WO2015005393A1 - Agent prophylactique ou thérapeutique pour l'anévrisme de l'aorte et aliment ou boisson emballé(e) - Google Patents

Agent prophylactique ou thérapeutique pour l'anévrisme de l'aorte et aliment ou boisson emballé(e) Download PDF

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Publication number
WO2015005393A1
WO2015005393A1 PCT/JP2014/068333 JP2014068333W WO2015005393A1 WO 2015005393 A1 WO2015005393 A1 WO 2015005393A1 JP 2014068333 W JP2014068333 W JP 2014068333W WO 2015005393 A1 WO2015005393 A1 WO 2015005393A1
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Prior art keywords
aortic aneurysm
epa
therapeutic agent
aneurysm
administration group
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PCT/JP2014/068333
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English (en)
Japanese (ja)
Inventor
信宏 財満
陽平 毛利
賢一 柳本
韓　力
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日本水産株式会社
学校法人近畿大学
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Priority to JP2015526379A priority Critical patent/JPWO2015005393A1/ja
Publication of WO2015005393A1 publication Critical patent/WO2015005393A1/fr

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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
    • A61K31/185—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
    • 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
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/56—Materials from animals other than mammals
    • A61K35/60—Fish, e.g. seahorses; Fish eggs
    • 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
    • A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
    • 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 pharmaceuticals and foods and drinks for preventing or treating aortic aneurysms.
  • An aortic aneurysm is a disease whose main lesion is progressive dilatation of the aorta. Progressive dilatation of the aorta eventually leads to rupture of the aorta, and the survival rate when ruptured is as low as 30%.
  • An aortic aneurysm is a disease that affects about 10% of Japanese men over the age of 65, and is a major disease that is located around the 10th place of death every year.
  • aortic aneurysms In the treatment of aortic aneurysms, the main focus is on preventing the rupture of the aneurysm, and when the aneurysm diameter exceeds a predetermined size, stent graft insertion or artificial blood vessel replacement is used. Although these therapies are effective at a relatively low mortality rate of 1 to 2%, the burden on the elderly is large. In addition, since there are no drug therapies or treatments for early patients with small aneurysm, these patients have no choice but to follow up until just before the risk of aneurysm rupture increases. Therefore, it is desired to develop a pharmacotherapy and a diet that can prevent and treat an aortic aneurysm.
  • Patent Document 1 describes an aneurysm progression preventive and / or therapeutic agent comprising a compound having PPAR ⁇ inhibitory activity as an active ingredient.
  • Fibroblasts that make up the outer wall of the abdominal aortic aneurysm wall express PPAR ⁇ by circulatory disturbance in the blood vessel wall, differentiate into adipocyte-like cells, abnormally accumulate triglycerides in the blood vessel wall, and weaken the blood vessel wall. Therefore, PPAR ⁇ is inhibited to prevent the onset, progress or rupture of an aneurysm and improve the prognosis of aneurysm patients.
  • Non-Patent Document 1 reports that docosahexaenoic acid (DHA) inhibits the expression of matrix metalloprotease (MMP).
  • DHA docosahexaenoic acid
  • MMP matrix metalloprotease
  • An object of the present invention is to provide a novel aortic aneurysm preventive or therapeutic agent capable of preventing and / or treating an aortic aneurysm, and a food or drink containing the same.
  • Histopathology of abdominal aortic aneurysms is characterized by rupture of elastic fibers and collagen fibers in the medial and outer membranes, infiltration of inflammatory cells such as lymphocytes and macrophages, and angiogenesis.
  • inflammatory cells such as lymphocytes and macrophages
  • angiogenesis angiogenesis
  • the present inventors analyzed the blood vessel wall of a patient with an abdominal aortic aneurysm by imaging mass spectrometry (IMS) and found that the blood vessel wall of the patient is in an ischemic state. It was. Furthermore, we succeeded in creating a model animal that develops an abdominal aortic aneurysm by artificially inducing ischemia in the rat abdominal aorta. The vascular wall of this model animal was consistent with human pathological features such as rupture of elastic and collagen fibers in the medial and outer membranes, infiltration of inflammatory cells such as macrophages, and angiogenesis.
