WO2010116425A1 - Inhibition de lésion pré-maligne dans le côlon, et agent prophylactique pour cancer colorectal - Google Patents

Inhibition de lésion pré-maligne dans le côlon, et agent prophylactique pour cancer colorectal Download PDF

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Publication number
WO2010116425A1
WO2010116425A1 PCT/JP2009/005019 JP2009005019W WO2010116425A1 WO 2010116425 A1 WO2010116425 A1 WO 2010116425A1 JP 2009005019 W JP2009005019 W JP 2009005019W WO 2010116425 A1 WO2010116425 A1 WO 2010116425A1
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Prior art keywords
kefir
colorectal
colorectal cancer
inhibitor
colon
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PCT/JP2009/005019
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English (en)
Japanese (ja)
Inventor
渡邊敦光
徳丸浩一郎
徳丸千之助
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日本ケフィア株式会社
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Priority to JP2011508077A priority Critical patent/JPWO2010116425A1/ja
Publication of WO2010116425A1 publication Critical patent/WO2010116425A1/fr

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    • 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
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/20—Milk; Whey; Colostrum
    • 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
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/74—Bacteria
    • A61K35/741—Probiotics
    • 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
    • A61K36/06—Fungi, e.g. yeasts
    • A61K36/062—Ascomycota
    • A61K36/064—Saccharomycetales, e.g. baker's yeast
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

