WO2023112973A1 - Proanthocyanidin-containing dyslipidemia improver, and functional foods, quasi-drugs, and drugs containing proanthocyanidin-containing dyslipidemia improver - Google Patents
Proanthocyanidin-containing dyslipidemia improver, and functional foods, quasi-drugs, and drugs containing proanthocyanidin-containing dyslipidemia improver Download PDFInfo
- Publication number
- WO2023112973A1 WO2023112973A1 PCT/JP2022/046115 JP2022046115W WO2023112973A1 WO 2023112973 A1 WO2023112973 A1 WO 2023112973A1 JP 2022046115 W JP2022046115 W JP 2022046115W WO 2023112973 A1 WO2023112973 A1 WO 2023112973A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- dyslipidemia
- proanthocyanidins
- improving
- improving agent
- proanthocyanidin
- 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.)
- Ceased
Links
Images
Classifications
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
- 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
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
-
- 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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
- A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
-
- 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)
-
- 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)
- A61K36/348—Cannabaceae
- A61K36/3482—Cannabis
-
- 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
- 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)
- A61K36/54—Lauraceae (Laurel family), e.g. cinnamon or sassafras
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
-
- 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
-
- 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
Definitions
- the present invention relates to dyslipidemia-improving agents containing proanthocyanidins, and functional foods, quasi-drugs, and pharmaceuticals containing the dyslipidemia-improving agents.
- proanthocyanidins have been used as food ingredients to improve the condition in which the levels of cholesterol and triglycerides dissolved in the blood are abnormally higher than the standard values (hereinafter referred to as dyslipidemia).
- Proanthocyanidins are a type of polyphenols consisting of a structure in which multiple flavan-3-ols are linked, and are contained in leaves, fruits, barks, etc. of various plants. While proanthocyanidins are avoided as an astringent component, they are used in foods and quasi-drugs as they are effective for dyslipidemia because they have functions as lipase inhibitors and antioxidants. (For example, Patent Document 1.).
- Proanthocyanidins have the advantage of being able to exhibit lipase inhibition and antioxidant effects within a short period of time once they are absorbed into the body.
- the formulated proanthocyanidins are sometimes already oxidized before ingestion, and in this case, the above-mentioned effects are lost, and the storage is poor. Evil was considered a problem.
- the present invention has been made in view of such circumstances, and can express an effect equivalent to the dyslipidemia improvement effect obtained by taking a predetermined number of times of proanthocyanidins with a smaller number of times of taking, and has storage stability and To provide a dyslipidemia-ameliorating agent with improved usability by improving astringency when ingested.
- the present invention also provides functional foods, quasi-drugs, and pharmaceuticals containing the same dyslipidemia-improving agent.
- the dyslipidemia-improving agent according to the present invention is (1) a dyslipidemia-improving agent composed of proanthocyanidin and an agent for improving the feeling of use, wherein the agent for improving the feeling of use is , free catechin and cyclic oligosaccharide.
- the dyslipidemia improving agent according to the present invention also has the following characteristics.
- the proanthocyanidin is a mixture of proanthocyanidins derived from at least two plant materials selected from acacia bark, cinnamon and hemp seed.
- the proanthocyanidin contains a polymer structure of 2 to 8 flavan-3-ols and has a molecular weight of 500 to 2,500.
- the dosage form is powder, fine granules, granules, hard capsules or tablets.
- the functional food according to the present invention contains (5) the above-mentioned dyslipidemia improving agent.
- the quasi-drug according to the present invention contains (6) the above-mentioned dyslipidemia improving agent.
- the drug according to the present invention contains (7) the above-mentioned dyslipidemia improving agent.
- the dyslipidemia-improving agent is composed of proanthocyanidins and an agent for improving the feeling of use, and the agent for improving the feeling of use contains a free catechin and a cyclic oligosaccharide. Therefore, a dyslipidemia-improving agent capable of exhibiting an effect equivalent to the dyslipidemia-improving action obtained by taking proanthocyanidins a predetermined number of times with a smaller number of times of ingestion and having improved storage stability and usability is provided. can do.
- proanthocyanidins are a mixture of proanthocyanidins derived from at least two plant materials selected from acacia bark, cinnamon, and hemp seeds, the dyslipidemia-improving action derived from proanthocyanidins is more consistent. can enjoy.
- the proanthocyanidin contains a polymer structure of 2 to 8 flavan-3-ols and has a molecular weight of 500 to 2500, the proanthocyanidin-derived dyslipidemia improving effect is more consistent. can enjoy.
- the dosage form is powder, fine granules, granules, hard capsules or tablets
- the dosage form suitable for the age group of the ingestor such as young people to the elderly, and the usage environment of the ingestor, such as whether or not it is portable. Ingestion of the dyslipidemia improving agent can be performed.
- the functional food according to the present invention contains the above-mentioned dyslipidemia-improving agent, it is possible to provide a dyslipidemia-improving agent that can be handled as a functional food.
- the quasi-drug according to the present invention contains the above-mentioned dyslipidemia-improving agent, it is possible to provide a dyslipidemia-improving agent that can be handled as a quasi-drug.
- the pharmaceutical according to the present invention contains the above-mentioned dyslipidemia-improving agent, it is possible to provide a dyslipidemia-improving agent that can be handled as a pharmaceutical.
- FIG. 3 is an explanatory diagram showing test results regarding the presence or absence of constituent components of a feel-enhancing agent.
- FIG. 2 is an explanatory diagram showing the results of a test in which differences in the origin of proanthocyanidins were investigated.
- FIG. 4 is an explanatory diagram showing the test results of free catechin, which is a feel-enhancing agent.
- FIG. 4 is an explanatory diagram showing test results regarding differences in tea leaves as free catechin sources.
- the present invention relates to a dyslipidemia-improving agent, and in particular, a dyslipidemia-improving agent composed of proanthocyanidins and an agent for improving the feeling of use, wherein the agent for improving the feeling of use contains free catechin and a cyclic oligosaccharide. It relates to a dyslipidemia improving agent characterized by:
- proanthocyanidins have functions as lipase inhibitors and antioxidants, so they have been added to foods and quasi-drugs for the purpose of improving and preventing dyslipidemia.
- proanthocyanidins react with digestive enzymes during the process of being absorbed into the body, or lose their action within a short period of time as they are metabolized.
- one of the reasons is that even if it is formulated, its action is impaired by oxidation before it is ingested.
- the present inventors have found that, when used in combination with a given composition, the lipase inhibitory action and antioxidant action of proanthocyanidins ingested into the body are expressed for a longer time than when used alone, and dyslipidemia is more easily treated. I thought it could be improved.
- the present invention has been completed based on such ideas and findings from long-term biochemical research, and is a dyslipidemia improving agent composed of proanthocyanidins, a feeling-improving agent, and the feeling of use.
- the improver is characterized by blending free catechin and cyclic oligosaccharide.
- the dyslipidemia-improving action means that LDL cholesterol in the blood is 140 mg/dL or more, HDL cholesterol is less than 40 mg/dL, or triglycerides in the fasting state (for example, no food for 10 hours or more). It refers to a drug that prevents or improves the condition in which is 150 mg/dL or more.
- dyslipidemia it is possible, for example, to remove plaque formed on the inner wall of blood vessels and prevent plaque formation. Since plaque clogs blood vessels and causes myocardial infarction and cerebral infarction, improving dyslipidemia can prevent these developments.
- Proanthocyanidins which have an action to improve dyslipidemia, form a carbon bond between the C-4 position of the flavan skeleton of flavan-3-ols and the C-8 position of the flavan skeleton of other flavan-3-ols. It is a compound whose basic skeleton is a structure in which a plurality of Proanthocyanidins are a kind of polyphenols and are contained in leaves, fruits, barks, etc. of various plants.
- Flavan-3-ols are a group of flavonoids having a 2-phenyl-3,4-dihydro-2H-chromen-3-ol skeleton, such as ( ⁇ )-catechin and (-)-epicatechin.
- Proanthocyanidins exist in various structures in plants due to modifications such as galloyl groups and sugars.
- the structure of the proanthocyanidin according to the present embodiment is not particularly limited, it preferably contains a polymer structure of 2 to 8 flavan-3-ols and has a molecular weight of 500 to 2,500. If the molecular weight is less than 500, the dyslipidemia-improving action derived from proanthocyanidins cannot be fully enjoyed.
- proanthocyanidins are not particularly limited, but proanthocyanidins derived from plant materials such as acacia bark, cinnamon, and hemp seeds have a polymeric structure of 2 to 8 flavan-3-ols. , and a large amount of proanthocyanidins having a molecular weight of 500 to 2,500.
- proanthocyanidins obtained from any two types of plant materials out of acacia bark, cinnamon, and hemp seeds are higher than when using proanthocyanidins obtained from one type of plant material. It has been found that a stronger dyslipidemia-improving effect is exhibited when used in combination with proanthocyanidins. Furthermore, it has been found that when proanthocyanidins obtained from three kinds of proanthocyanidins are mixed and used, a stronger dyslipidemia ameliorating effect is exhibited than when two kinds of proanthocyanidins are used.
- the usability improver is an agent for improving the usability felt when proanthocyanidins are ingested.
- a decrease in the feeling of use due to the cumbersome handling required to prevent it (hereinafter referred to as "handling difficulty"), and the need to take multiple doses per day in conventional proanthocyanidin formulations
- Handling difficulty Decreased feeling of use due to complexity (hereinafter referred to as “non-sustainability of improvement effect”), decrease of feeling of use due to difficulty in swallowing due to astringency of proanthocyanidins when taken orally (hereinafter referred to as "oral irritation
- oral irritation is an agent for improving and improving various factors that reduce the feeling of use.
- the usability improver consists of at least free catechin and cyclic oligosaccharide.
- Free catechins are unpolymerized monomeric catechins, and are collectively referred to as (-)-catechin, (-)-epicatechin, (-)-gallocatechin, and (-)-epigallocatechin. In particular, it is preferable to contain either (-)-epicatechin or (-)-epigallocatechin as the free catechin.
- (-)-Epicatechin and (-)-Epigallocatechin have a bitter taste, but the aftertaste is slightly sweet. If these are added to the feeling-improving agent, it becomes possible to reduce the astringent taste of proanthocyanidins and suppress the astringent taste when taken orally.
