JP2005247754A - Antitumor agent - Google Patents
Antitumor agent Download PDFInfo
- Publication number
- JP2005247754A JP2005247754A JP2004060821A JP2004060821A JP2005247754A JP 2005247754 A JP2005247754 A JP 2005247754A JP 2004060821 A JP2004060821 A JP 2004060821A JP 2004060821 A JP2004060821 A JP 2004060821A JP 2005247754 A JP2005247754 A JP 2005247754A
- Authority
- JP
- Japan
- Prior art keywords
- trans
- linoleic acid
- conjugated linoleic
- antitumor
- food
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000002246 antineoplastic agent Substances 0.000 title claims abstract description 23
- OYHQOLUKZRVURQ-IXWMQOLASA-N linoleic acid Natural products CCCCC\C=C/C\C=C\CCCCCCCC(O)=O OYHQOLUKZRVURQ-IXWMQOLASA-N 0.000 claims abstract description 51
- 229940108924 conjugated linoleic acid Drugs 0.000 claims abstract description 50
- 235000013305 food Nutrition 0.000 claims abstract description 31
- 230000000259 anti-tumor effect Effects 0.000 claims abstract description 27
- 235000014113 dietary fatty acids Nutrition 0.000 claims abstract description 15
- 229930195729 fatty acid Natural products 0.000 claims abstract description 15
- 239000000194 fatty acid Substances 0.000 claims abstract description 15
- 150000004665 fatty acids Chemical class 0.000 claims abstract description 11
- 229910052751 metal Chemical class 0.000 claims abstract description 9
- 239000002184 metal Chemical class 0.000 claims abstract description 9
- 150000003839 salts Chemical class 0.000 claims abstract description 9
- JBYXPOFIGCOSSB-XBLVEGMJSA-N 9E,11E-octadecadienoic acid Chemical compound CCCCCC\C=C\C=C\CCCCCCCC(O)=O JBYXPOFIGCOSSB-XBLVEGMJSA-N 0.000 claims description 93
- JBYXPOFIGCOSSB-UQGDGPGGSA-N rumenic acid Chemical compound CCCCCC\C=C/C=C/CCCCCCCC(O)=O JBYXPOFIGCOSSB-UQGDGPGGSA-N 0.000 claims description 12
- 235000019197 fats Nutrition 0.000 claims description 9
- 239000004480 active ingredient Substances 0.000 claims description 7
- -1 fatty acid esters Chemical class 0.000 claims description 5
- 239000000203 mixture Substances 0.000 abstract description 14
- 150000002148 esters Chemical class 0.000 abstract description 5
- JBYXPOFIGCOSSB-GOJKSUSPSA-N 9-cis,11-trans-octadecadienoic acid Chemical compound CCCCCC\C=C\C=C/CCCCCCCC(O)=O JBYXPOFIGCOSSB-GOJKSUSPSA-N 0.000 abstract 3
- 230000000694 effects Effects 0.000 description 15
- 239000003921 oil Substances 0.000 description 15
- 235000019198 oils Nutrition 0.000 description 15
- 230000004083 survival effect Effects 0.000 description 15
- 238000012360 testing method Methods 0.000 description 15
- 206010009944 Colon cancer Diseases 0.000 description 10
- 208000029742 colonic neoplasm Diseases 0.000 description 10
- GKJZMAHZJGSBKD-ANYPYVPJSA-N 10-trans-12-cis-linoleic acid Natural products CCCCCC=C\C=C\CCCCCCCCC(O)=O GKJZMAHZJGSBKD-ANYPYVPJSA-N 0.000 description 9
- 239000003925 fat Substances 0.000 description 9
- 230000009422 growth inhibiting effect Effects 0.000 description 9
- 206010028980 Neoplasm Diseases 0.000 description 8
- 238000000034 method Methods 0.000 description 6
- 238000009472 formulation Methods 0.000 description 5
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 150000001298 alcohols Chemical class 0.000 description 4
- 201000011510 cancer Diseases 0.000 description 4
- 230000000052 comparative effect Effects 0.000 description 4
- 230000001419 dependent effect Effects 0.000 description 4
- 239000002994 raw material Substances 0.000 description 4
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- OYHQOLUKZRVURQ-HZJYTTRNSA-N Linoleic acid Chemical compound CCCCC\C=C/C\C=C/CCCCCCCC(O)=O OYHQOLUKZRVURQ-HZJYTTRNSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 230000006907 apoptotic process Effects 0.000 description 3
- 235000013361 beverage Nutrition 0.000 description 3
- 235000014121 butter Nutrition 0.000 description 3
- 235000009508 confectionery Nutrition 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 239000008157 edible vegetable oil Substances 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 235000020778 linoleic acid Nutrition 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 235000008429 bread Nutrition 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 230000010261 cell growth Effects 0.000 description 2
- 235000013351 cheese Nutrition 0.000 description 2
- 238000013467 fragmentation Methods 0.000 description 2
- 238000006062 fragmentation reaction Methods 0.000 description 2
- 125000002541 furyl group Chemical group 0.000 description 2
- 125000005456 glyceride group Chemical group 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 235000013310 margarine Nutrition 0.000 description 2
- 239000003264 margarine Substances 0.000 description 2
- 239000011259 mixed solution Substances 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 235000014593 oils and fats Nutrition 0.000 description 2
- 235000012424 soybean oil Nutrition 0.000 description 2
- 239000003549 soybean oil Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 244000215068 Acacia senegal Species 0.000 description 1
- 201000004384 Alopecia Diseases 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- LNAVIIOBBICBIS-FPLXBDGTSA-N C(\C=C\C=CCCCCCCCCCCCCCCC)(=O)O Chemical compound C(\C=C\C=CCCCCCCCCCCCCCCC)(=O)O LNAVIIOBBICBIS-FPLXBDGTSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 238000008157 ELISA kit Methods 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 239000004367 Lipase Substances 0.000 description 1
- 102000004882 Lipase Human genes 0.000 description 1