Definitions

  • the present invention relates to a precancerous colorectal lesion suppressant containing kefir as an active ingredient, and a colorectal cancer preventive agent.
  • a lesion known as a colorectal precancerous lesion becomes colon cancer at a certain rate after a lapse of a certain period. It is known that if this precancerous lesion of the large intestine is suppressed, the occurrence of colorectal cancer is also suppressed.
  • Patent Document 1 Japanese Patent Laid-Open No. 2006-290856 discloses that glycosphingolipid derived from rice bran suppresses precancerous lesions of the large intestine and exhibits a colorectal cancer preventive action.
  • Kefir is fermented milk native to the Caucasus region of Russia, and is produced by fermenting animal milk such as cow milk using kefir grains (kefir grains, kefir bacteria) derived from the Caucasus region as inoculum (starter). Kefir grains behave as if they were a single organism, but scientifically, various microorganisms have become natural symbiotic organisms, such as Lactobacillus kefiri, and various species of the genus Leuconostoc, Lactococcus and Acetobacter.
  • lactose fermenting yeast eg Kluyveromyces marxianus
  • non-lactose fermenting yeast eg Saccharomyces unisporus, Saccharomyces cerevisiae, Saccharomyces exiguus.
  • lactose fermenting yeast eg Kluyveromyces marxianus
  • non-lactose fermenting yeast eg Saccharomyces unisporus, Saccharomyces cerevisiae, Saccharomyces exiguus.
  • kefir has been pointed out for various health maintenance and promotion functions, and is becoming popular as a healthy food.
  • Patent Document 2 discloses a food product obtained by adding nattokinase to kefir.
  • an object of the present invention is to provide a preventive agent (inhibitor) that can prevent the occurrence of colorectal cancer and the prevention (suppression) of the occurrence of precancerous colorectal lesions.
  • the present invention includes the following [1] to [2].
  • [1] A preventive agent for colorectal cancer comprising kefir as an active ingredient.
  • [2] A pre-colon cancer lesion inhibitor comprising kefir as an active ingredient.
  • the present invention also includes the following [3] to [4].
  • the present invention is also present in a colorectal cancer preventive agent, a colorectal cancer inhibitor, a colorectal precancerous lesion preventive agent, and a colorectal precancerous inhibitor, and is used for oral administration of a colorectal cancer preventive and oral
  • a colorectal cancer preventive agent a colorectal cancer inhibitor
  • a colorectal precancerous lesion preventive agent a colorectal precancerous lesion preventive agent
  • a colorectal precancerous inhibitor a colorectal precancerous inhibitor
  • kefir which is an active ingredient of the present invention, can be safely taken for a long time as a result of traditional eating experience. Therefore, this invention exists also in the said preventive agent and inhibitor for long-term taking, long-term administration, and long-term intake.
  • the present invention also includes the following [5] to [9].
  • [5] A method of preventing colorectal cancer by administering kefir.
  • [6] A method of suppressing precancerous colorectal lesions by administering kefir.
  • [7] The method according to [5] or [6], wherein kefir is orally administered.
  • Ingestion as a preventive or suppressor must be taken daily for a long time before symptoms occur, so even if it is a drug with a strong effect, there are concerns about its side effects and safety. Is not suitable for ingestion as a prophylactic or inhibitor.
  • kefir which is an active ingredient of the inhibitor (preventive agent) of the present invention, is a food that has been used for human consumption during historical years, high safety is ensured, Long-term daily intake can also be performed with confidence. That is, it is a great advantage of the present invention that it is possible to suppress (prevent) colorectal precancerous lesions and prevent (suppress) colorectal cancer without worrying about long-term daily intake.
  • FIG. 1A shows a photomicrograph of a HE-stained section of normal colon.
  • FIG. 1B shows a photomicrograph of a HE-stained section of the large intestine with ACF.
  • FIG. 1C is a view showing a micrograph of a section of a normal large intestine stained with Alcian blue-PAS.
  • FIG. 1D is a photomicrograph of a section of the large intestine with ACF stained with Alcian blue-PAS.
  • FIG. 2 is a view showing a photomicrograph of the large intestine having ACF stained with methylene blue.
  • the present invention resides in a preventive agent for colon cancer and a precancerous lesion inhibitor for colon, which contain kefir as an active ingredient.
  • the kefir used in the present invention can be manufactured based on a known manufacturing method.
  • Kefir can be produced by fermenting milk of animal milk, that is, cows, horses, sheep, goats, etc., but can preferably be produced by adding kefir grains to milk and fermentation.
  • soymilk kefir and plant kefir produced by adding kefir grains and fermenting them with soymilk or other plant-derived raw materials as starting materials can also be used.
  • production methods reference can be made, for example, to JP-A-62-83842 and JP-A-2006-75176.
  • Examples of the kefir used in the present invention include liquid and fluid kefir, and solids such as freeze-dried products thereof. These can be in the form of powder, granules, capsules containing them, and the like. What is obtained by formulating by a known method is also included.
  • Kefirs that can be suitably used are commercially available products such as NKG Kefir-D (manufactured by Nippon Kefir), NKG Kefir-P (manufactured by Nippon Kefir), NKG soybean milk kefir-SD (manufactured by Nippon Kefir). ), NKG Kefir YD-01 (manufactured by Nippon Kefir Co., Ltd.), NKG Kefir YL-01 (manufactured by Nippon Kefir Co., Ltd.), and NKG Kefir G-07 (manufactured by Nippon Kefir Co., Ltd.).
  • the colorectal cancer preventive agent and colorectal precancerous lesion inhibitor of the present invention comprise kefir as an active ingredient.
  • the colorectal cancer preventive agent and colorectal precancerous lesion inhibitor of the present invention may be various forms of kefir itself, or may contain components other than kefir.
  • the kefir may be a kefir containing live bacteria or a kefir containing dead bacteria.
  • the colorectal cancer preventive agent and colorectal precancerous lesion inhibitor of the present invention can be in various forms suitable for the administration method.
  • the colorectal cancer preventive agent and colorectal precancerous lesion inhibitor of the present invention are, for example, capsules, tablets, granules, powders, syrups, troches, sprays, emulsions, suppositories, injections, ointments, tapes. It can be in the form of an agent or the like. In the case of oral administration, it can be processed into tablets, capsules, troches, syrups, granules, powders, etc. and taken orally.
