of fatty acids, and can promote various essential fatty acids to cross the blood-brain barrier in an approximately equivalent manner, and keep the increase ratio of these fatty acids consistent, without changing the composition of brain lipids, and help maintain the homeostasis of brain lipids. In addition, the composition containing microalgae extract and fatty acids has the potential to increase the content of various fatty acids and total fatty acids in the heart.

综上所述,本发明可以提供一种可促进脂肪酸吸收及跨越血脑屏障的微藻提取物及其组合物的应用,通过将本公开的微藻提取物与脂肪酸配合使用,能够有助于促进使用者吸收脂肪酸,特别是提高心脏和大脑中的脂肪酸含量。In summary, the present invention can provide an application of a microalgae extract and a composition thereof that can promote fatty acid absorption and crossing the blood-brain barrier. By using the microalgae extract disclosed in the present invention in combination with fatty acids, it can help promote the user's absorption of fatty acids, especially increase the fatty acid content in the heart and brain.

虽然以上结合附图和示例对本公开进行了具体说明,但是可以理解,上述说明不以任何形式限制本公开。本领域技术人员在不偏离本公开的实质精神和范围的情况下可以根据需要对本公开进行变形和变化,这些变形和变化均落入本公开的范围内。 Although the present disclosure is specifically described above in conjunction with the accompanying drawings and examples, it is to be understood that the above description does not limit the present disclosure in any form. Those skilled in the art may modify and change the present disclosure as needed without departing from the essential spirit and scope of the present disclosure, and these modifications and changes all fall within the scope of the present disclosure.

Claims (30)

一种微藻提取物在促进脂肪酸吸收和/或脂肪酸跨越血脑屏障中的应用,其特征在于,所述微藻提取物含有极性脂,所述极性脂在所述微藻提取物中占比为30%至99.9%,所述脂肪酸为非所述微藻提取物中自带的脂肪酸。A use of a microalgae extract in promoting fatty acid absorption and/or fatty acid crossing the blood-brain barrier, characterized in that the microalgae extract contains polar lipids, the polar lipids account for 30% to 99.9% of the microalgae extract, and the fatty acids are fatty acids that are not native to the microalgae extract. 根据权利要求1所述的应用,其特征在于,The use according to claim 1, characterized in that 所述微藻提取物含有磷脂、糖脂和/或甜菜碱酯。The microalgae extract contains phospholipids, glycolipids and/or betaine esters. 根据权利要求1所述的应用,其特征在于,The use according to claim 1, characterized in that 所述微藻提取物与含脂肪酸或含脂肪酸的脂质衍生物的原料物理混合后使用,微藻提取物与所述原料中的脂肪酸的质量比为(1~50):(1~50),所述脂肪酸为棕榈酸(C16:0)、棕榈油酸(C16:1)、硬脂酸(C18:0)、油酸(C18:1n9c)、亚油酸(C18:2n6c)、α-亚麻酸(C18:3n3)、花生四烯酸(C20:4n6)、二十碳五烯酸(C20:5n3)、二十二碳六烯酸(C22:6n3)和二十二碳五烯酸(C22:5n6)中的任意一种或多种。The microalgae extract is physically mixed with a raw material containing fatty acids or lipid derivatives containing fatty acids and then used. The mass ratio of the microalgae extract to the fatty acids in the raw material is (1-50):(1-50), and the fatty acids are any one or more of palmitic acid (C16:0), palmitoleic acid (C16:1), stearic acid (C18:0), oleic acid (C18:1n9c), linoleic acid (C18:2n6c), α-linolenic acid (C18:3n3), arachidonic acid (C20:4n6), eicosapentaenoic acid (C20:5n3), docosahexaenoic acid (C22:6n3) and docosapentaenoic acid (C22:5n6). 