- 108090001060 Lipase Proteins 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 229930182558 Sterol Natural products 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000003172 anti-dna Effects 0.000 description 1
- 230000002583 anti-histone Effects 0.000 description 1
- 230000000340 anti-metabolite Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 229940100197 antimetabolite Drugs 0.000 description 1
- 239000002256 antimetabolite Substances 0.000 description 1
- 230000004596 appetite loss Effects 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 235000015173 baked goods and baking mixes Nutrition 0.000 description 1
- 229940076810 beta sitosterol Drugs 0.000 description 1
- LGJMUZUPVCAVPU-UHFFFAOYSA-N beta-Sitostanol Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(C)CCC(CC)C(C)C)C1(C)CC2 LGJMUZUPVCAVPU-UHFFFAOYSA-N 0.000 description 1
- NJKOMDUNNDKEAI-UHFFFAOYSA-N beta-sitosterol Natural products CCC(CCC(C)C1CCC2(C)C3CC=C4CC(O)CCC4C3CCC12C)C(C)C NJKOMDUNNDKEAI-UHFFFAOYSA-N 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 230000000711 cancerogenic effect Effects 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 231100000315 carcinogenic Toxicity 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- 235000015071 dressings Nutrition 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 235000019441 ethanol Nutrition 0.000 description 1
- 125000005313 fatty acid group Chemical group 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 230000009036 growth inhibition Effects 0.000 description 1
- 208000024963 hair loss Diseases 0.000 description 1
- 230000003676 hair loss Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000000265 homogenisation Methods 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 229910052738 indium Inorganic materials 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 235000019421 lipase Nutrition 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 208000019017 loss of appetite Diseases 0.000 description 1
- 235000021266 loss of appetite Nutrition 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000008268 mayonnaise Substances 0.000 description 1
- 235000010746 mayonnaise Nutrition 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 235000012149 noodles Nutrition 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 229920001542 oligosaccharide Polymers 0.000 description 1
- 150000002482 oligosaccharides Chemical class 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 235000015067 sauces Nutrition 0.000 description 1
- 239000004460 silage Substances 0.000 description 1
- KZJWDPNRJALLNS-VJSFXXLFSA-N sitosterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CC[C@@H](CC)C(C)C)[C@@]1(C)CC2 KZJWDPNRJALLNS-VJSFXXLFSA-N 0.000 description 1
- 229950005143 sitosterol Drugs 0.000 description 1
- 235000011888 snacks Nutrition 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 235000014214 soft drink Nutrition 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 150000003432 sterols Chemical class 0.000 description 1
- 235000003702 sterols Nutrition 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 235000019871 vegetable fat Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
Classifications
-
- 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
- A23L2/00—Non-alcoholic beverages; Dry compositions or concentrates therefor; Their preparation
- A23L2/38—Other non-alcoholic beverages
-
- 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
- A23L11/00—Pulses, i.e. fruits of leguminous plants, for production of food; Products from legumes; Preparation or treatment thereof
- A23L11/60—Drinks from legumes, e.g. lupine drinks
- A23L11/65—Soy drinks
-
- 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
- A61K31/201—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 one or two double bonds, e.g. oleic, linoleic acids
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K20/00—Accessory food factors for animal feeding-stuffs
-
- 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
- A23L2/00—Non-alcoholic beverages; Dry compositions or concentrates therefor; Their preparation
- A23L2/52—Adding ingredients
-
- 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
Abstract
Description
本発明は、9トランス,11トランス-共役リノール酸を有効成分とする抗腫瘍剤に関する。また、9トランス,11トランス-共役リノール酸を有効成分として配合した抗腫瘍用飲食品及び飼料に関する。 The present invention relates to an antitumor agent comprising 9trans, 11trans-conjugated linoleic acid as an active ingredient. The present invention also relates to an anti-tumor food and drink and feed containing 9-trans, 11-trans-conjugated linoleic acid as an active ingredient.
厚生労働省の「人口動態統計」における日本人の主要死因別年齢調整死亡率において、昭和５６年から現在に至るまで悪性新生物（癌）が第一位となっており、癌による死亡率は近年まで低下傾向を示さず、横ばいか、微増を示している。このため、癌の治療及び症状の軽減に適した治療方法を開発するために多くの研究が行われているが、化学治療の分野においては、抗生物質、代謝拮抗物質、アルキル化剤、ホルモン剤などが癌細胞に有効な抗腫瘍剤として見いだされているものの、これらの抗腫瘍剤は、癌細胞を攻撃するだけでなく、正常細胞にも作用することから、嘔吐、悪心、食欲不振、脱毛などの副作用を引き起こす問題が発生しており、これらの副作用が少ない新規な治療薬の開発が望まれている。 Malignant neoplasms (cancers) have been ranked first in the age-adjusted mortality rates by major cause of death in Japan in the "Demographic Statistics" of the Ministry of Health, Labor and Welfare from 1981 to the present. Until then, it has been flat or slightly increasing. For this reason, many studies have been conducted to develop treatment methods suitable for cancer treatment and symptom reduction. In the field of chemotherapy, antibiotics, antimetabolites, alkylating agents, hormone agents, etc. Although these anti-tumor agents not only attack cancer cells but also act on normal cells, vomiting, nausea, loss of appetite, and hair loss Problems that cause side effects such as these have occurred, and the development of new therapeutic agents with few such side effects is desired.