- the free catechin is preferably a mixture of free catechins obtained from at least two types of tea leaves selected from green tea leaves, roasted tea leaves, and black tea leaves.
- any two kinds of tea leaves It has been clarified that a higher dyslipidemia ameliorating effect is exhibited when the obtained free catechins are mixed and used. It has also been clarified that when free catechins obtained from three kinds of tea leaves are mixed and used, they show substantially the same dyslipidemia improvement effect as the two kinds.
- Cyclic oligosaccharide is a general term for oligosaccharides having a cyclic structure, and is a polysaccharide in which a plurality of glucoses are linked in a ring. More specifically, ⁇ -cyclodextrin consisting of six glucoses, ⁇ -cyclodextrin consisting of 7 glucoses, ⁇ -cyclodextrin consisting of 8 glucoses, and the like. Any of the above cyclodextrins may be employed as the cyclic oligosaccharide according to the present embodiment.
- Cyclic oligosaccharides have a structure in which the inside of the cyclic structure is hydrophobic and the outside is hydrophilic. Due to such a structure, cyclic oligosaccharides incorporate poorly water-soluble molecules within the cyclic structure and exhibit water solubility due to the hydrophilic action on the outside.
- the above-mentioned free catechins and cyclic oligosaccharides can improve the storage stability of proanthocyanidins and reduce astringency when used alone, but when used together, these effects can be further enhanced.
- the dosage form of the dyslipidemia improving agent according to the present embodiment is not particularly limited, and any dosage form such as powder, fine granules, granules, soft capsules, hard capsules, jelly-like, gummy-like, liquid or tablet can be selected. can do.
- powders, fine granules, granules, hard capsules, or tablets can prevent the interior of the dyslipidemia improving agent from coming into contact with air, thereby preventing deterioration due to oxidation and further increasing storage stability.
- dyslipidemia improving agent according to the present embodiment can also contain excipients, additives, auxiliary ingredients, etc. according to product design, in addition to proanthocyanidins and usability improvers.
- auxiliary ingredients include ingredients that impart further functions to the dyslipidemia-improving agent and enhance the improvement of dyslipidemia. Examples include dietary fiber, soybean protein, carotenoids, and the like. can be done.
- the above-mentioned antihypertensive agent can be used by blending it with functional foods, quasi-drugs, and pharmaceuticals.
- the functional food in the present invention is a concept that includes general food that does not contain pharmaceutical ingredients and is said to contribute to the maintenance and promotion of health. It includes general foods such as so-called supplements, and foods with health claims such as foods for specified health uses, foods with nutrient claims, and foods with function claims.
- quasi-drugs have a mild effect on the human body and are designated by the Minister of Health, Labor and Welfare. Examples include designated quasi-drugs sold at pharmacies or drug stores.
- compositions are intended to be used for the diagnosis, treatment, or prevention of diseases. and OTC drugs that are available.
- dyslipidemia-improving agent an effect equivalent to the dyslipidemia-improving action obtained by ingesting a predetermined number of proanthocyanidins can be expressed with a smaller number of times of ingestion, and storage stability and usability are improved. It is possible to provide a dyslipidemia improving agent that improves.
- the description of each structure mentioned above is an example of this invention, and is not limited to these.
- dyslipidemia improving agent according to the present embodiment will be further described with reference to actual production examples and results of effect confirmation tests.
- test formulation [1] Verification test of dyslipidemia-improving agent (1-1) Preparation of dyslipidemia-improving agent They were mixed to obtain a test formulation (food).
- the test formulation (food) was in the form of granules with a total amount of 1.5 g.
- sample formulations test formulations containing usability enhancers are referred to as sample formulations.
- a comparative formulation consisting of proanthocyanidins and excipients was also prepared.
- the formulations of sample formulations and comparative formulations are as shown in Table 1 below. In the table, the origin or substance name of each component is shown in parentheses. For proanthocyanidins, the blending amount as an acacia bark extract is shown. Acacia bark extract contains more than 600 mg/g of proanthocyanidins.
- Green tea leaves and roasted tea leaves in the table mainly indicate the amount of the free catechin source. Green tea leaves generally contain about 50 to 55 mg/g of free catechins, and hojicha leaves generally contain about 12 to 15 mg/g of free catechins.
- each of the 10 panelists was trained in a preliminary test conducted prior to the test so that the degree of color tone evaluation by visual observation was roughly the same by referring to a predetermined color sample of the same color system.
- the comparison tablet resulted in a larger color change than the sample formulation containing the usability improver.
- the usability enhancer improved the stability of the sample preparation, in other words, improved the handling difficulty.
- the blood LDL cholesterol level decreased the most when the sample formulation containing the usability improver was continuously ingested once a day (30 minutes before dinner).
- the usability-improving agent provides an effect equivalent to or greater than that obtained when the comparative formulation is ingested three times a day (30 minutes before each meal), even with a small number of ingestions.
- a non-sustainable improvement in amelioration of dyslipidemia was shown.
- Oral irritation confirmation test (astringency sensory evaluation test)
- the proanthocyanidins contained in the sample preparations are components with strong astringent and astringent tastes, and when added to foods, etc., it is known that the strongly irritating astringent and astringent tastes cause an unpleasant taste.
- 10 men and women (ages 20 to 60) who have been engaged in product prototyping and sensory evaluation for many years at an OEM manufacturing facility for health foods were selected as panelists to evaluate the odor and taste. .
- astringency since there are no objective evaluation methods, intensity units or scales, or standard substances, panelists were asked to rate the astringency on a 5-point scale (0 points: no astringency, 1 point: slightly astringent taste). 2 points: feel astringent but can drink without difficulty, 3 points: feel strong astringency and are difficult to drink, 4 points: feel extremely strong astringency and cannot drink.). The evaluation values were aggregated and the average value was obtained. Each panelist was allowed to appropriately ingest the preparation for comparison when confirmation of the standard of astringency was required.
- the comparative tablet had a stronger astringent taste than the sample formulation containing the usability improver. That is, it was shown that the astringent taste of proanthocyanidins in the sample formulation was alleviated by the usability improver, and the ease of drinking of the formulation was improved.
- the subjects were 10 subjects (5 males and 5 females) in a group (hereinafter referred to as a test group) ingesting the basic prescription A1 of the dyslipidemia improving agent according to this example, and a group in which the comparative sample X1 was ingested.
- a test group a group in which the comparative sample X1 was ingested.
- X1 group 10 people (5 men, 5 women), and 10 people (5 men, 5 women) in the group ingesting comparative sample X2 (hereinafter referred to as X2 group).
- 10 people (5 males, 5 females) were randomly assigned to a group to receive sample X3 (hereinafter referred to as X3 group) from males and females satisfying the condition of a blood LDL cholesterol level of less than 140 mg/dL.
- Groups X1 to X3 are also collectively referred to as a comparison group in the following description.
- the test group showed a decrease in the blood LDL cholesterol level, but in the comparison group, the decrease in the blood LDL cholesterol level was about 1/4 to 1/3 of the test group.
- the dyslipidemia-ameliorating agent containing both the free catechin and the cyclic oligosaccharide is more effective in improving the dyslipidemia.
- the total amount of proanthocyanidins was the same as in the basic formula P1, but the P7 group, which was given a comparative sample P7 containing acacia-derived proanthocyanidins, cinnamon-derived proanthocyanidins, and hemp seed-derived proanthocyanidins, showed a It was shown that the blood LDL cholesterol level decreased more than the ⁇ P6 group. In other words, it was shown that the effect of improving dyslipidemia is enhanced by combining multiple proanthocyanidins of different origins.
- D4-D6 groups ingested D6, and the total amount of free catechins is the same as samples D1 and D2, but sample D7 was selected from three sources of free catechins: green tea, roasted tea, and black tea. The D7 group was compared and examined. Sample D4 has the same formulation as basic formulation A1 in Table 2. The results are shown in FIG.
- no reduction in blood LDL cholesterol levels was observed.
- sample D6 in which two types of free catechin sources, hojicha leaves and black tea leaves, were selected showed a reduction in blood LDL cholesterol levels equivalent to that of the D4 group.
- the D7 group which was given sample D7, which was selected from green tea leaves, hojicha leaves, and black tea leaves, as free catechin sources, the blood LDL cholesterol level was shown to decrease more than the D4 to D6 groups. was done.
- the usability is improved in improving dyslipidemia, that is, dyslipidemia improving effect without increasing the amount of proanthocyanidin was shown to improve.
- the dyslipidemia improving agent As described above, according to the dyslipidemia improving agent according to the present embodiment, it is composed of proanthocyanidins and a feel-improving agent, and free catechins and cyclic oligosaccharides are added as the feel-improving agent. , the dyslipidemia-improving agent effect can be expressed with a smaller amount of proanthocyanidin, and an easy-to-drink dyslipidemia-improving agent with reduced bitterness can be provided.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Botany (AREA)
- Mycology (AREA)
- Medical Informatics (AREA)
- Biotechnology (AREA)
- Alternative & Traditional Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Microbiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Polymers & Plastics (AREA)
- Obesity (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Inorganic Chemistry (AREA)
- Nutrition Science (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Food Science & Technology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
Description
本発明は、プロアントシアニジンを含む脂質異常症改善剤並びに同脂質異常症改善剤を含む機能性食品、医薬部外品及び医薬品に関する。 The present invention relates to dyslipidemia-improving agents containing proanthocyanidins, and functional foods, quasi-drugs, and pharmaceuticals containing the dyslipidemia-improving agents.
従来、血液中に溶けているコレステロールや中性脂肪の値が基準値よりも異常に高い状態(以下、脂質異常症とも言う。)を改善する食品成分としてプロアントシアニジンが利用されている。 Conventionally, proanthocyanidins have been used as food ingredients to improve the condition in which the levels of cholesterol and triglycerides dissolved in the blood are abnormally higher than the standard values (hereinafter referred to as dyslipidemia).
