WO2017032270A1 - 预防和/或治疗心脑血管疾病的组合物 - Google Patents

预防和/或治疗心脑血管疾病的组合物 Download PDF

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WO2017032270A1
WO2017032270A1 PCT/CN2016/095979 CN2016095979W WO2017032270A1 WO 2017032270 A1 WO2017032270 A1 WO 2017032270A1 CN 2016095979 W CN2016095979 W CN 2016095979W WO 2017032270 A1 WO2017032270 A1 WO 2017032270A1
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parts
weight
lutein
proanthocyanidins
panax notoginseng
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PCT/CN2016/095979
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English (en)
French (fr)
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陈芳芳
廖炜程
刘华英
许素霞
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厦门金达威集团股份有限公司
厦门金达威生物科技有限公司
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Priority to US15/754,484 priority Critical patent/US10857108B2/en
Publication of WO2017032270A1 publication Critical patent/WO2017032270A1/zh

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/12—Ketones
    • A61K31/122—Ketones having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/115—Fatty acids or derivatives thereof; Fats or oils
    • A23L33/12—Fatty acids or derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A61K31/065—Diphenyl-substituted acyclic alcohols
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/20—Carboxylic 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/20—Carboxylic 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
    • A61K31/202—Carboxylic 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
    • A61K31/385—Heterocyclic compounds having sulfur as a ring hetero atom having two or more sulfur atoms in the same ring
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/66—Phosphorus compounds
    • A61K31/683—Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols
    • A61K31/685—Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols one of the hydroxy compounds having nitrogen atoms, e.g. phosphatidylserine, lecithin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/25—Araliaceae (Ginseng family), e.g. ivy, aralia, schefflera or tetrapanax
    • A61K36/258—Panax (ginseng)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4841—Filling excipients; Inactive ingredients
    • A61K9/4875—Compounds of unknown constitution, e.g. material from plants or animals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/06—Antiarrhythmics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/12—Antihypertensives
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs

Definitions

  • the present invention relates to the field of medicine and health food, and in particular to a composition for preventing and/or treating cardiovascular and cerebrovascular diseases.
  • Cardio-cerebral vascular disease is a general term for diseases of the heart and blood vessels of the heart. It refers to ischemic or hemorrhagic diseases of the heart, brain and whole body tissues caused by hyperlipidemia, blood viscosity, atherosclerosis, and hypertension. It is a common disease that seriously threatens the health of human beings, especially middle-aged and elderly people over 50 years old. Even with the most advanced and perfect treatment methods, more than 50% of survivors of cardiovascular and cerebrovascular accidents cannot fully take care of themselves. The number of people dying from cardiovascular and cerebrovascular diseases in the world is as high as 15 million, ranking first in all causes of death.
  • cardiovascular and cerebrovascular diseases are still mainly prevention, and the main means are to control risk factors and anti-thrombosis.
  • Risk factors for cardiovascular and cerebrovascular diseases fall into two broad categories, namely, risk factors that can be treated, such as hypertension, dyslipidemia, diabetes, smoking, etc., and other types of risk factors that cannot be treated, such as age, gender, and heredity. Control of blood pressure in the normal range, treatment of diabetes, smoking cessation, and treatment of dyslipidemia have been shown to significantly reduce cardiovascular and cerebrovascular events.
  • the inventors of the present invention have continually experimented and surprisingly discovered a series of combinations of components that have protective effects on cardiovascular and cerebrovascular diseases, which have an unexpected synergistic effect in preventing and/or treating cardiovascular and cerebrovascular diseases.
  • the present invention has been completed based on the above findings.
  • a first aspect of the invention provides a composition comprising at least two of docosahexaenoic acid or an ester thereof, coenzyme Q10, lipoic acid and phospholipids, for example two, three or four.
  • the composition comprises a combination selected from any one of the following items i) to xi):
  • Ix docosahexaenoic acid or its ester, lipoic acid and phospholipid
  • composition comprising a combination of docosahexaenoic acid or an ester thereof and coenzyme Q10;
  • the composition comprises a combination of docosahexaenoic acid or an ester thereof, coenzyme Q10, lipoic acid and phospholipids.
  • composition according to any one of the first aspects of the present invention, wherein the content of each component is calculated by weight percentage of one or more selected from the group consisting of:
  • composition of any of the invention, if any, wherein the weight fraction of one or more substances is selected from one or more of the following:
  • the coenzyme Q10 is in the range of 3 to 60 parts by weight (for example, 3 parts, 4 parts, 5 parts, 9 parts, 10 parts, 19 parts, 20 parts, 49 parts, 50 parts or 60 parts, for example, 4 to 50 parts) Parts, 5 to 20 parts, 9 to 19 parts or 8 to 13 parts);
  • c) parts by weight of lipoic acid is from 3 to 50 parts (for example, 3 parts, 4 parts, 5 parts, 9 parts, 10 parts, 19 parts, 20 parts, 39 parts, 40 parts or 50 parts, for example, 4 to 40 parts) Parts, 9 to 20 parts, 20 to 30 parts, 30 to 40 parts or 38 to 43 parts);
  • the proportion by weight of the phospholipid is 1 to 40 parts (for example, 1 part, 2 parts, 3 parts, 4 parts, 5 parts, 9 parts, 10 parts, 29 parts, 30 parts or 40 parts, for example, 5 to 10 parts) 10-20 parts, 2-30 parts, 30-40 parts or 3-8 parts).
  • the composition comprises a combination selected from any one of the following items i) to xi):
  • coenzyme Q10 and lipoic acid the parts by weight are 8 to 13 parts, 38 to 43 parts, respectively;
  • lipoic acid and phospholipids the parts by weight are 38 to 43 parts, respectively, 3 to 8 parts;
  • Ix docosahexaenoic acid or its ester, lipoic acid and phospholipid, the weight fraction of which is 18 to 23 parts, 38 to 43 parts, and 3 to 8 parts, respectively;
  • Coenzyme Q10, lipoic acid and phospholipid the parts by weight are 8-13 parts, 38-43 parts, 3-8 parts, respectively, and
  • the parts by weight are 3 to 43 parts, 3 parts to 53 parts, 3 parts to 43 parts, 1 part to 33 parts, respectively.
  • the parts by weight are 18 to 23 parts, 8 to 13 parts, 38 to 43 parts, and 3 to 8 parts, respectively.
  • a composition according to any one of the first aspects of the invention which is calculated as a percentage by weight Included from 0.5 to 80% of docosahexaenoic acid or an ester thereof, for example 5 to 80%, for example 5 to 60%, for example 5 to 57%, for example 5 to 40%, for example 5 to 30%, for example 5 to 25%, for example 5 to 10%, for example 10 to 57%, for example 10 to 40%, for example 10 to 30%, for example 10 to 25%, for example 10 to 20%, for example 20 to 57%, for example 20 to 40% For example, 20 to 30%, for example 20 to 25%, for example 30 to 57%, for example 30 to 40%, for example 40 to 57%.
  • docosahexaenoic acid or an ester thereof for example 5 to 80%, for example 5 to 60%, for example 5 to 57%, for example 5 to 40%, for example 5 to 30%, for example 5 to 25%, for example 5 to 10%, for example 10 to 57%, for example 10 to 40%, for example 10 to 30%, for example 10 to 25%
  • the docosahexaenoic acid or ester thereof is a microbial fermentation extract; preferably, the microorganism is selected from the group consisting of uranium, dinoflagellate, and Schizochytrium, Cryptophyta, diatoms and chlorella.
  • the ester of docosahexaenoic acid is selected from the group consisting of methyl docosahexaenoate, ethyl docosahexaenoate, docosahexaenoic acid glyceride One or more of isopropyl docosahexaenoate and docosahexaenoic acid phospholipid.
  • composition according to any one of the first aspects of the present invention which comprises 0.5 to 60% by weight of coenzyme Q10, for example 5 to 60%, 5 to 55%, for example 5 to 40%, for example 5 to 30%
  • coenzyme Q10 for example 5 to 60%, 5 to 55%, for example 5 to 40%, for example 5 to 30%
  • 5 to 20% for example 5 to 10%, for example 10 to 55%, for example 10 to 40%, for example 10 to 30%, for example 10 to 20%, for example 20 to 55%, for example 20 to 40%, for example 20 to 30%, for example 30 to 55%, for example 30 to 40%, for example 40 to 55%.
  • the coenzyme Q10 is a microbial fermentation extract; preferably, the microorganism is selected from the group consisting of Rhodospirillum rubrum, Rhodopseudomonas palustris, Rhodobacter sphaeroides, S. erythropolis And Rhodopseudomonas capsulata.
  • the coenzyme Q10 is selected from one or both of oxidized coenzyme Q10 and reduced coenzyme Q10.
  • composition according to any one of the first aspects of the present invention which comprises 0.5 to 60% by weight of lipoic acid, for example 5 to 60%, for example 5 to 50%, for example 5 to 40%, for example 5 to 30. %, for example 5 to 20%, for example 5 to 10%, for example 10 to 50%, for example 10 to 40%, for example 10 to 30%, for example 10 to 20%, for example 20 to 50%, for example 20 to 40%, For example, 20 to 30%, for example 30 to 50%, for example 30 to 40%, for example 40 to 50%.
  • lipoic acid for example 5 to 60%, for example 5 to 50%, for example 5 to 40%, for example 5 to 30. %, for example 5 to 20%, for example 5 to 10%, for example 10 to 50%, for example 10 to 40%, for example 10 to 30%, for example 10 to 20%, for example 20 to 50%, for example 20 to 40%, For example, 20 to 30%, for example 30 to 50%, for example 30 to 40%, for example 40 to 50%.