最近、合成の共役リノール酸が乳癌抑制作用を有する旨の報告がなされている（例えば、非特許文献1参照）。更に、共役リノール酸の異性体である、9シス,11トランス-共役リノール酸、および10トランス,12シス-共役リノール酸がいずれも同等の発ガン抑制効果を有する旨の報告（例えば、非特許文献2参照）や、10トランス,12シス-共役リノール酸が高い抗腫瘍活性を示すという報告（例えば、特許文献1参照）がなされている。一方、天然物中の共役リノール酸にはマイナーな9トランス, 11トランス-共役リノール酸が含まれるが、この9トランス, 11トランス-共役リノール酸の抗腫瘍効果に関しては全く知られていなかった。
本発明は、優れた抗腫瘍活性を有し、かつ安全性が高く副作用の少ない抗腫瘍剤、及び抗腫瘍用飲食品及び飼料を提供することを課題とする。 An object of the present invention is to provide an antitumor agent having excellent antitumor activity, high safety and few side effects, and food and drink for antitumor and feed.
本発明者等は抗腫瘍活性物質について鋭意研究を重ねた結果、共役リノール酸の異性体の中で優れた抗腫瘍活性を有するのは、既に高い抗腫瘍活性を示すと報告されている9シス, 11トランス-共役リノール酸や10トランス, 12シス-共役リノール酸ではなく、9トランス, 11トランス-共役リノール酸に高い抗腫瘍作用があることを見出し、この知見を基に本発明を完成させるに至った。すなわち、本発明は、9トランス, 11トランス-共役リノール酸を有効成分とする抗腫瘍剤、さらに具体的には9トランス, 11トランス-共役リノール酸の脂肪酸、あるいは脂肪酸エステルもしくは金属塩、またはその他の薬理学上許容される形態物を有効成分とする抗腫瘍剤に関するものである。また、本発明は、9トランス, 11トランス-共役リノール酸を配合した抗腫瘍用飲食品及び飼料に関するものである。 As a result of intensive studies on the antitumor active substances, the present inventors have reported that among the isomers of conjugated linoleic acid, it has already been reported to exhibit high antitumor activity. , 11-trans-conjugated linoleic acid and 10-trans, 12-cis-conjugated linoleic acid, not 9-trans, 11-trans-conjugated linoleic acid, has been found to have high antitumor activity, and the present invention is completed based on this finding It came to. That is, the present invention relates to an antitumor agent comprising 9trans, 11trans-conjugated linoleic acid as an active ingredient, more specifically, a fatty acid, fatty acid ester or metal salt of 9trans, 11trans-conjugated linoleic acid, or other It is related with the antitumor agent which uses the pharmacologically acceptable form of this as an active ingredient. The present invention also relates to antitumor food and drink and feed containing 9-trans and 11-trans-conjugated linoleic acid.
従来、共役リノール酸の２種の異性体である9シス,11トランス-共役リノール酸及び10トランス, 12シス-共役リノール酸が生物活性を有すると報告されていたが、9トランス, 11トランス-共役リノール酸の方がこれらの異性体より顕著に高い抗腫瘍効果を示すことは想到し得なかったことである。本発明によれば、優れた抗腫瘍活性を有し、かつ安全性が高く副作用の少ない、種々のタイプの癌（由来する組織などが異なる）の治療に有効な抗腫瘍剤を提供することができる。また、9トランス, 11トランス-共役リノール酸を配合した抗腫瘍用飲食品及び飼料を提供することができる。 Previously, 9 cis, 11 trans-conjugated linoleic acid and 10 trans, 12 cis-conjugated linoleic acid, two isomers of conjugated linoleic acid, were reported to have biological activity. It has not been conceivable that conjugated linoleic acid exhibits a significantly higher antitumor effect than these isomers. According to the present invention, it is possible to provide an antitumor agent that has an excellent antitumor activity, is safe and has few side effects, and is effective in treating various types of cancers (different in tissues derived from them). it can. In addition, anti-tumor food and drink and feed containing 9-trans and 11-trans-conjugated linoleic acid can be provided.
本発明においては、共役リノール酸の異性体の中で9トランス, 11トランス-共役リノール酸を有効成分とする抗腫瘍剤及び抗腫瘍用飲食品及び飼料である。9トランス, 11トランス-共役リノール酸は、食用油脂などのリノール酸あるいはリノール酸含有材料を原料とし、当分野では公知の方法を用いて目的の異性体を選択的に得るか、あるいは遊離の形態として高純度品が市販されているのでそれを使用することもできる。 In the present invention, among the isomers of conjugated linoleic acid, an antitumor agent, an antitumor food and drink, and a feed comprising 9trans, 11trans-conjugated linoleic acid as an active ingredient. 9-trans, 11-trans-conjugated linoleic acid is made from linoleic acid such as edible oils and fats or linoleic acid-containing materials, and the desired isomers can be selectively obtained using methods known in the art, or in free form As a high purity product is commercially available, it can be used.
9トランス, 11トランス-共役リノール酸の形態としては、脂肪酸のままでもよく、また脂肪酸エステルもしくは金属塩の形態であってもよい。エステルとしては、9トランス, 11トランス-共役リノール酸の脂肪酸と、炭素数1〜38、好ましくは1〜10のアルコール（例えば脂肪族アルコール、高級アルコールなど）、エチレングリコール、プロピレングリコールおよびグリセリンからなる群から選ばれた1種または2種以上のアルコール類、ポリグリセリン、ステロール類（β−シトステロールなど）、糖類（単糖、二糖、オリゴ糖、多糖など）、アスコルビン酸等とのエステルなどが挙げられる。また、金属塩としては、ナトリウム塩、カリウム塩、カルシウム塩、亜鉛塩およびマグネシウム塩などからなる群から選ばれた1種又は2種以上の金属塩などが挙げられる。さらに、本発明に使用される9トランス, 11トランス-共役リノール酸は、上記のエステルもしくは金属塩の形態の他に、アミドやリン脂質など薬理学上許容される他の任意の形態物であってもよい。
本発明の抗腫瘍剤の有効成分の具体的態様の一例として、乳製品由来の油脂などの9トランス, 11トランス-共役リノール酸含有油脂をカラムクロマトグラフィーを用いることにより、9トランス, 11トランス-共役リノール酸高含有油脂を分離分取して得ることができる。もちろん、リノール酸含有油脂をアルカリ共役化反応によって、9トランス, 11トランス-共役リノール酸含有油脂を得てもよい。
The form of 9-trans, 11-trans-conjugated linoleic acid may be a fatty acid, or may be a fatty acid ester or a metal salt. Esters include fatty acids of 9-trans and 11-trans-conjugated linoleic acids, and alcohols having 1 to 38 carbon atoms, preferably 1 to 10 carbons (for example, aliphatic alcohols and higher alcohols), ethylene glycol, propylene glycol, and glycerin. One or more alcohols selected from the group, polyglycerin, sterols (β-sitosterol, etc.), saccharides (monosaccharides, disaccharides, oligosaccharides, polysaccharides, etc.), esters with ascorbic acid, etc. Can be mentioned. Examples of the metal salt include one or more metal salts selected from the group consisting of sodium salt, potassium salt, calcium salt, zinc salt, magnesium salt and the like. Further, the 9-trans, 11-trans-conjugated linoleic acid used in the present invention may be any other pharmacologically acceptable form such as amide and phospholipid in addition to the above ester or metal salt form. May be.