プロアントシアニジンは、フラバン-3-オール類が複数個繋がった構造よりなるポリフェノール類の一種であり、様々な植物の葉、果実、樹皮などに含まれている。プロアントシアニジンは渋味成分として忌避される一方で、リパーゼ阻害剤としての機能や、抗酸化剤としての機能を有するため脂質異常症に有効であるとして食品や医薬部外品に配合されて利用されている(例えば、特許文献1。)。
Proanthocyanidins are a type of polyphenols consisting of a structure in which multiple flavan-3-ols are linked, and are contained in leaves, fruits, barks, etc. of various plants. While proanthocyanidins are avoided as an astringent component, they are used in foods and quasi-drugs as they are effective for dyslipidemia because they have functions as lipase inhibitors and antioxidants. (For example,
プロアントシアニジンは、体内に吸収されれば短時間の内にリパーゼの阻害や抗酸化作用を発揮できるという長所を有している。 Proanthocyanidins have the advantage of being able to exhibit lipase inhibition and antioxidant effects within a short period of time once they are absorbed into the body.
ところが、これらの作用は長時間に亘って発揮され続けるものではなく、十分な脂質異常症改善効果を得るには数時間ごとに摂取しなおす必要があった。 However, these effects do not last for a long period of time, and it was necessary to retake them every few hours in order to obtain a sufficient dyslipidemia improvement effect.
また、製剤化されたプロアントシアニジンは、摂取前に既に酸化していることもあり、この場合上述の作用を喪失するという保存性の悪さや、経口摂取すれば強い渋味を感じるため使用感の悪さが問題視されていた。 In addition, the formulated proanthocyanidins are sometimes already oxidized before ingestion, and in this case, the above-mentioned effects are lost, and the storage is poor. Evil was considered a problem.
本発明は、このような事情に鑑みてなされたものであって、所定回数のプロアントシアニジンの摂取により得られる脂質異常症改善作用と同等の効果をより少ない摂取回数で発現できると共に、保存性や摂取時の渋味の改善により使用感が向上した脂質異常症改善剤を提供するものである。 The present invention has been made in view of such circumstances, and can express an effect equivalent to the dyslipidemia improvement effect obtained by taking a predetermined number of times of proanthocyanidins with a smaller number of times of taking, and has storage stability and To provide a dyslipidemia-ameliorating agent with improved usability by improving astringency when ingested.
また本発明では、同脂質異常症改善剤を含有する機能性食品や医薬部外品、医薬品についても提供する。 The present invention also provides functional foods, quasi-drugs, and pharmaceuticals containing the same dyslipidemia-improving agent.
上記従来の課題を解決するために、本発明に係る脂質異常症改善剤は、(1)プロアントシアニジンと使用感向上剤とにより構成した脂質異常症改善剤であって、前記使用感向上剤は、遊離型カテキンと環状オリゴ糖とを配合してなることとした。 In order to solve the above-mentioned conventional problems, the dyslipidemia-improving agent according to the present invention is (1) a dyslipidemia-improving agent composed of proanthocyanidin and an agent for improving the feeling of use, wherein the agent for improving the feeling of use is , free catechin and cyclic oligosaccharide.
また、本発明に係る脂質異常症改善剤では、以下の点にも特徴を有する。
(2)前記プロアントシアニジンは、アカシア樹皮、シナモン、麻種子から選ばれる少なくとも2以上の植物素材に由来するプロアントシアニジンの混合物であること。
(3)前記プロアントシアニジンは、2~8個のフラバン-3-オール類の重合体構造を含み、分子量が500~2500であること。
(4)剤形を粉末、細粒、顆粒、ハードカプセル又は錠剤とすることとした。
In addition, the dyslipidemia improving agent according to the present invention also has the following characteristics.
(2) The proanthocyanidin is a mixture of proanthocyanidins derived from at least two plant materials selected from acacia bark, cinnamon and hemp seed.
(3) The proanthocyanidin contains a polymer structure of 2 to 8 flavan-3-ols and has a molecular weight of 500 to 2,500.
(4) The dosage form is powder, fine granules, granules, hard capsules or tablets.
また、本発明に係る機能性食品では、(5)上述の脂質異常症改善剤を含むこととした。 In addition, the functional food according to the present invention contains (5) the above-mentioned dyslipidemia improving agent.
また、本発明に係る医薬部外品では、(6)上述の脂質異常症改善剤を含むこととした。 In addition, the quasi-drug according to the present invention contains (6) the above-mentioned dyslipidemia improving agent.
また、本発明に係る医薬品では、(7)上述の脂質異常症改善剤を含むこととした。 In addition, the drug according to the present invention contains (7) the above-mentioned dyslipidemia improving agent.
本発明に係る脂質異常症改善剤によれば、プロアントシアニジンと使用感向上剤とにより構成した脂質異常症改善剤であって、前記使用感向上剤は、遊離型カテキンと環状オリゴ糖とを配合してなるため、所定回数のプロアントシアニジンの摂取により得られる脂質異常症改善作用と同等の効果をより少ない摂取回数で発現できると共に、保存性と使用感とを改善した脂質異常症改善剤を提供することができる。 According to the dyslipidemia-improving agent according to the present invention, the dyslipidemia-improving agent is composed of proanthocyanidins and an agent for improving the feeling of use, and the agent for improving the feeling of use contains a free catechin and a cyclic oligosaccharide. Therefore, a dyslipidemia-improving agent capable of exhibiting an effect equivalent to the dyslipidemia-improving action obtained by taking proanthocyanidins a predetermined number of times with a smaller number of times of ingestion and having improved storage stability and usability is provided. can do.
また、前記プロアントシアニジンは、アカシア樹皮、シナモン、麻種子から選ばれる少なくとも2以上の植物素材に由来するプロアントシアニジンの混合物であることとすれば、プロアントシアニジン由来の脂質異常症改善作用をより堅実に享受することができる。 In addition, if the proanthocyanidins are a mixture of proanthocyanidins derived from at least two plant materials selected from acacia bark, cinnamon, and hemp seeds, the dyslipidemia-improving action derived from proanthocyanidins is more consistent. can enjoy.
また、前記プロアントシアニジンは、2~8個のフラバン-3-オール類の重合体構造を含み、分子量が500~2500であることとすれば、プロアントシアニジン由来の脂質異常症改善作用をより堅実に享受することができる。 In addition, if the proanthocyanidin contains a polymer structure of 2 to 8 flavan-3-ols and has a molecular weight of 500 to 2500, the proanthocyanidin-derived dyslipidemia improving effect is more consistent. can enjoy.
また、剤形を粉末、細粒、顆粒、ハードカプセル又は錠剤であることとすれば、若年層から年配者までといった摂取者の年齢層や、持ち運びの有無など摂取者の使用環境に適した剤形で脂質異常症改善剤の摂取を行うことができる。 In addition, if the dosage form is powder, fine granules, granules, hard capsules or tablets, the dosage form suitable for the age group of the ingestor, such as young people to the elderly, and the usage environment of the ingestor, such as whether or not it is portable. Ingestion of the dyslipidemia improving agent can be performed.
また、本発明に係る機能性食品では、上述の脂質異常症改善剤を含むこととしたため、機能性食品としての取り扱いが可能な脂質異常症改善剤を提供することができる。 In addition, since the functional food according to the present invention contains the above-mentioned dyslipidemia-improving agent, it is possible to provide a dyslipidemia-improving agent that can be handled as a functional food.
また、本発明に係る医薬部外品では、上述の脂質異常症改善剤を含むこととしたため、医薬部外品としての取り扱いが可能な脂質異常症改善剤を提供することができる。 In addition, since the quasi-drug according to the present invention contains the above-mentioned dyslipidemia-improving agent, it is possible to provide a dyslipidemia-improving agent that can be handled as a quasi-drug.
また、本発明に係る医薬品では、上述の脂質異常症改善剤を含むこととしたため、医薬品としての取り扱いが可能な脂質異常症改善剤を提供することができる。 In addition, since the pharmaceutical according to the present invention contains the above-mentioned dyslipidemia-improving agent, it is possible to provide a dyslipidemia-improving agent that can be handled as a pharmaceutical.
本発明は脂質異常症改善剤に関し、特にプロアントシアニジンと使用感向上剤とにより構成した脂質異常症改善剤であって、前記使用感向上剤は、遊離型カテキンと環状オリゴ糖とを配合してなることを特徴とする脂質異常症改善剤に関するものである。 The present invention relates to a dyslipidemia-improving agent, and in particular, a dyslipidemia-improving agent composed of proanthocyanidins and an agent for improving the feeling of use, wherein the agent for improving the feeling of use contains free catechin and a cyclic oligosaccharide. It relates to a dyslipidemia improving agent characterized by:
従来、プロアントシアニジンは、リパーゼ阻害剤としての機能や、抗酸化剤としての機能を有することから、脂質異常症の改善や予防を目的として食品や医薬部外品などに配合されている。 Conventionally, proanthocyanidins have functions as lipase inhibitors and antioxidants, so they have been added to foods and quasi-drugs for the purpose of improving and preventing dyslipidemia.
ところが、プロアントシアニジン単体の使用では、脂質異常症を十分に改善できるものではなかった。 However, the use of proanthocyanidins alone did not sufficiently improve dyslipidemia.
この原因について本発明者らは、プロアントシアニジンが体内に吸収される過程で消化酵素と反応したり、代謝されることで短時間の内にその作用を失うことが原因と考えている。また、製剤化しても酸化によって摂取される前にその作用が損なわれることが原因の一つとも考えている。 The present inventors believe that the reason for this is that proanthocyanidins react with digestive enzymes during the process of being absorbed into the body, or lose their action within a short period of time as they are metabolized. In addition, we believe that one of the reasons is that even if it is formulated, its action is impaired by oxidation before it is ingested.
そして本発明者らは、所定の組成物と併用することで、体内に摂取されたプロアントシアニジンのリパーゼ阻害作用や抗酸化作用を単体での使用時よりも長く発現させ、脂質異常症をより簡便に改善できるものと考えた。 And the present inventors have found that, when used in combination with a given composition, the lipase inhibitory action and antioxidant action of proanthocyanidins ingested into the body are expressed for a longer time than when used alone, and dyslipidemia is more easily treated. I thought it could be improved.