  • the lipoic acid is selected from one or both of oxidized lipoic acid and reduced lipoic acid; preferably, the reduced lipoic acid is dihydrolipoic acid.
  • a composition according to any one of the first aspects of the invention which comprises by weight percent 0.1 to 60% of phospholipids, for example 2 to 50%, for example 2% to 35%, for example 2 to 30%, for example 2 to 15%, for example 2 to 10%, for example 10 to 35%, for example 10 to 30%, For example 10 to 20%, for example 20 to 35%, for example 20 to 30%, for example 30 to 35%, such as 5%, for example 20%.
  • the phospholipid is selected from the group consisting of a hydroxylated phospholipid, a phosphatidylcholine, a phosphatidylethanolamine, a phosphatidylserine, a phosphatidylglycerol, a diphosphatidylglycerol, a phosphatidylinositol, a sphingomyelin, and the like.
  • the phospholipid is selected from the group consisting of hydroxylated lecithin and phosphatidylserine.
  • the phospholipid is a natural soybean extract.
  • composition according to any of the first aspects of the present invention which further comprises one or more (e.g., two, three, four or five) selected from the group consisting of proanthocyanidins, soy isoflavones, leaves Flavin, Panax notoginseng saponins and ⁇ -glucan.
  • one or more selected from the group consisting of proanthocyanidins, soy isoflavones, leaves Flavin, Panax notoginseng saponins and ⁇ -glucan.
  • composition according to any one of the first aspects of the present invention, wherein the content of each component is calculated by weight percentage of one or more selected from the group consisting of:
  • composition of any of the present invention further comprises one or more of the following: proanthocyanidins, soy isoflavones, lutein, panax notoginseng saponins, and beta-glucans,
  • it further comprises a combination selected from any one of the following items 1) to 9):
  • soy isoflavones, lutein and ⁇ -glucan
  • soy isoflavones total saponins of notoginseng and ⁇ -glucan
  • it further comprises a combination selected from any one of the following 1), 7) and 10) to 14):
  • proanthocyanidins proanthocyanidins, soy isoflavones, lutein and ⁇ -glucan;
  • proanthocyanidins proanthocyanidins, soy isoflavones, lutein, total saponins of Panax notoginseng and ⁇ -glucan;
  • composition of any of the invention, if any, wherein the weight fraction of one or more substances is selected from one or more of the following:
  • the parts by weight of proanthocyanidins are 0.5 to 15 parts (for example, 0.5 parts, 1 part, 2 parts, 3 parts, 4 parts, 8 parts, 9 parts or 10 parts, for example, 0.5 to 10 parts, 1 to 8 parts, 2 parts) ⁇ 4 parts or 1.8 to 2.3 parts);
  • the part by weight of the soybean isoflavone is 0.1 to 6 parts (for example, 0.1 part, 0.2 part, 0.3 part, 0.4 part, 0.5 part, 1.3 part, 1.6 part, 3.2 part or 4 part, further, for example, 0.1 to 4 parts, 0.5 to 3.2 parts, 1.3 to 1.6 parts or 0.3 to 0.5 parts);
  • the weight fraction of lutein is 0.1 to 12 parts (for example, 0.3 parts, 0.4 parts, 0.7 parts, 0.8 parts, 1.5 parts, 1.6 parts, 1.8 parts, 3.3 parts, 3.6 parts, 7.3 parts, 8.1 parts or 9)
  • 0.3 to 9 parts, 1 to 8 parts, 3 to 7 parts or 1.3 to 1.8 parts For example, 0.3 to 9 parts, 1 to 8 parts, 3 to 7 parts or 1.3 to 1.8 parts
  • the total saponin of Panax notoginseng is 0.1-6 parts by weight (for example, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.8, 1.3, 1.6, 3.2 or 4 parts, and further, for example, 0.2 to 4 parts, 0.5 to 3 parts) Parts, 1 to 2 parts or 0.3 to 0.5 parts); and
  • the weight fraction of ⁇ -glucan is 0.1 to 6 parts (for example, 0.1, 0.2, 0.3, 0.4, 0.5, 1.2 parts, 1.6 parts, 3.0 parts, 3.6 parts or 4 parts, and further, for example, 0.1 to 4 parts, 0.3 to 3 parts, 0.5 to 1.6 parts or 0.3 to 0.5 parts).
  • composition of any of the present invention further comprises one or more of the following: proanthocyanidins, soy isoflavones, lutein, panax notoginseng saponins, and beta-glucans,
  • it further comprises a combination selected from any one of the following items 1) to 9):
  • proanthocyanidins soy isoflavones and lutein, the parts by weight are 1.8 to 2.3 parts, 0.3 to 0.5 parts, and 1.3 to 1.8 parts, respectively;
  • Proanthocyanidins, soy isoflavones and total saponins of Panax notoginseng the parts by weight are 1.8-2.3 parts, 0.3-0.5 parts, 0.3-0.5 parts, respectively;
  • proanthocyanidins soy isoflavones and ⁇ -glucan, the parts by weight are 1.8-2.3 parts, 0.3-0.5 parts, 0.3-0.5 parts, respectively;
  • proanthocyanidins, lutein and total saponins of Panax notoginseng the parts by weight are 1.8-2.3 parts, 1.3-1.8 parts, 0.3-0.5 parts, respectively;
  • Proanthocyanidins, lutein and ⁇ -glucan the parts by weight are 1.8-2.3 parts, 0.3-0.5 parts, 0.3-0.5 parts, respectively;
  • Soy isoflavones, lutein and total saponins of Panax notoginseng the parts by weight are 0.3-0.5 parts, 1.3-1.8 parts, 0.3-0.5 parts, respectively;
  • soy isoflavones, lutein and ⁇ -glucan the parts by weight are 0.3-0.5 parts, 1.3-1.8 parts, 0.3-0.5 parts, respectively;
  • soy isoflavones total saponins of notoginseng and ⁇ -glucan, the parts by weight are 0.3-0.5 parts, 0.3-0.5 parts, 0.3-0.5 parts, respectively;
  • it further comprises one selected from the following 1), 7) and 10) to 14) The combination:
  • proanthocyanidins soy isoflavones and lutein, the parts by weight are 1.8 to 2.3 parts, 0.3 to 0.5 parts, and 1.3 to 1.8 parts, respectively;
  • Soy isoflavones, lutein and total saponins of Panax notoginseng the parts by weight are 0.3-0.5 parts, 1.3-1.8 parts, 0.3-0.5 parts, respectively;
  • proanthocyanidins proanthocyanidins, soy isoflavones, lutein and total saponins of Panax notoginseng, the parts by weight are 1.8-2.3 parts, 0.3-0.5 parts, 1.3-1.8 parts, 0.3-0.5 parts, respectively;
  • proanthocyanidins soy isoflavones, lutein and ⁇ -glucan, the parts by weight are 1.8-2.3 parts, 0.3-0.5 parts, 1.3-1.8 parts, 0.3-0.5 parts, respectively;
  • proanthocyanidins proanthocyanidins, lutein, panax notoginseng saponins and ⁇ -glucans in a weight fraction of 1.8 to 2.3 parts, 1.3 to 1.8 parts, 0.3 to 0.5 parts, and 0.3 to 0.5 parts, respectively;
  • soy isoflavone, lutein, panax notoginseng and ⁇ -glucan the parts by weight are 0.3-0.5 parts, 1.3-1.8 parts, 0.3-0.5 parts, 0.3-0.5 parts, respectively;
  • proanthocyanidins proanthocyanidins, soy isoflavones, lutein and total saponins of Panax notoginseng, the parts by weight are 1.8-2.3 parts, 0.3-0.5 parts, 1.3-1.8 parts, 0.3-0.5 parts, respectively;
  • soy isoflavone, lutein, panax notoginseng and ⁇ -glucan the parts by weight are 0.3-0.5 parts, 1.3-1.8 parts, 0.3-0.5 parts, 0.3-0.5 parts, respectively;
  • the parts by weight are 0.5-10 parts, 0.1-4 parts, 0.3-9 parts, 0.2-4 parts, 0.1 ⁇ 4 parts; preferably, the parts by weight are 1.8 to 2.3 parts, 0.3 to 0.5 parts, 1.3 to 1.8 parts, 0.3 to 0.5 parts, and 0.3 to 0.5 parts, respectively.
  • Proanthocyanidins, soy isoflavones, lutein, total saponins of Panax notoginseng and ⁇ -glucan the parts by weight are 0.5-10 parts, 0.1-4 parts, 0.3-9 parts, 0.2-4 parts, 0.1 ⁇ 4 parts; preferably, the parts by weight are 1.8 to 2.3 parts, 0.3 to 0.5 parts, 1.3 to 1.8 parts, 0.3 to 0.5, respectively. Parts, 0.3 to 0.5 parts.
  • the composition further comprises proanthocyanidins, soy isoflavones, lutein, and panax notoginseng saponins, or soy isoflavones, lutein, panax notoginseng saponins, and beta-glucans, or Proanthocyanidins, soy isoflavones, lutein, total saponins of Panax notoginseng and ⁇ -glucan, at which time the mass ratio of each component is (1 to 400): (2 to 250): (1 to 200): (5 ⁇ 20): (2 to 5): 1: (2 to 5): (0.1 to 5): (0.1 to 5).
  • the composition comprises docosahexaenoic acid or an ester thereof, coenzyme Q10, lipoic acid, phospholipids, proanthocyanidins, soy isoflavones, lutein, total saponins of Panax notoginseng and ⁇ - Glucan, at which time the mass ratio of the above components is (1 to 400): (2 to 250): (1 to 200): (5 to 20): (2 to 5): 1: (2 to 5) ): (0.1 to 5): (0.1 to 5).