  • IMS imaging mass spectrometry
  • the present inventors evaluated the influence of n-3 highly unsaturated fatty acid having anti-inflammatory action on the onset of abdominal aortic aneurysm in a model animal using the model animal produced by the method described above. As a result, it has been found that eicosapentaenoic acid (EPA), which is known to have various functions, has an effect of preventing and / or treating an aortic aneurysm, and has arrived at the present invention.
  • EPA eicosapentaenoic acid
  • the present invention provides a preventive or therapeutic agent for aortic aneurysms containing eicosapentaenoic acid as an active ingredient.
  • the present invention also provides the preventive or therapeutic agent for aortic aneurysm, wherein the eicosapentaenoic acid is contained as an extract of seafood.
  • the present invention also provides a preventive or therapeutic agent for the above-mentioned aortic aneurysm, which further contains docosahexaenoic acid.
  • the present invention also provides a packaged food or drink containing the agent for preventing or treating aortic aneurysm.
  • the preventive or therapeutic agent for aortic aneurysm and the packaged food according to the present invention contain eicosapentaenoic acid as an active ingredient, and therefore can prevent the onset of aortic aneurysm and reduce the aortic aneurysm. .
  • the agent for preventing or treating an aortic aneurysm according to the present invention contains eicosapentaenoic acid (hereinafter also referred to as “EPA”) as an active ingredient.
  • EPA eicosapentaenoic acid
  • EPA is one of the polyunsaturated fatty acids of n-3 fatty acids and is a 20 carbon carboxylic acid with 5 cis double bonds.
  • EPA used in the present invention may be natural or artificially obtained. EPA can treat and extract oils and fats obtained mainly from seafood and microorganisms by conventional methods such as deoxidation, decolorization, deodorization, degumming and dewaxing. In the present invention, EPA may be contained, for example, as an extract of seafood or microorganisms.
  • Seafood extracts are, for example, fish oil and liver oil. Seafood is a general term for marine animals as generally recognized in the art, and includes, for example, herring, mackerel, salmon, sardines, and Antarctic krill. Examples of microorganisms include microalgae such as Labyrinthula.
  • the prophylactic or therapeutic agent for an aortic aneurysm of the present invention can contain any amount of EPA, for example, the daily dose is preferably 3 mg / kg body weight or more, particularly preferably 30 mg / kg body weight or more. It can contain. If it is such a dose, as shown in the Example mentioned later, sufficient prevention or treatment effect of an aortic aneurysm can be acquired.
  • the upper limit of the daily dose of EPA is not particularly limited, but may be, for example, 1000 mg / kg body weight or less. EPA has long experience in other applications and can be used without considering safety issues.
  • Prevention or treatment of an aortic aneurysm suppresses aortic dilation, suppresses aortic aneurysm development, inhibits collagen and elastic fiber degradation, reduces aortic aneurysm, prevents aortic aneurysm rupture, etc. This refers to preventing the onset of an aortic aneurysm and suppressing or improving the progression of an aortic aneurysm.
  • the present invention can be used as a prophylactic or therapeutic agent for aortic aneurysms.
  • the preventive or therapeutic agent for an aortic aneurysm of the present invention may further contain docosahexaenoic acid (hereinafter also referred to as “DHA”).
  • DHA is a carboxylic acid cage (22: 6) cage with 22 carbon chains containing 6 double bonds, for example, all having cis-type double bonds at positions 4, 7, 10, 13, 16 and 19. And compounds classified as n-3 fatty acids.
  • DHA may be contained as an extract of seafood as described above.
  • the preventive or therapeutic agent for an aortic aneurysm of the present invention may further contain components other than EPA.
  • it can further contain carriers, excipients, binders, disintegrants, lubricants, colorants and the like suitable for the use of the present invention.
  • carriers and excipients examples include lactose, glucose, sucrose, mannitol, potato starch, corn starch, calcium carbonate, calcium phosphate, calcium sulfate and crystalline cellulose.
  • binder examples include starch, gelatin, syrup, tragacanth gum, polyvinyl alcohol, polyvinyl ether, polyvinyl pyrrolidone, hydroxypropyl cellulose, methyl cellulose, ethyl cellulose, carboxymethyl cellulose, and the like.
  • disintegrant examples include starch, agar, gelatin powder, crystalline cellulose, calcium carbonate, sodium hydrogen carbonate, sodium alginate, sodium carboxymethylcellulose, and carboxymethylcellulose calcium.