本発明はこのような着想と長年の生化学的研究による知見に基づいて完成されたものであり、プロアントシアニジンと、使用感向上剤と、より構成した脂質異常症改善剤であり、前記使用感向上剤は、遊離型カテキンと環状オリゴ糖とを配合してなることを特徴としている。なお、上記着想に関する説明は本発明の理解に供すべく記載したものであって、本発明者らが現時点で想定する機序である。従って、必ずしも正しい機序であることを保証するものではなく、また本発明の特許性には何ら影響を与えるもので無いことに留意されたい。 The present invention has been completed based on such ideas and findings from long-term biochemical research, and is a dyslipidemia improving agent composed of proanthocyanidins, a feeling-improving agent, and the feeling of use. The improver is characterized by blending free catechin and cyclic oligosaccharide. The above description of the idea is provided for the purpose of understanding the present invention, and is the mechanism assumed by the present inventors at present. Therefore, it should be noted that it does not necessarily guarantee the correct mechanism and does not affect the patentability of the present invention.
ここで脂質異常症改善作用とは、空腹時(例えば、10時間以上食事を摂っていない状態)において、血液中のLDLコレステロールが140mg/dL以上、HDLコレステロールが40mg/dL未満、又は中性脂肪が150mg/dL以上となる状態を予防したり改善したりするものをいう。 Here, the dyslipidemia-improving action means that LDL cholesterol in the blood is 140 mg/dL or more, HDL cholesterol is less than 40 mg/dL, or triglycerides in the fasting state (for example, no food for 10 hours or more). It refers to a drug that prevents or improves the condition in which is 150 mg/dL or more.
脂質異常症改善作用によって、例えば、血管の内壁に形成されたプラークを除去したり、プラークの発生を予防したりすることができる。プラークは血管を詰まらせて心筋梗塞や脳梗塞の原因となるため、脂質異常症を改善すればこれらの発症を防ぐことができる。 By improving dyslipidemia, it is possible, for example, to remove plaque formed on the inner wall of blood vessels and prevent plaque formation. Since plaque clogs blood vessels and causes myocardial infarction and cerebral infarction, improving dyslipidemia can prevent these developments.
脂質異常症の改善作用を有するプロアントシアニジンは、フラバン-3-オール類のフラバン骨格のC-4位と、別のフラバン-3-オール類のフラバン骨格のC-8位とが炭素結合を形成し、複数個繋がった構造を基本骨格とする化合物である。プロアントシアニジンは、ポリフェノール類の一種であり、様々な植物の葉、果実、樹皮などに含まれている。フラバン-3-オール類は2-フェニル-3,4-ジヒドロ-2H-クロメン-3-オール骨格を有するフラボノイドの一群であり、例えば(±)-カテキンや(-)-エピカテキンがある。 Proanthocyanidins, which have an action to improve dyslipidemia, form a carbon bond between the C-4 position of the flavan skeleton of flavan-3-ols and the C-8 position of the flavan skeleton of other flavan-3-ols. It is a compound whose basic skeleton is a structure in which a plurality of Proanthocyanidins are a kind of polyphenols and are contained in leaves, fruits, barks, etc. of various plants. Flavan-3-ols are a group of flavonoids having a 2-phenyl-3,4-dihydro-2H-chromen-3-ol skeleton, such as (±)-catechin and (-)-epicatechin.
プロアントシアニジンは、植物体内では、ガロイル基や糖などの修飾により種々の構造で存在している。本実施形態に係るプロアントシアニジンの構造は特に限定されるものではないが、2~8個のフラバン-3-オール類の重合体構造を含み、特に分子量が500~2500であることが好ましい。仮に、分子量が500未満であれば、プロアントシアニジンに由来する脂質異常症改善作用を十分に享受することができない。また一方で、9個以上のフラバン-3-オール類で構成されていたり、分子量が2500よりも大きい場合は、脂質異常症改善作用は十分に享受できるものの、使用感向上剤を併用しても酸化を十分に防いだり、渋味を確実に軽減することができないため好適ではない。 Proanthocyanidins exist in various structures in plants due to modifications such as galloyl groups and sugars. Although the structure of the proanthocyanidin according to the present embodiment is not particularly limited, it preferably contains a polymer structure of 2 to 8 flavan-3-ols and has a molecular weight of 500 to 2,500. If the molecular weight is less than 500, the dyslipidemia-improving action derived from proanthocyanidins cannot be fully enjoyed. On the other hand, when it is composed of 9 or more flavan-3-ols or has a molecular weight of more than 2500, although the effect of improving dyslipidemia can be fully enjoyed, even if it is used in combination with a feeling improver It is not suitable because it cannot sufficiently prevent oxidation or reliably reduce astringency.
プロアントシアニジンの由来は特に限定されるものではないが、アカシア樹皮、シナモン、麻種子などの植物素材に由来するプロアントシアニジンは、2~8個のフラバン-3-オール類の重合体構造を有し、且つ分子量が500~2500であるプロアントシアニジンを多く含有するため特に好適である。 The origin of proanthocyanidins is not particularly limited, but proanthocyanidins derived from plant materials such as acacia bark, cinnamon, and hemp seeds have a polymeric structure of 2 to 8 flavan-3-ols. , and a large amount of proanthocyanidins having a molecular weight of 500 to 2,500.
また、発明者らが行った実験によれば、アカシア樹皮、シナモン、麻種子のうち1種の植物素材より得られたプロアントシアニジンを使用する場合よりも、何れか2種の植物素材より得られたプロアントシアニジンを混合させて使用した場合の方が、より強い脂質異常症改善作用を示すことが分かっている。更に、3種より得られたプロアントシアニジンを混合させて使用した場合は、2種の場合に比しても強い脂質異常症改善作用を示すことも分かっている。 In addition, according to experiments conducted by the inventors, proanthocyanidins obtained from any two types of plant materials out of acacia bark, cinnamon, and hemp seeds are higher than when using proanthocyanidins obtained from one type of plant material. It has been found that a stronger dyslipidemia-improving effect is exhibited when used in combination with proanthocyanidins. Furthermore, it has been found that when proanthocyanidins obtained from three kinds of proanthocyanidins are mixed and used, a stronger dyslipidemia ameliorating effect is exhibited than when two kinds of proanthocyanidins are used.
使用感向上剤とは、プロアントシアニジンを摂取する際に感じる使用感を向上させるための剤であり、たとえば、暗所保存や冷所保存、低湿度下での保存などの如く経時的な劣化を防止するために必要な取扱いに伴う繁雑さに由来した使用感の低下(以下、「ハンドリング困難性」と称す。)や、従来のプロアントシアニジン製剤における一日あたり複数回の服用の必要性に伴う繁雑さに由来した使用感の低下(以下、「改善作用の非持続性」と称す。)、経口摂取時のプロアントシアニジンの渋みによる嚥下困難性による使用感の低下(以下、「口腔内刺激性」と称す。)など、種々の使用感の低下要素を改善し向上させるための剤である。 The usability improver is an agent for improving the usability felt when proanthocyanidins are ingested. A decrease in the feeling of use due to the cumbersome handling required to prevent it (hereinafter referred to as "handling difficulty"), and the need to take multiple doses per day in conventional proanthocyanidin formulations Decreased feeling of use due to complexity (hereinafter referred to as "non-sustainability of improvement effect"), decrease of feeling of use due to difficulty in swallowing due to astringency of proanthocyanidins when taken orally (hereinafter referred to as "oral irritation It is an agent for improving and improving various factors that reduce the feeling of use.
使用感向上剤は、少なくとも遊離型カテキンと環状オリゴ糖とより構成している。 The usability improver consists of at least free catechin and cyclic oligosaccharide.
遊離型カテキンは、重合していない単量体のカテキン類であり、(-)-カテキン、(-)-エピカテキン、(-)-ガロカテキン、(-)-エピガロカテキンの総称をいう。特に、遊離型カテキンとして、 (-)-エピカテキン、(-)-エピガロカテキンの何れか一方を含有することが好ましい。 Free catechins are unpolymerized monomeric catechins, and are collectively referred to as (-)-catechin, (-)-epicatechin, (-)-gallocatechin, and (-)-epigallocatechin. In particular, it is preferable to contain either (-)-epicatechin or (-)-epigallocatechin as the free catechin.
(-)-エピカテキン、(-)-エピガロカテキンは、苦味があるものの後味に微かな甘みを感じる。これらを使用感向上剤に配合すれば、プロアントシアニジンの渋味を軽減し、経口摂取時の渋味をより堅実に抑えることが可能となる。 (-)-Epicatechin and (-)-Epigallocatechin have a bitter taste, but the aftertaste is slightly sweet. If these are added to the feeling-improving agent, it becomes possible to reduce the astringent taste of proanthocyanidins and suppress the astringent taste when taken orally.
発明者らが行った実験によれば、少なくとも(-)-エピカテキン、(-)-エピガロカテキンのいずれかを遊離型カテキンとして使用感向上剤に配合すれば、他の単量体のカテキン類のみを配合した場合に比して脂質異常症改善剤の使用感を向上させることを明らかにしている。すなわち、ハンドリング困難性、改善作用の非持続性、および口腔内刺激性など、種々の使用感の低下要素を確実に改善し向上させることができる。 According to experiments conducted by the inventors, if at least either (-)-epicatechin or (-)-epigallocatechin is added as a free catechin to a feel-enhancing agent, other monomeric catechins It has been clarified that the feeling of use of the dyslipidemia improving agent is improved compared to the case where only the similar is blended. That is, it is possible to reliably improve and improve various factors that reduce the feeling of use, such as difficulty in handling, non-sustainability of improving action, and irritation in the oral cavity.
遊離型カテキンは、緑茶葉、ほうじ茶葉、紅茶葉から選ばれる少なくとも2種の茶葉に由来して得た遊離型カテキンの混合物を原料として用いるのが好ましい。 The free catechin is preferably a mixture of free catechins obtained from at least two types of tea leaves selected from green tea leaves, roasted tea leaves, and black tea leaves.
発明者らが行った実験によれば、緑茶葉、ほうじ茶葉、紅茶葉のうち1種の茶葉より得られた遊離型カテキンを使用感向上剤に配合する場合よりも、何れか2種の茶葉より得られた遊離型カテキンを混合させて使用した場合の方が、より高い脂質異常症改善作用を示すことを明らかにしている。また、3種の茶葉より得られた遊離型カテキンを混合させて使用した場合も、2種の場合と略同じ程度に脂質異常症改善作用を示すことを明らかにしている。 According to the experiments conducted by the inventors, when free catechins obtained from one kind of tea leaves selected from green tea leaves, roasted tea leaves, and black tea leaves are blended into the usability improver, any two kinds of tea leaves It has been clarified that a higher dyslipidemia ameliorating effect is exhibited when the obtained free catechins are mixed and used. It has also been clarified that when free catechins obtained from three kinds of tea leaves are mixed and used, they show substantially the same dyslipidemia improvement effect as the two kinds.