  • composition according to any of the first aspects of the invention which comprises from 0.1 to 15% by weight of proanthocyanidins, for example from 0.1 to 11%, for example from 0.1 to 1%, for example from 1 to 11%.
  • the proanthocyanidins are from grape seed extract.
  • composition according to any of the first aspects of the invention which comprises from 0.1 to 8% by weight of soy isoflavones, for example from 0.1 to 5.5%.
  • the soy isoflavones are derived from a soybean germ extract.
  • composition according to any one of the first aspects of the present invention which comprises 0.1 to 10% by weight of lutein, for example 0.1 to 1%, for example 1 to 10%, for example 0.5 to 10%, for example 0.5 to 5%.
  • the lutein is from a marigold extract.
  • composition according to any one of the first aspects of the present invention which comprises 0.1 to 8% by weight of total saponins of Panax notoginseng, for example 0.1 to 6%, for example 0.1 to 1%, such as 0.1 to 3%, for example 1 ⁇ 6%.
  • the Panax notoginseng saponins are from the Panax notoginseng extract.
  • composition according to any of the first aspects of the present invention which comprises 0.1 to 8% by weight of ⁇ -glucan, for example 0.1 to 6%, for example 0.1 to 1%, for example 0.1 to 3%, for example 1 to 6%.
  • the beta glucan is an oat extract.
  • composition of any of the present invention further comprises a carrier oil, preferably, if present, the carrier oil is from 0.1 to 85 parts by weight.
  • composition of any of the inventions the balance being a carrier oil.
  • composition according to any of the first aspects of the invention the balance being a carrier oil.
  • the carrier oil is selected from one or more of natural vegetable oils, natural animal fats and synthetic oils selected from the group consisting of soybean oil, rapeseed oil, olive oil, sesame oil, and corn oil.
  • soybean oil rapeseed oil, olive oil, sesame oil, and corn oil.
  • the medium chain triglyceride is selected from one or both of saturated caprylic triglyceride and saturated capric triglyceride.
  • the composition of any one of the present invention wherein the medium chain triglyceride is selected from the group consisting of saturated caprylic triglyceride and saturated capric triglyceride and caprylic acid glyceride;
  • the carrier oil comprises at least glyceryl caprylate.
  • composition according to any one of the first aspects of the present invention which is an oil agent or a suspension or a soft capsule, a hard capsule, a microcapsule, a tablet, a powder, a pill, an emulsion, a suspension, etc. Dosage form.
  • a second aspect of the invention provides a process for the preparation of a composition according to any of the first aspects of the invention, comprising the steps of:
  • the components are weighed and mixed to obtain the composition; preferably, the step of filtering is further included after mixing; more preferably, the step of removing bubbles is further included after mixing.
  • the mixing may employ at least one of conventional stirring, shear emulsification, and high pressure homogenization; preferably, the mixing is carried out at 30 to 80 ° C, preferably 50 to 70 ° C, For example, 60 ° C; preferably, the mixing is carried out in a vacuum or an inert gas atmosphere.
  • a third aspect of the invention provides the use of a composition according to any of the first aspects of the invention for the preparation of a dietary supplement or a health food, preferably for the preparation of a prophylactic and/or dyslipidemia Or the use of dietary supplements or health foods for cardiovascular and cerebrovascular diseases. .
  • a fourth aspect of the invention provides the use of a composition according to any of the first aspects of the invention for the manufacture of a medicament for the prevention and/or treatment of dyslipidemia or cardiovascular and cerebrovascular diseases.
  • a fifth aspect of the invention provides the use of a composition according to any of the first aspects of the invention for the prevention and/or treatment of dyslipidemia or cardiovascular and cerebrovascular diseases.
  • a sixth aspect of the invention provides a method of preventing and/or treating dyslipidemia or cardiovascular and cerebrovascular disease in an individual in need thereof, comprising administering to the individual a therapeutically effective amount of a composition according to any of the invention.
  • the dyslipidemia comprises hyperlipidemia (eg hypercholesterolemia and/or hypertriglyceridemia), or elevated total cholesterol selected from blood, low density lipoprotein cholesterol liters One or more of high, elevated triglycerides, and decreased high density lipoprotein cholesterol.
  • hyperlipidemia eg hypercholesterolemia and/or hypertriglyceridemia
  • elevated total cholesterol selected from blood, low density lipoprotein cholesterol liters
  • low density lipoprotein cholesterol liters One or more of high, elevated triglycerides, and decreased high density lipoprotein cholesterol.
  • the cardiovascular and cerebrovascular diseases are selected from the group consisting of arteriosclerosis, hypertension, hyperlipidemia, cerebral infarction, cerebral hemorrhage, coronary heart disease, angina pectoris, myocardial ischemia, myocardial infarction, heart failure, and arrhythmia.
  • DHA docosahexaenoic acid
  • extracts are either commercially available or are prepared by extraction methods well known in the art, the source of which does not constitute a limitation on the composition of the compositions of the present invention.
  • phospholipid as used in the present invention includes phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylglycerol, diphosphatidylglycerol, phosphatidylinositol, and sphingomyelin.
  • Coenzyme Q10 as used in the present invention, which includes both oxidized and reduced forms, is a fat-soluble antioxidant.
  • lipoic acid as used in the present invention is a sulfur-containing octacarbon fatty acid, an enzyme present in mitochondria which can be converted to reduced dihydrolipoic acid in mammalian cells.
  • the term "grape seed extract” as used in the present invention is an effective active nutrient extracted from natural grape seed, rich in proanthocyanidins and polyphenols.
  • the proanthocyanidins referred to as OPC, are currently the most internationally recognized natural antioxidants for scavenging free radicals in humans.
  • soybean isoflavone as used in the present invention is a type of secondary metabolite formed in the growth of soybean.
  • ricecan extract used in the present invention is rich in panax notoginseng saponins.
  • oil extract as used in the present invention is rich in ?-glucan.
  • dietary supplement as used in the present invention is also called a nutritional supplement, a nutritional supplement, a nutrient, a dietary supplement, etc., and is used as an auxiliary means of diet to supplement the amino acids and traces required by the human body. Elements, vitamins, minerals, etc., to achieve the purpose of improving the health of the body and reducing the risk of disease.
  • composition of the present invention can be administered in any manner known per se, such as oral, intramuscular, subcutaneous, etc., such as tablets (e.g., buccal tablets, chewable tablets), capsules (e.g., soft capsules, hard capsules, microcapsules). ), oils, powders, pills, emulsions and suspensions, expectorants, transdermal agents, microencapsulated agents, implants, syrups, and the like. It may be a general preparation, a sustained release preparation, a controlled release preparation, and various microparticle delivery systems.
  • the preparation of the various dosage forms can be prepared by reference to the teachings in the field, and various biodegradable or biocompatible carriers well known in the art can be widely used in order to form the unit dosage form into tablets.
  • compositions of the present invention include, but are not limited to, ion exchangers, alumina, aluminum stearate, lecithin, serum proteins such as human serum albumin, buffer substances such as phosphates, glycerol, sorbic acid, Sorbic acid Potassium, a mixture of partially glycerides of saturated plant fatty acids, water, salt or electrolytes such as protamine sulfate, disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salts, colloidal silica, magnesium trisilicate, poly Vinyl pyrrolidone, cellulosic material, polyethylene glycol, carboxymethyl cellulose hook, polyacrylate, beeswax, wool vinegar, and the like.
  • the amount of the carrier in the pharmaceutical composition may be from 1% by weight to 98% by weight, usually about 80% by weight.
  • the local anesthetic, preservative, buffer, etc. may be directly dissolved in the carrier.
  • the dosage of the composition of the present invention depends on a number of factors, such as the nature and severity of the disease to be prevented or treated, the sex, age, weight, sensitivity and individual response of the patient or animal, the particular compound employed, administration Route, number of doses, and desired therapeutic effects.
  • the above dosages may be administered in a single dosage form or divided into several, for example two, three or four dosage forms.
  • the single maximum dose will generally not exceed 30 mg/kg body weight, for example 0.001 to 30 mg/kg, preferably 0.01 to 5 mg/kg, and the preferred dose range is 0.5 to 2 mg/kg body weight. However, in some cases, it is also possible to use a single dose of 30 mg/kg or more or 0.001 mg/kg or less.
  • the present invention provides a combination of components having cardio-cerebral vascular protective effects that achieve unexpected synergistic effects in the prevention and/or treatment of cardiovascular and cerebrovascular diseases.
  • the composition of the present invention can effectively reduce the levels of total cholesterol (TC) and triglyceride (TG) in serum of rats and can significantly increase the level of high density lipoprotein cholesterol (HDL-C).
  • TC total cholesterol
  • TG triglyceride
  • HDL-C high density lipoprotein cholesterol
  • the raw materials used in Examples 1-37 are all commercially available, food grade or pharmaceutical grade, mainly The specifications of the raw materials are shown in Table 1, and the composition of the compositions is shown in Table 2.
  • Docosahexaenoic acid The docosahexaenoic acid content is 55% Oxidized coenzyme Q10 Oxidized coenzyme Q10 content is 98% Reduced coenzyme Q10 Reduced coenzyme Q10 content is 98% Oxidized lipoic acid Oxidized lipoic acid content is 99% Dihydrolipoic acid Dihydrolipoic acid content is 99% Soy lecithin Total phosphorus content is 60% Phosphatidylserine Phosphatidylserine content is 98% Modified phospholipid Hydroxylated lecithin content is 60% Grape seed extract Proanthocyanidin content is 99% Soybean germ extract Soy isoflavone content is 80% Marigold extract Lutein content is 90% Panax notoginseng extract Panax notoginseng total saponin content is 80% Oat extract ⁇ -glucan content is 75%
  • Feeding animals with high cholesterol and lipid diets can form an animal model of lipid metabolism disorder, and then give the animal test samples, can test the effect of the test sample on hyperlipidemia, and can determine the absorption of lipids in the test sample. , the formation of lipoproteins, the degradation of lipids or the effects of excretion.