  • examples of lubricants include magnesium stearate, hydrogenated vegetable oil, talc and macrogol.
  • any colorant that is allowed to be added to pharmaceuticals can be used.
  • the preventive or therapeutic agent for an aortic aneurysm of the present invention may be sucrose, gelatin, purified shellac, gelatin, glycerin, sorbitol, ethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone, cellulose phthalate acetate, if necessary. It may be coated with one or more layers such as hydroxypropylmethylcellulose phthalate, methyl methacrylate and methacrylic acid polymer. Moreover, you may add a pH adjuster, a buffering agent, a stabilizer, a solubilizer, etc. as needed.
  • the preventive or therapeutic agent for an aortic aneurysm of the present invention can be provided as a preparation of any form.
  • the present invention includes tablets such as sugar-coated tablets, buccal tablets, coated tablets and chewable tablets, capsules including troches, pills, powders and soft capsules, granules, suspensions, emulsions, and dry syrups as orally administered preparations. It can be a liquid preparation such as a syrup preparation and an elixir.
  • the present invention also provides for parenteral administration, intravenous injection, subcutaneous injection, intraperitoneal injection, intramuscular injection, transdermal administration, nasal administration, pulmonary administration, enteral administration, buccal administration and transmucosal administration. And the like.
  • it can be an injection, a transdermal absorption tape, an aerosol, a suppository and the like.
  • the preventive or therapeutic agent for aortic aneurysm of the present invention can be produced using any method.
  • the preventive or therapeutic agent for aortic aneurysm of the present invention is prepared by mixing EPA with various materials as described above so as to have a desired content using a known production method, and then in a desired form. It can be produced by molding as a preparation.
  • the preventive or therapeutic agent for an aortic aneurysm of the present invention can be used for pharmaceuticals, quasi drugs and foods and drinks.
  • the preventive or therapeutic agent for aortic aneurysm of the present invention is a food or drink, for example, a general food, a food for specified health use, a nutritional functional food, a nutritional supplement, a functional food, a food for the sick, a food for the elderly, etc. Can be.
  • the present invention can be, for example, a food / beverage product displaying that it is a food for specified health use, a food / beverage product displaying an aortic aneurysm prevention effect, or an improvement effect.
  • the preventive or therapeutic agent for aortic aneurysm of the present invention can be used as a food material to be added to, mixed with, or applied to other foods.
  • the present invention also provides a packaged food or drink containing the above-mentioned preventive or therapeutic agent for an aortic aneurysm.
  • the container-packed food / beverage product of the present invention is a food / beverage product provided in a state where the above-mentioned preventive or therapeutic agent for an aortic aneurysm is filled in a container and sealed. That is, the container-packed food / beverage of this invention is a container-packed food / beverage for preventing or improving aortic aneurysm containing EPA.
  • the food and drink can be filled in the container after the sterilization treatment.
  • the container-packed food / beverage product of the present invention may be concentrated and processed so as to be diluted or ingested without dilution.
  • a container generally used for food and drink can be used, and for example, a retort pouch, a paper pack, a PET bottle, a metal can, a glass bottle, and the like can be used.
  • the container-packed food / beverage products of this invention can be manufactured using arbitrary methods. For example, EPA can be mixed with various materials as described above to the desired content and filled into containers as described above according to any food production procedure.
  • the container-packed food or drink of the present invention is not particularly limited, but can be contained so that, for example, the daily intake of EPA is preferably 3 mg / kg body weight or more, particularly preferably 30 mg / kg body weight or more. If it is such a dose, as shown in the Example mentioned later, sufficient prevention or treatment effect of an aortic aneurysm can be acquired.
  • the container-packed food / beverage products of this invention are not specifically limited, For example, the upper limit of the intake per day of EPA may be 1000 mg / kg body weight or less.
  • the packaged food of the present invention can be suitably used for the prevention and / or improvement of an aortic aneurysm.
  • it can be used for diet therapy for patients such as elderly people who are difficult to perform treatments such as stent graft insertion and artificial blood vessel replacement, or patients with an initial stage having a small aneurysm diameter.