根据权利要求1所述的应用,其特征在于,The use according to claim 1, characterized in that 所述微藻提取物与含脂肪酸或含脂肪酸的脂质衍生物的原料物理混合后使用,微藻提取物与所述原料中的脂肪酸的质量比为(1~50):(1~50),所述脂质衍生物选自甘油酯型脂肪酸、乙酯型脂肪酸、磷脂型脂肪酸、糖脂型脂肪酸、固醇酯型脂肪酸和/或鞘脂型脂肪酸中的任意一种或多种。The microalgae extract is physically mixed with a raw material containing fatty acids or lipid derivatives containing fatty acids and then used, the mass ratio of the microalgae extract to the fatty acids in the raw material is (1-50):(1-50), and the lipid derivative is selected from any one or more of glyceride fatty acids, ethyl ester fatty acids, phospholipid fatty acids, glycolipid fatty acids, sterol ester fatty acids and/or sphingolipid fatty acids. 根据权利要求1所述的应用,其特征在于,The use according to claim 1, characterized in that 所述微藻提取物来自于蓝藻、绿藻或红藻。The microalgae extract is derived from blue algae, green algae or red algae. 根据权利要求1所述的应用,其特征在于,The use according to claim 1, characterized in that 所述微藻提取物来自于拟微球藻、异胶藻、三角褐指藻、新月菱形藻、雨生红球藻、裸藻、螺旋藻、球状念珠藻、小球藻、盐藻和莱茵衣藻中的任意一种或多种。The microalgae extract is from any one or more of Nannochloropsis spp., Heteroglea spp., Phaeodactylum triangularis, Nitzschia closterium, Haematococcus pluvialis, Euglena, Spirulina, Nostoc sphericalensis, Chlorella vulgaris, Dunaliella and Chlamydomonas reinhardtii. 一种微藻提取物在提高心脏中脂肪酸含量上的应用,其特征在于,所述微藻提取物含有极性脂,所述极性脂在所述微藻提取物中占比为30%至99.9%,所述脂肪酸为非所述微藻提取物中自带的脂肪酸。An application of a microalgae extract for increasing the fatty acid content in the heart, characterized in that the microalgae extract contains polar lipids, the polar lipids account for 30% to 99.9% of the microalgae extract, and the fatty acids are fatty acids that are not native to the microalgae extract. 根据权利要求7所述的应用,其特征在于,The use according to claim 7, characterized in that 所述微藻提取物含有磷脂、糖脂和/或甜菜碱酯。The microalgae extract contains phospholipids, glycolipids and/or betaine esters. 根据权利要求7所述的应用,其特征在于,The use according to claim 7, characterized in that 所述微藻提取物与含脂肪酸或含脂肪酸的脂质衍生物的原料物理混合后使用,微藻提取物与所述原料中的脂肪酸的质量比为(1~50):(1~50),所述脂肪酸为棕榈酸(C16:0)、棕榈油酸(C16:1)、硬脂酸(C18:0)、油酸(C18:1n9c)、亚油酸(C18:2n6c)、α-亚麻酸(C18:3n3)、花生四烯酸(C20:4n6)、二十碳五烯酸(C20:5n3)、二十二碳六烯酸(C22:6n3)和二十二碳五烯酸(C22:5n6)中的任意一种或多种。The microalgae extract is physically mixed with a raw material containing fatty acids or lipid derivatives containing fatty acids and then used. The mass ratio of the microalgae extract to the fatty acids in the raw material is (1-50):(1-50), and the fatty acids are any one or more of palmitic acid (C16:0), palmitoleic acid (C16:1), stearic acid (C18:0), oleic acid (C18:1n9c), linoleic acid (C18:2n6c), α-linolenic acid (C18:3n3), arachidonic acid (C20:4n6), eicosapentaenoic acid (C20:5n3), docosahexaenoic acid (C22:6n3) and docosapentaenoic acid (C22:5n6). 根据权利要求7所述的应用,其特征在于,The use according to claim 7, characterized in that 所述微藻提取物与含脂肪酸或含脂肪酸的脂质衍生物的原料物理混合后使用,微藻提取物与所述原料中的脂肪酸的质量比为(1~50):(1~50),所述脂质衍生物选自甘油酯型脂肪酸、乙酯型脂肪酸、磷脂型脂肪酸、糖脂型脂肪酸、固醇酯型脂肪酸和/或鞘脂型脂肪酸中的任意一种或多种。