WO2008007450A1 - Food, drink and medicinal composition having antitumor effect - Google Patents

Food, drink and medicinal composition having antitumor effect Download PDF

Info

Publication number
WO2008007450A1
WO2008007450A1 PCT/JP2006/322571 JP2006322571W WO2008007450A1 WO 2008007450 A1 WO2008007450 A1 WO 2008007450A1 JP 2006322571 W JP2006322571 W JP 2006322571W WO 2008007450 A1 WO2008007450 A1 WO 2008007450A1
Authority
WO
WIPO (PCT)
Prior art keywords
extract
tumor
feverfew
food
drink
Prior art date
Application number
PCT/JP2006/322571
Other languages
French (fr)
Japanese (ja)
Inventor
Osamu Masaki
Chieko Asamori
Original Assignee
Mmt Co., Ltd.
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Mmt Co., Ltd. filed Critical Mmt Co., Ltd.
Priority to JP2006549204A priority Critical patent/JPWO2008007450A1/en
Publication of WO2008007450A1 publication Critical patent/WO2008007450A1/en

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/28Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23LFOODS, 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
    • A23L33/00Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105Plant extracts, their artificial duplicates or their derivatives
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • A61P35/04Antineoplastic agents specific for metastasis
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23VINDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00Food compositions, function of food ingredients or processes for food or foodstuffs

Definitions

  • the present invention relates to foods and drinks and pharmaceutical compositions having a tumor-suppressing action, and methods for suppressing tumors.
  • a food and drink and a pharmaceutical composition containing an extract of an Asteraceae plant, and a method for suppressing a tumor characterized by administering an extract of an Asteraceae plant to a patient, and a method for suppressing the tumor The present invention relates to the use of asteraceae extracts in the manufacture of pharmaceutical compositions.
  • Tumors are considered to be one of the most difficult diseases to treat, and various studies have been conducted on the treatment, new therapies and drugs have been developed, and treatment results have been improved. However, many of these therapies and drugs are burdensome to patients and have significant side effects. In particular, metastatic tumors are difficult to treat, and many studies have been made (see Non-Patent Document 1, etc.). Recently, as a cancer treatment that is kind to the body, treatment using immune cell therapy and Chinese medicine, or health foods derived from mushroom extracts and plant extracts, etc. have been developed. ing.
  • the problem to be solved by the present invention is to provide a treatment for tumors that is effective and superior in strength to patients.
  • food and drink and pharmaceutical composition comprising an extract of a asteraceae plant, in particular feverfew, which exhibits a remarkable tumor-suppressing effect upon ingestion and is highly safe. Things are provided. Furthermore, a method for suppressing a tumor characterized by administering an extract of Asteraceae plant, specifically feverfew to a patient, and a medicinal plant in manufacturing a pharmaceutical composition for suppressing a tumor, more specifically feverfew Use of the extract is also provided. Therefore, an effective, body-friendly, tumor suppressor treatment is provided.
  • the present invention provides the following:
  • a pharmaceutical composition for suppressing a tumor comprising an extract of a asteraceae plant
  • a method for suppressing a tumor which comprises feeding on an extract of an Asteraceae plant
  • a method for suppressing a tumor in a patient comprising administering an extract of a asteraceae plant to the patient;
  • FIG. 1 is a graph showing the time course of survival rate when a feverfew extract or parthenolide is administered to tumor mice.
  • the solid line is the vehicle control group
  • the dashed line is the nortenolide 40 mg ZkgZ daily oral administration group
  • the dashed line is the feverfew extract 222 mg ZkgZ oral oral administration group.
  • the feverfew extract 222 mg ZkgZ day-treated group showed a significant difference from the vehicle control group (P 0.05, Log-Rank test).
  • FIG. 2 is a graph showing the results of observing the size of the tumor primary lesion over time.
  • the black circles are the vehicle control group, the white squares are the baltenolide 40 mg ZkgZ oral administration group, and the black triangles are the feverfew extract 222 mg ZkgZ oral administration group.
  • Vertical bars indicate standard deviation
  • FIG. 3 is a graph showing the change in body weight over time when feverfew extract or cisbratine is administered to tumor mice.
  • the black circle is the vehicle control group
  • the white square is the feverfew extract 222 mgZkgZ daily oral administration group
  • the black square is the feverfew extract 888 mgZkgZ daily oral administration group
  • the white triangle is the cisplatin lOmgZkgZ day intraperitoneal administration group.
  • FIG. 4 is a graph showing the time course of survival rate when feverfew extract or cisbratine is administered to tumor mice.
  • the solid line is the vehicle control group
  • the dashed line is the feverfew extract 222 mgZkgZ daily oral administration group
  • the broken line is the feverfew extract 888 mgZ kg / day oral administration group
  • the dotted line is the cisplatin lOmgZkgZ day intraperitoneal administration group.
  • the feverfew extract 888mgZkgZ day group showed a significant difference from the vehicle control group (p ⁇ 0.05, Log-Rank test).
  • the present invention relates to a food and drink for suppressing tumors, which contains an extract of a plant containing sesquiterpene ratatones.
  • to suppress tumor is to treat tumor It includes prevention as well.
  • the plant extract used in the food and drink of the present invention is not particularly limited as long as it is a plant extract containing sesquiterbene lactones.
  • Examples of plants containing a large amount of sesquiterpene ratatones include asteraceae plants, such as plants of the genus Artemisia and dandelions. Therefore, in one aspect, the present invention provides a food and drink for suppressing tumors, which contains an extract of a asteraceae plant.
  • parthenolide has been reported to have various physiological activities so far, and as shown in Japanese Patent Application Laid-Open No. 2005-35951, it suppresses tumor metastasis and exerts an animal life-prolonging effect. It has been shown. Therefore, it is preferable to use plants with a high content of valthenolide.
  • plants include asteraceae plants, preferably plants belonging to the genus Artemisia, particularly preferably Tanacetum parthenium (also referred to as fever-fu).
  • a particularly preferred plant extract for use in the present invention is feverfew extract.
  • parthenolide when feverfew extract is orally administered to animals, only a very small amount of parthenolide is administered in terms of parthenolide, but even in this case, a tumor suppression effect superior to that of bartenolide alone is obtained. (See Examples).
  • Plant extracts can be obtained by general methods.
  • the extraction site may be any site as long as it is an aerial part of the plant, but in the case of an Asteraceae plant such as feverfew, a preferable extraction site is a leaf.
  • the extract may be obtained by immersing the plant in a solvent as it is, but the extraction efficiency is higher when the contents are extracted by crushing the force.
  • Plants may be raw or dried. For drying, a known drying method such as warm air drying or air drying can be used. Various plant crushing means can be used.
  • Suspension / extraction media include ether, methanol, ethanol, or a mixture of ethanol and water. Suspension media should be less toxic Those that are non-toxic or non-toxic are preferred. From this viewpoint, ethanol or a mixture of ethanol and water is particularly preferable as a suspension / extraction medium.
  • Extraction conditions such as temperature and time during suspension 'extraction can be selected according to the type and amount of plants. Usually, it is extracted at room temperature and normal pressure for several hours to several days.
  • the above-ground parts of plants, such as leaves and stems are directly dried by a known drying method such as hot air drying or air drying, and pulverized to obtain a food or drink or pharmaceutical of the present invention. May be used in the composition
  • the obtained extract is subjected to a known method such as decantation, filtration, or centrifugation to obtain a solid content and a particulate matter. Can be removed.
  • the obtained extract may be concentrated by a known method such as evaporation.
  • the obtained extract may be dried by a known method to obtain a solid such as a powder.
  • the obtained extract may be further purified and used by known methods such as various chromatography and precipitation methods.
  • the plant extract used in the food and drink according to the present invention can be obtained as described above. These extracts can be made into various forms using known methods according to the use form and purpose, and prepared into liquid, semi-solid, solid (for example, powder such as freeze-dried powder), etc. Can do.
  • An Asteraceae plant extract can be blended with various foods to obtain the foods and drinks of the present invention.
  • These asteraceae plant extracts are of low toxicity or non-toxic because they are derived from natural products, and can be incorporated into any food or drink.
  • the extract may be blended with juice or a noove seasoning.
  • the food and drink of the present invention can be a health food, a functional nutritional food, or a food for specified health use (so-called “tokuho”).
  • supplements are mentioned as a preferred form of the food and drink of the present invention.
  • the supplement may be in any shape that can be taken orally, such as tablets, capsules, granules, and powders (e.g., freeze-dried powder). Etc.), suspensions, drinks, elixirs, possible forms, jelly forms and the like.
  • These supplements are used in the food and pharmaceutical fields.
  • a general process such as mixing and encapsulation can be used.
  • Soft capsules and hard capsules can also be appropriately selected according to the purpose.
  • the extract can be dissolved or suspended in a less toxic medium such as ethanol.
  • a less toxic medium such as ethanol.
  • the usual processes such as mixing, drying, grinding and sieving can also be used.
  • a carrier or excipient is used in the production of supplements, the type and amount can be selected according to the practice in the pharmaceutical field.
  • solid carriers or excipients include talc, carboxymethylcellulose, sucrose, and wheat flour.
  • the liquid carrier include water, ethanol, and edible fats and oils.
  • the food and drink of the present invention is effective in suppressing all tumors. Since sesquiterpene ratatones are contained in the plant extract of the present invention, as in JP-A-2005-35951, the food and drink of the present invention is also effective for tumor suppression, particularly tumor metastasis suppression. To promote the survival of animals.
  • Asteraceae extract per day depends on the amount of sesquiterbene lactones, especially nortenolide contained. In the case of feverfew extract, it is common to take about 0.05g to 50g per day for adults (weight 70kg), and it is appropriate to eat or eat about 0.15g to 15g. is there.
  • the food and drink or supplement of the present invention not only asteraceae plant extracts but also one or more other active ingredients may be mixed.
  • chemotherapy such as antitumor agents (eg, fluorouracil, bleomycin, paclitaxel, cisplatin), hormone agents (eg, tamoxifen, phosfestol), immunostimulants (eg, arabinoxylan, chitosan, esukoggi), etc.
  • the agent and the food and drink of the present invention may be used in combination.
  • a person who has already undergone treatment such as chemotherapy, surgery, radiation therapy, hormone therapy, and immunotherapy can promote the therapeutic effect by eating the food or drink of the present invention.
  • the dose of the drug can be reduced, and treatment can be realized with ease for the patient.
  • the food and drink of the present invention includes not only human but also non-human animal feed.
  • the present invention provides a pharmaceutical composition for tumor suppression comprising an Asteraceae extract, preferably a feverfew extract.
  • the active ingredient in the pharmaceutical composition of the present invention is the above-mentioned Asteraceae plant extract, preferably feverfew extract.
  • a product obtained by purifying these extracts and increasing the content of barthenolide may be used.
  • the pharmaceutical composition of the present invention can be formulated into various dosage forms.
  • the pharmaceutical composition of the present invention is preferably in a dosage form suitable for oral administration.