  • the present invention also provides a method for preventing or treating an aortic aneurysm comprising administering to a mammal, preferably a human, an amount of eicosapentaenoic acid effective for the prevention and / or treatment of the aortic aneurysm. .
  • the present invention also provides a method for preventing or treating an aortic aneurysm comprising administering to a mammal, preferably a human, an agent for preventing or treating an aneurysm containing eicosapentaenoic acid as an active ingredient. To do.
  • the present invention also provides the above method, wherein eicosapentaenoic acid is contained in the preventive or therapeutic agent as an extract of seafood.
  • the present invention also provides the above method, wherein the preventive or therapeutic agent further contains docosahexaenoic acid.
  • the present invention also provides a method for preventing or treating an aortic aneurysm comprising administering to a mammal, preferably a human, a packaged food or drink containing the above-mentioned preventive or therapeutic agent.
  • Mammals to be subjected to the method of the present invention include, for example, humans, mice, rats, cats, dogs, cows, pigs, sheep, goats and horses.
  • Effective amount refers to a prophylactically or therapeutically effective amount that inhibits aortic dilatation and aortic aneurysm development compared to a corresponding subject who has not received such an amount. It means any amount that produces effects such as inhibiting, inhibiting collagen and elastic fiber degradation, reducing aortic aneurysm, or preventing aortic aneurysm rupture.
  • Eicosapentaenoic acid can be administered by any route including oral and parenteral administration. Moreover, eicosapentaenoic acid can be administered in the form of, for example, the preventive or therapeutic agent of the present invention and the packaged food or drink of the present invention. Eicosapentaenoic acid can be administered at various time intervals at once or over a period of time according to an appropriate dosing schedule.
  • model animals were produced by the following method. Six-week-old (160-180 g) male SD rats were used. After pre-breeding for 1 week, 1145 mg / kg body weight / day triolein (manufactured by Wako Pure Chemical Industries, Ltd.) (control group) and 1145 mg / kg body weight / day EPA-rich purified fish oil (EPA amount 300 mg / kg body weight) ) (EPA high administration group) was forcibly orally administered to rats for 1 week each. Thereafter, a catheter was inserted into the rat abdominal aorta, and an aortic aneurysm model animal was created by ligating the abdominal aorta together with the inserted catheter. Thereafter, the administration was continued for another 4 weeks, followed by euthanasia.
  • triolein manufactured by Wako Pure Chemical Industries, Ltd.
  • EPA-rich purified fish oil EPA amount 300 mg / kg body weight
  • EPA high administration group was forcibly orally administered to rats for 1 week
  • the EPA low administration group was produced using the same method.
  • the EPA low administration group was orally administered a sample of 1145 mg / kg body weight / day (30 mg / kg body weight as the EPA amount), which was a 1: 9 mixture of purified EPA-rich fish oil and triolein.
  • FIG. 1 shows abdominal aortic aneurysms formed in the control group and the high EPA administration group
  • Fig. 1 (a) shows an abdominal aortic aneurysm in one control group
  • Fig. 1 (b) shows an EPA high 1 shows an abdominal aortic aneurysm in one animal in an administration group.
  • FIG. 1 shows that the abdominal aortic aneurysm formed in the high EPA administration group tended to be small compared to the control group.
  • FIG. 2 and FIG. 3 are graphs comparing the diameter and expansion ratio of the abdominal aortic dilatation formed in the control group and the high EPA administration group
  • FIG. 2 shows the diameter of the dilation (mm)
  • FIG. Indicates an expanded / non-expanded aneurysm diameter (expansion ratio).
  • the average expansion ratio of the control group was 5.0
  • the average expansion ratio of the high EPA administration group was 2.5 (FIG. 3).
  • FIG. 3 There was no significant difference in the diameter of the non-expanded part in both groups.
  • the tissue sections were washed with distilled water for 1 minute, and then stained with hematoxylin for 10 minutes for nuclear staining. After washing with distilled water, it was immersed in 1% hydrochloric acid and 70% ethanol for 10 seconds and then washed with running water. Then, it was immersed in distilled water for 10 minutes and immersed in eosin for 5 minutes. The operation of immersing in 80 and 90% ethanol for 1 minute each and immersing in 100% ethanol for 1 minute was repeated twice. Then, it was clarified by putting it in xylene for 5 minutes. Encapsulated with Enteran New, and observed using a biological microscope (CX21LED; manufactured by Olympus Corporation).