  • TC total cholesterol
  • TG triglyceride
  • HDL-C high density lipoprotein
  • High fat diet 78.8% basic feed, 1% cholesterol, 10% egg yolk powder, 10% lard, 0.2% bile salt.
  • Standard feed basic feed.
  • the trial consisted of 39 groups, the first group was the control group of high-fat diet (administered with high-fat diet), the second group was the standard diet group (giving standard feed), and the other groups were given oral high-fat diet daily.
  • the test samples prepared in Examples 1 to 37 were administered to the stomach 2 ml each time, 3 times a day, and the test time was 30 days.
  • Rats were fed basal diet for 10 days in the experimental environment, and then tail blood was taken to determine serum total cholesterol (TC), triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C) levels. According to the TC level, they were randomly divided into 39 groups, and were reared according to the method described in the above 4, and the body weight was weighed regularly, and fasted for 16 hours at the end of the test to measure serum TC, TG, and HDL-C levels. The results are shown in Table 3-5:
  • Example 30 The nutritional composition of Example 30 was taken as the content of the soft capsule.
  • the preparation method of the soft capsule is as follows: 150 g of gelatin, 90 g of glycerin, 180 g of purified water, 10 g of caramel color, 2 g of capsicum red, 1.5 g of titanium dioxide, and the glycerin and purified water are put into a sol tank, heated to 60 ° C, and put into gelatin. Continue to heat to 65 ° C to dissolve, then the caramel color, capsicum red, and titanium dioxide which have been dissolved and mixed and filtered are put into the sol tank, stirred for 25 minutes, then vacuumed to remove the bubbles, and the rubber solution is prepared, and kept at 60 ° C for use. .
  • the soft capsule contents obtained by the above preparation and the rubber solution are subjected to a step of pelleting, shaping, drying, picking and packaging, thereby obtaining a soft capsule having a specification of 450 mg/granule.

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Abstract

一种预防和/或治疗心脑血管疾病的组合物，及其制备方法和用途，其中，所述组合物包含二十二碳六烯酸或其酯、辅酶Q10、硫辛酸和磷脂中的至少两种。所述组合物用于制备膳食补充剂或保健食品的用途，优选用于制备预防和/或治疗血脂异常或心脑血管疾病的膳食补充剂或保健食品的用途。

Description

预防和/或治疗心脑血管疾病的组合物 技术领域
本发明涉及医药和保健食品领域，具体涉及预防和/或治疗心脑血管疾病的组合物。
背景技术
心脑血管疾病是心脏血管和脑血管的疾病统称，泛指由于高脂血症、血液黏稠、动脉粥样硬化、高血压等所导致的心脏、大脑及全身组织发生缺血性或出血性疾病，是一种严重威胁人类，特别是50岁以上中老年人健康的常见病，即使应用目前最先进、完善的治疗手段，仍有50％以上的心脑血管意外幸存者生活不能完全自理，全世界每年死于心脑血管疾病的人数高达1500万人，居各种死因首位。
目前心脑血管疾病仍然是以预防为主，主要手段是控制危险因素和抗栓。心脑血管疾病发生的危险因素分为两大类，即可以处理的危险因素，如高血压、血脂紊乱、糖尿病、吸烟等，另一类是不可处理的危险因素，如年龄、性别和遗传。已经证明，控制血压在正常范围、治疗糖尿病、戒烟和治疗血脂紊乱可以明显降低心脑血管事件的发生。
现有技术已经公开了多种物质对于预防和治疗心脑血管疾病具有一定作用，但从未揭示何种组合会表现出协同作用。
发明内容
本发明的发明人经过不断实验，令人惊喜的发现了一系列对心脑血管具有保护作用的成分的组合，其在预防和/或治疗心脑血管疾病方面产生了预料不到的协同效应，本发明即是基于以上发现而完成。
本发明的第一方面提供一种组合物，其包含二十二碳六烯酸或其酯、辅酶Q10、硫辛酸和磷脂中的至少两种，例如两种、三种或四种。
在本发明的一个实施方案中，所述组合物包含选自以下i)至xi)项中任意一项所述的组合：
i)二十二碳六烯酸或其酯以及辅酶Q10；
ii)二十二碳六烯酸或其酯以及硫辛酸；
iii)二十二碳六烯酸或其酯以及磷脂；
iv)辅酶Q10和硫辛酸；
v)辅酶Q10和磷脂；
vi)硫辛酸和磷脂；
vii)二十二碳六烯酸或其酯、辅酶Q10和硫辛酸；
viii)二十二碳六烯酸或其酯、辅酶Q10和磷脂；
ix)二十二碳六烯酸或其酯、硫辛酸和磷脂；
x)辅酶Q10、硫辛酸和磷脂；和
xi)二十二碳六烯酸或其酯、辅酶Q10、硫辛酸和磷脂；
优选地，所述组合物，其包含二十二碳六烯酸或其酯以及辅酶Q10的组合；
更优选地，所述组合物，其包含二十二碳六烯酸或其酯、辅酶Q10、硫辛酸和磷脂的组合。
根据本发明第一方面任一项所述的组合物，其中各组分的含量按重量百分比计算选自以下的一项或多项：
1)0.5～80％(例如5～60％)的二十二碳六烯酸或其酯；
2)0.5～60％(例如5～55％)的辅酶Q10；
3)0.5～60％(例如5～50％)的硫辛酸；和
4)0.1～60％(例如2～35％)的磷脂。
在一个实施方案中，本发明任一项的组合物，如果有，其中，一个或多个物质的重量份数选自以下的一项或多项：
a)二十二碳六烯酸或其酯的重量份数为3～50份(例如3份、4份、5份、9份、10份、19份、20份、38份、39份或50份，再例如5～39份、18～23份或者9～19份)；
b)辅酶Q10的重量份数为3～60份(例如3份、4份、5份、9份、10份、19份、20份、49份、50份或60份，再例如4～50份，5～20份，9～19份或者8～13份)；
c)硫辛酸的重量份数为3～50份(例如3份、4份、5份、9份、10份、19份、20份、39份、40份或50份，再例如4～40份、9～20份20～30份、30～40份或者38～43份)；和
d)磷脂的重量份数为1～40份(例如1份、2份、3份、4份、5份、9份、10份、29份、30份或40份，再例如5～10份、10～20份、2～30份、30～40份或者3～8份)。
在一个实施方案中，所述组合物包含选自以下i)至xi)项中任意一项所述的组合：
i)二十二碳六烯酸或其酯以及辅酶Q10，其重量份数分别为18～23份、8～13份；
ii)二十二碳六烯酸或其酯以及硫辛酸，其重量份数分别为18～23份、38～43份；
iii)二十二碳六烯酸或其酯以及磷脂，其重量份数分别为18～23份、3～8份；