環状オリゴ糖は、環状構造を有するオリゴ糖の総称であって、複数個のグルコースが環状に連なった形態の多糖類であり、より具体的には、6個のグルコースよりなるα-シクロデキストリン、7個のグルコースよりなるβ-シクロデキストリン、8個のグルコースよりなるγ-シクロデキストリンなどである。本実施形態に係る環状オリゴ糖は、上記いずれのシクロデキストリンを採用してもよい。 Cyclic oligosaccharide is a general term for oligosaccharides having a cyclic structure, and is a polysaccharide in which a plurality of glucoses are linked in a ring. More specifically, α-cyclodextrin consisting of six glucoses, β-cyclodextrin consisting of 7 glucoses, γ-cyclodextrin consisting of 8 glucoses, and the like. Any of the above cyclodextrins may be employed as the cyclic oligosaccharide according to the present embodiment.
環状オリゴ糖は、環状構造の内側が疎水性、外側が親水性という構造を持つ。このような構造によって、環状オリゴ糖は、難水溶性分子を環状構造内に取込み、かつ、外側の親水性の作用によって水への溶解性を示す。 Cyclic oligosaccharides have a structure in which the inside of the cyclic structure is hydrophobic and the outside is hydrophilic. Due to such a structure, cyclic oligosaccharides incorporate poorly water-soluble molecules within the cyclic structure and exhibit water solubility due to the hydrophilic action on the outside.
上述した遊離型カテキンと環状オリゴ糖は、それぞれを単独で使用すればプロアントシアニジンの保存性向上や渋味軽減を可能とするが、併用することでこれらの作用をより高めることができる。 The above-mentioned free catechins and cyclic oligosaccharides can improve the storage stability of proanthocyanidins and reduce astringency when used alone, but when used together, these effects can be further enhanced.
また一方で、所定回数のプロアントシアニジンの摂取により得られる脂質異常症改善作用と同等の効果をより少ない摂取回数で発現するためには、遊離型カテキンと環状オリゴ糖とを併用する必要がある。 On the other hand, it is necessary to use free catechins and cyclic oligosaccharides in combination in order to achieve an effect equivalent to the dyslipidemia-improving effect obtained by taking proanthocyanidins a predetermined number of times with a smaller number of intakes.
本実施形態に係る脂質異常症改善剤の剤形は特に限定されるものではなく、例えば粉末、細粒、顆粒、ソフトカプセル、ハードカプセル、ゼリー状、グミ状、液体又は錠剤など、あらゆる剤形を選択することができる。特に、粉末、細粒、顆粒、ハードカプセル又は錠剤とすれば、脂質異常症改善剤の内部と空気とが接触することを回避できるため酸化による劣化を防ぎ保存性を更に高めることができる。 The dosage form of the dyslipidemia improving agent according to the present embodiment is not particularly limited, and any dosage form such as powder, fine granules, granules, soft capsules, hard capsules, jelly-like, gummy-like, liquid or tablet can be selected. can do. In particular, powders, fine granules, granules, hard capsules, or tablets can prevent the interior of the dyslipidemia improving agent from coming into contact with air, thereby preventing deterioration due to oxidation and further increasing storage stability.
また、本実施形態に係る脂質異常症改善剤は、プロアントシアニジンと使用感向上剤の他に、製品設計に応じた賦形剤や添加剤、補助成分などを含むこともできる。 In addition, the dyslipidemia improving agent according to the present embodiment can also contain excipients, additives, auxiliary ingredients, etc. according to product design, in addition to proanthocyanidins and usability improvers.
賦形剤としては、例えば、固形剤の場合には、乳糖や結晶セルロース、デンプンなどとすることができる。また、添加剤としては、例えば、安定剤、甘味剤、抗酸化剤、着香剤、着色剤、保存剤を挙げることができる。また、補助成分としては、脂質異常症改善剤に更なる機能を付与したり、脂質異常症改善を高める成分を挙げることができ、一例としては、食物繊維、大豆タンパク質、カロテノイド類などを挙げることができる。 As excipients, for example, in the case of solid formulations, lactose, crystalline cellulose, starch, and the like can be used. Examples of additives include stabilizers, sweeteners, antioxidants, flavoring agents, coloring agents, and preservatives. In addition, auxiliary ingredients include ingredients that impart further functions to the dyslipidemia-improving agent and enhance the improvement of dyslipidemia. Examples include dietary fiber, soybean protein, carotenoids, and the like. can be done.
上述の高血圧症改善剤は、機能性食品、医薬部外品、医薬品に配合して使用することができる。 The above-mentioned antihypertensive agent can be used by blending it with functional foods, quasi-drugs, and pharmaceuticals.
ここで、本発明における機能性食品は、医薬品成分を含まない健康の保持増進に寄与するとされる食品全般を包含する概念であり、例えば、栄養補助食品や健康補助食品、栄養調整食品のほか、所謂サプリメントなどの一般食品であったり、特定保健用食品や栄養機能食品、機能性表示食品の如き保健機能食品も含まれる。 Here, the functional food in the present invention is a concept that includes general food that does not contain pharmaceutical ingredients and is said to contribute to the maintenance and promotion of health. It includes general foods such as so-called supplements, and foods with health claims such as foods for specified health uses, foods with nutrient claims, and foods with function claims.
また医薬部外品は、人体に対する作用がおだやかで厚生労働大臣が指定するものであり、例えば、薬局またはドラッグストア等で市販されている指定医薬部外品が挙げられる。 In addition, quasi-drugs have a mild effect on the human body and are designated by the Minister of Health, Labor and Welfare. Examples include designated quasi-drugs sold at pharmacies or drug stores.
また医薬品は、病気の診断、治療または予防に使用されることを目的とされているものであり、例えば、病院で医師が処方する医療用医薬品であったり、薬局またはドラッグストア等で市販されているOTC医薬品が挙げられる。 Pharmaceuticals are intended to be used for the diagnosis, treatment, or prevention of diseases. and OTC drugs that are available.
このように、上述した脂質異常症改善剤によれば、所定回数のプロアントシアニジンの摂取により得られる脂質異常症改善作用と同等の効果をより少ない摂取回数で発現できると共に、保存性と使用感とを改善した脂質異常症改善剤を提供することができる。なお、上述した各構成の説明は本発明の一例であり、これらに限定されるものではない。 Thus, according to the above-described dyslipidemia-improving agent, an effect equivalent to the dyslipidemia-improving action obtained by ingesting a predetermined number of proanthocyanidins can be expressed with a smaller number of times of ingestion, and storage stability and usability are improved. It is possible to provide a dyslipidemia improving agent that improves In addition, the description of each structure mentioned above is an example of this invention, and is not limited to these.
ここから
以下、本実施形態に係る脂質異常症改善剤について、実際の製造例や効果確認試験の結果を参照しながら更に説明する。
From Here Hereinafter, the dyslipidemia improving agent according to the present embodiment will be further described with reference to actual production examples and results of effect confirmation tests.
〔1〕脂質異常症改善剤の確認試験
(1―1)脂質異常症改善剤の調整
プロアントシアニジンと、使用感向上剤としての遊離型カテキン及び環状オリゴ糖と、賦形剤としての澱粉とを混合して、被験製剤(食品)とした。被験製剤(食品)は、全量1.5gの顆粒状とした。以下、使用感向上剤を含む被験製剤をサンプル製剤と呼称する。
[1] Verification test of dyslipidemia-improving agent (1-1) Preparation of dyslipidemia-improving agent They were mixed to obtain a test formulation (food). The test formulation (food) was in the form of granules with a total amount of 1.5 g. Hereinafter, test formulations containing usability enhancers are referred to as sample formulations.
また比較のため、プロアントシアニジンと、賦形剤とよりなる比較対象製剤(食品)を調製した。サンプル製剤と比較対象製剤の処方は、下記表1に示すとおりである。なお、表中において、括弧内にそれぞれの成分の由来若しくは物質名を示す。プロアントシアニジンは、アカシア樹皮抽出物としての配合量を示す。アカシア樹皮抽出物には、600 mg/g以上のプロアントシアニジンが含まれる。また、表中の緑茶葉及びほうじ茶葉は、主として遊離型カテキン源としての配合量を示す。緑茶葉には、一般的に50~55 mg/g程度の遊離型カテキン、ほうじ茶葉には、一般的に12~15 mg/g程度の遊離型カテキンがそれぞれ含まれる。 For comparison, a comparative formulation (food) consisting of proanthocyanidins and excipients was also prepared. The formulations of sample formulations and comparative formulations are as shown in Table 1 below. In the table, the origin or substance name of each component is shown in parentheses. For proanthocyanidins, the blending amount as an acacia bark extract is shown. Acacia bark extract contains more than 600 mg/g of proanthocyanidins. Green tea leaves and roasted tea leaves in the table mainly indicate the amount of the free catechin source. Green tea leaves generally contain about 50 to 55 mg/g of free catechins, and hojicha leaves generally contain about 12 to 15 mg/g of free catechins.
(1-2)脂質異常症改善剤の安定性評価試験
安定性評価試験では、調整した製剤の安定性を、製剤の色調の経時的変化に着目してハンドリング困難性を評価するため、室温25℃で蛍光灯(40000ルクス)の明かりに3ヶ月間曝した、サンプル製剤及び比較対象製剤を試験に供した。評価は、健康食品等のOEM製造を行う事業所内にて長年にわたり商品試作や官能評価に携わる男女10名(20~60歳)をパネリストとして選定し、目視による色調評価を行った。色調は4段階(1:ほとんど色の変化無し、2:わずかに色が変化した、3:色が変化した、4:かなり変化した)であり、ぞれぞれの評価点を集計し、その平均値を求めた。図1にその結果を示す。
(1-2) Stability evaluation test of dyslipidemia improving agent In the stability evaluation test, the stability of the prepared preparation was evaluated by focusing on the change in color tone of the preparation over time and the difficulty of handling. A sample formulation and a control formulation exposed to fluorescent light (40000 lux) at °C for 3 months were submitted for testing. For the evaluation, 10 men and women (
また、10名の各パネリストは、試験に先立って行われた予備試験にて、所定の同色系統の色見本を参照することで、目視による色調評価の度合いがおおよそ揃うように訓練が行われている。 In addition, each of the 10 panelists was trained in a preliminary test conducted prior to the test so that the degree of color tone evaluation by visual observation was roughly the same by referring to a predetermined color sample of the same color system. there is
図1に示すように、比較対象錠剤の方が使用感向上剤を含むサンプル製剤より色調変化が大きくなる結果となった。すなわち、使用感向上剤によりサンプル製剤の安定性が向上したこと、言い換えるとハンドリング困難性が改善されたことが示された。 As shown in Figure 1, the comparison tablet resulted in a larger color change than the sample formulation containing the usability improver. In other words, it was shown that the usability enhancer improved the stability of the sample preparation, in other words, improved the handling difficulty.