  • Administration of the colorectal cancer preventive agent and colorectal precancerous lesion inhibitor of the present invention includes, for example, oral administration and parenteral administration, preferably oral administration or enteral administration, particularly preferably oral administration. .
  • the colorectal cancer preventive agent and colorectal precancerous lesion inhibitor of the present invention can also be administered in combination with food and drink, feed, and the like.
  • the colon cancer preventive agent and colon precancerous lesion inhibitor of the present invention can be in the form of food and drink. That is, this invention exists also in the functional food for colon cancer prevention and colon precancerous lesion suppression. As a shape suitable for a functional food, a tablet-like supplement can be exemplified. This makes it possible to accurately grasp the intake amount of active ingredients. Furthermore, the colorectal cancer preventive agent and colorectal precancerous lesion inhibitor of the present invention can be in the form of food additives. That is, this invention exists also in the food additive for colon cancer prevention and colon precancerous lesion suppression.
  • the colorectal cancer preventive agent and colorectal precancerous lesion inhibitor of the present invention can be produced, for example, by formulating kefir with any additive such as a pharmaceutically acceptable excipient.
  • a pharmaceutically acceptable excipient In the case of formulation, the content of kefir in the formulation is usually 0.01 to 50% by mass, preferably 0.1 to 25.0% by mass.
  • known pharmaceutically acceptable excipients, binders, disintegrants, lubricants, stabilizers, flavoring agents, diluents, injection solvents and the like can be used.
  • a known production method can be used for formulation.
  • the preventive agent for colorectal cancer and the inhibitor for precancerous colorectal lesion of the present invention include auxiliary components commonly used in the field of medicine and food, for example, lactose, sucrose, liquid sugar, honey, stearin, as necessary.
  • auxiliary components commonly used in the field of medicine and food for example, lactose, sucrose, liquid sugar, honey, stearin, as necessary.
  • Magnesium acid, hydroxypropyl cellulose, various vitamins, citric acid, malic acid, amino acids, fragrances, inorganic salts and the like can be added.
  • the dose and frequency of administration of kefir which is an active ingredient according to the present invention, vary depending on the administration method, treatment period, age, weight, etc., but the dose can be appropriately selected from the range of usually 1 mg to 50 g per day for an adult. The number of times can be appropriately selected from a range of once to several times a day.
  • Kefir is a traditional food that has been eaten and consumed for historical years, so there are no side effects and high safety. There is no.
  • colorectal precancerous lesions become colorectal cancer at a certain rate after a certain period of time. What are the environmental factors that cause this colorectal precancerous lesion, and among the precancerous colorectal lesions, what are the environmental factors that may or may not become colon cancer? It still has not been clarified as to whether or not to branch off. However, it is known that if this colorectal precancerous lesion is suppressed, the occurrence of colorectal cancer is also suppressed. In the present invention, as demonstrated by the experiment described in the examples, the effect is exhibited by suppressing the precancerous lesion of the large intestine in the large intestine.
  • the bait used was an oriental yeast MF powder bait.
  • Nippon Kefir Co., Ltd. freeze-dried NKG Kefir YD-01 (sterilized at 90 ° C for 20 minutes, killed), NKG Kefir YL-01 (viable) and NKG Kefir G-07 (doubled cells, viable) ) was mixed in the feed to 2% and given to the animals.
  • Food and drinking water were ad libitum. The intake of food and drinking water was measured. From 6 weeks of age, 15 mg / kg of azoxymethane (Azoxymethane) (AOM, Amagasaki Laboratories Co., Ltd.) was subcutaneously administered three times at weekly intervals.
  • the animals were necropsied, the large intestine was removed from the anus to the cecum (approximately 20cm), opened to the long axis, the feces were removed, the folds were spread flat, and sandwiched between paper towels, 10% neutral formalin solution Fixed for more than a day. Labeled and washed with water for more than 2 hours. Thereafter, the cells were stained at room temperature for 30 minutes while shaking in 0.1% methylene blue solution. Immediately, from the anus to the cecum was carefully observed with a stereomicroscope at a magnification of 1 or more times, and the number of ACFs was counted.
  • ACF Aberrant crypt foci
  • FIG. 2 An example of the ACF morphology observed in this way is shown in FIG. 2 (stereomicroscope ⁇ 2). Based on observation with a stereomicroscope as shown in FIG. 2, sections of the cross section were further stained and observed with a microscope.
  • 1A to 1D are micrographs ( ⁇ 200) stained by comparing sections of normal and ACF-containing sections.
  • ACF was 74.8 ⁇ 15.1 in the MF group, 40.9 ⁇ 19.2 and 41.2 ⁇ 18.8 in the YD group and YL group, and 52.3 ⁇ 26.0 in the G group, respectively, and significantly decreased in any kefir group compared to the MF group (Table). 1).
  • the total number of AC in the MF group is 136.7 ⁇ 32.3, while the YD group is 76.5 ⁇ 34.1, the YL group is 74.4 ⁇ 32.8, and the G group is 89.2 ⁇ 51.4. It was.
  • the average number of AC per ACF was 1.82 ⁇ 0.16 in the MF group, 1.92 ⁇ 0.20 in the YD group, 1.87 ⁇ 0.21 in the YL group, and 1.65 ⁇ 0.16 in the G group, and no significant difference was observed in all groups (Table 1).
  • FIG. 1A, FIG. 1B, FIG. 1C, and FIG. 1D are photomicrographs showing a comparison between normal colon and ACF, and sections stained with HE staining and Alcian blue-PAS staining, respectively. ⁇ 200).
  • 1A and 1C are photographs of a normal large intestine
  • FIGS. 1B and 1D are photographs of a large intestine having ACF.
  • 1A and 1B are photographs by HE staining
  • FIGS. 1C and 1D are photographs by Alcian blue-PAS staining.
  • the arrows in the photographs of FIGS. 1B and 1D indicate typical ACF locations.
  • FIG. 2 is a photomicrograph taken with a stereomicroscope ( ⁇ 2) showing the large intestine with ACF stained with methylene blue.
  • the arrows in the photograph of FIG. 2 indicate typical ACF positions.
  • kefir was found to significantly suppress colon precancerous lesions by oral administration.
  • the efficacy of this kefir was exhibited by any form of kefir, and was exhibited by both live and dead bacteria.
  • the efficacy of this kefir was effectively exerted on animals, particularly mammals.
  • the present invention provides an agent for inhibiting (preventing) colorectal precancerous lesions and an agent for preventing (suppressing) colorectal cancer.
  • the inhibitor and the preventive agent of the present invention are particularly suitable for ingestion as a prophylactic or inhibitory agent because daily ingestion over a long period can be performed with peace of mind.
  • the present invention is an industrially useful invention.