iv)辅酶Q10和硫辛酸，其重量份数分别为8～13份、38～43份；
v)辅酶Q10和磷脂，其重量份数分别为8～13份、3～8份；
vi)硫辛酸和磷脂，其重量份数分别为38～43份、3～8份；
vii)二十二碳六烯酸或其酯、辅酶Q10和硫辛酸，其重量份数分别为18～23份、8～13份、38～43份；
viii)二十二碳六烯酸或其酯、辅酶Q10和磷脂，其重量份数分别为18～23份、8～13份、3～8份；
ix)二十二碳六烯酸或其酯、硫辛酸和磷脂，其重量份数分别为18～23份、38～43份、3～8份；
x)辅酶Q10、硫辛酸和磷脂，其重量份数分别为8～13份、38～43份、3～8份，和
xi)二十二碳六烯酸或其酯、辅酶Q10、硫辛酸和磷脂，其重量份数分别为3份～43份、3份～53份、3份～43份、1份～33份，优选地，其重量份数分别为18～23份、8～13份、38～43份、3～8份。
根据本发明第一方面任一项所述的组合物，其按重量百分比计算 包含0.5～80％的二十二碳六烯酸或其酯，例如5～80％，例如5～60％，例如5～57％，例如5～40％，例如5～30％，例如5～25％，例如5～10％，例如10～57％，例如10～40％，例如10～30％，例如10～25％，例如10～20％，例如20～57％，例如20～40％，例如20～30％，例如20～25％，例如30～57％，例如30～40％，例如40～57％。
在本发明的实施方案中，所述二十二碳六烯酸或其酯为微生物发酵提取物；优选地，所述微生物选自吾肯式壶藻、双鞭甲藻、裂殖壶菌、隐甲藻、硅藻和小球藻。
在本发明的实施方案中，所述二十二碳六烯酸的酯选自二十二碳六烯酸甲酯、二十二碳六烯酸乙酯、二十二碳六烯酸甘油酯、二十二碳六烯酸异丙酯和二十二碳六烯酸磷脂中的一种或多种。
根据本发明第一方面任一项所述的组合物，其按重量百分比包含0.5～60％的辅酶Q10，例如5～60％，5～55％，例如5～40％，例如5～30％，例如5～20％，例如5～10％，例如10～55％，例如10～40％，例如10～30％，例如10～20％，例如20～55％，例如20～40％，例如20～30％，例如30～55％，例如30～40％，例如40～55％。
在本发明的实施方案中，所述辅酶Q10为微生物发酵提取物；优选地，所述微生物选自深红红螺菌、沼泽红假单胞菌、类球红细菌、嗜硫小红卵菌和荚膜红假单胞菌。
在本发明的实施方案中，所述辅酶Q10选自氧化型辅酶Q10和还原型辅酶Q10中的一种或两种。
根据本发明第一方面任一项所述的组合物，其按重量百分比包含0.5～60％的硫辛酸，例如5～60％，例如5～50％，例如5～40％，例如5～30％，例如5～20％，例如5～10％，例如10～50％，例如10～40％，例如10～30％，例如10～20％，例如20～50％，例如20～40％，例如20～30％，例如30～50％，例如30～40％，例如40～50％。
在本发明的实施方案中，所述硫辛酸选自氧化型硫辛酸和还原型硫辛酸中的一种或两种；优选地，所述还原型硫辛酸为二氢硫辛酸。
根据本发明第一方面任一项所述的组合物，其按重量百分比包含 0.1～60％的磷脂，例如2～50％，例如2％～35％，例如2～30％，例如2～15％，例如2～10％，例如10～35％，例如10～30％，例如10～20％，例如20～35％，例如20～30％，例如30～35％，例如5％，例如20％。
在本发明的实施方案中，所述磷脂选自羟化磷脂、磷脂酰胆碱、磷脂酰乙醇胺、磷脂酰丝氨酸、磷脂酰甘油、二磷脂酰甘油、磷脂酰肌醇、鞘磷脂等中的一种或几种；优选地，所述磷脂选自羟化卵磷脂和磷脂酰丝氨酸。
在本发明的一个实施方案中，所述磷脂为天然大豆提取物。
根据本发明第一方面任一项所述的组合物，其还包含选自以下物质的一种或多种(例如两种，三种，四种或五种)：原花青素、大豆异黄酮、叶黄素、三七总皂苷和β-葡聚糖。
根据本发明第一方面任一项所述的组合物，其中各组分的含量按重量百分比计算选自以下的一项或多项：
(1)0.1～15％(例如0.1～11％)的原花青素；
(2)0.1～8％(例如0.1～5.5％)的大豆异黄酮；
(3)0.1～10％(例如0.5～10％)的叶黄素；
(4)0.1～8％(例如0.1～6％)的三七总皂苷；和
(5)0.1～8％(例如0.1～6％)的β-葡聚糖。
在一个实施方案中，本发明任一项的组合物，其还包含以下物质中的一种或多种：原花青素、大豆异黄酮、叶黄素、三七总皂苷和β-葡聚糖，
例如其还包含选自以下1)～9)项中任意一项所述的组合：
1)原花青素、大豆异黄酮和叶黄素；
2)原花青素、大豆异黄酮和三七总皂苷；
3)原花青素、大豆异黄酮和β-葡聚糖；
4)原花青素、叶黄素和三七总皂苷；
5)原花青素、叶黄素和β-葡聚糖；
6)原花青素、三七总皂苷和β-葡聚糖；
7)大豆异黄酮、叶黄素和三七总皂苷；
8)大豆异黄酮、叶黄素和β-葡聚糖；和
9)大豆异黄酮、三七总皂苷和β-葡聚糖；
优选地，其还包含选自以下1)、7)和10)～14)项中任意一项所述的组合：
1)原花青素、大豆异黄酮和叶黄素；
7)大豆异黄酮、叶黄素和三七总皂苷；
10)叶黄素、三七总皂苷和β-葡聚糖；
11)原花青素、大豆异黄酮、叶黄素和三七总皂苷；
12)原花青素、大豆异黄酮、叶黄素和β-葡聚糖；
13)原花青素、叶黄素、三七总皂苷和β-葡聚糖；和
14)大豆异黄酮、叶黄素、三七总皂苷和β-葡聚糖；
进一步优选地，其还包含选自以下11)、14)和15)项中任意一项所述的组合：
11)原花青素、大豆异黄酮、叶黄素和三七总皂苷；
14)大豆异黄酮、叶黄素、三七总皂苷和β-葡聚糖；和
15)原花青素、大豆异黄酮、叶黄素、三七总皂苷和β-葡聚糖；
更进一步优选地，其还包含以下15)项所述的组合：
15)原花青素、大豆异黄酮、叶黄素、三七总皂苷和β-葡聚糖。
在一个实施方案中，本发明任一项的组合物，如果有，其中，一个或多个物质的重量份数选自以下的一项或多项：
e)原花青素的重量份数为0.5～15份(例如0.5份、1份、2份、3份、4份、8份、9份或10份，例如0.5～10份、1～8份、2～4份或者1.8～2.3份)；
f)大豆异黄酮的重量份数为0.1～6份(例如0.1份、0.2份、0.3份、0.4份、0.5份、1.3份、1.6份、3.2份或4份，再例如0.1～4份、0.5～3.2份、1.3～1.6份或者0.3～0.5份)；
g)叶黄素的重量份数为0.1～12份(例如0.3份、0.4份、0.7份、0.8份、1.5份、1.6份、1.8份、3.3份、3.6份、7.3份、8.1份或9份，再例如0.3～9份、1～8份、3～7份或者1.3～1.8份)；
h)三七总皂苷的重量份数为0.1～6份(例如0.1、0.2、0.3、0.4、0.5、0.6、0.8、1.3、1.6、3.2或4份，再例如0.2～4份、0.5～3份、1～2份或者0.3～0.5份)；和
i)β-葡聚糖的重量份数为0.1～6份(例如0.1、0.2、0.3、0.4、0.5、1.2份、1.6份、3.0份、3.6份或4份，再例如0.1～4份、0.3～3份、0.5～1.6份或0.3～0.5份)。
在一个实施方案中，本发明任一项的组合物，其还包含以下物质中的一种或多种：原花青素、大豆异黄酮、叶黄素、三七总皂苷和β-葡聚糖，
例如其还包含选自以下1)～9)项中任意一项所述的组合：
1)原花青素、大豆异黄酮和叶黄素，其重量份数分别为1.8～2.3份、0.3～0.5份、1.3～1.8份；
2)原花青素、大豆异黄酮和三七总皂苷，其重量份数分别为1.8～2.3份、0.3～0.5份、0.3～0.5份；
3)原花青素、大豆异黄酮和β-葡聚糖，其重量份数分别为1.8～2.3份、0.3～0.5份、0.3～0.5份；
4)原花青素、叶黄素和三七总皂苷，其重量份数分别为1.8～2.3份、1.3～1.8份、0.3～0.5份；
5)原花青素、叶黄素和β-葡聚糖，其重量份数分别为1.8～2.3份、0.3～0.5份、0.3～0.5份；
6)原花青素、三七总皂苷和β-葡聚糖，其重量份数分别为1.8～2.3份、1.3～1.8份、0.3～0.5份；
7)大豆异黄酮、叶黄素和三七总皂苷，其重量份数分别为0.3～0.5份、1.3～1.8份、0.3～0.5份；
8)大豆异黄酮、叶黄素和β-葡聚糖，其重量份数分别为0.3～0.5份、1.3～1.8份、0.3～0.5份；和
9)大豆异黄酮、三七总皂苷和β-葡聚糖，其重量份数分别为0.3～0.5份、0.3～0.5份、0.3～0.5份；
优选地，其还包含选自以下1)、7)和10)～14)项中任意一项所述 的组合：
1)原花青素、大豆异黄酮和叶黄素，其重量份数分别为1.8～2.3份、0.3～0.5份、1.3～1.8份；
7)大豆异黄酮、叶黄素和三七总皂苷，其重量份数分别为0.3～0.5份、1.3～1.8份、0.3～0.5份；
10)叶黄素、三七总皂苷和β-葡聚糖，其重量份数分别为1.3～1.8份、0.3～0.5份、0.3～0.5份；
11)原花青素、大豆异黄酮、叶黄素和三七总皂苷，其重量份数分别为1.8～2.3份、0.3～0.5份、1.3～1.8份、0.3～0.5份；
12)原花青素、大豆异黄酮、叶黄素和β-葡聚糖，其重量份数分别为1.8～2.3份、0.3～0.5份、1.3～1.8份、0.3～0.5份；