  • a dosage form suitable for oral administration For example, tablets, capsules, granules , Powder, drinks and so on.
  • sesquiterpene ratatones such as parthenolide are used as the active ingredient
  • the pharmaceutical composition of the present invention is preferably in a dosage form suitable for oral administration and topical administration, but administration by other administration routes. Is also possible.
  • These dosage forms can be produced by methods known in the pharmaceutical field.
  • the pharmaceutical composition of the present invention is effective in suppressing any tumor.
  • the pharmaceutical composition of the present invention also contains tumor suppression, particularly in the case where sesquiterpene ratatones are contained in the plant extract of the present invention! It is effective in suppressing tumor metastasis and promotes the survival of animals.
  • the active ingredient in the pharmaceutical composition of the present invention is an Asteraceae plant extract, taking a feverfew extract as an example, the daily dose is 0 per day for an adult (body weight 70 kg). About 05g to 5Og is common, and about 0.15g to 15g is appropriate. These dosages can be changed as appropriate by the doctor according to the patient's symptoms, disease site, sex, age, weight, presence of side effects, and other factors such as treatment being received.
  • the pharmaceutical composition of the present invention not only asteraceae plant extracts and parthenolides, but also one or more other active ingredients may be mixed.
  • chemotherapy such as antitumor agents (for example, fluorouracil, bleomycin, paclitaxel, cisplatin), hormone agents (for example, tamoxifen, phosfestol), immunostimulants (for example, alapinoxylan, chitosan, ezoukogi, etc.)
  • An agent and the pharmaceutical composition of the present invention may be used in combination.
  • a person receiving treatment such as therapy to promote the therapeutic effect by administering the pharmaceutical composition of the present invention.
  • the pharmaceutical composition of the present invention is used in combination, the dose of the drug can be reduced, and the patient can be treated with superior therapy.
  • the pharmaceutical composition of the present invention includes not only a human but also a non-human animal pharmaceutical composition such as a veterinary pharmaceutical composition.
  • the present invention relates to a method for inhibiting a tumor, characterized by feeding on an extract of an Asteraceae plant. Eating means eating and drinking from the mouth. Normally, the extracts of Asteraceae plants are provided in the form of food and drink, but may be provided in the form of supplements. The form of food and drink and supplements are as described above.
  • a preferable extract of the Asteraceae plant in the above method is a feverfew extract.
  • the tumor suppressed by the above method is a metastatic tumor.
  • the present invention relates to a method for suppressing a tumor in a patient, characterized by administering an extract of an Asteraceae plant to the patient.
  • An extract of the Asteraceae plant may be given to the patient as it is, but is preferably given to the patient in the form of a pharmaceutical composition.
  • the dosage form and route of administration of the pharmaceutical composition are as described above for the pharmaceutical composition of the present invention.
  • a preferable extract of the Asteraceae plant is a feverfew extract.
  • the tumor suppressed by the above method is a metastatic tumor.
  • the present invention provides the use of an extract of a asteraceae plant in the manufacture of food and drink for tumor suppression.
  • the food and drink may be in the form of a supplement.
  • the form of food and drink and supplements are as described above.
  • a preferable extract of the Asteraceae plant in the above use is a feverfew extract.
  • the tumor suppressed by the use is a metastatic tumor.
  • the present invention provides the use of an extract of Asteraceae in the manufacture of a pharmaceutical composition for tumor suppression.
  • the form of the pharmaceutical composition produced by this use, the route of administration, and the amount of Asteraceae extract to be administered are as described above.
  • a preferred extract of the Asteraceae plant in the above use is feverfew extract.
  • the tumor suppressed by the use is a metastatic tumor.
  • tumor suppression includes prevention, prevention or suppression of tumor development, suppression or termination of tumor development, and suppression or elimination of tumor metastasis.
  • Example 1 Effect of feverfew extract and parthenolide on the survival rate of tumor mice
  • Feverfew Extract (batch number: 051016-107) manufactured by HANDA FINE CHEMICALS was used as the feverfew extract. The content of parthenolide in this extract was about 0.9%. Parthenolide manufactured by sigma (purity of 90% or more) was used. The feverfew extract was dissolved in a 0.5 wZv% aqueous solution of methylcellulose and orally administered to the animals using a metal sonde (once a day, administration volume lOmLZkgZ). Feverfew extract The dose was 222 mgZkgZ day, and the dose of parthenolide was 40 mgZkgZ day. The vehicle control group received 0.5 wZv% methylcellulose aqueous solution. The number of animals per experiment was 10.
  • the animal used was a male C3H / HeN Sic mouse (Sankyo Lab Service Co., Ltd.), which was conditioned at 3 weeks of age and weighing 9-14 g, and used at 4 weeks of age. During the experiment period, animals were given solid feed MF (Oriental Yeast Co., Ltd.) and filter-sterilized tap water freely.
  • a tumor model was prepared as follows.
  • a tumor model was prepared by subcutaneously injecting 5 lxlO (in 100 L) mouse tumor cells (LM8 cells of an osteosarcoma cell line) into the back of a 4-week-old mouse that had undergone intensive hair removal. After preparing the tumor model, feverfew extract and vehicle were orally administered once a day for 8 weeks, and the survival rate was calculated.
  • Figure 1 shows the experimental results. Life-survival effect was observed in the feverfew extract-administered group, especially in the feverfew extract 222 mgZkgZ day-administered group. The survival rate was about 0.1, whereas the survival rate of the feverfew extract 222 mg ZkgZ day administration group was about 0.45).
  • the dose of feverfew extract 222 mgZkgZ days corresponds to parthenolide 2.0 mg / kg / day. It is surprising that a high tumor suppressive effect was obtained when the extract was administered orally. The reason may be a synergistic effect of other components contained in the feverfew extract. In addition, the essential oil components in the extract are considered to have worked well.
  • the safety of the feverfew extract used in the above experiments was investigated.
  • the test method was the OECD chemical test guideline (TG420) fixed dose method, and Sic: ICR female mice were used.
  • TG420 OECD chemical test guideline
  • Sic ICR female mice were used.
  • the LD value of pear extract was evaluated to be 2000 mgZkg or more.
  • the mutagenicity of feverfew extract used in the above experiment was determined using Salmonell as a test bacterium. atyphimurium TA100, TA1535, TA98, TA1537 and Escherichia coli WP2 uvrA were used in the absence and presence of S9mix. As a result, the mutagenicity was not observed even at the dose of 5000 gZ plate. From these results, it was proved that feverfew extract is extremely safe and safe.
  • the feverfew extract and parthenolide were the same as in Example 1.
  • the method of administration to animals was also the same as in Example 1.
  • the doses were feverfew extract 222 mgZkgZ day and parthenolide 40 mg / kg / day, and 0.5 w / v% methylcellulose aqueous solution was orally administered to the vehicle control group.
  • mice Os C3H / HeN Sic mice (Sankyo Lab Service Co., Ltd.), which were used for experiments at the age of 3 weeks and acclimated to those with body weights of 10.3 to 13.6 g. did.
  • animals were freely given solid feed MF (Oriental Yeast Co., Ltd.) and filter-sterilized tap water.
  • a tumor model was prepared as follows.
  • a tumor model was prepared by subcutaneously injecting 5 lxlO (in 100 L) mouse tumor cells (LM8 cells of an osteosarcoma cell line) into the back of a 5 week-old mouse that had been brutally removed.
  • 5 lxlO in 100 L
  • mouse tumor cells LM8 cells of an osteosarcoma cell line
  • the feverfew extract, nortenolide and vehicle are orally administered once a day, and at the time when death occurred and transfer to the lung was observed (treatment initiation force was also on the 34th day)
  • Primary tumors, lungs and liver were removed and embedded in paraffin.
  • Lung specimens are sliced horizontally at the center of the left lobe, stained with hematoxylin 'eosin (HE), photographed under a microscope, photographed into a computer, and image analysis software (Image Tool ver .3.00, UTHSCSA) was used to determine the lung area and metastasis area, and the ratio (%) of the metastasis area to the lung area was calculated.
  • HE hematoxylin 'eosin
  • Vehicle control 101 248024 1154618 21. 48 c. / Retenolite, '
  • the feverfew extract and parthenolide were the same as in Examples 1 and 2.
  • the method of administration to animals was also the same as in Examples 1 and 2.
  • the dosage was feverfew extract 222 mg / kg / day, parthenolide 40 mg ZkgZ day, and the vehicle control group was given 0.5 w / v% methylcellulose aqueous solution.
  • the animals used were the same as in Example 2, and 8 animals were used per group.
  • the animal used was a male C3H / HeN Sic mouse (Sankyo Lab Service Co., Ltd.), which was conditioned at 3 weeks of age and weighing 10 to 14 g and used in the experiment at 5 weeks of age. During the experiment period, animals were given solid feed MF (Oriental Yeast Co., Ltd.) and filter-sterilized tap water freely.
  • the tumor model was prepared in the same manner as in Example 2. After the tumor model was created, feverfew extract, nortenolide and vehicle were orally administered once a day, and the tumor size (major axis and minor axis) was changed three times a week from 2 weeks to the 33rd day after tumor cell transplantation. Vernier caliper (CD-I The tumor volume was calculated using 5PS, Mitutoyo). The volume was assumed to be an ellipsoidal sphere and was calculated using the following formula:
  • Tumor volume 4 ⁇ 3 ⁇ (minor axis Z2xminor axis Z2xmajor axis Z2)
  • Figure 2 shows the experimental results.
  • the increase in the primary tumor volume was most suppressed, and a marked effect began to appear around day 26. About 40% of the nest tumor volume.
  • the group treated with nortenolide 40 mg ZkgZ no significant difference was observed from the vehicle control group. If the content of nortenolide in the feverfew extract is 0.9%, the dose of feverfew extract 222 mg / kg / day corresponds to the date of barthenolide 2. OmgZkgZ. In this experiment as well, it was found that when the extract was orally administered, a significant primary volume reduction effect was obtained.
  • Example 4 Comparison of body weight change in feverfew extract administration group and body weight change in cisbratine administration group
  • Feverfew Extract (batch number: 051016-107) manufactured by HANDA FINE CHEMICALS was used as the feverfew extract.
  • the content of parthenolide in this extract was about 0.9%.
  • the feverfew extract was dissolved in 0.5 wZv% methylcellulose aqueous solution and orally administered to the animals using a metal sonde (once daily, administration volume lOmLZkgZ times).
  • the dosage of feverfew extract was 222 mgZkgZ days and 888 mgZkgZ days.
  • cisplatin 0.5 mg / ml injection was administered after calculating the necessary amount based on the body weight of the animals.
  • the cisbratin dose was lOmgZkg, and intraperitoneal injection was performed using an injection needle (26G, manufactured by Terumo Corporation) and a syringe (1 mL capacity, manufactured by Terumone Soil).
  • the vehicle control group was orally administered with 0.5 wZv% methylcellulose aqueous solution.