The microalgae extract is physically mixed with a raw material containing fatty acids or lipid derivatives containing fatty acids and then used, the mass ratio of the microalgae extract to the fatty acids in the raw material is (1-50):(1-50), and the lipid derivative is selected from any one or more of glyceride fatty acids, ethyl ester fatty acids, phospholipid fatty acids, glycolipid fatty acids, sterol ester fatty acids and/or sphingolipid fatty acids. 根据权利要求7所述的应用,其特征在于,The use according to claim 7, characterized in that 所述微藻提取物来自于蓝藻、绿藻或红藻。The microalgae extract is derived from blue algae, green algae or red algae. 根据权利要求7所述的应用,其特征在于,The use according to claim 7, characterized in that 所述微藻提取物来自于拟微球藻、异胶藻、三角褐指藻、新月菱形藻、雨生红球藻、裸藻、螺旋藻、球状念珠藻、小球藻、盐藻和莱茵衣藻中的任意一种或多种。The microalgae extract is from any one or more of Nannochloropsis spp., Heteroglea spp., Phaeodactylum triangularis, Nitzschia closterium, Haematococcus pluvialis, Euglena, Spirulina, Nostoc sphericalensis, Chlorella vulgaris, Dunaliella and Chlamydomonas reinhardtii. 一种微藻提取物在提高大脑中脂肪酸含量上的应用,其特征在于,所述微藻提取物含有极性脂,所述极性脂在所述微藻提取物中占比为30%至99.9%,所述脂肪酸为非所述微藻提取物中自带的脂肪酸。 An application of a microalgae extract for increasing the fatty acid content in the brain, characterized in that the microalgae extract contains polar lipids, the polar lipids account for 30% to 99.9% of the microalgae extract, and the fatty acids are fatty acids that are not native to the microalgae extract. 根据权利要求13所述的应用,其特征在于,The use according to claim 13, characterized in that 所述微藻提取物含有磷脂、糖脂和/或甜菜碱酯。The microalgae extract contains phospholipids, glycolipids and/or betaine esters. 根据权利要求13所述的应用,其特征在于,The use according to claim 13, characterized in that 所述微藻提取物与含脂肪酸或含脂肪酸的脂质衍生物的原料物理混合后使用,微藻提取物与所述原料中的脂肪酸的质量比为(1~50):(1~50),所述脂肪酸为棕榈酸(C16:0)、棕榈油酸(C16:1)、硬脂酸(C18:0)、油酸(C18:1n9c)、亚油酸(C18:2n6c)、α-亚麻酸(C18:3n3)、花生四烯酸(C20:4n6)、二十碳五烯酸(C20:5n3)、二十二碳六烯酸(C22:6n3)和二十二碳五烯酸(C22:5n6)中的任意一种或多种。The microalgae extract is physically mixed with a raw material containing fatty acids or lipid derivatives containing fatty acids and then used. The mass ratio of the microalgae extract to the fatty acids in the raw material is (1-50):(1-50), and the fatty acids are any one or more of palmitic acid (C16:0), palmitoleic acid (C16:1), stearic acid (C18:0), oleic acid (C18:1n9c), linoleic acid (C18:2n6c), α-linolenic acid (C18:3n3), arachidonic acid (C20:4n6), eicosapentaenoic acid (C20:5n3), docosahexaenoic acid (C22:6n3) and docosapentaenoic acid (C22:5n6). 根据权利要求13所述的应用,其特征在于,The use according to claim 13, characterized in that 所述微藻提取物与含脂肪酸或含脂肪酸的脂质衍生物的原料物理混合后使用,微藻提取物与所述原料中的脂肪酸的质量比为(1~50):(1~50),所述脂质衍生物选自甘油酯型脂肪酸、乙酯型脂肪酸、磷脂型脂肪酸、糖脂型脂肪酸、固醇酯型脂肪酸和/或鞘脂型脂肪酸中的任意一种或多种。The microalgae extract is physically mixed with a raw material containing fatty acids or lipid derivatives containing fatty acids and then used, the mass ratio of the microalgae extract to the fatty acids in the raw material is (1-50):(1-50), and the lipid derivative is selected from any one or more of glyceride fatty acids, ethyl ester fatty acids, phospholipid fatty acids, glycolipid fatty acids, sterol ester fatty acids and/or sphingolipid fatty acids. 根据权利要求13所述的应用,其特征在于,The use according to claim 13, characterized in that 所述微藻提取物来自于蓝藻、绿藻或红藻。