(1-3)脂質異常症改善剤による脂質異常症改善作用の確認試験
次に、表1に示したサンプル製剤を、男女10名(20~60歳、血中LDLコレステロール値が140 mg/dL未満)の被験者に対して、1日1回(夕食30分前)4週間継続摂取させ、採血により血中LDLコレステロール値を評価した。また、表1に示した比較対象製剤を、1日3回(毎食30分前)、または1日1回(夕食30分前)4週間継続摂取させ、採血により血中LDLコレステロール値を評価した。その結果を図2に示す。
(1-3) Confirmation test of dyslipidemia-improving action by dyslipidemia-improving agent (less than 30 minutes before dinner) for 4 weeks, and the blood LDL cholesterol level was evaluated by collecting blood. In addition, the comparative formulation shown in Table 1 was continuously taken three times a day (30 minutes before each meal) or once a day (30 minutes before dinner) for 4 weeks, and the blood LDL cholesterol level was evaluated by collecting blood. . The results are shown in FIG.
図2に示すように、使用感向上剤を含むサンプル製剤を1日1回(夕食30分前)継続摂取させた場合に、最も血中LDLコレステロール値が低下する結果となった。すなわち、使用感向上剤により、少ない摂取回数でも、比較対象製剤を1日3回(毎食30分前)摂取した場合と、同等もしくはそれ以上の効果が得られることが示された。言い換えると、脂質異常症の改善作用の非持続性の改善が示された。 As shown in Figure 2, the blood LDL cholesterol level decreased the most when the sample formulation containing the usability improver was continuously ingested once a day (30 minutes before dinner). In other words, it was shown that the usability-improving agent provides an effect equivalent to or greater than that obtained when the comparative formulation is ingested three times a day (30 minutes before each meal), even with a small number of ingestions. In other words, a non-sustainable improvement in amelioration of dyslipidemia was shown.
(1-4)口腔内刺激性確認試験(渋味の官能評価試験)
サンプル製剤に含まれるプロアントシアニジンは、強い渋味、収斂味をもつ成分で、食品等に添加した場合、強い刺激を伴う渋味、収斂味によって不快な味となることが知られている。渋味の官能評価試験では、健康食品等のOEM製造を行う事業所内にて長年にわたり商品試作や官能評価に携わる男女10名(20~60歳)をパネリストとして選定し、臭いや味について評価した。
(1-4) Oral irritation confirmation test (astringency sensory evaluation test)
The proanthocyanidins contained in the sample preparations are components with strong astringent and astringent tastes, and when added to foods, etc., it is known that the strongly irritating astringent and astringent tastes cause an unpleasant taste. In the astringency sensory evaluation test, 10 men and women (
渋味の評価については、客観的評価方法、強さの単位や尺度、標準物質が定められていないため、パネリストは、5段階( 0 点: 渋味を感じない、1 点: わずかに渋味を感じる、2 点: 渋味を感じるが無理なく飲める、3 点: 渋味を強く感じ飲みにくい、4 点: 渋味を著しく強く感じ飲めない。)で渋味を評価した。評価値を集計し、平均値を求めた。なお、渋味の基準について確認が必要なときは、各パネリストは適宜比較対象製剤を摂取することが許可された。 Regarding the evaluation of astringency, since there are no objective evaluation methods, intensity units or scales, or standard substances, panelists were asked to rate the astringency on a 5-point scale (0 points: no astringency, 1 point: slightly astringent taste). 2 points: feel astringent but can drink without difficulty, 3 points: feel strong astringency and are difficult to drink, 4 points: feel extremely strong astringency and cannot drink.). The evaluation values were aggregated and the average value was obtained. Each panelist was allowed to appropriately ingest the preparation for comparison when confirmation of the standard of astringency was required.
また、10名の各パネリストは、官能試験に先立って行われた予備官能試験にて、プロアントシアニジンを渋味成分とし、種々のバランスにて希釈した水溶液を試飲させることで、渋味評価の度合いがおおよそ揃うように訓練が行われている。渋味評価の結果を図3に示す。 In addition, in a preliminary sensory test conducted prior to the sensory test, each of the 10 panelists was given proanthocyanidins as an astringent component and diluted with various balances. Training is carried out so that the The results of astringency evaluation are shown in FIG.
図3に示すように、比較対象錠剤の方が使用感向上剤を含むサンプル製剤より渋味が強く感じられる結果となった。すなわち、使用感向上剤によりサンプル製剤のプロアントシアニジンの渋味が緩和され製剤の飲みやすさが向上したことが示された。 As shown in Fig. 3, the comparative tablet had a stronger astringent taste than the sample formulation containing the usability improver. That is, it was shown that the astringent taste of proanthocyanidins in the sample formulation was alleviated by the usability improver, and the ease of drinking of the formulation was improved.
〔2〕構成成分の差異と脂質異常症改善作用との関係の検討
(2-1)使用感向上剤の構成成分を欠く場合の効果確認試験
次に、使用感向上剤を構成する遊離型カテキン(緑茶葉由来、ほうじ茶葉由来)や環状オリゴ糖(β-シクロデキストリン)のいずれかを欠いた場合における効果の確認を行った。また本試験では、比較のために基本処方の製剤と、使用感向上剤を含まない製剤についても試験に供した。試験に供した4つのサンプルの処方を表2に示す。なお、表中において、括弧内にそれぞれの成分の由来若しくは物質名を示す。表中のプロアントシアニジンは、アカシア樹皮抽出物としての配合量を示す。また、表中の緑茶葉及びほうじ茶葉は、主として遊離型カテキン源としての各茶葉粉末の配合量を示す。
[2] Investigation of the relationship between the difference in the constituent components and the dyslipidemia-improving action (2-1) Effect confirmation test in the absence of the constituent components of the usability improver Next, the free catechin that constitutes the usability improver (derived from green tea leaves, derived from hojicha leaves) and cyclic oligosaccharides (β-cyclodextrin) were confirmed. In this test, for comparison, a formulation with a basic formula and a formulation containing no usability improver were also tested. Table 2 shows the formulations of the four samples tested. In the table, the origin or substance name of each component is shown in parentheses. Proanthocyanidins in the table indicate the compounding amount as an acacia bark extract. Green tea leaves and roasted tea leaves in the table mainly indicate the blending amount of each tea leaf powder as a source of free catechins.
また、効果確認試験(ヒト試験)は、男女10名(20~60歳、血中LDLコレステロール値140 mg/dL未満)の被験者に対して、表2の組成で調製した製剤を1日1回(夕食30分前)12週間継続摂取させて行った。効果確認は、摂取前、摂取4週間後、8週間後、12週間後に採血を実施し、血中LDLコレステロール値を測定することにより行った。その結果を図4に示す。 In addition, in the effect confirmation test (human test), 10 male and female subjects (20 to 60 years old, blood LDL cholesterol level less than 140 mg/dL) were given a formulation prepared with the composition shown in Table 2 once a day. (30 minutes before dinner) Continuous ingestion for 12 weeks. The effect was confirmed by collecting blood before ingestion, 4 weeks, 8 weeks and 12 weeks after ingestion and measuring the blood LDL cholesterol level. The results are shown in FIG.
なお、被験者は本実施例に係る脂質異常症改善剤の基本処方A1を摂取させる群(以下、被験群という。)に10名(男性5名、女性5名)、比較サンプルX1を摂取させる群(以下、X1群という。)に10名(男性5名、女性5名)、比較サンプルX2を摂取させる群(以下、X2群という。)に10名(男性5名、女性5名)、比較サンプルX3を摂取させる群(以下、X3群という。)に10名(男性5名、女性5名)を、血中LDLコレステロール値140 mg/dL未満の条件を満たす男女からそれぞれランダムに割り当てた。なお、以下の説明においてX1~X3群を総称して比較群ともいう。 The subjects were 10 subjects (5 males and 5 females) in a group (hereinafter referred to as a test group) ingesting the basic prescription A1 of the dyslipidemia improving agent according to this example, and a group in which the comparative sample X1 was ingested. (hereinafter referred to as X1 group.) 10 people (5 men, 5 women), and 10 people (5 men, 5 women) in the group ingesting comparative sample X2 (hereinafter referred to as X2 group). 10 people (5 males, 5 females) were randomly assigned to a group to receive sample X3 (hereinafter referred to as X3 group) from males and females satisfying the condition of a blood LDL cholesterol level of less than 140 mg/dL. Groups X1 to X3 are also collectively referred to as a comparison group in the following description.
図4に示すように、被験群では血中LDLコレステロール値の低下がみられたが、比較群では、血中LDLコレステロール値の低下は被験群の1/4~1/3程度であった。すなわち、脂質異常症改善剤の使用感向上剤としては、遊離型カテキンと環状オリゴ糖の両方を含む方が、脂質異常症の改善効果が高いことが示された。 As shown in Figure 4, the test group showed a decrease in the blood LDL cholesterol level, but in the comparison group, the decrease in the blood LDL cholesterol level was about 1/4 to 1/3 of the test group. In other words, it was shown that the dyslipidemia-ameliorating agent containing both the free catechin and the cyclic oligosaccharide is more effective in improving the dyslipidemia.