  • the number of animals per experiment was 10.
  • the animals used were Os C3H / HeN Sic mice (Sankyo Lab Service Co., Ltd.), which were used for experiments at the age of 3 weeks and acclimated to weights from 9.9 to 13.8 g. did. Animals during the experiment Solid feed MF (manufactured by Oriental Yeast Co., Ltd.) and filter-sterilized tap water were freely given.
  • a tumor model was prepared as follows.
  • a tumor model was prepared by subcutaneously injecting 5 lxlO (in 100 L) mouse tumor cells (LM8 cells of an osteosarcoma cell line) into the back of a 4-week-old mouse that had undergone intensive hair removal. After the tumor model was created, feverfew extract and vehicle were orally administered once a day for a maximum of 6 weeks, and the weight of each animal was measured to calculate the survival rate. Cisbratin was administered intraperitoneally one week after the tumor model was prepared.
  • Figure 3 shows the experimental results.
  • weight loss was observed after the 6th day of administration compared to the control group, and this tendency continued until the end of the experimental period.
  • feverfew extract 888 mgZkg and 222 mgZkg groups there was no significant decrease in body weight compared to the control group.
  • Example 5 Ratio of survival rate of feverfew extract administration group to survival rate of cisbratine administration group
  • Figure 4 shows the experimental results.
  • the feverfew extract 888 mgZkg group there was no significant decrease in survival rate over 42 days.
  • the decrease in survival rate was well suppressed, and the survival rate on day 42 was 0.7.
  • the survival rate in the splatin group was 0.4 on day 40 (same as the control group at this point), and the survival rate was lower than that in the feverfew extract group.
  • feverfew extract has been shown to extremely effectively suppress the decrease in the survival rate of tumor animals. Considering the toxicity and side effects of cisbratine, administer a large amount for tumor suppression effect equivalent to or better than feverfew extract I can't. However, cisbratine is expensive. On the other hand, as shown in Example 4, feverfew extract is highly safe and has an excellent tumor suppression effect. Moreover, feverfew extract exhibits an excellent tumor suppressive effect when administered orally. In addition, feverfew extract is much cheaper than anticancer drugs such as cisbratine. Considering these points, feverfew extract is considered to have excellent effects and usefulness that are not found in conventional anticancer agents!
  • the present invention is useful in the fields of health foods and pharmaceuticals.

Abstract

It is intended to provide a food, a drink and a medicinal composition containing an extract of an asteraceous plant, more specifically speaking fever few (Tanacetum parthenium), which exerts a remarkable antitumor effect when orally taken. Moreover, it is intended to provide a method of inhibiting tumor characterized by comprising administering an extract of an asteraceous plant, more specifically speaking, fever few (Tanacetum parthenium), to a patient; use of an extract of an asteraceous plant, more specifically speaking fever few (Tanacetum parthenium), in producing a medicinal composition for inhibiting tumor; and so on.

Description

明 細 書  Specification
腫瘍抑制作用を有する飲食物および医薬組成物  Food / drink and pharmaceutical composition having tumor suppressive action
技術分野  Technical field
[0001] 本発明は、腫瘍抑制作用を有する飲食物および医薬組成物、ならびに腫瘍の抑制 方法などに関する。詳細には、キク科植物の抽出物を含有する飲食物および医薬組 成物、ならびにキク科植物の抽出物を患者に投与することを特徴とする腫瘍の抑制 方法、および腫瘍を抑制するための医薬組成物の製造におけるキク科植物の抽出 物の使用などに関する。  [0001] The present invention relates to foods and drinks and pharmaceutical compositions having a tumor-suppressing action, and methods for suppressing tumors. Specifically, a food and drink and a pharmaceutical composition containing an extract of an Asteraceae plant, and a method for suppressing a tumor characterized by administering an extract of an Asteraceae plant to a patient, and a method for suppressing the tumor The present invention relates to the use of asteraceae extracts in the manufacture of pharmaceutical compositions.
背景技術  Background art
[0002] 腫瘍は最も治療が困難な疾病の 1つとされ、その治療に関して様々な研究がなされ 、新たな治療法や治療薬が開発され、治療成績も向上している。し力しながら、これら の治療法や治療薬の多くは患者への負担が大きぐ副作用も大きい。とりわけ、転移 性の腫瘍は治療が困難であり、多くの研究がなされている (非特許文献 1等参照)。 最近になって、体に優しい癌治療として、免疫細胞療法や漢方を用いた治療、ある いはキノコ抽出物や植物抽出物に由来する健康食品等が開発されている力 有効 性が疑問視されている。  [0002] Tumors are considered to be one of the most difficult diseases to treat, and various studies have been conducted on the treatment, new therapies and drugs have been developed, and treatment results have been improved. However, many of these therapies and drugs are burdensome to patients and have significant side effects. In particular, metastatic tumors are difficult to treat, and many studies have been made (see Non-Patent Document 1, etc.). Recently, as a cancer treatment that is kind to the body, treatment using immune cell therapy and Chinese medicine, or health foods derived from mushroom extracts and plant extracts, etc. have been developed. ing.
特干文献 1: Ann F.し hambers et al. Clinical argets for Anti— Metastasis Therap y" in Advances in CANCER RESEARCH (2000), pages 91—121 (Academic Press). 発明の開示  Special Reference 1: Ann F. Hambers et al. Clinical argets for Anti— Metastasis Therapy "in Advances in CANCER RESEARCH (2000), pages 91-121 (Academic Press). Disclosure of the Invention
発明が解決しょうとする課題  Problems to be solved by the invention
[0003] 本発明の解決課題は、有効でし力も患者に優 、腫瘍の治療を提供することであ る。 [0003] The problem to be solved by the present invention is to provide a treatment for tumors that is effective and superior in strength to patients.
課題を解決するための手段  Means for solving the problem
[0004] 上記事情および課題に鑑みて本発明者らは鋭意研究を重ね、キク科植物、詳細に はナツシロギクの抽出物を動物に経口投与した場合に顕著な腫瘍抑制作用を見出 し、本発明を完成するに至った。 [0004] In view of the above circumstances and problems, the present inventors have conducted extensive research, and found that a remarkable tumor-suppressing effect was found when orally administered to the animal an Asteraceae plant, specifically feverfew extract. The invention has been completed.
発明の効果 [0005] 本発明によれば、経口摂取にて顕著な腫瘍抑制作用を発揮し、しカゝも安全性の高 い、キク科植物、詳細にはナツシロギクの抽出物を含む飲食物および医薬組成物が 提供される。さらに、キク科植物、詳細にはナツシロギクの抽出物を患者に投与する ことを特徴とする腫瘍の抑制方法、および腫瘍を抑制するための医薬組成物の製造 におけるキク科植物、詳細にはナツシロギクの抽出物の使用なども提供される。した がって、有効で体に優 U、腫瘍抑制治療が提供される。 The invention's effect [0005] According to the present invention, food and drink and pharmaceutical composition comprising an extract of a asteraceae plant, in particular feverfew, which exhibits a remarkable tumor-suppressing effect upon ingestion and is highly safe. Things are provided. Furthermore, a method for suppressing a tumor characterized by administering an extract of Asteraceae plant, specifically feverfew to a patient, and a medicinal plant in manufacturing a pharmaceutical composition for suppressing a tumor, more specifically feverfew Use of the extract is also provided. Therefore, an effective, body-friendly, tumor suppressor treatment is provided.
[0006] すなわち、本発明は、下記のものを提供する:  [0006] That is, the present invention provides the following:
(1)キク科植物の抽出物を含有する、腫瘍を抑制するための飲食物; (1) Foods and drinks for suppressing tumors, containing an extract of Asteraceae plants;
(2)キク科植物がナツシロギクである、 (1)記載の飲食物; (2) The food and drink according to (1), wherein the Asteraceae plant is feverfew.
(3)腫瘍が転移性のものである、 (1)または(2)記載の飲食物;  (3) The food or drink according to (1) or (2), wherein the tumor is metastatic.
(4)サプリメントである、 (1)〜(3)の 、ずれかに記載の飲食物;  (4) The food or drink according to any one of (1) to (3), which is a supplement;
(5)キク科植物の抽出物を含有する、腫瘍を抑制するための医薬組成物; (5) A pharmaceutical composition for suppressing a tumor, comprising an extract of a asteraceae plant;
(6)キク科植物がナツシロギクである、 (5)記載の医薬組成物; (6) The pharmaceutical composition according to (5), wherein the Asteraceae plant is feverfew.
(7)腫瘍が転移性のものである、 (5)または (6)記載の医薬組成物;  (7) The pharmaceutical composition according to (5) or (6), wherein the tumor is metastatic.
(8)キク科植物の抽出物を摂食することを特徴とする、腫瘍を抑制する方法; (8) A method for suppressing a tumor, which comprises feeding on an extract of an Asteraceae plant;
(9)キク科植物の抽出物が飲食物またはサプリメントとして提供される、 (8)記載の 方法; (9) The method according to (8), wherein an extract of Asteraceae is provided as a food or drink or a supplement;
(10)キク科植物がナツシロギクである、 (8)または(9)記載の方法;  (10) The method according to (8) or (9), wherein the Asteraceae plant is feverfew.
(11)腫瘍が転移性のものである、 (8)な 、し(10)の 、ずれかに記載の方法; (11) The method according to any one of (8) and (10), wherein the tumor is metastatic.
(12)キク科植物の抽出物を患者に投与することを特徴とする、患者における腫瘍 の抑制方法; (12) A method for suppressing a tumor in a patient, comprising administering an extract of a asteraceae plant to the patient;
( 13)キク科植物がナツシロギクである、(12)記載の方法;  (13) The method according to (12), wherein the Asteraceae plant is feverfew.
(14)腫瘍が転移性のものである、( 12)または( 13)記載の方法;  (14) The method according to (12) or (13), wherein the tumor is metastatic;
(15)腫瘍の抑制のための飲食物の製造における、キク科植物の抽出物の使用; (15) Use of an extract of Asteraceae in the manufacture of food and drink for tumor suppression;
( 16)飲食物がサプリメントである( 15)記載の方法; (16) The method according to (15), wherein the food or drink is a supplement;
(17)キク科植物がナツシロギクである、 (15)または(16)記載の方法; (17) The method according to (15) or (16), wherein the Asteraceae plant is feverfew;
(18)腫瘍が転移性のものである、( 15)ないし( 17)の 、ずれかに記載の方法;(18) The method according to any one of (15) to (17), wherein the tumor is metastatic.
(19)腫瘍の抑制のための医薬組成物の製造における、キク科植物の抽出物の使 用; (19) Use of an extract of Asteraceae in the manufacture of a pharmaceutical composition for tumor suppression for;
(20)キク科植物がナツシロギクである、 (19)記載の方法;  (20) The method according to (19), wherein the Asteraceae plant is feverfew.
(21)腫瘍が転移性のものである、 (19)または(20)記載の方法。  (21) The method according to (19) or (20), wherein the tumor is metastatic.