The microalgae extract is derived from blue algae, green algae or red algae. 根据权利要求13所述的应用,其特征在于,The use according to claim 13, characterized in that 所述微藻提取物来自于拟微球藻、异胶藻、三角褐指藻、新月菱形藻、雨生红球藻、裸藻、螺旋藻、球状念珠藻、小球藻、盐藻和莱茵衣藻中的任意一种或多种。The microalgae extract is from any one or more of Nannochloropsis spp., Heteroglea spp., Phaeodactylum triangularis, Nitzschia closterium, Haematococcus pluvialis, Euglena, Spirulina, Nostoc sphericalensis, Chlorella vulgaris, Dunaliella and Chlamydomonas reinhardtii. 一种组合物,其特征在于,包含微藻提取物、以及非所述微藻提取物中自带的脂肪酸,所述微藻提取物含有极性脂,所述极性脂在所述微藻提取物中占比为30%至99.9%。A composition, characterized in that it comprises a microalgae extract and fatty acids not contained in the microalgae extract, wherein the microalgae extract contains polar lipids, and the polar lipids account for 30% to 99.9% of the microalgae extract. 根据权利要求19所述的组合物,其特征在于,The composition according to claim 19, characterized in that 所述微藻提取物含有磷脂、糖脂和/或甜菜碱酯。 The microalgae extract contains phospholipids, glycolipids and/or betaine esters. 根据权利要求19所述的组合物,其特征在于,The composition according to claim 19, characterized in that 所述微藻提取物与含脂肪酸或含脂肪酸的脂质衍生物的原料物理混合后使用,微藻提取物与所述原料中的脂肪酸的质量比为(1~50):(1~50),所述脂肪酸为棕榈酸(C16:0)、棕榈油酸(C16:1)、硬脂酸(C18:0)、油酸(C18:1n9c)、亚油酸(C18:2n6c)、α-亚麻酸(C18:3n3)、花生四烯酸(C20:4n6)、二十碳五烯酸(C20:5n3)、二十二碳六烯酸(C22:6n3)和二十二碳五烯酸(C22:5n6)中的任意一种或多种。The microalgae extract is physically mixed with a raw material containing fatty acids or lipid derivatives containing fatty acids and then used. The mass ratio of the microalgae extract to the fatty acids in the raw material is (1-50):(1-50), and the fatty acids are any one or more of palmitic acid (C16:0), palmitoleic acid (C16:1), stearic acid (C18:0), oleic acid (C18:1n9c), linoleic acid (C18:2n6c), α-linolenic acid (C18:3n3), arachidonic acid (C20:4n6), eicosapentaenoic acid (C20:5n3), docosahexaenoic acid (C22:6n3) and docosapentaenoic acid (C22:5n6). 根据权利要求19所述的组合物,其特征在于,The composition according to claim 19, characterized in that 所述微藻提取物与含脂肪酸或含脂肪酸的脂质衍生物的原料物理混合后使用,微藻提取物与所述原料中的脂肪酸的质量比为(1~50):(1~50),所述脂质衍生物选自甘油酯型脂肪酸、乙酯型脂肪酸、磷脂型脂肪酸、糖脂型脂肪酸、固醇酯型脂肪酸和/或鞘脂型脂肪酸中的任意一种或多种。The microalgae extract is physically mixed with a raw material containing fatty acids or lipid derivatives containing fatty acids and then used, the mass ratio of the microalgae extract to the fatty acids in the raw material is (1-50):(1-50), and the lipid derivative is selected from any one or more of glyceride fatty acids, ethyl ester fatty acids, phospholipid fatty acids, glycolipid fatty acids, sterol ester fatty acids and/or sphingolipid fatty acids. 根据权利要求19所述的组合物,其特征在于,The composition according to claim 19, characterized in that 所述微藻提取物来自于蓝藻、绿藻或红藻。The microalgae extract is derived from blue algae, green algae or red algae. 根据权利要求19所述的组合物,其特征在于,The composition according to claim 19, characterized in that 所述微藻提取物来自于拟微球藻、异胶藻、三角褐指藻、新月菱形藻、雨生红球藻、裸藻、螺旋藻、球状念珠藻、小球藻、盐藻和莱茵衣藻中的任意一种或多种。The microalgae extract is from any one or more of Nannochloropsis spp., Heteroglea spp., Phaeodactylum triangularis, Nitzschia closterium, Haematococcus pluvialis, Euglena, Spirulina, Nostoc sphericalensis, Chlorella vulgaris, Dunaliella and Chlamydomonas reinhardtii. 