As an example of a specific embodiment of the active ingredient of the antitumor agent of the present invention, 9 trans, 11 trans- It can be obtained by separating and separating a conjugated linoleic acid-rich oil. Of course, a 9-trans, 11-trans-conjugated linoleic acid-containing oil / fat may be obtained by subjecting the linoleic acid-containing oil / fat to an alkali conjugation reaction.
本発明による抗腫瘍剤、抗腫瘍用飲食品及び飼料は、9トランス, 11トランス-共役リノール酸を含有してなるものであり、脂肪酸やグリセリドからなる油脂製品の形態が好ましい。脂肪酸の形態としては、上記のようにして得られた9トランス, 11トランス-共役リノール酸含有脂肪酸を使用することができ、グリセリドの形態としては上記のようにして得られた脂肪酸とグリセリンを通常の方法によりリパーゼを用いてエステル化したものを用いることができる。また本発明においては、9トランス, 11トランス-共役リノール酸が他の種々のエステル、金属塩、その他の薬理学上許容される形態物またはこれらの混合物の形態であってもよいことは前記した通りである。 The antitumor agent, antitumor food and drink and feed according to the present invention contain 9-trans, 11-trans-conjugated linoleic acid, and are preferably in the form of fats and oils products comprising fatty acids and glycerides. As the fatty acid form, the 9-trans, 11-trans-conjugated linoleic acid-containing fatty acid obtained as described above can be used. As the glyceride form, the fatty acid and glycerin obtained as described above are usually used. Those esterified with lipase by the above method can be used. In the present invention, 9trans, 11trans-conjugated linoleic acid may be in the form of other various esters, metal salts, other pharmacologically acceptable forms, or mixtures thereof. Street.
本発明の抗腫瘍剤を医薬品として用いる場合、その形態は特に制限されるものではなく、投与方法や適用される腫瘍の種類、形状および存在部位などの条件に応じて、注射液、座薬、軟膏、錠剤、カプセル、散剤、顆粒剤、ドリンク剤などの種々の形態を適宜選択することができる。従って、上記したような本発明の抗腫瘍剤をそのまま医薬として用いることができるほか、必要に応じて担体、希釈剤もしくは賦形剤など通常の種々の添加物（例えば糖類、デンプン類、アルコール類、アラビアゴムなど）と組合せることができる。 When the antitumor agent of the present invention is used as a pharmaceutical product, its form is not particularly limited, and depending on the administration method and the conditions such as the type, shape, and location of the applied tumor, injection solution, suppository, ointment Various forms such as tablets, capsules, powders, granules, and drinks can be appropriately selected. Accordingly, the antitumor agent of the present invention as described above can be used as a medicine as it is, and various usual additives such as carriers, diluents or excipients (eg, sugars, starches, alcohols) as necessary. , Gum arabic, etc.).
本発明による抗腫瘍剤の摂取もしくは投与量は、治療上有効量であり、腫瘍の種類などにより一概に言えないが、体重60Kgの成人の場合、1日当たり上記9トランス, 11トランス-共役リノール酸の量として通常10〜5000mg、好ましくは20〜3000mgである。また本発明の抗腫瘍剤は公知の抗腫瘍剤あるいは他の治療剤と併用することもできる。 The ingestion or dosage of the antitumor agent according to the present invention is a therapeutically effective amount and cannot be generally stated depending on the type of tumor, etc., but in the case of an adult with a body weight of 60 kg, the above 9 trans, 11 trans-conjugated linoleic acid per day The amount is usually 10 to 5000 mg, preferably 20 to 3000 mg. The antitumor agent of the present invention can also be used in combination with known antitumor agents or other therapeutic agents.