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Abstract

L'invention porte sur un agent prophylactique pour cancer colorectal et sur un inhibiteur de lésion pré-maligne dans le côlon. Chacun de l'agent prophylactique et de l'inhibiteur comprend du kéfir en tant qu'ingrédient actif.
PCT/JP2009/005019 2009-03-30 2009-09-30 Inhibition de lésion pré-maligne dans le côlon, et agent prophylactique pour cancer colorectal WO2010116425A1 (fr)

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JP2011508077A JPWO2010116425A1 (ja) 2009-03-30 2009-09-30 大腸前がん病変抑制剤及び大腸がん予防剤

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JP2009-081760 2009-03-30

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS6283842A (ja) * 1985-10-08 1987-04-17 Sennosuke Tokumaru 凍結乾燥ヨ−グルトとその製造方法
JPH0937711A (ja) * 1995-07-28 1997-02-10 Sennosuke Tokumaru 健康食品
JP2000166467A (ja) * 1998-12-10 2000-06-20 Nippon Kefia Kk 乳発酵産物及びハーブ類を含有してなる健康食品
WO2002076240A1 (fr) * 2001-03-22 2002-10-03 Nihon Kefir Co., Ltd. Aliments dietetiques contenant de la kinase de natto et produits laitiers fermentes

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS6283842A (ja) * 1985-10-08 1987-04-17 Sennosuke Tokumaru 凍結乾燥ヨ−グルトとその製造方法
JPH0937711A (ja) * 1995-07-28 1997-02-10 Sennosuke Tokumaru 健康食品
JP2000166467A (ja) * 1998-12-10 2000-06-20 Nippon Kefia Kk 乳発酵産物及びハーブ類を含有してなる健康食品
WO2002076240A1 (fr) * 2001-03-22 2002-10-03 Nihon Kefir Co., Ltd. Aliments dietetiques contenant de la kinase de natto et produits laitiers fermentes

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
CENESIZ,S. ET AL.: "The effect of kefir on glutathione (GSH), malondialdehyde (MDA) and nitric oxide (NO) levels in mice with colonic abnormal crypt formation (ACF) induced by azoxymethane (AOM), DTW.", DEUTSCHE TIERARZTLICHE WOCHENSCHRIFT, vol. 115, no. 1, 2008, pages 15 - 19 *
HIROMITSU WATANABE ET AL.: "Hakko Nyuseihin Kefir ni yoru Daicho Zengan Byohen no Yokusei", THE JOURNAL OF JAPAN MIBYO SYSTEM ASSOCIATION, vol. 14, no. SUP.1, 2008, pages 58 *
MICHINORI KUBO ET AL.: "Caucasus-gata Hakkonyu Kefir no Yakuri Kassei Kenkyu (1st report) Ko Shuyo Kassei ni Tsuite Sono 1", JOURNAL OF THE PHARMACEUTICAL SOCIETY OF JAPAN, vol. 112, no. 7, 1992, pages 489 - 495 *
TORU NISHIZAKI, KENKO SHOKUHIN HYAKKA, 2003, pages 359 - 361 *

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