13)原花青素、叶黄素、三七总皂苷和β-葡聚糖，其重量份数分别为1.8～2.3份、1.3～1.8份、0.3～0.5份、0.3～0.5份；和
14)大豆异黄酮、叶黄素、三七总皂苷和β-葡聚糖，其重量份数分别为0.3～0.5份、1.3～1.8份、0.3～0.5份、0.3～0.5份；
进一步优选地，其还包含选自以下11)、14)和15)项中任意一项所述的组合：
11)原花青素、大豆异黄酮、叶黄素和三七总皂苷，其重量份数分别为1.8～2.3份、0.3～0.5份、1.3～1.8份、0.3～0.5份；
14)大豆异黄酮、叶黄素、三七总皂苷和β-葡聚糖，其重量份数分别为0.3～0.5份、1.3～1.8份、0.3～0.5份、0.3～0.5份；和
15)原花青素、大豆异黄酮、叶黄素、三七总皂苷和β-葡聚糖，其重量份数分别为0.5～10份、0.1～4份、0.3～9份、0.2～4份、0.1～4份；优选地，其重量份数分别为1.8～2.3份、0.3～0.5份、1.3～1.8份、0.3～0.5份、0.3～0.5份。
更进一步优选地，其还包含以下15)项所述的组合：
15)原花青素、大豆异黄酮、叶黄素、三七总皂苷和β-葡聚糖，其重量份数分别为0.5～10份、0.1～4份、0.3～9份、0.2～4份、0.1～4份；优选地，其重量份数分别为1.8～2.3份、0.3～0.5份、1.3～1.8份、0.3～0.5 份、0.3～0.5份。
在本发明的一个实施方案中，所述组合物其还包含原花青素、大豆异黄酮、叶黄素和三七总皂苷，或者大豆异黄酮、叶黄素、三七总皂苷和β-葡聚糖，或者原花青素、大豆异黄酮、叶黄素、三七总皂苷和β-葡聚糖，此时各组分的质量比为(1～400)∶(2～250)∶(1～200)∶(5～20)∶(2～5)∶1∶(2～5)∶(0.1～5)∶(0.1～5)。
在本发明的一个实施方案中，所述组合物包含二十二碳六烯酸或其酯、辅酶Q10、硫辛酸、磷脂、原花青素、大豆异黄酮、叶黄素、三七总皂苷和β-葡聚糖，此时上述各组分的质量比为(1～400)∶(2～250)∶(1～200)∶(5～20)∶(2～5)∶1∶(2～5)∶(0.1～5)∶(0.1～5)。
根据本发明第一方面任一项所述的组合物，其按重量百分比包含0.1～15％的原花青素，例如0.1～11％，例如0.1～1％，例如1～11％。
在本发明的一个实施方案中，所述原花青素来自葡萄籽提取物。
根据本发明第一方面任一项所述的组合物，其按重量百分比包含0.1～8％的大豆异黄酮，例如0.1～5.5％。
在本发明的一个实施方案中，所述大豆异黄酮来自大豆胚芽提取物。
根据本发明第一方面任一项所述的组合物，其按重量百分比包含0.1～10％的叶黄素，例如0.1～1％，例如1～10％，例如0.5～10％，例如0.5～5％。
在本发明的一个实施方案中，所述叶黄素来自万寿菊提取物。
根据本发明第一方面任一项所述的组合物，其按重量百分比包含0.1～8％的三七总皂苷，例如0.1～6％，例如0.1～1％，例如0.1～3％，例如1～6％。
在本发明的一个实施方案中，所述三七总皂苷来自三七提取物。
根据本发明第一方面任一项所述的组合物，其按重量百分比包含0.1～8％的β-葡聚糖，例如0.1～6％，例如0.1～1％，例如0.1～3％，例如1～6％。
在本发明的一个实施方案中，所述β-葡聚糖为燕麦提取物。
在一个实施方案中，本发明任一项的组合物，其还包含载体油，优选地，如果有，载体油的重量份数为0.1～85份。
在一个实施方案中，本发明任一项的组合物，余量为载体油。
根据本发明第一方面任一项所述的组合物，余量为载体油。
在本发明的实施方案中，所述载体油选自天然植物油脂、天然动物油脂和人工合成油脂中的一种或几种，其选自大豆油、菜籽油、橄榄油、芝麻油、玉米油、棕榈油、葵花油、芥子油、米糠油、椰子油、亚麻籽油、月见草油、大蒜油、荷荷巴油、猪油、牛脂、鱼油、黄油和中链甘油三酯中的一种或几种，优选地，所述中链甘油三酯选自饱和辛酸甘油三酯和饱和癸酸甘油三酯中的一种或两种。
在一个实施方案中，本发明任一项的组合物，所述中链甘油三酯选自饱和辛酸甘油三酯和饱和癸酸甘油三酯和辛癸酸甘油酯中的一种或多种；优选地，所述载体油至少包括辛癸酸甘油酯。
根据本发明第一方面任一项所述的组合物，其为油剂或混悬剂或与辅料制成软胶囊、硬胶囊、微胶囊、片剂、散剂、丸剂、乳剂和混悬剂等剂型。
本发明第二方面提供本发明第一方面任一项的组合物的制备方法，其包含以下步骤：
称取各组分，混合即得所述组合物；优选地，混合后还包括过滤的步骤；更优选地，混合后还包括脱除气泡的步骤。
在本发明的实施方案中，所述混合可采用常规搅拌、剪切乳化和高压均质中的至少一种方法；优选地，所述混合在30～80℃下进行，优选50～70℃，例如60℃；优选地，所述混合在真空或惰性气体环境中进行。
本发明第三方面提供本发明第一方面任一项的组合物用于制备膳食补充剂或保健食品的用途，优选用于制备预防和/或治疗血脂异常 或心脑血管疾病的膳食补充剂或保健食品的用途。。
本发明的第四方面提供本发明第一方面任一项的组合物在制备预防和/或治疗血脂异常或心脑血管疾病的药物中的用途。
本发明第五方面提供本发明第一方面任一项的组合物用于预防和/或治疗血脂异常或心脑血管疾病的用途。
本发明第六方面提供在有需要的个体中预防和/或治疗血脂异常或心脑血管疾病的方法，其包括向所述个体施用治疗有效量的根据本发明任一项的组合物。
在本发明的实施方案中，所述血脂异常包括高血脂症(例如高胆固醇血症和/或高甘油三酯血症)，或者选自血中的总胆固醇升高、低密度脂蛋白胆固醇升高、甘油三酯升高和高密度脂蛋白胆固醇降低中的一项或多项。
在本发明的实施方案中，所述心脑血管疾病选自动脉硬化、高血压、高血脂、脑梗塞、脑出血、冠心病、心绞痛、心肌缺血、心肌梗塞、心力衰竭和心律失常。
下面对本发明的各个方面和特点作进一步的描述。
本发明使用的各种术语和短语具有本领域技术人员公知的一般含义，即便如此，本发明仍然希望再次对这些术语和短语更详尽的说明和解释，提及的术语和短语如有与公知含义不一致的，以本发明所表述的含义为准。
本发明中使用的术语“二十二碳六烯酸”即为DHA。
本发明所述的“提取物”为市售可得的或采用本领域公知的提取方法制备得到，所述提取物的来源不构成对本发明组合物各组成成分的限制。
本发明中使用的术语“磷脂”，其包括磷脂酰胆碱、磷脂酰乙醇胺、磷脂酰丝氨酸、磷脂酰甘油、二磷脂酰甘油及磷脂酰肌醇和鞘磷脂等。
本发明中使用的术语“辅酶Q10”，其包括氧化型和还原型，是一种脂溶性抗氧化剂。
本发明中使用的术语“硫辛酸”为一种含硫八碳脂肪酸，是一种存在于线粒体的酶，在哺乳动物细胞内可以转化为还原型的二氢硫辛酸。
本发明中使用的术语“葡萄籽提取物”是从天然葡萄籽中提取的有效活性营养成份，富含原花青素和多酚。所述原花青素，简称OPC，是目前国际上公认的清除人体内自由基最有效的天然抗氧化剂。
本发明中使用的术语“万寿菊提取物”，其富含叶黄素和玉米黄质。所述叶黄素，别名类胡萝卜素、胡萝卜醇、植物黄体素、核黄体、万寿菊花素及植物叶黄素等，英文名为Lutein。
本发明中使用的术语“大豆异黄酮”是大豆生长中形成的一类次级代谢产物。
本发明中使用的术语“三七提取物”，其富含三七总皂苷。
本发明中使用的术语“燕麦提取物”，其富含β-葡聚糖。
本发明中使用的术语“膳食补充剂”(dietary supplement)又称营养补充剂、营养补充品、营养剂、饮食补充剂等，是作为饮食的辅助手段，用来补充人体所需的氨基酸、微量元素、维生素、矿物质等，达到提高机体健康水平和降低疾病风险的目的。
本发明的组合物可以以已知的任何方式给药，如口服、肌肉、皮下等，给药剂型例如片剂(例如口含片、咀嚼片)、胶囊(例如软胶囊、硬胶囊、微胶囊)、油剂、散剂、丸剂、乳剂和混悬剂、酏剂、透皮剂、微囊包埋剂、埋植剂、糖浆剂等。可以是普通制剂、缓释制剂、控释制剂及各种微粒给药系统。各种剂型的制备可参考本领域教科书教导制备，为了将单位给药剂型制成片剂，可以广泛使用本领域公知的各种生物可降解的或生物相容载体。本发明的组合物中含有的药用载体包括但不局限于：离子交换剂，氧化铝，硬脂酸铝，卵磷脂，血清蛋白如人血清蛋白，缓冲物质如磷酸盐，甘油，山梨酸，山梨酸 钾，饱和植物脂肪酸的部分甘油酯混合物，水，盐或电解质，如硫酸鱼精蛋白，磷酸氢二钠，磷酸氢钾，氯化钠，锌盐，胶态氧化硅，三硅酸镁，聚乙烯吡咯烷酮，纤维素物质，聚乙二醇，羧甲基纤维素钩，聚丙烯酸酯，蜂蜡，羊毛醋等。载体在药物组合物中的含量可以是1重量％～98重量％，通常大约占到80重量％，为方便起见，局部麻醉剂，防腐剂，缓冲剂等可直接溶于载体中。
本发明所述组合物的给药剂量取决于许多因素，例如所要预防或治疗疾病的性质和严重程度，患者或动物的性别、年龄、体重，敏感性及个体反应，所用的具体化合物，给药途径，给药次数以及所希望达到的治疗效果等。上述剂量可以单一剂量形式或分成几个，例如二、三、四个剂量形式给药。单个最大剂量一般不超过30mg/Kg体重，例如0.001～30mg/Kg，优选0.01～5mg/Kg，较佳剂量范围为0.5～2mg/Kg体重。但是，在某些情况下，也可能使用30mg/Kg体重以上或者0.001mg/Kg以下的单个剂量。
发明的有益效果