(2-2)プロアントシアニジンの由来の違いによる効果の検討
次に、プロアントシアニジンの由来の違いにより脂質異常症改善効果に差異が生じるか否かについての確認を行った。また本試験では、比較のために基本処方の製剤と、使用感向上剤を含まない製剤についても試験に供した。試験に供した4つのサンプルの処方を表3に示す。なお、表3中に示すP1は、先に説明した表2におけるA1と同じ基本処方である。なお、表中において、括弧内にそれぞれの成分の由来若しくは物質名を示す。また、表中のプロアントシアニジンは、アカシアについてはアカシア樹皮抽出物として、シナモンについてはシナモン粉末として、麻種子については麻種子抽出物として、のそれぞれの配合量を示す。さらに、表中の緑茶葉及びほうじ茶葉は、主として遊離型カテキン源としての各茶葉粉末のそれぞれ配合量を示す。
(2-2) Investigation of effects due to different origins of proanthocyanidins Next, it was confirmed whether differences in the origins of proanthocyanidins caused differences in the dyslipidemia improving effect. In this test, for comparison, a formulation with a basic formula and a formulation containing no usability improver were also tested. Table 3 shows the formulations of the four samples tested. P1 shown in Table 3 is the same basic prescription as A1 in Table 2 described above. In the table, the origin or substance name of each component is shown in parentheses. In addition, proanthocyanidins in the table indicate the amount of acacia bark extract, cinnamon powder, and hemp seed extract for acacia, cinnamon, and hemp seed. Furthermore, green tea leaves and roasted tea leaves in the table mainly indicate the blending amounts of each tea leaf powder as the source of free catechins.
またヒト試験は、上述の方法に準じて行った。基本処方P1を摂取させたP1群を被験群とし、比較サンプルP2~P7を摂取させたP2群~P7群を比較群とした。結果を図5に示す。 In addition, human tests were conducted according to the method described above. The P1 group ingested the basic prescription P1 was defined as the test group, and the P2 to P7 groups ingested the comparative samples P2 to P7 were defined as the comparison groups. The results are shown in FIG.
図5に示すように、シナモン由来のプロアントシアニジンを単独で含む比較サンプルP2を摂取させたP2群及び麻種子由来のプロアントシアニジンを単独で含む比較サンプルP3を摂取させたP3群は、血中LDLコレステロール値の低下について、アカシア由来のプロアントシアニジンを含む基本処方P1を摂取させたP1群と比較し、同等の変化を示した。また、プロアントシアニジンとしての総量は基本処方P1と同じであるが、アカシア由来のプロアントシアニジン、シナモン由来のプロアントシアニジン及び麻種子由来のプロアントシアニジンから選ばれる2種のプロアントシアニジンを含む比較サンプルP4,P5,P6をそれぞれ摂取させたP4群~P6群につては、P1群よりも血中LDLコレステロール値の低下が大きくなった。さらに、プロアントシアニジンとしての総量は基本処方P1と同じであるが、アカシア由来のプロアントシアニジン、シナモン由来のプロアントシアニジン及び麻種子由来のプロアントシアニジンを含む比較サンプルP7を摂取させたP7群では、P4群~P6群よりもさらに血中LDLコレステロール値の低下することが示された。すなわち、プロアントシアニジンは、由来の異なるものを複数組み合わせることにより、脂質異常症の改善効果が向上することが示された。 As shown in FIG. 5, the P2 group ingested the comparative sample P2 containing only cinnamon-derived proanthocyanidins and the P3 group ingesting the comparative sample P3 containing only hemp seed-derived proanthocyanidins had blood LDL Compared with the P1 group, which received the basic formula P1 containing proanthocyanidins derived from acacia, the same change in cholesterol level was shown. Comparative samples P4 and P5 containing two types of proanthocyanidins selected from proanthocyanidins derived from acacia, proanthocyanidins derived from cinnamon, and proanthocyanidins derived from hemp seeds, although the total amount of proanthocyanidins is the same as that of the basic formulation P1. The blood LDL cholesterol levels in the P4 to P6 groups, which received P6, decreased more than the P1 group. Furthermore, the total amount of proanthocyanidins was the same as in the basic formula P1, but the P7 group, which was given a comparative sample P7 containing acacia-derived proanthocyanidins, cinnamon-derived proanthocyanidins, and hemp seed-derived proanthocyanidins, showed a It was shown that the blood LDL cholesterol level decreased more than the ~P6 group. In other words, it was shown that the effect of improving dyslipidemia is enhanced by combining multiple proanthocyanidins of different origins.
(2-2)カテキンの違いによる効果の検討
表1-3に示すように、基本処方においては、使用感向上剤の構成成分である遊離型カテキン源として緑茶葉、ほうじ茶葉を選択している。茶葉には、遊離カテキンとして、(-)-カテキン、(-)-エピカテキン、(-)-ガロカテキン、(-)-エピガロカテキンが含まれているが、遊離カテキンのうちいずれのカテキンが脂質異常症に対して最も高い改善効果を示すのかについて検討を行った。試験に供した4つのサンプルの処方を表4に示す。なお、表中において、括弧内にそれぞれの成分の由来若しくは物質名を示す。プロアントシアニジンは、アカシア樹皮抽出物としての配合量を示す。
(2-2) Investigation of effects due to differences in catechins As shown in Table 1-3, in the basic formulation, green tea leaves and roasted tea leaves are selected as sources of free catechins, which are constituents of the feel-enhancing agent. . Tea leaves contain (-)-catechin, (-)-epicatechin, (-)-gallocatechin, and (-)-epigallocatechin as free catechins. A study was conducted to see if the highest improvement effect was shown for abnormal symptoms. Table 4 shows the formulations of the four samples tested. In the table, the origin or substance name of each component is shown in parentheses. For proanthocyanidins, the blending amount as an acacia bark extract is shown.
また、ヒト試験は、上述の方法に準じて行った。表4に示すように、遊離型カテキンとしてエピカテキンを含むサンプルC1を摂取させたC1群、遊離型カテキンとしてエピガロカテキンを含むサンプルC2を摂取させたC2群、遊離型カテキンに替えてその他のカテキンを含むサンプルC3およびC4を摂取させたC3群及びC4群を比較して検討した。なお、その他カテキンA及びBは、遊離型カテキンではない任意のカテキンである。結果を図6に示す。 In addition, human tests were conducted according to the method described above. As shown in Table 4, C1 group ingested sample C1 containing epicatechin as free catechin, C2 group ingesting sample C2 containing epigallocatechin as free catechin, and other The C3 and C4 groups, which received samples C3 and C4 containing catechin, were compared and examined. In addition, other catechins A and B are arbitrary catechins that are not free catechins. The results are shown in FIG.
図6に示すように、遊離型カテキンとしてエピカテキン、エピガロカテキンのいずれかを摂取したC1群及びC2群では、摂取期間を経るにしたがって、血中LDLコレステロール値が良好に低下することが示された。図6におけるC1群及びC2群の血中LDLコレステロール値の変化は、図4を参照して説明した基本処方A1を摂取したA1群と同等のものであった。一方で、C3群及びC4群の血中LDLコレステロール値の低下はわずかなものであり、良好な脂質異常症の改善効果は確認できなかった。以上のことから、遊離型カテキンであるエピカテキン及びエピガロカテキンが、脂質異常症改善剤の使用感を向上させる使用感向上剤として機能していることが確認された。 As shown in FIG. 6, in the C1 group and the C2 group ingesting either epicatechin or epigallocatechin as free catechins, the blood LDL cholesterol level decreased favorably over the period of ingestion. was done. Changes in blood LDL cholesterol levels in groups C1 and C2 in FIG. 6 were equivalent to those in group A1 ingesting the basic formulation A1 described with reference to FIG. On the other hand, the reduction in blood LDL cholesterol levels in the C3 and C4 groups was only slight, and a favorable improvement effect on dyslipidemia could not be confirmed. From the above, it was confirmed that epicatechin and epigallocatechin, which are free catechins, function as feel-enhancing agents that improve the feeling of use of dyslipidemia-improving agents.
(2-2)茶葉の違いによる効果の検討
表1-3に示すように、基本処方においては、使用感向上剤の構成成分である遊離型カテキン源として緑茶葉、ほうじ茶葉を選択している。茶葉に含まれる、カテキンは、発酵により影響を受けやすいことから、茶葉の違いが脂質異常症の改善効果にどのような影響を及ぼすかについて検討を行った。試験に供した7つのサンプルの処方を表5に示す。なお、表中において、括弧内にそれぞれの成分の由来若しくは物質名を示す。また、表中のプロアントシアニジンは、アカシア樹皮抽出物としての配合量を示す。さらに、表中の緑茶葉、ほうじ茶葉及び紅茶葉は、主として遊離型カテキン源としての各茶葉粉末のそれぞれの配合量を示す。紅茶葉には、一般的に9~11mg/g程度の遊離型カテキンが含まれる。
(2-2) Investigation of the effects of different tea leaves As shown in Table 1-3, in the basic formulation, green tea leaves and roasted tea leaves were selected as free catechin sources, which are constituents of the feel-enhancing agent. . Since catechins contained in tea leaves are easily affected by fermentation, we investigated how different tea leaves affect the improvement effect of dyslipidemia. Table 5 shows the formulations of the seven samples tested. In the table, the origin or substance name of each component is shown in parentheses. In addition, proanthocyanidins in the table indicate the compounding amount as an acacia bark extract. Furthermore, green tea leaves, roasted tea leaves, and black tea leaves in the table mainly indicate the amounts of the respective tea leaf powders as free catechin sources. Black tea leaves generally contain about 9 to 11 mg/g of free catechins.
また、ヒト試験は、上述の方法に準じて行った。表5に示すように、遊離型カテキン源として緑茶を選択したサンプルD1を摂取させたD1群、遊離型カテキン源としてほうじ茶を選択したサンプルD2を摂取させたD2群、遊離型カテキン源として緑茶を選択したサンプルD3を摂取させたD3群、遊離型カテキンの総量はサンプルD1,D2と同量であるが、遊離型カテキン源として、緑茶、ほうじ茶、紅茶のうちから2種を選択したサンプルD4~D6を摂取させたD4~D6群、及び、遊離型カテキンの総量はサンプルD1,D2と同量であるが、遊離型カテキン源として緑茶、ほうじ茶、紅茶の3種を選択したサンプルD7を摂取させたD7群を比較して検討した。なお、サンプルD4は、表2における基本処方A1と同じ処方である。結果を図7に示す。 In addition, human tests were conducted according to the method described above. As shown in Table 5, group D1 ingested sample D1 in which green tea was selected as the source of free catechins, group D2 ingested sample D2 in which hojicha was selected as the source of free catechins, and group D2 ingested green tea as the source of free catechins. Group D3, who ingested selected sample D3, had the same total amount of free catechins as samples D1 and D2, but samples D4 and D4, in which two types of free catechin sources were selected from among green tea, hojicha, and black tea. D4-D6 groups ingested D6, and the total amount of free catechins is the same as samples D1 and D2, but sample D7 was selected from three sources of free catechins: green tea, roasted tea, and black tea. The D7 group was compared and examined. Sample D4 has the same formulation as basic formulation A1 in Table 2. The results are shown in FIG.