図面の簡単な説明  Brief Description of Drawings
[0007] [図 1]図 1は、腫瘍マウスにナツシロギク抽出物またはパルテノライドを投与した場合 の生存率の経時変化を示すグラフである。実線はビヒクル対照群、破線はノ ルテノラ イド 40mgZkgZ日経口投与群、 1点破線はナツシロギク抽出物 222mgZkgZ日 経口投与群である。ナツシロギク抽出物 222mgZkgZ日投与群はビヒクル対照群と の間で有意差を示した(Pく 0. 05, Log -Rank test)。  [0007] FIG. 1 is a graph showing the time course of survival rate when a feverfew extract or parthenolide is administered to tumor mice. The solid line is the vehicle control group, the dashed line is the nortenolide 40 mg ZkgZ daily oral administration group, and the dashed line is the feverfew extract 222 mg ZkgZ oral oral administration group. The feverfew extract 222 mg ZkgZ day-treated group showed a significant difference from the vehicle control group (P 0.05, Log-Rank test).
[図 2]図 2は、腫瘍原発巣の大きさを経時的に観察した結果を示すグラフである。黒 丸はビヒクル対照群、白四角はバルテノライド 40mgZkgZ日経口投与群、黒三角 はナツシロギク抽出物 222mgZkgZ日経口投与群である。縦棒は標準偏差を示す  FIG. 2 is a graph showing the results of observing the size of the tumor primary lesion over time. The black circles are the vehicle control group, the white squares are the baltenolide 40 mg ZkgZ oral administration group, and the black triangles are the feverfew extract 222 mg ZkgZ oral administration group. Vertical bars indicate standard deviation
[図 3]図 3は、腫瘍マウスにナツシロギク抽出物またはシスブラチンを投与した場合の 体重の経時変化を示すグラフである。黒丸はビヒクル対照群、白四角はナツシロギク 抽出物 222mgZkgZ日経口投与群、黒四角はナツシロギク抽出物 888mgZkgZ 日経口投与群、白三角はシスブラチン lOmgZkgZ日腹腔内投与群である。 *は < 0. 05で、 * *は p< 0. 01で対照群との有意差があることを示す(Studentの tー検 定の後 F—検定)。 [FIG. 3] FIG. 3 is a graph showing the change in body weight over time when feverfew extract or cisbratine is administered to tumor mice. The black circle is the vehicle control group, the white square is the feverfew extract 222 mgZkgZ daily oral administration group, the black square is the feverfew extract 888 mgZkgZ daily oral administration group, and the white triangle is the cisplatin lOmgZkgZ day intraperitoneal administration group. * Indicates <0. 05, ** indicates p <0.01, indicating a significant difference from the control group (Student's t-test followed by F-test).
[図 4]図 4は、腫瘍マウスにナツシロギク抽出物またはシスブラチンを投与した場合の 生存率の経時変化を示すグラフである。実線はビヒクル対照群、 1点破線はナツシロ ギク抽出物 222mgZkgZ日経口投与群、 2点破線はナツシロギク抽出物 888mgZ kg/日経口投与群、点線はシスブラチン lOmgZkgZ日腹腔内投与群である。ナツ シロギク抽出物 888mgZkgZ日投与群はビヒクル対照群との間で有意差を示した( p< 0. 05, Log -Rank test)。  [FIG. 4] FIG. 4 is a graph showing the time course of survival rate when feverfew extract or cisbratine is administered to tumor mice. The solid line is the vehicle control group, the dashed line is the feverfew extract 222 mgZkgZ daily oral administration group, the broken line is the feverfew extract 888 mgZ kg / day oral administration group, and the dotted line is the cisplatin lOmgZkgZ day intraperitoneal administration group. The feverfew extract 888mgZkgZ day group showed a significant difference from the vehicle control group (p <0.05, Log-Rank test).
発明を実施するための最良の形態  BEST MODE FOR CARRYING OUT THE INVENTION
[0008] 本発明は、セスキテルペンラタトン類を含む植物の抽出物を含有する、腫瘍を抑制 するための飲食物に関するものである。ここで、腫瘍を抑制するとは、腫瘍の治療の みならず予防も包含する。本発明の飲食物に使用される植物抽出物はセスキテルべ ンラクトン類を含む植物の抽出物であれば、植物の種類は特に制限はない。セスキ テルペンラタトンを多く含む植物の例としては、キク科植物が挙げられ、例えばョモギ 属の植物やタンポポなどが挙げられる。したがって、本発明は 1の態様において、キ ク科植物の抽出物を含有する、腫瘍を抑制するための飲食物を提供する。セスキテ ルペンラタトン類のなかでもパルテノライドはこれまで種々の生理活性を有することが 報告されて 、る物質であり、特開 2005 - 35951に示すように腫瘍の転移を抑制し、 動物の延命効果を発揮することが示されている。したがって、バルテノライド含有量の 高い植物を用いることが好ましい。そのような植物としてはキク科植物、好ましくはョモ ギ属の植物、特に好ましくはナツシロギク(Tanacetum parthenium) (フィーバーフュー ともいう)が挙げられる。したがって、本発明に使用される特に好ましい植物抽出物は ナツシロギクの抽出物である。ナツシロギクの植物体、特に葉には通常 0. 2〜0. 9% 程度のパルテノライドが含まれている。驚くべきことに、ナツシロギク抽出物を動物に 経口投与した場合に、パルテノライドに換算すると極めて少量のパルテノライドしか投 与しな 、場合であっても、バルテノライド単品の場合よりも優れた腫瘍抑制効果が得 られることが判明した (実施例参照)。 [0008] The present invention relates to a food and drink for suppressing tumors, which contains an extract of a plant containing sesquiterpene ratatones. Here, to suppress tumor is to treat tumor It includes prevention as well. The plant extract used in the food and drink of the present invention is not particularly limited as long as it is a plant extract containing sesquiterbene lactones. Examples of plants containing a large amount of sesquiterpene ratatones include asteraceae plants, such as plants of the genus Artemisia and dandelions. Therefore, in one aspect, the present invention provides a food and drink for suppressing tumors, which contains an extract of a asteraceae plant. Among the sesquiterpene ratatones, parthenolide has been reported to have various physiological activities so far, and as shown in Japanese Patent Application Laid-Open No. 2005-35951, it suppresses tumor metastasis and exerts an animal life-prolonging effect. It has been shown. Therefore, it is preferable to use plants with a high content of valthenolide. Examples of such plants include asteraceae plants, preferably plants belonging to the genus Artemisia, particularly preferably Tanacetum parthenium (also referred to as fever-fu). Thus, a particularly preferred plant extract for use in the present invention is feverfew extract. Feverfew plants, especially leaves, usually contain about 0.2 to 0.9% parthenolide. Surprisingly, when feverfew extract is orally administered to animals, only a very small amount of parthenolide is administered in terms of parthenolide, but even in this case, a tumor suppression effect superior to that of bartenolide alone is obtained. (See Examples).
植物の抽出物は一般的方法により得ることができる。抽出部位は植物の地上部で あればいずれの部位でもよいが、ナツシロギクなどのキク科植物の場合、好ましい抽 出部位は葉である。植物をそのまま溶媒に浸漬して抽出物を得てもよいが、破砕して 力も内容物を抽出するほうが抽出効率が高い。植物は生のままでも、乾燥したもので あってもよい。乾燥には、温風乾燥、風乾などの公知の乾燥方法を用いることができ る。植物の破砕手段は各種のものが使用可能である。例えば、手もみ、ポッタ一一ェ ルベージェムホモジナイザーなどのホモジナイザー、ワーリングブレンダーなどのブレ ンダ一、ダイノーミルなどの破砕器、フレンチプレス、乳鉢および乳棒、らいかい器、 液体窒素による凍結および破砕、超音波処理などの手段により植物を破砕すること ができる。植物の破砕物を適当な媒体に懸濁し、内容物の抽出を行う。所望により、 抽出時に撹拌してもよい。懸濁 ·抽出媒体としては、エーテル、メタノール、エタノー ル、あるいはエタノールと水の混合物などが挙げられる。懸濁媒体は、毒性の低いも の、あるいは無毒であるものが好ましい。かかる観点から、エタノール、あるいはェタノ ールと水の混合物が特に好ましい懸濁 ·抽出媒体として挙げられる。懸濁'抽出時の 温度、時間などの抽出条件は植物の種類、量などに応じて選択することができる。通 常には、常温'常圧で、数時間ないし数日間抽出する。また、植物の地上部、例えば 、葉や茎などをそのまま、温風乾燥、風乾などの公知の乾燥方法により乾燥させ、粉 砕することにより粉末ィ匕したものを、本発明の飲食物や医薬組成物に使用してもよい Plant extracts can be obtained by general methods. The extraction site may be any site as long as it is an aerial part of the plant, but in the case of an Asteraceae plant such as feverfew, a preferable extraction site is a leaf. The extract may be obtained by immersing the plant in a solvent as it is, but the extraction efficiency is higher when the contents are extracted by crushing the force. Plants may be raw or dried. For drying, a known drying method such as warm air drying or air drying can be used. Various plant crushing means can be used. For example, hand grinders, homogenizers such as potter belge gem homogenizers, blenders such as Waring blenders, crushers such as dyno mills, french presses, mortars and pestles, rabies, freezing and crushing with liquid nitrogen, super Plants can be crushed by means such as sonication. The plant crushed material is suspended in an appropriate medium, and the contents are extracted. If desired, stirring may be performed during extraction. Suspension / extraction media include ether, methanol, ethanol, or a mixture of ethanol and water. Suspension media should be less toxic Those that are non-toxic or non-toxic are preferred. From this viewpoint, ethanol or a mixture of ethanol and water is particularly preferable as a suspension / extraction medium. Extraction conditions such as temperature and time during suspension 'extraction can be selected according to the type and amount of plants. Usually, it is extracted at room temperature and normal pressure for several hours to several days. In addition, the above-ground parts of plants, such as leaves and stems, are directly dried by a known drying method such as hot air drying or air drying, and pulverized to obtain a food or drink or pharmaceutical of the present invention. May be used in the composition
[0010] 得られた抽出物をそのまま使用してもよぐ必要ならば、得られた抽出物を、デカン テーシヨン、ろ過、または遠心分離などの公知方法に付して固形分および粒子状物 質を除去することができる。得られた抽出物を、例えばエバポレーシヨンなどの公知 方法により濃縮してもよい。得られた抽出物を、公知方法により乾燥させて、粉末等 の固体としてもよい。また、得られた抽出物を、例えば各種クロマトグラフィーや沈殿 法などの公知方法により、さらに精製して用いてもよい。 [0010] If it is necessary to use the obtained extract as it is, the obtained extract is subjected to a known method such as decantation, filtration, or centrifugation to obtain a solid content and a particulate matter. Can be removed. The obtained extract may be concentrated by a known method such as evaporation. The obtained extract may be dried by a known method to obtain a solid such as a powder. The obtained extract may be further purified and used by known methods such as various chromatography and precipitation methods.