根据权利要求19所述的组合物,其特征在于,The composition according to claim 19, characterized in that 所述组合物是食品、药品、保健品、动物营养或兽药,所述组合物还含有药剂学、普通食品、保健食品或特殊医学食品法规允许使用的辅料。The composition is food, medicine, health product, animal nutrition or veterinary medicine, and the composition also contains auxiliary materials permitted by the laws and regulations of pharmacy, common food, health food or special medical food. 根据权利要求19所述的组合物,其特征在于,所述组合物应用于制备改善大脑功能和/或改善眼部功能的制剂中。The composition according to claim 19 is characterized in that the composition is used in the preparation of a preparation for improving brain function and/or improving eye function. 根据权利要求19所述的组合物,其特征在于,The composition according to claim 19, characterized in that 所述改善大脑功能的制剂包括改善认知功能障碍、缓解神经退行性病变、减轻注意力缺陷多动障碍、缓解抑郁症、减轻焦虑症、减轻大脑炎症、青少儿智力开发、改善阿尔兹海默症及其相关症状、和改善抑郁症的制剂中的任意一种或多种。The preparations for improving brain function include any one or more of preparations for improving cognitive dysfunction, alleviating neurodegenerative lesions, alleviating attention deficit hyperactivity disorder, alleviating depression, alleviating anxiety, alleviating brain inflammation, developing the intelligence of adolescents and children, improving Alzheimer's disease and its related symptoms, and improving depression. 根据权利要求19所述的组合物,其特征在于,The composition according to claim 19, characterized in that 所述改善眼部功能的制剂包括减轻干眼症、减少视网膜病变、减少角膜问题、减轻年龄相关性黄斑变性、和防治儿童视力发育问题的制剂中的任意一种或多种。The preparations for improving eye function include any one or more of preparations for alleviating dry eye, reducing retinopathy, reducing corneal problems, alleviating age-related macular degeneration, and preventing and treating children's vision development problems. 根据权利要求19所述的组合物,其特征在于,The composition according to claim 19, characterized in that 所述组合物应用于制备预防高血压、预防冠心病、减缓心力衰竭进展、减缓动脉粥样硬化的进展、促进心肌梗死后的康复、和/或促进心肌再生和心脏功能的恢复的制剂中。The composition is used in preparing preparations for preventing hypertension, preventing coronary heart disease, slowing down the progression of heart failure, slowing down the progression of atherosclerosis, promoting recovery after myocardial infarction, and/or promoting myocardial regeneration and recovery of cardiac function. 根据权利要求19所述的组合物,其特征在于,The composition according to claim 19, characterized in that 所述组合物应用于制备增强大脑细胞生长调节、提高认知功能、促进营养补充、抑制炎症和/或抑制细胞凋亡的制剂中。 The composition is used in preparing preparations for enhancing brain cell growth regulation, improving cognitive function, promoting nutritional supplementation, inhibiting inflammation and/or inhibiting cell apoptosis.
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POORNA C. R. YALAGALA, DHAVAMANI SUGASINI, SRIDEVI DASARATHI, KALIPADA PAHAN, PAPASANI V. SUBBAIAH: "Dietary lysophosphatidylcholine-EPA enriches both EPA and DHA in the brain: potential treatment for depression", JOURNAL OF LIPID RESEARCH, vol. 60, no. 3, 1 March 2019 (2019-03-01), US , pages 566 - 578, XP055723784, ISSN: 0022-2275, DOI: 10.1194/jlr.M090464 *

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