本发明提供了一系列具有心脑血管保护作用的成分的组合，其在预防和/或治疗心脑血管疾病方面取得了预料不到的协同作用。在脂代谢紊乱动物模型中，本发明的组合物能有效降低大鼠血清中总胆固醇(TC)、甘油三酯(TG)水平并能显著提高高密度脂蛋白胆固醇(HDL-C)水平，相较于单一组分的应用，具有明显的协同作用。
具体实施方式
下面将结合实施例对本发明的实施方案进行详细描述，但是本领域技术人员将会理解，下列实施例仅用于说明本发明，而不应视为限定本发明的范围。实施例中未注明具体条件者，按照常规条件或制造商建议的条件进行。所用试剂或仪器未注明生产厂商者，均为可以通过市购获得的常规产品。
实施例1-37所用原料均为市场购得，为食品级或医药级，主要 原料的规格如表1所示，组合物配方如表2所示。
表1主要原料规格表
原料名称 规格
二十二碳六烯酸藻油 二十二碳六烯酸含量为55％
氧化型辅酶Q10 氧化型辅酶Q10含量为98％
还原型辅酶Q10 还原型辅酶Q10含量为98％
氧化型硫辛酸 氧化型硫辛酸含量为99％
二氢硫辛酸 二氢硫辛酸含量为99％
大豆磷脂 总磷含量为60％
磷脂酰丝氨酸 磷脂酰丝氨酸含量为98％
改性磷脂 羟化卵磷脂含量为60％
葡萄籽提取物 原花青素含量为99％
大豆胚芽提取物 大豆异黄酮含量为80％
万寿菊提取物 叶黄素含量为90％
三七提取物 三七总皂苷含量为80％
燕麦提取物 β-葡聚糖含量为75％
Figure PCTCN2016095979-appb-000001
Figure PCTCN2016095979-appb-000002
Figure PCTCN2016095979-appb-000003
实施例38降低血脂功能测试
1原理
用高胆固醇和脂类饲料喂养动物可形成脂代谢紊乱动物模型，再给予动物受试样品，可检测受试样品对高血脂症的影响，并可判定受试样品对脂质的吸收、脂蛋白的形成、脂质的降解或排泄产生的影响。
2仪器及试剂
解剖器械，分光光度计，自动生化分析仪，胆固醇，胆盐，血清总胆固醇(TC)，甘油三酯(TG)，高密度脂蛋白(HDL-C)测定试剂盒。
3动物选择及饲料
选取健康成年雄性SD大鼠，体重为150～200g，每组10只。
高脂饲料：78.8％基础饲料，1％胆固醇、10％蛋黄粉、10％猪油、0.2％胆盐。
标准饲料：基础饲料。
4方法
试验设39个组，第1组为高脂饮食的对照组(给予高脂饲料)，第2组为标准饮食组(给予标准饲料)，其余各组分别每天给予高脂饮食的同时经口灌胃给予实施例1～37制备的的受试样品，每次2ml，每天3次，试验时间为30天。
5试验步骤
在实验环境下对大鼠饲喂基础饲料观察10天，然后取尾血，测定血清总胆固醇(TC)，甘油三酯(TG)，高密度脂蛋白胆固醇(HDL-C)水平。根据TC水平，随机分成39组，按上述4中所述方法进行饲养，定期称量体重，于试验结束禁食16小时，测血清TC，TG，HDL-C水平。结果如表3-5所示：
表3血清总胆固醇(TC)测试结果
Figure PCTCN2016095979-appb-000004
Figure PCTCN2016095979-appb-000005
表4血清甘油三酯(TG)测试结果
Figure PCTCN2016095979-appb-000006
Figure PCTCN2016095979-appb-000007
表5血清高密度脂蛋白胆固醇(HDL-C)测试结果
Figure PCTCN2016095979-appb-000008
Figure PCTCN2016095979-appb-000009
上述试验结果证明了本发明的组合物与它们的单一成分相比具有 预料不到的协同效应。
实施例39制备软胶囊制剂
制备软胶囊内容物：取实施例30的营养组合物作为软胶囊的内容物。
软胶囊的胶皮的制备方法为：称取明胶150g、甘油90g、纯化水180g、焦糖色10g、辣椒红2g、二氧化钛1.5g，将甘油、纯化水投入溶胶罐中，加热至60℃，投入明胶继续加热至65℃使其溶解，再将已经溶解混匀并过滤后的焦糖色、辣椒红、二氧化钛投入溶胶罐内，搅拌25min后抽真空脱尽气泡，制得胶皮溶液，60℃保温，备用。
将上述的制备得到的软胶囊内容物与胶皮溶液经过压丸、定型、干燥、拣丸和包装步骤，即得规格为450mg/粒的软胶囊。
尽管本发明的具体实施方式已经得到详细的描述，本领域技术人员将会理解。根据已经公开的所有教导，可以对那些细节进行各种修改和替换，这些改变均在本发明的保护范围之内。本发明的全部范围由所附权利要求及其任何等同物给出。

Claims (25)

  1. 组合物，其包含二十二碳六烯酸或其酯、辅酶Q10、硫辛酸和磷脂中的至少两种。
  2. 权利要求1的组合物，其包含选自以下i)至xi)项中任意一项所述的组合：
    i)二十二碳六烯酸或其酯以及辅酶Q10；
    ii)二十二碳六烯酸或其酯以及硫辛酸；
    iii)二十二碳六烯酸或其酯以及磷脂；
    iv)辅酶Q10和硫辛酸；
    v)辅酶Q10和磷脂；
    vi)硫辛酸和磷脂；
    vii)二十二碳六烯酸或其酯、辅酶Q10和硫辛酸；
    viii)二十二碳六烯酸或其酯、辅酶Q10和磷脂；
    ix)二十二碳六烯酸或其酯、硫辛酸和磷脂；
    x)辅酶Q10、硫辛酸和磷脂；和
    xi)二十二碳六烯酸或其酯、辅酶Q10、硫辛酸和磷脂；
    优选地，所述组合物，其包含二十二碳六烯酸或其酯以及辅酶Q10的组合；
    更优选地，所述组合物，其包含二十二碳六烯酸或其酯、辅酶Q10、硫辛酸和磷脂的组合。
  3. 权利要求2的组合物，其中各组分的含量按重量百分比计算选自以下的一项或多项：
    1)0.5～80％(例如5～60％)的二十二碳六烯酸或其酯；
    2)0.5～60％(例如5～55％)的辅酶Q10；
    3)0.5～60％(例如5～50％)的硫辛酸；和
    4)0.1～60％(例如2～35％)的磷脂。
  4. 权利要求1～3任一项的组合物，如果有，其中，一个或多个物质的重量份数选自以下的一项或多项：
    a)二十二碳六烯酸或其酯的重量份数为3～50份(例如18～23份)；
    b)辅酶Q10的重量份数为3～60份(例如8～13份)；
    c)硫辛酸的重量份数为3～50份(例如38～43份)；和
    d)磷脂的重量份数为1～40份(例如3～8份)。
  5. 权利要求1～4任一项的组合物，其包含选自以下i)至xi)项中任意一项所述的组合：
    i)二十二碳六烯酸或其酯以及辅酶Q10，其重量份数分别为18～23份、8～13份；
    ii)二十二碳六烯酸或其酯以及硫辛酸，其重量份数分别为18～23份、38～43份；
    iii)二十二碳六烯酸或其酯以及磷脂，其重量份数分别为18～23份、3～8份；
    iv)辅酶Q10和硫辛酸，其重量份数分别为8～13份、38～43份；
    v)辅酶Q10和磷脂，其重量份数分别为8～13份、3～8份；
    vi)硫辛酸和磷脂，其重量份数分别为38～43份、3～8份；
    vii)二十二碳六烯酸或其酯、辅酶Q10和硫辛酸，其重量份数分别为18～23份、8～13份、38～43份；
    viii)二十二碳六烯酸或其酯、辅酶Q10和磷脂，其重量份数分别为18～23份、8～13份、3～8份；
    ix)二十二碳六烯酸或其酯、硫辛酸和磷脂，其重量份数分别为18～23份、38～43份、3～8份；
    x)辅酶Q10、硫辛酸和磷脂，其重量份数分别为8～13份、38～43份、3～8份，和
    xi)二十二碳六烯酸或其酯、辅酶Q10、硫辛酸和磷脂，其重量份数分别为3份～43份、3份～53份、3份～43份、1份～33份；优选地， 其重量份数分别为18～23份、8～13份、38～43份、3～8份。
  6. 权利要求1～5任一项的组合物，所述二十二碳六烯酸的酯选自二十二碳六烯酸甲酯、二十二碳六烯酸乙酯、二十二碳六烯酸甘油酯、二十二碳六烯酸异丙酯和二十二碳六烯酸磷脂中的一种或多种。
  7. 权利要求1～6任一项的组合物，所述辅酶Q10选自氧化型辅酶Q10和还原型辅酶Q10中的一种或两种。
  8. 权利要求1～7任一项的组合物，所述硫辛酸选自氧化型硫辛酸和还原型硫辛酸中的一种或两种；优选地，所述还原型硫辛酸为二氢硫辛酸。
  9. 权利要求1～8任一项的组合物，所述磷脂选自羟化磷脂、磷脂酰胆碱、磷脂酰乙醇胺、磷脂酰丝氨酸、磷脂酰甘油、二磷脂酰甘油、磷脂酰肌醇、鞘磷脂等中的一种或多种；优选地，所述磷脂选自羟化卵磷脂和磷脂酰丝氨酸。
  10. 权利要求1～9任一项的组合物，其还包含以下物质中的一种或多种：原花青素、大豆异黄酮、叶黄素、三七总皂苷和β-葡聚糖，
    例如其还包含选自以下1)～9)项中任意一项所述的组合：
    1)原花青素、大豆异黄酮和叶黄素；
    2)原花青素、大豆异黄酮和三七总皂苷；
    3)原花青素、大豆异黄酮和β-葡聚糖；
    4)原花青素、叶黄素和三七总皂苷；
    5)原花青素、叶黄素和β-葡聚糖；
    6)原花青素、三七总皂苷和β-葡聚糖；
    7)大豆异黄酮、叶黄素和三七总皂苷；
    8)大豆异黄酮、叶黄素和β-葡聚糖；和
    9)大豆异黄酮、三七总皂苷和β-葡聚糖；