[0011] 本発明の飲食物に使用する植物抽出物は上記のようにして得ることができる力 ナ ッシロギク抽出物は巿販もされており、これを使用しても力まわない。これらの抽出物 は、使用形態や目的等に応じて、公知方法を用いて種々の形態とすることができ、液 体、半固体、固体 (例えば凍結乾燥粉末などの粉末)などに調製することができる。  [0011] The plant extract used in the food and drink according to the present invention can be obtained as described above. These extracts can be made into various forms using known methods according to the use form and purpose, and prepared into liquid, semi-solid, solid (for example, powder such as freeze-dried powder), etc. Can do.
[0012] キク科植物抽出物、特にナツシロギク抽出物を種々の飲食物に配合して、本発明 の飲食物を得ることができる。これらのキク科植物抽出物は天然物由来のため毒性 が低ぐあるいは無毒であり、あらゆる飲食物に配合することができる。例えば、抽出 物をジュースゃノヽーブ系調味料などに配合してもよい。本発明の飲食物は、健康食 品、栄養機能食品、あるいは特定保健用食品(いわゆる「トクホ」)などにすることがで きる。  [0012] An Asteraceae plant extract, particularly a feverfew extract, can be blended with various foods to obtain the foods and drinks of the present invention. These asteraceae plant extracts are of low toxicity or non-toxic because they are derived from natural products, and can be incorporated into any food or drink. For example, the extract may be blended with juice or a noove seasoning. The food and drink of the present invention can be a health food, a functional nutritional food, or a food for specified health use (so-called “tokuho”).
[0013] とりわけ、本発明の飲食物の好ましい形態として、サプリメントが挙げられる。サプリ メントの形状は、経口摂取可能な形状であればいずれの形状であってもよぐ例えば 、一般の食品の形状であってもよぐ錠剤、カプセル剤、顆粒、粉末 (例えば凍結乾 燥粉末等)、懸濁液、ドリンク剤、エリキシル、チユアブル形態、ゼリー状などの形状で あってもよい。これらのサプリメントは、食品分野や製薬分野で用いられているプロセ スに準じて製造することができる。例えば、錠剤形状のサプリメントを製造する場合に は、製薬分野で用いられている混合、乾燥、打錠等の一般的なプロセスを用いること ができる。また例えば、カプセル剤の形状の場合には、混合、カプセル封入等の一 般的なプロセスを用いることができる。ソフトカプセル、ハードカプセルも目的に応じて 適宜選択することができる。液体のサプリメントを製造するにはエタノール等の毒性の 低い媒体に抽出物を溶解ないし懸濁することができる。粉末や顆粒のサプリメントを 製造するには、やはり通常の混合、乾燥、粉砕、ふるい分けなどのプロセスを用いる ことができる。サプリメントの製造に担体や賦形剤を用いる場合には、その種類や量 は製薬分野の慣習に準じて選択することができる。固体の担体または賦形剤としては 、例えばタルク、カルボキシメチルセルロース、ショ糖、小麦粉などがある。液体の担 体としては、例えば水、エタノール、食用油脂などがある。 [0013] In particular, supplements are mentioned as a preferred form of the food and drink of the present invention. The supplement may be in any shape that can be taken orally, such as tablets, capsules, granules, and powders (e.g., freeze-dried powder). Etc.), suspensions, drinks, elixirs, possible forms, jelly forms and the like. These supplements are used in the food and pharmaceutical fields. Can be manufactured according to For example, when manufacturing a tablet-shaped supplement, a general process such as mixing, drying, and tableting used in the pharmaceutical field can be used. For example, in the case of a capsule form, a general process such as mixing and encapsulation can be used. Soft capsules and hard capsules can also be appropriately selected according to the purpose. To produce a liquid supplement, the extract can be dissolved or suspended in a less toxic medium such as ethanol. In order to produce powder and granule supplements, the usual processes such as mixing, drying, grinding and sieving can also be used. When a carrier or excipient is used in the production of supplements, the type and amount can be selected according to the practice in the pharmaceutical field. Examples of solid carriers or excipients include talc, carboxymethylcellulose, sucrose, and wheat flour. Examples of the liquid carrier include water, ethanol, and edible fats and oils.
[0014] 本発明の飲食物はあらゆる腫瘍の抑制に効果がある。本発明の植物抽出物中に セスキテルペンラタトンが含まれていることから、特開 2005— 35951の場合と同様に 、本発明の飲食物もまた、腫瘍の抑制、特に腫瘍の転移抑制に効果を発揮し、動物 の延命を促進する。  [0014] The food and drink of the present invention is effective in suppressing all tumors. Since sesquiterpene ratatones are contained in the plant extract of the present invention, as in JP-A-2005-35951, the food and drink of the present invention is also effective for tumor suppression, particularly tumor metastasis suppression. To promote the survival of animals.
[0015] 1日あたりのキク科植物抽出物の摂取量または摂食量は、含有されるセスキテルべ ンラクトン類、特にノルテノライド量に依存する。ナツシロギク抽出物であれば、成人( 体重 70kg)の場合 1日あたり、 0. 05g〜50g程度を摂取するのが一般的であり、 0. 15g〜 15g程度を摂取または摂食するのが適当である。  [0015] The intake or intake of Asteraceae extract per day depends on the amount of sesquiterbene lactones, especially nortenolide contained. In the case of feverfew extract, it is common to take about 0.05g to 50g per day for adults (weight 70kg), and it is appropriate to eat or eat about 0.15g to 15g. is there.
[0016] 本発明の飲食物やサプリメント中には、キク科植物抽出物のみならず、 1種または それ以上の他の有効成分が混合されていてもよい。例えば、抗腫瘍剤(例えば、フル ォロウラシル、ブレオマイシン、パクリタキセル、シスプラチンなど)、ホルモン剤(例え ば、タモキシフェン、ホスフェストロールなど)、免疫賦活剤(例えば、ァラビノキシラン 、キトサン、ェゾゥコギなど)等の化学療法剤と本発明の飲食物とを併用してもよい。 例えば、すでに化学療法、外科療法、放射線療法、ホルモン療法、免疫療法などの 治療を受けている人が、本発明の飲食物を摂食することにより、治療効果を促進する ことも可能である。本発明の飲食物を併用すれば、薬物の投与量を低減でき、患者 に優し 、治療を実現することができる。 [0017] 本発明の飲食物はヒト用のみならず、ヒト以外の動物の飼料も包含する。 [0016] In the food and drink or supplement of the present invention, not only asteraceae plant extracts but also one or more other active ingredients may be mixed. For example, chemotherapy such as antitumor agents (eg, fluorouracil, bleomycin, paclitaxel, cisplatin), hormone agents (eg, tamoxifen, phosfestol), immunostimulants (eg, arabinoxylan, chitosan, esukoggi), etc. The agent and the food and drink of the present invention may be used in combination. For example, a person who has already undergone treatment such as chemotherapy, surgery, radiation therapy, hormone therapy, and immunotherapy can promote the therapeutic effect by eating the food or drink of the present invention. When the food and drink of the present invention is used in combination, the dose of the drug can be reduced, and treatment can be realized with ease for the patient. [0017] The food and drink of the present invention includes not only human but also non-human animal feed.
[0018] 本発明は、さらなる態様において、キク科植物抽出物、好ましくはナツシロギク抽出 物を含有する腫瘍抑制用の医薬組成物を提供する。本発明の医薬組成物中の有効 成分は、上記のキク科植物抽出物、好ましくはナツシロギク抽出物である。また、有効 成分として、これらの抽出物を精製してバルテノライド含量を高めたものを用いてもよ い。 [0018] In a further aspect, the present invention provides a pharmaceutical composition for tumor suppression comprising an Asteraceae extract, preferably a feverfew extract. The active ingredient in the pharmaceutical composition of the present invention is the above-mentioned Asteraceae plant extract, preferably feverfew extract. Further, as an active ingredient, a product obtained by purifying these extracts and increasing the content of barthenolide may be used.
[0019] 本発明の医薬組成物を種々の剤形に処方することができる。有効成分としてナツシ ロギク抽出物などのキク科植物の抽出物を用いる場合には、本発明の医薬組成物は 経口投与に適した剤形とすることが好ましぐ例えば、錠剤、カプセル剤、顆粒、粉末 、ドリンク剤などとすることができる。また、有効成分としてパルテノライドのようなセスキ テルペンラタトン類を用いる場合には、本発明の医薬組成物は経口投与および局所 投与に適した剤形とするのが好ましいが、他の投与経路による投与も可能である。こ れらの剤形は製薬分野において公知の方法により製造することができる。  [0019] The pharmaceutical composition of the present invention can be formulated into various dosage forms. When using an extract of Asteraceae plants such as feverfew extract as an active ingredient, the pharmaceutical composition of the present invention is preferably in a dosage form suitable for oral administration. For example, tablets, capsules, granules , Powder, drinks and so on. When sesquiterpene ratatones such as parthenolide are used as the active ingredient, the pharmaceutical composition of the present invention is preferably in a dosage form suitable for oral administration and topical administration, but administration by other administration routes. Is also possible. These dosage forms can be produced by methods known in the pharmaceutical field.
[0020] 本発明の医薬組成物はあらゆる腫瘍の抑制に効果がある。本発明の植物抽出物 中にセスキテルペンラタトンが含まれて!/、ること力ら、特開 2005 - 35951の場合と同 様に、本発明の医薬組成物もまた、腫瘍の抑制、特に腫瘍の転移抑制に効果を発 揮し、動物の延命を促進する。  [0020] The pharmaceutical composition of the present invention is effective in suppressing any tumor. As in the case of JP 2005-35951, the pharmaceutical composition of the present invention also contains tumor suppression, particularly in the case where sesquiterpene ratatones are contained in the plant extract of the present invention! It is effective in suppressing tumor metastasis and promotes the survival of animals.
[0021] 本発明の医薬組成物中の有効成分がキク科植物抽出物の場合、ナツシロギク抽出 物を例にとるとその 1日の投与量は、成人 (体重 70kg)の場合 1日あたり、 0. 05g〜5 Og程度が一般的であり、 0. 15g〜15g程度が適当である。これらの投与量は、患者 の症状、疾患部位、性別、年齢、体重、副作用の有無、他に受けている治療等の因 子に応じて医師が適宜変更できるものである。  [0021] When the active ingredient in the pharmaceutical composition of the present invention is an Asteraceae plant extract, taking a feverfew extract as an example, the daily dose is 0 per day for an adult (body weight 70 kg). About 05g to 5Og is common, and about 0.15g to 15g is appropriate. These dosages can be changed as appropriate by the doctor according to the patient's symptoms, disease site, sex, age, weight, presence of side effects, and other factors such as treatment being received.