図7に示すように、遊離型カテキン源として緑茶葉のみを選択したサンプルD1を摂取させたD1群、遊離カテキン源としてほうじ茶葉のみを選択したサンプルD2を摂取させたD2群は、及び、遊離型カテキン源として紅茶葉のみを選択したサンプルD3を摂取させたD3群は、基本処方A1と同じ遊離型カテキン源として緑茶葉とほうじ茶葉の2種を選択したサンプルD4を摂取させたD4群よりも、血中LDLコレステロール値の低下がみられなかった。また、遊離型カテキン源として緑茶葉と紅茶葉の2種を選択したサンプルD5及び遊離型カテキン源としてほうじ茶葉と紅茶葉の2種を選択したサンプルD6をそれぞれ摂取させたD5群およびD6群では、D4群と同等の血中LDLコレステロール値の低下が示された。さらに、遊離型カテキン源として緑茶葉、ほうじ茶葉及び紅茶葉の3種を選択したサンプルD7を摂取させたD7群では、D4群~D6群よりもさらに血中LDLコレステロール値の低下することが示された。すなわち、使用感向上剤としての遊離型カテキン源として、異なる茶葉を複数組み合わせることにより、脂質異常症の改善において使用感が向上、すなわち、プロアントシアニジンの配合量を増大させることなく脂質異常症改善作用が向上することが示された。 As shown in FIG. 7, the D1 group ingested sample D1 in which only green tea leaves were selected as the free catechin source, the D2 group ingested sample D2 in which only hojicha leaves were selected as the free catechin source, and the free Group D3, ingesting sample D3, in which only black tea leaves were selected as the source of catechins, was superior to group D4, ingesting sample D4, in which two kinds of free catechins, green tea leaves and roasted tea leaves, were selected as the same source of free catechins as in basic prescription A1. However, no reduction in blood LDL cholesterol levels was observed. In addition, in the D5 and D6 groups, sample D5 in which two types of free catechin sources, green tea leaves and black tea leaves, were selected, and sample D6, in which two types of free catechin sources, hojicha leaves and black tea leaves, were selected, were ingested. , showed a reduction in blood LDL cholesterol levels equivalent to that of the D4 group. Furthermore, in the D7 group, which was given sample D7, which was selected from green tea leaves, hojicha leaves, and black tea leaves, as free catechin sources, the blood LDL cholesterol level was shown to decrease more than the D4 to D6 groups. was done. That is, by combining a plurality of different tea leaves as a free catechin source as a usability improving agent, the usability is improved in improving dyslipidemia, that is, dyslipidemia improving effect without increasing the amount of proanthocyanidin was shown to improve.
上述してきたように、本実施形態に係る脂質異常症改善剤によれば、プロアントシアニジンと使用感向上剤とにより構成し、使用感向上剤として、遊離型カテキンと環状オリゴ糖を配合したことから、脂質異常症改善剤効果をより少ない量のプロアントシアニジンの量で発現させることができ、しかも、苦味が低減された飲みやすい脂質異常症改善剤を提供することができる。 As described above, according to the dyslipidemia improving agent according to the present embodiment, it is composed of proanthocyanidins and a feel-improving agent, and free catechins and cyclic oligosaccharides are added as the feel-improving agent. , the dyslipidemia-improving agent effect can be expressed with a smaller amount of proanthocyanidin, and an easy-to-drink dyslipidemia-improving agent with reduced bitterness can be provided.
最後に、上述した各実施の形態の説明は本発明の一例であり、本発明は上述の実施の形態に限定されることはない。このため、上述した各実施の形態以外であっても、本発明に係る技術的思想を逸脱しない範囲であれば、設計等に応じて種々の変更が可能であることは勿論である。 Finally, the description of each embodiment described above is an example of the present invention, and the present invention is not limited to the above-described embodiments. Therefore, it goes without saying that various modifications other than the above-described embodiments can be made in accordance with the design and the like within the scope not departing from the technical idea of the present invention.
Claims (7)
前記使用感向上剤は、遊離型カテキンと環状オリゴ糖とを配合してなることを特徴とする脂質異常症改善剤。 A dyslipidemia improving agent comprising a proanthocyanidin and a usability improving agent,
An agent for improving dyslipidemia, wherein the agent for improving the feeling of use comprises a mixture of free catechin and cyclic oligosaccharide.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2023553145A JP7537812B2 (en) | 2021-12-14 | 2022-12-14 | Dyslipidemia improving agent containing proanthocyanidin, and functional foods, quasi-drugs and medicines containing said dyslipidemia improving agent |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2021202736 | 2021-12-14 | ||
| JP2021-202736 | 2021-12-14 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2023112973A1 true WO2023112973A1 (en) | 2023-06-22 |
Family
ID=86774340
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/JP2022/046115 Ceased WO2023112973A1 (en) | 2021-12-14 | 2022-12-14 | Proanthocyanidin-containing dyslipidemia improver, and functional foods, quasi-drugs, and drugs containing proanthocyanidin-containing dyslipidemia improver |
Country Status (2)
| Country | Link |
|---|---|
| JP (1) | JP7537812B2 (en) |
| WO (1) | WO2023112973A1 (en) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH104919A (en) * | 1996-06-21 | 1998-01-13 | Toyo Seito Kk | Food and drink and its production |
| JP2006016367A (en) * | 2004-07-05 | 2006-01-19 | Suntory Ltd | Lipase inhibitor |
| WO2007125644A1 (en) * | 2006-04-26 | 2007-11-08 | Ito En, Ltd. | Fat absorption inhibitor |
| JP2010503609A (en) * | 2006-05-05 | 2010-02-04 | オムニカ ゲーエムベーハー | Kiwi extract |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2006022082A (en) | 2003-11-17 | 2006-01-26 | Toyo Shinyaku:Kk | Lipid metabolism improver |
-
2022
- 2022-12-14 JP JP2023553145A patent/JP7537812B2/en active Active
- 2022-12-14 WO PCT/JP2022/046115 patent/WO2023112973A1/en not_active Ceased
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH104919A (en) * | 1996-06-21 | 1998-01-13 | Toyo Seito Kk | Food and drink and its production |
| JP2006016367A (en) * | 2004-07-05 | 2006-01-19 | Suntory Ltd | Lipase inhibitor |
| WO2007125644A1 (en) * | 2006-04-26 | 2007-11-08 | Ito En, Ltd. | Fat absorption inhibitor |
| JP2010503609A (en) * | 2006-05-05 | 2010-02-04 | オムニカ ゲーエムベーハー | Kiwi extract |
Also Published As
| Publication number | Publication date |
|---|---|
| JP7537812B2 (en) | 2024-08-21 |
| JPWO2023112973A1 (en) | 2023-06-22 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU628514B2 (en) | Inhibitive agent against activity of alpha-amylase | |
| KR101412221B1 (en) | Composition of antiobesity containing Lycium chinensis leaf extract powder and betaine as effective ingredients | |
| US20120052138A1 (en) | Composition comprising green tea extract | |
| US20030161903A1 (en) | Carbohydrate Aborption Inhibitor and Method for Manufacturing the Same | |
| US20070275104A1 (en) | Food Compositions and Methods of Treating Periodontal Disease | |
| US20090175843A1 (en) | Composition for prevention or treatment of urinary tract infection | |
| CA2564326A1 (en) | Nutritional composition which promotes weight loss, burns calories, increases thermogenesis, supports energy metabolism and/or suppresses appetite | |
| US20240325348A1 (en) | Kaempferol analog-containing composition | |
| JP6335508B2 (en) | Growth hormone secretagogue | |
| Vieira et al. | A beverage containing ora-pro-nobis flour improves intestinal health, weight, and body composition: A double-blind randomized prospective study | |
| WO2007019526A2 (en) | Compositions and methods for controlling glucose and lipid uptake from foods | |
| JP2009173652A (en) | Composition for inhibiting neutral fat absorption comprising black tea extract as an active ingredient | |
| CN101254223A (en) | New use of pericarpium Granati and semen Granati extract for improving prostate symptom | |
| WO2004112510A1 (en) | Movement physiology improver | |
| WO2020175579A1 (en) | Composition containing plant-derived extract and/or plant-derived processed product | |
| WO2023112973A1 (en) | Proanthocyanidin-containing dyslipidemia improver, and functional foods, quasi-drugs, and drugs containing proanthocyanidin-containing dyslipidemia improver | |
| US12194052B2 (en) | Chlorophyll composition | |
| KR20220110931A (en) | Compositions for preventing, improving or treating periodontal disease containing dendropanax morbifera lev. extracts | |
| Airaodion et al. | Chemical composition and nutraceutical potential of velvet tamarind (Dialium guineense Wild) fruit pulp | |
| KR101142759B1 (en) | Composition for Improving Inflammatory Bowel Disease | |
| WO2010075611A1 (en) | Composition comprising proanthocyanidin, proteolytic enzyme and aloe vera/agave species substance | |
| WO2005074961A1 (en) | Body fat-controlling agent | |
| JP2007051096A (en) | Oral composition | |
| JPWO2005082390A1 (en) | Fat accumulation inhibitor | |
| US20180110792A1 (en) | Compositions and methods for inhibiting glycation reactions |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 22907496 Country of ref document: EP Kind code of ref document: A1 |
|
| WWE | Wipo information: entry into national phase |
Ref document number: 2023553145 Country of ref document: JP |
|
| NENP | Non-entry into the national phase |
Ref country code: DE |
|
| 122 | Ep: pct application non-entry in european phase |
Ref document number: 22907496 Country of ref document: EP Kind code of ref document: A1 |