    优选地，其还包含选自以下1)、7)和10)～14)项中任意一项所述的组合：
    1)原花青素、大豆异黄酮和叶黄素；
    7)大豆异黄酮、叶黄素和三七总皂苷；
    10)叶黄素、三七总皂苷和β-葡聚糖；
    11)原花青素、大豆异黄酮、叶黄素和三七总皂苷；
    12)原花青素、大豆异黄酮、叶黄素和β-葡聚糖；
    13)原花青素、叶黄素、三七总皂苷和β-葡聚糖；和
    14)大豆异黄酮、叶黄素、三七总皂苷和β-葡聚糖；
    进一步优选地，其还包含选自以下11)、14)和15)项中任意一项所述的组合：
    11)原花青素、大豆异黄酮、叶黄素和三七总皂苷；
    14)大豆异黄酮、叶黄素、三七总皂苷和β-葡聚糖；和
    15)原花青素、大豆异黄酮、叶黄素、三七总皂苷和β-葡聚糖；
    更进一步优选地，其还包含以下15)项所述的组合：
    15)原花青素、大豆异黄酮、叶黄素、三七总皂苷和β-葡聚糖。
  11. 权利要求10的组合物，其中各组分的含量按重量百分比计算选自以下的一项或多项：
    (1)0.1～15％(例如0.1～11％)的原花青素；
    (2)0.1～8％(例如0.1～5.5％)的大豆异黄酮；
    (3)0.1～10％(例如0.5～10％)的叶黄素；
    (4)0.1～8％(例如0.1～6％)的三七总皂苷；和
    (5)0.1～8％(例如0.1～6％)的β-葡聚糖。
  12. 权利要求10～11任一项的组合物，如果有，其中，一个或多个物质的重量份数选自以下的一项或多项：
    e)原花青素的重量份数为0.5～15份(例如1.8～2.3份)，
    f)大豆异黄酮的重量份数为0.1～6份(例如0.3～0.5份)，
    g)叶黄素的重量份数为0.1～12份(例如1.3～1.8份)，
    h)三七总皂苷的重量份数为0.1～6份(例如0.3～0.5份)，和
    i)β-葡聚糖的重量份数为0.1～6份(例如0.3～0.5份)。
  13. 权利要求1～12任一项的组合物，其还包含以下物质中的一种或多种：原花青素、大豆异黄酮、叶黄素、三七总皂苷和β-葡聚糖，
    例如其还包含选自以下1)～9)项中任意一项所述的组合：
    1)原花青素、大豆异黄酮和叶黄素，其重量份数分别为1.8～2.3份、0.3～0.5份、1.3～1.8份；
    2)原花青素、大豆异黄酮和三七总皂苷，其重量份数分别为1.8～2.3份、0.3～0.5份、0.3～0.5份；
    3)原花青素、大豆异黄酮和β-葡聚糖，其重量份数分别为1.8～2.3份、0.3～0.5份、0.3～0.5份；
    4)原花青素、叶黄素和三七总皂苷，其重量份数分别为1.8～2.3份、1.3～1.8份、0.3～0.5份；
    5)原花青素、叶黄素和β-葡聚糖，其重量份数分别为1.8～2.3份、0.3～0.5份、0.3～0.5份；
    6)原花青素、三七总皂苷和β-葡聚糖，其重量份数分别为1.8～2.3份、1.3～1.8份、0.3～0.5份；
    7)大豆异黄酮、叶黄素和三七总皂苷，其重量份数分别为0.3～0.5份、1.3～1.8份、0.3～0.5份；
    8)大豆异黄酮、叶黄素和β-葡聚糖，其重量份数分别为0.3～0.5份、1.3～1.8份、0.3～0.5份；和
    9)大豆异黄酮、三七总皂苷和β-葡聚糖，其重量份数分别为0.3～0.5份、0.3～0.5份、0.3～0.5份；
    优选地，其还包含选自以下1)、7)和10)～14)项中任意一项所述的组合：
    1)原花青素、大豆异黄酮和叶黄素，其重量份数分别为1.8～2.3 份、0.3～0.5份、1.3～1.8份；
    7)大豆异黄酮、叶黄素和三七总皂苷，其重量份数分别为0.3～0.5份、1.3～1.8份、0.3～0.5份；
    10)叶黄素、三七总皂苷和β-葡聚糖，其重量份数分别为1.3～1.8份、0.3～0.5份、0.3～0.5份；
    11)原花青素、大豆异黄酮、叶黄素和三七总皂苷，其重量份数分别为1.8～2.3份、0.3～0.5份、1.3～1.8份、0.3～0.5份；
    12)原花青素、大豆异黄酮、叶黄素和β-葡聚糖，其重量份数分别为1.8～2.3份、0.3～0.5份、1.3～1.8份、0.3～0.5份；
    13)原花青素、叶黄素、三七总皂苷和β-葡聚糖，其重量份数分别为1.8～2.3份、1.3～1.8份、0.3～0.5份、0.3～0.5份；和
    14)大豆异黄酮、叶黄素、三七总皂苷和β-葡聚糖，其重量份数分别为0.3～0.5份、1.3～1.8份、0.3～0.5份、0.3～0.5份；
    进一步优选地，其还包含选自以下11)、14)和15)项中任意一项所述的组合：
    11)原花青素、大豆异黄酮、叶黄素和三七总皂苷，其重量份数分别为1.8～2.3份、0.3～0.5份、1.3～1.8份、0.3～0.5份；
    14)大豆异黄酮、叶黄素、三七总皂苷和β-葡聚糖，其重量份数分别为0.3～0.5份、1.3～1.8份、0.3～0.5份、0.3～0.5份；和
    15)原花青素、大豆异黄酮、叶黄素、三七总皂苷和β-葡聚糖，其重量份数分别为0.5～10份、0.1～4份、0.3～9份、0.2～4份、0.1～4份；优选地，其重量份数分别为1.8～2.3份、0.3～0.5份、1.3～1.8份、0.3～0.5份、0.3～0.5份；
    更进一步优选地，其还包含以下15)项所述的组合：
    15)原花青素、大豆异黄酮、叶黄素、三七总皂苷和β-葡聚糖，其重量份数分别为0.5～10份、0.1～4份、0.3～9份、0.2～4份、0.1～4份；优选地，其重量份数分别为1.8～2.3份、0.3～0.5份、1.3～1.8份、0.3～0.5份、0.3～0.5份。
  14. 权利要求1～13任一项的组合物，其还包含载体油，
    优选地，如果有，载体油的重量份数为0.1～85份。
  15. 权利要求14的组合物，所述载体油选自天然植物油脂、天然动物油脂和人工合成油脂中的一种或多种，
    例如选自大豆油、菜籽油、橄榄油、芝麻油、玉米油、棕榈油、葵花油、芥子油、米糠油、椰子油、亚麻籽油、月见草油、大蒜油、荷荷巴油、猪油、牛脂、鱼油、黄油和中链甘油三酯中的一种或多种；
    优选地，所述中链甘油三酯选自饱和辛酸甘油三酯和饱和癸酸甘油三酯中的一种或两种。
  16. 权利要求15的组合物，所述中链甘油三酯选自饱和辛酸甘油三酯和饱和癸酸甘油三酯和辛癸酸甘油酯中的一种或多种；
    优选地，所述载体油至少包括辛癸酸甘油酯。
  17. 权利要求1～16任一项的组合物，其为油剂、混悬剂或与辅料制成软胶囊、硬胶囊、微胶囊、片剂、散剂、丸剂、乳剂和混悬剂等剂型。
  18. 权利要求1～17任一项的组合物的制备方法，其包含以下步骤：
    称取各组分，混合即得所述组合物；优选地，混合后还包括过滤的步骤；更优选地，混合后还包括脱除气泡的步骤。
  19. 权利要求18的方法，所述混合可采用常规搅拌、剪切乳化和高压均质中的至少一种方法；优选地，所述混合在30～80℃下进行，优选50～70℃，例如60℃；优选地，所述混合在真空或惰性气体环境中进行。
  20. 权利要求1～17任一项的组合物用于制备膳食补充剂或保健食品的用途，优选用于制备预防和/或治疗血脂异常或心脑血管疾病的膳食补充剂或保健食品的用途。
  21. 权利要求1～17任一项的组合物在制备预防和/或治疗血脂异常或心脑血管疾病的药物中的用途。
  22. 权利要求1～17任一项的组合物，其用于预防和/或治疗血脂异常或心脑血管疾病的用途。
  23. 在有需要的个体中预防和/或治疗血脂异常或心脑血管疾病的方法，其包括向所述个体施用治疗有效量的权利要求1～17中任一项的组合物。
  24. 权利要求20～22任一项的用途或权利要求23的方法，所述血脂异常包括高脂血症(例如高胆固醇血症和/或高甘油三酯血症)，或者选自血中的总胆固醇升高、低密度脂蛋白胆固醇升高、甘油三酯升高和高密度脂蛋白胆固醇降低中一项或多项。
  25. 权利要求20～22任一项的用途或权利要求23的方法，所述心脑血管疾病选自动脉粥样硬化、高血压、高血脂、脑梗塞、脑出血、冠心病、心绞痛、心肌缺血、心肌梗塞、心力衰竭和心律失常。
PCT/CN2016/095979 2015-08-25 2016-08-19 预防和/或治疗心脑血管疾病的组合物 WO2017032270A1 (zh)

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CN105878374A (zh) * 2016-04-12 2016-08-24 程凤森 一种含丹参脂溶性成分和辅酶q10的组合物及其制备方法及采用该组合物的药物
DE102020115238A1 (de) * 2020-06-09 2021-12-09 Pm-International Ag Nahrungsergänzungsmittel und Nahrungsmittel
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