[0022] 本発明の医薬組成物中には、キク科植物抽出物やパルテノライドのみならず、 1種 またはそれ以上の他の有効成分が混合されていてもよい。例えば、抗腫瘍剤 (例え ば、フルォロウラシル、ブレオマイシン、パクリタキセル、シスプラチンなど)、ホルモン 剤(例えば、タモキシフェン、ホスフェストロールなど)、免疫賦活剤(例えば、ァラピノ キシラン、キトサン、ェゾゥコギなど)等の化学療法剤と本発明の医薬組成物とを併用 してもよい。例えば、すでに化学療法、外科療法、放射線療法、ホルモン療法、免疫 療法などの治療を受けている人が、本発明の医薬組成物を投与することにより、治療 効果を促進することも可能である。本発明の医薬組成物を併用すれば、薬物の投与 量を低減でき、患者に優 U、治療を実現することができる。 [0022] In the pharmaceutical composition of the present invention, not only asteraceae plant extracts and parthenolides, but also one or more other active ingredients may be mixed. For example, chemotherapy such as antitumor agents (for example, fluorouracil, bleomycin, paclitaxel, cisplatin), hormone agents (for example, tamoxifen, phosfestol), immunostimulants (for example, alapinoxylan, chitosan, ezoukogi, etc.) An agent and the pharmaceutical composition of the present invention may be used in combination. For example, already chemotherapy, surgery, radiation therapy, hormone therapy, immunity It is also possible for a person receiving treatment such as therapy to promote the therapeutic effect by administering the pharmaceutical composition of the present invention. When the pharmaceutical composition of the present invention is used in combination, the dose of the drug can be reduced, and the patient can be treated with superior therapy.
[0023] 本発明の医薬組成物はヒト用のみならず、ヒト以外の動物用の医薬組成物、例えば 、獣医用の医薬組成物も包含する。  [0023] The pharmaceutical composition of the present invention includes not only a human but also a non-human animal pharmaceutical composition such as a veterinary pharmaceutical composition.
[0024] 本発明は、さらなる態様において、キク科植物の抽出物を摂食することを特徴とす る、腫瘍を抑制する方法に関する。摂食とは、口から飲食することをいう。通常には、 キク科植物の抽出物は飲食物の形態で提供されるが、サプリメントの形態で提供され てもよい。飲食物やサプリメントの形態については上で説明したとおりである。  [0024] In a further aspect, the present invention relates to a method for inhibiting a tumor, characterized by feeding on an extract of an Asteraceae plant. Eating means eating and drinking from the mouth. Normally, the extracts of Asteraceae plants are provided in the form of food and drink, but may be provided in the form of supplements. The form of food and drink and supplements are as described above.
[0025] 上記方法におけるキク科植物の抽出物の摂食量は上で説明したとおりである。  [0025] The intake of the extract of the Asteraceae plant in the above method is as described above.
[0026] 上記方法において好ましいキク科植物の抽出物はナツシロギク抽出物である。  [0026] A preferable extract of the Asteraceae plant in the above method is a feverfew extract.
[0027] 上記方法において、キク科植物抽出物のみならず、 1種またはそれ以上の他の有 効成分を併用してもよ!ヽ。他の有効成分は上で列挙したものであってもよ ヽ。  [0027] In the above method, not only asteraceae plant extracts but also one or more other active ingredients may be used in combination! Other active ingredients may be those listed above.
[0028] 上記方法により抑制される好ま 、腫瘍は転移性腫瘍である。  [0028] Preferably, the tumor suppressed by the above method is a metastatic tumor.
[0029] 上記方法はヒトのみならずヒト以外の動物にも適用できる。  [0029] The above method can be applied not only to humans but also to animals other than humans.
[0030] 本発明は、さらなる態様において、キク科植物の抽出物を患者に投与することを特 徴とする、患者における腫瘍の抑制方法に関する。キク科植物の抽出物をそのまま 患者に与えてもよいが、好ましくは医薬組成物の形態として患者に与える。医薬組成 物の剤形および投与経路は、本発明の医薬組成物に関して上で説明したとおりであ る。  [0030] In a further aspect, the present invention relates to a method for suppressing a tumor in a patient, characterized by administering an extract of an Asteraceae plant to the patient. An extract of the Asteraceae plant may be given to the patient as it is, but is preferably given to the patient in the form of a pharmaceutical composition. The dosage form and route of administration of the pharmaceutical composition are as described above for the pharmaceutical composition of the present invention.
[0031] 上記方法におけるキク科植物の抽出物の投与量は上で説明したとおりである。  [0031] The dosage of the extract of the Asteraceae plant in the above method is as described above.
[0032] 上記方法において好ましいキク科植物の抽出物はナツシロギク抽出物である。 [0032] In the above method, a preferable extract of the Asteraceae plant is a feverfew extract.
[0033] 上記方法において、キク科植物の抽出物のみならず、 1種またはそれ以上の他の 有効成分を併用してもよ!ヽ。他の有効成分は上で列挙したものであってもよ ヽ。 [0033] In the above method, not only an extract of Asteraceae but also one or more other active ingredients may be used in combination! Other active ingredients may be those listed above.
[0034] 上記方法により抑制される好ま 、腫瘍は転移性腫瘍である。 [0034] Preferably, the tumor suppressed by the above method is a metastatic tumor.
[0035] 上記方法はヒトのみならずヒト以外の動物にも適用できる。 [0035] The above method can be applied not only to humans but also to animals other than humans.
[0036] 本発明は、さらなる態様において、腫瘍の抑制のための飲食物の製造における、キ ク科植物の抽出物の使用を提供する。飲食物はサプリメントの形態であってもよい。 飲食物やサプリメントの形態については上で説明したとおりである。 [0036] In a further aspect, the present invention provides the use of an extract of a asteraceae plant in the manufacture of food and drink for tumor suppression. The food and drink may be in the form of a supplement. The form of food and drink and supplements are as described above.
[0037] 上記使用におけるキク科植物の抽出物の摂取量は上で説明したとおりである。  [0037] The intake of the extract of the Asteraceae plant in the above use is as described above.
[0038] 上記使用において好ましいキク科植物の抽出物はナツシロギク抽出物である。 [0038] A preferable extract of the Asteraceae plant in the above use is a feverfew extract.
[0039] 上記使用にお!/、て、キク科植物抽出物のみならず、 1種またはそれ以上の他の有 効成分を併用してもよ!ヽ。他の有効成分は上で列挙したものであってもよ ヽ。 [0039] For the above use! /, Not only asteraceae plant extracts but also one or more other active ingredients may be used in combination! Other active ingredients may be those listed above.
[0040] 上記使用により抑制される好ま 、腫瘍は転移性腫瘍である。 [0040] Preferably, the tumor suppressed by the use is a metastatic tumor.
[0041] 上記使用はヒトのみならずヒト以外の動物にも適用できる。 [0041] The above use can be applied not only to humans but also to animals other than humans.
[0042] 本発明は、さらなる態様において、腫瘍の抑制のための医薬組成物の製造におけ る、キク科植物の抽出物の使用を提供する。この使用により製造される医薬組成物の 形態、投与経路、投与すべきキク科植物の抽出物の量は上で説明したとおりである。  [0042] In a further aspect, the present invention provides the use of an extract of Asteraceae in the manufacture of a pharmaceutical composition for tumor suppression. The form of the pharmaceutical composition produced by this use, the route of administration, and the amount of Asteraceae extract to be administered are as described above.
[0043] 上記使用において好ましいキク科植物の抽出物はナツシロギク抽出物である。  [0043] A preferred extract of the Asteraceae plant in the above use is feverfew extract.
[0044] 上記使用にお!/、て、キク科植物抽出物のみならず、 1種またはそれ以上の他の有 効成分を併用してもよ!ヽ。他の有効成分は上で列挙したものであってもよ ヽ。  [0044] In the above use! /, Not only the Asteraceae plant extract, but also one or more other active ingredients may be used in combination! Other active ingredients may be those listed above.
[0045] 上記使用により抑制される好ま 、腫瘍は転移性腫瘍である。  [0045] Preferably, the tumor suppressed by the use is a metastatic tumor.
[0046] 上記使用はヒトのみならずヒト以外の動物にも適用できる。  [0046] The use described above can be applied not only to humans but also to animals other than humans.
[0047] なお、本明細書において、腫瘍の抑制とは、腫瘍の発生を予防、防止または抑制 すること、腫瘍の発達を抑制または停止させること、腫瘍の転移を抑制または無くす ことを包含する。  [0047] In the present specification, tumor suppression includes prevention, prevention or suppression of tumor development, suppression or termination of tumor development, and suppression or elimination of tumor metastasis.
[0048] 以下に実施例を示して本発明をより具体的かつ詳細に説明するが、本発明は実施 例に限定されるものではない。  [0048] The present invention will be described more specifically and in detail below with reference to examples, but the present invention is not limited to the examples.
実施例 1  Example 1
[0049] 実施例 1:ナツシロギク抽出物およびパルテノライドの腫瘍マウス生存率上昇効果 [0049] Example 1: Effect of feverfew extract and parthenolide on the survival rate of tumor mice
,験方法および材料  Test methods and materials
ナツシロギク抽出物は HANDA FINE CHEMICALS社製の Feverfew Extract (バッチ 番号: 051016— 107)を使用した。この抽出物中のパルテノライド含量は約 0. 9% であった。パルテノライドは sigma社製のもの(純度 90%以上)を用いた。ナツシロギク 抽出物を 0. 5 wZv%メチルセルロース水溶液中に溶解して動物に金属製ゾンデを 用いて経口投与した(1日 1回、投与体積 lOmLZkgZ回)。ナツシロギク抽出物の 投与量は 222mgZkgZ日、パルテノライドの投与量は 40mgZkgZ日とした。ビヒク ル対照群には 0. 5wZv%メチルセルロース水溶液を与えた。各実験あたりの動物数 は 10匹とした。 Feverfew Extract (batch number: 051016-107) manufactured by HANDA FINE CHEMICALS was used as the feverfew extract. The content of parthenolide in this extract was about 0.9%. Parthenolide manufactured by sigma (purity of 90% or more) was used. The feverfew extract was dissolved in a 0.5 wZv% aqueous solution of methylcellulose and orally administered to the animals using a metal sonde (once a day, administration volume lOmLZkgZ). Feverfew extract The dose was 222 mgZkgZ day, and the dose of parthenolide was 40 mgZkgZ day. The vehicle control group received 0.5 wZv% methylcellulose aqueous solution. The number of animals per experiment was 10.
[0050] 使用動物はォスの C3H/HeN Sicマウス(三協ラボサービス株式会社)であり、 3週齢 、体重 9〜14gのものを馴化して 4週齢で実験に使用した。実験期間中は動物に固 形飼料 MF (オリエンタル酵母株式会社製)およびフィルター滅菌した水道水を自由 に与えた。  [0050] The animal used was a male C3H / HeN Sic mouse (Sankyo Lab Service Co., Ltd.), which was conditioned at 3 weeks of age and weighing 9-14 g, and used at 4 weeks of age. During the experiment period, animals were given solid feed MF (Oriental Yeast Co., Ltd.) and filter-sterilized tap water freely.