  • FIG. 4 is a diagram showing the results of HE staining of tissue pieces in the control group and the high EPA administration group.
  • FIG. 4A is the control group
  • FIG. 4B is the EPA high administration group
  • FIG. 4C is the control group.
  • FIG. 4D shows the high EPA administration group.
  • the scale bars of A and B in FIG. 4 indicate 500 ⁇ m
  • the scale bars of C and D in FIG. 4 indicate 200 ⁇ m.
  • FIG. 4 shows that vascular wall thickening tended to be suppressed in the high EPA administration group compared to the control group.
  • Weigert's iron hematoxylin solution consists of Weiger's iron hematoxylin solution I (1% hematoxylin (SIGMA) and 96% ethanol) and Weigert iron hematoxylin solution II (2% ferric chloride (Nacalai Tesque) and 0.25% hydrochloric acid). And were mixed 1: 1.
  • the Wangyson solution was prepared by mixing Wangyson solution P (Wako Pure Chemical Industries, Ltd.) and 1% Sirius Red (WALDECK) at a ratio of 20: 1.
  • Tissue sections were washed with distilled water for 1 minute. After putting on Weigert's iron hematoxylin solution for 10 minutes, it was washed with distilled water. It was immersed in hydrochloric acid alcohol for 10 seconds and washed with distilled water. Thereafter, the plate was immersed in Wangyson solution for 15 minutes, washed with distilled water, and then immersed in 100% ethanol (manufactured by Nacalai Tesque) for 30 seconds. Encapsulated with Enteran New (manufactured by MERCK), the ratio of collagen fiber area in blood vessels observed with a polarizing microscope after drying was quantified with Image J.
  • FIG. 5 is a graph showing the results of PSR staining of tissue pieces in the control group and the high EPA administration group
  • FIG. 6 is a graph comparing collagen fiber areas in the control group and the high EPA administration group. As shown in FIGS. 5 and 6, the amount of collagen fibers in the high EPA administration group was significantly higher than that in the control group. From these results, it was suggested that the degradation of collagen fibers was suppressed by the administration of EPA-rich purified fish oil.
  • Weigert's iron hematoxylin solution (manufactured by Nacalai Tesque Co., Ltd.) consists of Weigert's iron hematoxylin solution I (1% hematoxylin (manufactured by SIGMA) and 96% ethanol) and Weigert iron hematoxylin solution II (2% ferric chloride (Nacalai Tesque Corporation). And 0.25% hydrochloric acid) were mixed at 1: 1.
  • One-Geeson liquid was prepared by mixing One-Geeson liquid P (manufactured by Wako Pure Chemical Industries, Ltd.) and One-Geeson liquid F (5 g acidic fuchsin (manufactured by WALDECK) and 500 ml distilled water) at a ratio of 100: 15.
  • the tissue section was washed with distilled water for 1 minute, and then applied to Weigertresol fuchsin solution (manufactured by Nacalai Tesque) for 60 minutes. After applying to 100% ethanol (manufactured by Nacalai Tesque Co., Ltd.) for 3 minutes 3 times, it was washed with water for 2 minutes. Then, it was put on Weigert's iron hematoxylin solution for 10 minutes and washed with water for 10 minutes. Then, it was placed in Wangyson's solution for 3 minutes, three times for 1 minute in 70% ethanol, and twice for 1 minute each in 90, 100% ethanol.
  • FIG. 7 is a diagram showing typical elastic plates belonging to each elastic plate grade.
  • FIG. 8 shows the percentage (%) of individuals corresponding to each elastic plate grade evaluation standard in each administration group.
  • the proportion of individuals that meet the elastic plate grade evaluation criteria in each treatment group is 50% for grade 4 and 25% for grade 2 and 3 in the control group, while high EPA is administered.
  • Grade 4 was 12.5%
  • Grade 3 was 37.5%
  • Grade 2 was 50%. From these results, it was shown that the elastic fiber degradation tends to be suppressed in the high EPA administration group.
  • FIG. 9 is a graph comparing the abdominal aortic dilatation formed in the control group and the low EPA administration group (average of 3 individuals). From this result, it was shown that even when EPA was administered at 30 mg / kg body weight / day, the development of abdominal aortic aneurysms tended to be suppressed.