本発明の9トランス, 11トランス-共役リノール酸を飲食品に配合して抗腫瘍用飲食品とするには、例えば、食用油、マーガリン、バターその他の油脂に、9トランス, 11トランス-共役リノール酸を直接配合してもよく、また、9トランス, 11トランス-共役リノール酸を水と混合して乳化物を調製し、これをソース、ドレッシング、チーズフード、菓子、パン、麺類、飲料、スナック食品等の飲食品に配合してもよい。さらに、9トランス, 11トランス-共役リノール酸をゼラチン等を用いてカプセル化し、このカプセルをサプリメント食品として用いたり、飲料、菓子、ガム、キャンディー等に配合してもよい。このように、本発明による抗腫瘍剤、抗腫瘍用飲食品あるいは飼料（ペットフードを含む）は、上記に例示したような9トランス,11トランス-共役リノール酸含有油脂製品の形態で用いることができるほか、食用油脂組成物（植物性油脂、動物性油脂、加工油脂など）、食用乳化油脂組成物（マーガリン、マヨネーズなど）、ベーカリー製品（パン、ケーキ類）、調理食品（惣菜など）、飲料（ジュース、ソフトドリンク類）などの飲食品や飼料（サイレージ、ペットフードなど）に混合して用いてもよい。 In order to mix the 9-trans, 11-trans-conjugated linoleic acid of the present invention into foods and drinks to produce anti-tumor foods and drinks, for example, edible oil, margarine, butter and other oils, Acids may be blended directly, or 9 trans, 11 trans-conjugated linoleic acid is mixed with water to prepare an emulsion, which is sauce, dressing, cheese food, confectionery, bread, noodles, beverages, snacks You may mix | blend with food-drinks, such as foodstuffs. Further, 9-trans, 11-trans-conjugated linoleic acid may be encapsulated using gelatin or the like, and the capsule may be used as a supplement food, or may be blended in beverages, confectionery, gum, candy and the like. Thus, the antitumor agent, antitumor food and drink or feed (including pet food) according to the present invention can be used in the form of a 9-trans, 11-trans-conjugated linoleic acid-containing oil or fat product as exemplified above. In addition, edible oil and fat compositions (vegetable oils and fats, animal fats and oils, processed oils and fats), edible emulsified oil and fat compositions (margarine, mayonnaise, etc.), bakery products (bread, cakes, etc.), cooked foods (prepared foods, etc.), beverages It may be used by mixing with food and drink such as (juice, soft drinks) and feed (silage, pet food, etc.).
本発明において、一般食品中に配合する場合は、配合量は飲食品中の油脂含量によって多少変動するが、食品中、9トランス, 11トランス-共役リノール酸の量として通常１〜５重量％程度である。1重量％に満たないと効果が弱く、5重量％を超えると常温乃至冷蔵庫中で脂質成分の酸化が起きることがある。
なお、本明細書において、％表示は特に断りのない限り重量％基準である。
In the present invention, when blended in general foods, the blending amount varies somewhat depending on the fat and oil content in the food and drink, but is usually about 1 to 5% by weight as the amount of 9-trans, 11-trans-conjugated linoleic acid in the food. It is. If it is less than 1% by weight, the effect is weak, and if it exceeds 5% by weight, oxidation of lipid components may occur at room temperature or in a refrigerator.
In the present specification, “%” is based on “% by weight” unless otherwise specified.
以下の試験例、実施例により本発明を更に具体的に説明するが、本発明はこの試験例、実施例によって限定されるものではない。 The present invention will be described more specifically with reference to the following test examples and examples, but the present invention is not limited to these test examples and examples.
9トランス, 11トランス-共役リノール酸を用いてガン細胞の増殖抑制試験を行った。9トランス, 11トランス-共役リノール酸と比較するために、比較例として多くの論文で増殖抑制効果が報告されている9シス, 11トランス-共役リノール酸、9シス, 11シス-共役リノール酸、10トランス,12シス-共役リノール酸の3種の共役リノール酸異性体を用いた。MEM培地で24時間培養したヒト結腸癌Caco-2細胞に、9トランス, 11トランス-共役リノール酸、9シス, 11トランス-共役リノール酸、9シス, 11シス-共役リノール酸、10トランス,12シス-共役リノール酸をそれぞれ200μM添加し、添加後24時間、48時間、及び72時間培養し、ヒト結腸癌Caco-2細胞の生残率を測定した。 Nine-trans, 11-trans-conjugated linoleic acid was used to carry out cancer cell growth inhibition tests. To compare with 9trans, 11trans-conjugated linoleic acid, 9cis, 11trans-conjugated linoleic acid, 9cis, 11cis-conjugated linoleic acid, which have been reported to inhibit growth in many papers as comparative examples, Three conjugated linoleic acid isomers of 10 trans, 12 cis-conjugated linoleic acid were used. In human colon cancer Caco-2 cells cultured for 24 hours in MEM medium, 9 trans, 11 trans-conjugated linoleic acid, 9 cis, 11 trans-conjugated linoleic acid, 9 cis, 11 cis-conjugated linoleic acid, 10 trans, 12 Cis-conjugated linoleic acid was added at 200 μM, and cultured for 24, 48, and 72 hours, and the survival rate of human colon cancer Caco-2 cells was measured.
結果を図１に示す。試験の結果、何れの共役リノール酸（CLA）異性体も経時的に生残率の低下を引き起こしたが、中でも、9トランス, 11トランス-共役リノール酸を添加した培地は添加後24時間培養で、生残率が早くも30％強となり、添加後78時間培養では生残率が0％近くになり、顕著な増殖抑制効果を示している。比較した他の共役リノール酸異性体も経時的に生残率の低下を引き起こしてはいるものの、添加後24時間培養での生残率はいずれも60〜80％であり、添加後78時間培養での生残率は15〜55％にとどまっている。多くの論文で顕著な増殖抑制効果が報告されている9シス, 11トランス-共役リノール酸、9シス, 11シス-共役リノール酸、10トランス,12シス-共役リノール酸よりも、本発明で用いる9トランス, 11トランス-共役リノール酸の方が顕著な増殖抑制効果を持つことが明らかとなった。 The results are shown in FIG. As a result of the test, all the conjugated linoleic acid (CLA) isomers caused a decrease in the survival rate over time, but the medium supplemented with 9trans, 11trans-conjugated linoleic acid was cultured for 24 hours after addition. The survival rate is as high as 30% at the earliest, and the survival rate is close to 0% in the culture for 78 hours after the addition, showing a remarkable growth inhibitory effect. Although the other conjugated linoleic acid isomers compared also cause a decrease in the survival rate over time, the survival rate in the culture for 24 hours after the addition is 60 to 80% in all cases, and the culture is continued for 78 hours after the addition. Survival rate is only 15-55%. It is used in the present invention rather than 9 cis, 11 trans-conjugated linoleic acid, 9 cis, 11 cis-conjugated linoleic acid, 10 trans, 12 cis-conjugated linoleic acid, which have been reported to have a significant growth inhibitory effect in many papers. 9trans and 11trans-conjugated linoleic acid were found to have a more prominent inhibitory effect.