[0051] 腫瘍モデルを以下のようにして作製した。 4週齢のあら力じめ除毛したマウスの背部 に lxlO5個(100 L中)のマウス腫瘍細胞(骨肉腫細胞株の LM8細胞)を皮下注射 して腫瘍モデルを作製した。腫瘍モデルを作製した後、 8週間にわたり 1日 1回ナツシ ロギク抽出物およびビヒクルを経口投与し、生存率を算出した。 [0051] A tumor model was prepared as follows. A tumor model was prepared by subcutaneously injecting 5 lxlO (in 100 L) mouse tumor cells (LM8 cells of an osteosarcoma cell line) into the back of a 4-week-old mouse that had undergone intensive hair removal. After preparing the tumor model, feverfew extract and vehicle were orally administered once a day for 8 weeks, and the survival rate was calculated.
[0052] 睡菓  [0052] Sleeper
実験結果を図 1に示す。ナツシロギク抽出物投与群において延命効果が見られ、 特にナツシロギク抽出物 222mgZkgZ日投与群における延命効果が大きぐパル テノライド 40mgZkgZ日投与群よりも延命効果が大き力つた(50日目でビヒクル対 照群の生存率が約 0. 1であるのに対し、ナツシロギク抽出物 222mgZkgZ日投与 群の生存率は約 0. 45であった)。ナツシロギク抽出物中のパルテノライド含量を 0. 9 %とすると、ナツシロギク抽出物 222mgZkgZ日という投与量はパルテノライド 2. 0 mg/kg/日に相当する。抽出物を経口投与した場合に高い腫瘍抑制効果が得ら れたことは驚くべきことである。その理由としてはナツシロギク抽出物中に含まれる他 の成分による相乗作用が考えられる。また、抽出物中の精油成分がうまく作用したと ち考免られる。  Figure 1 shows the experimental results. Life-survival effect was observed in the feverfew extract-administered group, especially in the feverfew extract 222 mgZkgZ day-administered group. The survival rate was about 0.1, whereas the survival rate of the feverfew extract 222 mg ZkgZ day administration group was about 0.45). When the content of parthenolide in feverfew extract is 0.9%, the dose of feverfew extract 222 mgZkgZ days corresponds to parthenolide 2.0 mg / kg / day. It is surprising that a high tumor suppressive effect was obtained when the extract was administered orally. The reason may be a synergistic effect of other components contained in the feverfew extract. In addition, the essential oil components in the extract are considered to have worked well.
[0053] 上記実験に用いたナツシロギク抽出物の安全性につ!、て調べた。試験方法は OE CD化学テストガイドライン(TG420)の固定用量法とし、 Sic: ICR系のメスのマウスを 用いた。その結果、ナツシロギク抽出物 2000mgZkg用量でも動物の死亡例はなく 、一般状態にも異常は認められず、体重増加も順調であった。これらの結果から、ナ ッシロギク抽出物の LD 値は 2000mgZkg用量以上と評価された。  [0053] The safety of the feverfew extract used in the above experiments was investigated. The test method was the OECD chemical test guideline (TG420) fixed dose method, and Sic: ICR female mice were used. As a result, there was no animal death even at the dose of feverfew extract 2000 mgZkg, no abnormalities were observed in the general condition, and weight gain was also steady. Based on these results, the LD value of pear extract was evaluated to be 2000 mgZkg or more.
50  50
[0054] また、上記実験に用いたナツシロギク抽出物の変異原性を、検定菌として Salmonell a typhimurium TA100, TA1535, TA98, TA1537および Escherichia coli WP2 uvrAを 用い、 S9mix非存在下および存在下で調べた。その結果、用量 5000 gZプレート でも変異原性は認められな力つた。これらの結果から、ナツシロギク抽出物はきわめ て安全性の高 、ものであることがわ力つた。 [0054] In addition, the mutagenicity of feverfew extract used in the above experiment was determined using Salmonell as a test bacterium. atyphimurium TA100, TA1535, TA98, TA1537 and Escherichia coli WP2 uvrA were used in the absence and presence of S9mix. As a result, the mutagenicity was not observed even at the dose of 5000 gZ plate. From these results, it was proved that feverfew extract is extremely safe and safe.
実施例 2  Example 2
[0055] ¾施例 2:ナツシロギク抽出物およびパルテノライ の脯痕転移 ¾制効菜 [0055] ¾ Example 2: feverfew extract and parthenolic trace transfer
,験方法および材料  Test methods and materials
ナツシロギク抽出物およびパルテノライドは実施例 1と同じものを使用した。動物へ の投与方法も実施例 1と同じであった。投与量はナツシロギク抽出物 222mgZkgZ 日、パルテノライド 40mg/kg/日とし、ビヒクル対照群には 0. 5w/v%メチルセル ロース水溶液を経口投与した。  The feverfew extract and parthenolide were the same as in Example 1. The method of administration to animals was also the same as in Example 1. The doses were feverfew extract 222 mgZkgZ day and parthenolide 40 mg / kg / day, and 0.5 w / v% methylcellulose aqueous solution was orally administered to the vehicle control group.
[0056] 使用動物はォスの C3H/HeN Sicマウス(三協ラボサービス株式会社)であり、 3週齢 、体重 10. 3〜13. 6gのものを馴化して 5週齢で実験に使用した。実験期間中は動 物に固形飼料 MF (オリエンタル酵母株式会社製)およびフィルター滅菌した水道水 を自由に与えた。 [0056] The animals used were Os C3H / HeN Sic mice (Sankyo Lab Service Co., Ltd.), which were used for experiments at the age of 3 weeks and acclimated to those with body weights of 10.3 to 13.6 g. did. During the experimental period, animals were freely given solid feed MF (Oriental Yeast Co., Ltd.) and filter-sterilized tap water.
[0057] 腫瘍モデルを以下のようにして作製した。 5週齢のあら力じめ除毛したマウスの背部 に lxlO5個(100 L中)のマウス腫瘍細胞(骨肉腫細胞株の LM8細胞)を皮下注射 して腫瘍モデルを作製した。腫瘍モデルを作製した後、 1日 1回ナツシロギク抽出物 、ノルテノライドおよびビヒクルを経口投与し、死亡例が認められ、なおかつ肺への転 移が認められた時点 (処置開始力も 34日目)で動物の原発性腫瘍、肺および肝臓を 取り出し、パラフィン包埋を行った。肺の標本は左葉の中心部を水平方向に薄切し、 へマトキシリン'ェォジン (HE)染色を行い、顕微鏡下で写真を撮り、写真をコンビュ 一ターに取り込み、画像解析ソフト(Image Tool ver.3.00, UTHSCSA)を用いて肺面 積および転移巣面積を求め、肺面積に対する転移巣面積の割合 (%)を算出した。 [0057] A tumor model was prepared as follows. A tumor model was prepared by subcutaneously injecting 5 lxlO (in 100 L) mouse tumor cells (LM8 cells of an osteosarcoma cell line) into the back of a 5 week-old mouse that had been brutally removed. Once the tumor model has been created, the feverfew extract, nortenolide and vehicle are orally administered once a day, and at the time when death occurred and transfer to the lung was observed (treatment initiation force was also on the 34th day) Primary tumors, lungs and liver were removed and embedded in paraffin. Lung specimens are sliced horizontally at the center of the left lobe, stained with hematoxylin 'eosin (HE), photographed under a microscope, photographed into a computer, and image analysis software (Image Tool ver .3.00, UTHSCSA) was used to determine the lung area and metastasis area, and the ratio (%) of the metastasis area to the lung area was calculated.
[0058] 睡菓  [0058] Sleeper
実験結果を表 1に示す。  Table 1 shows the experimental results.
[0059] [表 1] 処置群 動物数 移集 si積 巾 ή積 転移巣面積の割合 [0059] [Table 1] Treatment group Number of animals Transfer si product Width Sputum area Ratio of metastatic foci area
(ピクセル) (ピクセル) { )  (Pixel) (pixel) {)
ヒクル対照 101 248024 1154618 21. 48 ハ。 /レテノライト、'  Vehicle control 101 248024 1154618 21. 48 c. / Retenolite, '
40mg/kg/曰 204 86319 923261 9. 35  40mg / kg / 曰 204 86 319 923 261 9. 35
ナツシロキ "タ抽出物  Fever extract
222mg/kg/日 305 2307 950363 0. 24  222 mg / kg / day 305 2307 950 363 0. 24
[0060] ナツシロギク抽出物 222mgZkgZ日投与群において肺への転移面積が最も小さ ぐ転移巣面積の割合はわずか 0. 24%であった。ノ ルテノライド 40mgZkgZ日投 与群においても肺への転移抑制効果が見られた力 ナツシロギク抽出物 222mgZk gZ日投与群よりも効果が劣っており、転移巣面積の割合は 9. 35%であった。一方 、ビヒクル対照群においては転移巣面積の割合は 21. 48%であった。ナツシロギク 抽出物中のパルテノライド含量を 0. 9%とすると、ナツシロギク抽出物 222mgZkgZ 日という投与量はノルテノライド 2. Omg/kg/日に相当する。この実験においても 抽出物を経口投与した場合に顕著な腫瘍転移抑制効果が得られることがわ力つた。 実施例 3 [0060] In the feverfew extract 222 mgZkgZ day-administered group, the ratio of the metastatic area with the smallest lung metastasis area was only 0.24%. The effect of inhibiting metastasis to the lungs was also observed in the group given the 40 mg ZkgZ daily dose of northenolide. On the other hand, in the vehicle control group, the ratio of the metastatic area was 21.48%. If the content of parthenolide in feverfew extract is 0.9%, the dose of feverfew extract 222 mgZkgZ days corresponds to nortenolide 2. Omg / kg / day. In this experiment, it was also found that when the extract was administered orally, a remarkable tumor metastasis inhibitory effect was obtained. Example 3
[0061] ¾ 列 3 :ナツシロギク抽出物およびパルテノライ の原 縮小効菜 [0061] ¾ Row 3: Feverfew extract and parthenola
,験方法および材料  Test methods and materials
ナツシロギク抽出物およびパルテノライドは実施例 1および 2と同じものを使用した。 動物への投与方法も実施例 1および 2と同じであった。投与量はナツシロギク抽出物 222mg/kg/日、パルテノライド 40mgZkgZ日とし、ビヒクル対照群には 0. 5w/ v%メチルセルロース水溶液を与えた。使用動物も実施例 2と同じであり、一群につき 8匹を使用した。  The feverfew extract and parthenolide were the same as in Examples 1 and 2. The method of administration to animals was also the same as in Examples 1 and 2. The dosage was feverfew extract 222 mg / kg / day, parthenolide 40 mg ZkgZ day, and the vehicle control group was given 0.5 w / v% methylcellulose aqueous solution. The animals used were the same as in Example 2, and 8 animals were used per group.