  • FIG. 10 is a diagram showing the results of PSR staining of tissue pieces in a control group and a low EPA administration group.
  • FIG. 10 (a) shows the control group
  • FIG. 10 (b) shows the EPA low administration group.
  • FIG. 11 is a graph comparing collagen fiber areas in the control group and the low EPA administration group. As shown in FIGS. 10 and 11, the amount of collagen fibers in the low EPA administration group was significantly higher than that in the control group. From these results, it was suggested that degradation of collagen fibers was suppressed even when EPA was administered at 30 mg / kg body weight / day.
  • FIG. 12 is a diagram showing the results of EVG staining of tissue pieces in a control group and a low EPA administration group.
  • FIG. 12 (a) shows the control group
  • FIG. 12 (b) shows the EPA low administration group.
  • the evaluation of the elastic plate grade was 4 (disappearance of the elastic plate) in the control group, whereas it was 3 (partial disappearance of the elastic plate) in the low EPA administration group. From these results, it was suggested that even when EPA was administered at 30 mg / kg body weight / day, the degradation of elastic fibers tended to be suppressed.
  • Test Example 9 In order to evaluate the effect when EPA was administered in the early stage of aneurysm formation, the following test was conducted. As model animals, 6-week-old male SD rats were used. After preliminary breeding for 12 days, a catheter was inserted into the rat abdominal aorta to produce an aortic aneurysm model animal, and the abdominal aorta was ligated together with the inserted catheter. One day after the treatment at the initial stage of aortic aneurysm formation, 1145 mg / kg body weight / day triolein was added to the control group, and 1145 mg / kg body weight / day EPA-rich purified fish oil (300 mg / kg as the EPA amount) was administered to the EPA administration group. Body weight) was forcibly administered orally and continued for up to 4 weeks. Individuals who died during the administration period were opened, and the presence or absence of abdominal aortic aneurysm was evaluated.
  • FIG. 13 is a graph showing mortality due to ruptured abdominal aortic aneurysm in the control group and the EPA administration group. As shown in FIG. 13, the mortality rates due to ruptured abdominal aortic aneurysms in the control group and the EPA administration group were 50% and 12.5%, respectively.
  • the present invention can be suitably used for medicines and foods and drinks for preventing, improving or treating aortic aneurysms.

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Abstract

L'objet de la présente invention est de fournir un nouvel agent prophylactique ou thérapeutique pour l'anévrisme de l'aorte, l'anévrisme de l'aorte pouvant par là-même être prévenu et/ou traité, et un aliment ou une boisson emballé(e) le comprenant. Conformément aux résultats de l'évaluation des effets d'acides gras hautement insaturés de type n-3 sur l'anévrisme de l'aorte au moyen de l'utilisation de modèles animaux de l'anévrisme de l'aorte, il a été découvert selon la présente invention que l'acide eicosapentaénoïque (EPA) présente des effets préventifs et thérapeutiques sur l'anévrisme de l'aorte. Ainsi, l'invention porte sur un agent prophylactique ou thérapeutique pour l'anévrisme de l'aorte qui comprend l'acide eicosapentaénoïque utilisé en tant que principe actif. L'invention concerne également un aliment ou une boisson emballé(e) comprenant l'agent prophylactique ou thérapeutique pour l'anévrisme de l'aorte.
PCT/JP2014/068333 2013-07-09 2014-07-09 Agent prophylactique ou thérapeutique pour l'anévrisme de l'aorte et aliment ou boisson emballé(e) WO2015005393A1 (fr)

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Cited By (1)

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Publication number Priority date Publication date Assignee Title
WO2020256095A1 (fr) 2019-06-21 2020-12-24 学校法人近畿大学 Composition pharmaceutique pour la prophylaxie d'un anévrisme aortique et aliment traité

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Publication number Priority date Publication date Assignee Title
WO2006053184A2 (fr) * 2004-11-10 2006-05-18 The Trustees Of Columbia University In The City Of New York Procedes de traitement ou de prevention de maladie vasculaire
WO2010127099A2 (fr) * 2009-04-29 2010-11-04 Amarin Corporation Plc Compositions pharmaceutiques comprenant de l'epa et un agent cardiovasculaire et leurs procédés d'utilisation

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