9トランス, 11トランス-共役リノール酸の増殖抑制効果を調べるために、その濃度依存性について調べた。試験例１と同様にMEM培地で24時間培養したヒト結腸癌Caco-2細胞を用い、9トランス, 11トランス-共役リノール酸をそれぞれ50μM、100μM、及び200μM添加し、増殖抑制試験を行った。添加後、24時間、48時間、及び72時間培養し、ヒト結腸癌Caco-2細胞の生残率を測定した。比較例として、多くの論文で顕著な増殖抑制効果が報告されている9シス, 11トランス-共役リノール酸を200μM添加したものと、共役リノール酸からの変換が予想されているフラニル環をもつ9, 12-epoxy-9, 11octadecanoic acidについても細胞生残率へ与える影響を調べた。 In order to investigate the growth inhibitory effect of 9trans, 11trans-conjugated linoleic acid, its concentration dependency was examined. In the same manner as in Test Example 1, human colon cancer Caco-2 cells cultured for 24 hours in MEM medium were used, and 9 trans and 11 trans-conjugated linoleic acid were added to 50 μM, 100 μM, and 200 μM, respectively, and a growth inhibition test was performed. After the addition, the cells were cultured for 24 hours, 48 hours, and 72 hours, and the survival rate of human colon cancer Caco-2 cells was measured. As a comparative example, 9 cis, 11 trans-conjugated linoleic acid added with 200 μM, which has been reported to have a remarkable growth inhibitory effect in many papers, and a furanyl ring that is expected to be converted from conjugated linoleic acid 9 , 12-epoxy-9, 11octadecanoic acid were also examined for their effects on cell survival.
結果を図２に示す。試験の結果、9トランス, 11トランス-共役リノール酸のいずれについても、50μM〜200μMまで濃度依存的な効果が示された。一方、共役リノール酸からの変換が予想されている9, 12-epoxy-9, 11octadecanoic acidの効果は比較例として用いた9シス, 11トランス-共役リノール酸と同程度であり、本発明で用いる9トランス, 11トランス-共役リノール酸の効果には及ばなかった。 The results are shown in FIG. As a result of the test, a concentration-dependent effect was shown from 50 μM to 200 μM for both 9trans and 11trans-conjugated linoleic acid. On the other hand, the effect of 9, 12-epoxy-9, 11 octadecanoic acid, which is expected to be converted from conjugated linoleic acid, is similar to that of 9 cis, 11 trans-conjugated linoleic acid used as a comparative example, and is used in the present invention. The effects of 9trans and 11trans-conjugated linoleic acid were not affected.
また、9シス, 11トランス-共役リノール酸よりもカルボキシル基側に炭素鎖長が２つ長い11シス,13トランス-eicosadienoic acidが細胞生残率へ与える影響についても調べたが、その効果は9シス, 11トランス-共役リノール酸と同程度であり、9トランス, 11トランス-共役リノール酸の効果には及ばなかった。したがって、Caco-2細胞生残率への影響は、共役脂肪酸の二重結合構造によって大きく異なり、特にトランス, トランス構造を持つ9トランス, 11トランス -共役リノール酸が効果的であることが明らかとなった。 In addition, the effect of 11 cis, 13 trans-eicosadienoic acid, which is two carbon chains longer to the carboxyl group than 9 cis, 11 trans-conjugated linoleic acid, on cell survival rate was also investigated. It was similar to cis, 11 trans-conjugated linoleic acid and did not reach the effect of 9 trans, 11 trans-conjugated linoleic acid. Therefore, the effect on the survival rate of Caco-2 cells varies greatly depending on the double bond structure of the conjugated fatty acid, and it is clear that 9-trans and 11-trans-conjugated linoleic acid with trans and trans structures are particularly effective. became.
9トランス, 11トランス -共役リノール酸と9シス, 11トランス-共役リノール酸のアポトーシス誘導能を比較する試験を行った。試験例１と同様にMEM培地で24時間培養したヒト結腸癌Caco-2細胞の断片化DNAに、9トランス, 11トランス-共役リノール酸をそれぞれ50μM、100μM、200μM添加し、添加後、12時間、24時間、及び48時間後の断片化DNA量を測定した。ヒト結腸癌Caco-2細胞の断片化DNA量は、抗DNA抗体及び抗ヒストン抗体を用いた細胞死検出ELISAキット（ロシュ・ダイアグノスティック株式会社製）により測定した。比較例として、多くの論文で顕著な増殖抑制効果が報告されている9シス, 11トランス-共役リノール酸を100μM、及び200μM添加したものと、コントロールとしてCaco-2細胞の断片化DNAに共役リノール酸を添加しないものを用い、9トランス, 11トランス-共役リノール酸と同様に測定した。 A test was conducted to compare the ability of 9trans, 11trans-conjugated linoleic acid and 9cis, 11trans-conjugated linoleic acid to induce apoptosis. As in Test Example 1, 50 μM, 100 μM, and 200 μM of 9 trans, 11 trans-conjugated linoleic acid were added to the fragmented DNA of human colon cancer Caco-2 cells cultured in MEM medium for 24 hours, and then added for 12 hours. After 24 hours and 48 hours, the amount of fragmented DNA was measured. The amount of fragmented DNA of human colon cancer Caco-2 cells was measured by a cell death detection ELISA kit (Roche Diagnostics) using an anti-DNA antibody and an anti-histone antibody. As a comparative example, 9 cis, 11 trans-conjugated linoleic acid, which has been reported to have a significant growth inhibitory effect in many papers, was added to 100 μM and 200 μM, and conjugated linole was used as a control to fragmented DNA of Caco-2 cells. Measurements were made in the same manner as in 9-trans and 11-trans-conjugated linoleic acid, using an acid-free addition.
結果を図３に示す。試験の結果、9トランス, 11トランス-共役リノール酸は、濃度依存的、経時的にDNA断片化を引き起こした。また、この効果は9シス, 11トランス-共役リノール酸よりもかなり顕著であった。従って、9シス, 11トランス-共役リノール酸よりも9トランス, 11トランス-共役リノール酸の方が顕著なアポトーシス誘導能を有することが明らかとなった。 The results are shown in FIG. As a result of the test, 9trans, 11trans-conjugated linoleic acid caused DNA fragmentation over time in a concentration-dependent manner. This effect was also significantly more pronounced than 9 cis, 11 trans-conjugated linoleic acid. Therefore, it was revealed that 9-trans, 11-trans-conjugated linoleic acid has a greater ability to induce apoptosis than 9-cis, 11-trans-conjugated linoleic acid.
以上の試験結果から明らかなように、9トランス, 11トランス -共役リノール酸
を添加した培地は添加後24時間培養で、ヒト結腸癌Caco-2細胞の生残率が早くも30％強となり、添加後78時間培養では生残率が0％近くになり、顕著な増殖抑制効果を示している。経時的な増殖抑制効果に加えて、濃度依存的な増殖抑制効果も確認することができた。さらに、ヒト結腸癌Caco-2細胞の断片化DNAに添加し経時的に断片化DNA量を測定した試験も、濃度依存的、経時的にDNA断片化を引き起こす結果となった。しかも、特筆すべきことに、多くの論文で顕著な増殖抑制効果が報告されている9シス, 11トランス-共役リノール酸、9シス, 11シス-共役リノール酸、10トランス,12シス-共役リノール酸よりも、本試験で用いた9トランス, 11トランス-共役リノール酸の方が、格別に顕著なCaco-2細胞の増殖抑制効果を持つことが明らかとなった。
As is clear from the above test results, the medium supplemented with 9-trans, 11-trans-conjugated linoleic acid was cultured for 24 hours after the addition, and the survival rate of human colon cancer Caco-2 cells was already over 30%, In the culture for 78 hours after the addition, the survival rate is close to 0%, indicating a remarkable growth inhibitory effect. In addition to the growth inhibitory effect over time, a concentration-dependent growth inhibitory effect could also be confirmed. Furthermore, a test in which the amount of fragmented DNA added to the fragmented DNA of human colon cancer Caco-2 cells and measured over time also resulted in DNA fragmentation over time in a concentration-dependent manner. Moreover, it should be noted that 9 cis, 11 trans-conjugated linoleic acid, 9 cis, 11 cis-conjugated linoleic acid, 10 trans, 12 cis-conjugated linoleic acid, which have been reported to have a remarkable growth inhibitory effect in many papers. It was revealed that the 9-trans and 11-trans-conjugated linoleic acid used in this study had a significantly more remarkable Caco-2 cell growth inhibitory effect than the acid.
9トランス, 11トランス-共役リノール酸を用いて、表１に示す配合に従い、抗腫瘍剤を調製した。調製は、精製大豆油と9トランス, 11トランス-共役リノール酸以外の全原材料を、水に溶解後、攪拌羽根を用いて混合した。精製大豆油と9トランス, 11トランス-共役リノール酸を添加し、混合溶液を80℃まで加温した。その後、ホモミキサーを用いて、5000回転／分で10分間攪拌処理を行なった。次に150kg/cm２ にて均質化処理を行ない濃縮した後、噴霧乾燥して本発明の粉末状抗腫瘍剤を調製した。 An antitumor agent was prepared according to the formulation shown in Table 1 using 9trans, 11trans-conjugated linoleic acid. In the preparation, all raw materials other than refined soybean oil and 9-trans, 11-trans-conjugated linoleic acid were dissolved in water and then mixed using a stirring blade. Purified soybean oil and 9trans, 11trans-conjugated linoleic acid were added, and the mixed solution was heated to 80 ° C. Thereafter, the mixture was stirred for 10 minutes at 5000 rpm using a homomixer. Next, the mixture was homogenized at 150 kg / cm 2 and concentrated, and then spray-dried to prepare the powdered antitumor agent of the present invention.
9トランス, 11トランス-共役リノール酸を用いて、表２に示す配合に従い、油脂含有食品を調製した。調製は、バターオイルと9トランス, 11トランス-共役リノール酸以外の全原材料を水に溶解し、攪拌羽根を用いて混合した。バターオイルと9トランス, 11トランス-共役リノール酸を添加し、混合溶液を80℃まで加温した。その後、ホモミキサーを用いて、5000回転／分で10分間攪拌処理を行なった。次いで150kg/cm２ にて均質化処理を行ない本発明の油脂含有食品を調製した。この油脂含有食品は、抗腫瘍用コーヒー用クリームとして用いられる。 Using 9 trans, 11 trans-conjugated linoleic acid, an oil-containing food was prepared according to the formulation shown in Table 2. In the preparation, all raw materials other than butter oil and 9-trans, 11-trans-conjugated linoleic acid were dissolved in water and mixed using a stirring blade. Butter oil and 9 trans, 11 trans-conjugated linoleic acid were added, and the mixed solution was heated to 80 ° C. Thereafter, the mixture was stirred for 10 minutes at 5000 rpm using a homomixer. Subsequently, the homogenization process was performed at 150 kg / cm < 2 > and the oil-containing food of this invention was prepared. This oil-containing food is used as an anti-tumor coffee cream.
9トランス, 11トランス-共役リノール酸を用いて、表３に示す配合に従い、油脂含有食品を調製した。調製は、表３に示した配合で原料を混合した後、85℃で乳化して、本発明の抗腫瘍用プロセスチーズを製造した。 Using 9 trans, 11 trans-conjugated linoleic acid, an oil-containing food was prepared according to the formulation shown in Table 3. In the preparation, the raw materials were mixed in the formulation shown in Table 3, and then emulsified at 85 ° C. to produce the anti-tumor process cheese of the present invention.
表４に示した配合で原料を混合して、常法により、抗腫瘍用イヌ飼育用飼料（ドッグフード）を製造した。
9ｔ11ｔCLA；9トランス, 11トランス-共役リノール酸
9ｃ11ｔCLA；9シス, 11トランス-共役リノール酸
9ｃ11ｃCLA；9シス, 11シス-共役リノール酸
10ｔ12ｃCLA；10トランス,12シス-共役リノール酸
図２のフラニル環は9, 12-epoxy-9,11octadecanoic acidを表す。
図３のコントロールは共役リノール酸無添加のものを表す。
9t11tCLA; 9trans, 11trans-conjugated linoleic acid
9c11tCLA; 9cis, 11trans-conjugated linoleic acid
9c11cCLA; 9cis, 11cis-conjugated linoleic acid
10t12cCLA; 10trans, 12cis-conjugated linoleic acid The furanyl ring in FIG. 2 represents 9,12-epoxy-9,11octadecanoic acid.
The control in FIG. 3 represents the one without conjugated linoleic acid added.
Claims (5)
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2004060821A JP2005247754A (en) | 2004-03-04 | 2004-03-04 | Antitumor agent |
| PCT/JP2005/003631 WO2005084661A1 (en) | 2004-03-04 | 2005-03-03 | Antitumor agent |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2004060821A JP2005247754A (en) | 2004-03-04 | 2004-03-04 | Antitumor agent |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JP2005247754A true JP2005247754A (en) | 2005-09-15 |
Family
ID=34918031
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2004060821A Pending JP2005247754A (en) | 2004-03-04 | 2004-03-04 | Antitumor agent |
Country Status (2)
| Country | Link |
|---|---|
| JP (1) | JP2005247754A (en) |
| WO (1) | WO2005084661A1 (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007282574A (en) * | 2006-04-17 | 2007-11-01 | T Hasegawa Co Ltd | Conjugate linoleic acid-containing emulsified composition and drink |
| JP2008088080A (en) * | 2006-09-29 | 2008-04-17 | Pharma Frontier Kk | G-protein conjugate type receptor inhibitor, medicine and method of screening |
| WO2013146437A1 (en) * | 2012-03-26 | 2013-10-03 | シーシーアイ株式会社 | 3-decenoic acid derivative and use for same |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9062276B2 (en) | 2012-12-03 | 2015-06-23 | Board Of Trustees Of The University Of Arkansas | Conjugated linoleic acid rich vegetable oil production from linoleic rich oils by heterogeneous catalysis |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH11209279A (en) * | 1998-01-05 | 1999-08-03 | Natural Ltd As | Method for decreasing body weight and treating obesity |
-
2004
- 2004-03-04 JP JP2004060821A patent/JP2005247754A/en active Pending
-
2005
- 2005-03-03 WO PCT/JP2005/003631 patent/WO2005084661A1/en active Application Filing
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH11209279A (en) * | 1998-01-05 | 1999-08-03 | Natural Ltd As | Method for decreasing body weight and treating obesity |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007282574A (en) * | 2006-04-17 | 2007-11-01 | T Hasegawa Co Ltd | Conjugate linoleic acid-containing emulsified composition and drink |
| JP2008088080A (en) * | 2006-09-29 | 2008-04-17 | Pharma Frontier Kk | G-protein conjugate type receptor inhibitor, medicine and method of screening |
| WO2013146437A1 (en) * | 2012-03-26 | 2013-10-03 | シーシーアイ株式会社 | 3-decenoic acid derivative and use for same |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2005084661A1 (en) | 2005-09-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US7056949B2 (en) | Oil/fat composition | |
| KR100951756B1 (en) | Oil composition | |
| US8853192B2 (en) | Fat or oil composition | |
| EP1544281B1 (en) | Fat composition | |
| US7410663B2 (en) | Oil or fat composition | |
| US20100280112A1 (en) | Composition Enriched in Diglyceride with Conjugated Linoleic Acid | |
| JP2008069184A (en) | Oil-and-fat composition | |
| KR101757002B1 (en) | Eating-assisting oil or fat composition for persons who have difficulty in swallowing/chewing, and food for persons who have difficulty in swallowing/chewing | |
| JP2007290989A (en) | Gip(gastric inhibitory polypeptide) secretion inhibitor | |
| KR20040095263A (en) | Body temperature elevating agents | |
| US20100210723A1 (en) | Lipase inhibitor | |
| KR101916490B1 (en) | Organogel for assisting intake of food for persons with difficulty in swallowing/chewing and food for persons with difficulty in swallowing/chewing | |
| JP2009269865A (en) | Oral administration agent | |
| JP2005247754A (en) | Antitumor agent | |
| JP4268473B2 (en) | Oil composition | |
| JP4191420B2 (en) | Edible oil and fat composition comprising a licorice hydrophobic extract | |
| JP2009269864A (en) | Agent for increasing phospholipid-bound arachidonic acid | |
| JP2003171272A (en) | Antitumor agent including 10 trans, 12 cis-conjugated linoleic acid as an active ingredient | |
| EP2484358A1 (en) | Agent for inhibiting decrease of visceral fat in patient with parkinson's disease | |
| JP2017155025A (en) | Lipid composition | |
| JP2004292421A (en) | Hypertension preventing agent containing conjugated fatty acid as active component and use thereof | |
| JP5479696B2 (en) | In vivo plasmalogen increasing agent | |
| JPWO2003074042A1 (en) | Uncoupling protein expression enhancer | |
| JP2020162445A (en) | Fat composition for powdery fat, and powdery fat | |
| JP2018035119A (en) | Pharmaceutical composition for prevention or treatment of dermatitis |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20070302 |
|
| RD02 | Notification of acceptance of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7422 Effective date: 20100319 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20100602 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20101014 |