[0062] 使用動物はォスの C3H/HeN Sicマウス(三協ラボサービス株式会社)であり、 3週齢 、体重 10〜14gのものを馴化して 5週齢で実験に使用した。実験期間中は動物に固 形飼料 MF (オリエンタル酵母株式会社製)およびフィルター滅菌した水道水を自由 に与えた。  [0062] The animal used was a male C3H / HeN Sic mouse (Sankyo Lab Service Co., Ltd.), which was conditioned at 3 weeks of age and weighing 10 to 14 g and used in the experiment at 5 weeks of age. During the experiment period, animals were given solid feed MF (Oriental Yeast Co., Ltd.) and filter-sterilized tap water freely.
[0063] 腫瘍モデルの作製は実施例 2と同じ方法で行った。腫瘍モデルを作製した後、 1日 1回ナツシロギク抽出物、ノ ルテノライドおよびビヒクルを経口投与し、腫瘍細胞移植 2週間後より 33日目まで、 1週間に 3回腫瘍サイズ (長径および短径)をノギス (CD-I 5PS, Mitutoyo)で計測し、腫瘍体積を算出した。体積は楕円球体と仮定し、下式にて 算出した: [0063] The tumor model was prepared in the same manner as in Example 2. After the tumor model was created, feverfew extract, nortenolide and vehicle were orally administered once a day, and the tumor size (major axis and minor axis) was changed three times a week from 2 weeks to the 33rd day after tumor cell transplantation. Vernier caliper (CD-I The tumor volume was calculated using 5PS, Mitutoyo). The volume was assumed to be an ellipsoidal sphere and was calculated using the following formula:
腫瘍体積 = 4Ζ3 π (短径 Z2x短径 Z2x長径 Z2)  Tumor volume = 4Ζ3 π (minor axis Z2xminor axis Z2xmajor axis Z2)
[0064] 薩菓 [0064] Confectionery
実験結果を図 2に示す。ナツシロギク抽出物 222mgZkgZ日投与群において原 発巣腫瘍体積の増加が最も抑制され、 26日目あたりから顕著な効果が出始め、 33 日目においてナツシロギク抽出物 222mgZkgZ日投与群ではビヒクル対照群の原 発巣腫瘍体積の約 40%であった。ノ ルテノライド 40mgZkgZ日投与群においては ビヒクル対照群との有意差は見られな力つた。ナツシロギク抽出物中のノ ルテノライド 含量を 0. 9%とすると、ナツシロギク抽出物 222mg/kg/日という投与量はバルテ ノライド 2. OmgZkgZ日に相当する。この実験においても抽出物を経口投与した場 合に顕著な原発巣体積減少効果が得られることがわ力つた。  Figure 2 shows the experimental results. In the feverfew extract 222 mg ZkgZ day-administered group, the increase in the primary tumor volume was most suppressed, and a marked effect began to appear around day 26. About 40% of the nest tumor volume. In the group treated with nortenolide 40 mg ZkgZ, no significant difference was observed from the vehicle control group. If the content of nortenolide in the feverfew extract is 0.9%, the dose of feverfew extract 222 mg / kg / day corresponds to the date of barthenolide 2. OmgZkgZ. In this experiment as well, it was found that when the extract was orally administered, a significant primary volume reduction effect was obtained.
実施例 4  Example 4
[0065] 実施例 4:ナツシロギク抽出物投与群の体重変化とシスブラチン投与群の体重変化 の比較  [0065] Example 4: Comparison of body weight change in feverfew extract administration group and body weight change in cisbratine administration group
実,験方法および材料  Fruits, test methods and materials
ナツシロギク抽出物は HANDA FINE CHEMICALS社製の Feverfew Extract (バッチ 番号: 051016— 107)を使用した。この抽出物中のパルテノライド含量は約 0. 9% であった。ナツシロギク抽出物を 0. 5wZv%メチルセルロース水溶液中に溶解して 動物に金属製ゾンデを用いて経口投与した(1日 1回、投与体積 lOmLZkgZ回)。 ナツシロギク抽出物の投与量は 222mgZkgZ日および 888mgZkgZ日とした。シ スプラチンとしては 0. 5mg/mlの注射剤を、動物の体重を基に必要量を算出して 投与した。シスブラチン投与量は lOmgZkgとし、注射針(26G、テルモ社製)および 注射筒(lmL容量、テルモネ土製)を用いて腹腔内注射した。ビヒクル対照群には 0. 5 wZv%メチルセルロース水溶液を経口投与した。各実験あたりの動物数は 10匹とし た。  Feverfew Extract (batch number: 051016-107) manufactured by HANDA FINE CHEMICALS was used as the feverfew extract. The content of parthenolide in this extract was about 0.9%. The feverfew extract was dissolved in 0.5 wZv% methylcellulose aqueous solution and orally administered to the animals using a metal sonde (once daily, administration volume lOmLZkgZ times). The dosage of feverfew extract was 222 mgZkgZ days and 888 mgZkgZ days. As cisplatin, 0.5 mg / ml injection was administered after calculating the necessary amount based on the body weight of the animals. The cisbratin dose was lOmgZkg, and intraperitoneal injection was performed using an injection needle (26G, manufactured by Terumo Corporation) and a syringe (1 mL capacity, manufactured by Terumone Soil). The vehicle control group was orally administered with 0.5 wZv% methylcellulose aqueous solution. The number of animals per experiment was 10.
[0066] 使用動物はォスの C3H/HeN Sicマウス(三協ラボサービス株式会社)であり、 3週齢 、体重 9. 9〜13. 8gのものを馴化して 4週齢で実験に使用した。実験期間中は動物 に固形飼料 MF (オリエンタル酵母株式会社製)およびフィルター滅菌した水道水を 自由に与えた。 [0066] The animals used were Os C3H / HeN Sic mice (Sankyo Lab Service Co., Ltd.), which were used for experiments at the age of 3 weeks and acclimated to weights from 9.9 to 13.8 g. did. Animals during the experiment Solid feed MF (manufactured by Oriental Yeast Co., Ltd.) and filter-sterilized tap water were freely given.
[0067] 腫瘍モデルを以下のようにして作製した。 4週齢のあら力じめ除毛したマウスの背部 に lxlO5個(100 L中)のマウス腫瘍細胞(骨肉腫細胞株の LM8細胞)を皮下注射 して腫瘍モデルを作製した。腫瘍モデルを作製した後、最長で 6週間にわたり 1日 1 回ナツシロギク抽出物およびビヒクルを経口投与し、各動物の体重を測定し、生存率 を算出した。シスブラチンは腫瘍モデル作製 1週間後に腹腔内投与を行った。 [0067] A tumor model was prepared as follows. A tumor model was prepared by subcutaneously injecting 5 lxlO (in 100 L) mouse tumor cells (LM8 cells of an osteosarcoma cell line) into the back of a 4-week-old mouse that had undergone intensive hair removal. After the tumor model was created, feverfew extract and vehicle were orally administered once a day for a maximum of 6 weeks, and the weight of each animal was measured to calculate the survival rate. Cisbratin was administered intraperitoneally one week after the tumor model was prepared.
[0068] 薩菓 [0068] Confectionery
実験結果を図 3に示す。シスブラチン投与群では、対照群と比較して投与後 6日目 以降体重の低下が見られ、実験期間終了時までその傾向が持続した。一方、ナツシ ロギク抽出物 888mgZkg投与群および 222mgZkg投与群では、対照群と比較し て体重の低下は見られな力つた。これらの結果から、ナツシロギク抽出物は副作用が なぐあるいはあったとしてもごく僅かであると考えられ、安全性が高いことがわ力つた  Figure 3 shows the experimental results. In the cisbratin-administered group, weight loss was observed after the 6th day of administration compared to the control group, and this tendency continued until the end of the experimental period. On the other hand, in the feverfew extract 888 mgZkg and 222 mgZkg groups, there was no significant decrease in body weight compared to the control group. These results indicate that feverfew extract has few or no side effects and is highly safe.
実施例 5 Example 5
[0069] 実施例 5:ナツシロギク抽出物投与群の生存率とシスブラチン投与群の生存率の比 実,験方法および材料  [0069] Example 5: Ratio of survival rate of feverfew extract administration group to survival rate of cisbratine administration group
実施例 4に記載したのと同じであつた。  Same as described in Example 4.
[0070] 薩菓 [0070] Confectionery
実験結果を図 4に示す。ナツシロギク抽出物 888mgZkg投与群では、 42日間に わたり生存率の有意な低下は認められな力つた。ナツシロギク抽出物 222mgZkg投 与群でも生存率の低下がよく抑えられ、 42日目の生存率は 0. 7であった。一方、シ スプラチン投与群では、 40日目に生存率が 0. 4となり(この時点で対照群の生存率 と同じ)、ナツシロギク抽出物投与群よりも生存率が低力つた。  Figure 4 shows the experimental results. In the feverfew extract 888 mgZkg group, there was no significant decrease in survival rate over 42 days. Even in the feverfew extract 222 mgZkg group, the decrease in survival rate was well suppressed, and the survival rate on day 42 was 0.7. On the other hand, the survival rate in the splatin group was 0.4 on day 40 (same as the control group at this point), and the survival rate was lower than that in the feverfew extract group.
[0071] これらの結果より、ナツシロギク抽出物は、腫瘍動物の生存率の低下を極めて効果 的に抑制することがわ力つた。シスブラチンの毒性および副作用を考慮すると、ナツ シロギク抽出物と同程度あるいはそれ以上の腫瘍抑制効果を狙って大量に投与する ことができない。し力も、シスブラチンは高価である。一方、ナツシロギク抽出物は、実 施例 4に示すように安全性が高ぐし力も腫瘍抑制効果が優れている。さらにナツシロ ギク抽出物は経口投与にて優れた腫瘍抑制作用を発揮する。そのうえナツシロギク 抽出物はシスブラチン等の抗癌剤よりもずっと安価である。これらの点も考慮すると、 ナツシロギク抽出物は従来の抗癌剤にはな 、優れた効果および有用性を有すると!ヽ える。 [0071] From these results, the feverfew extract has been shown to extremely effectively suppress the decrease in the survival rate of tumor animals. Considering the toxicity and side effects of cisbratine, administer a large amount for tumor suppression effect equivalent to or better than feverfew extract I can't. However, cisbratine is expensive. On the other hand, as shown in Example 4, feverfew extract is highly safe and has an excellent tumor suppression effect. Moreover, feverfew extract exhibits an excellent tumor suppressive effect when administered orally. In addition, feverfew extract is much cheaper than anticancer drugs such as cisbratine. Considering these points, feverfew extract is considered to have excellent effects and usefulness that are not found in conventional anticancer agents!
産業上の利用可能性 Industrial applicability
本発明は、健康食品の分野および医薬品の分野等において有用である。  The present invention is useful in the fields of health foods and pharmaceuticals.

Claims

請求の範囲 The scope of the claims
[I] キク科植物の抽出物を含有する、腫瘍を抑制するための飲食物。  [I] A food and drink for suppressing tumors, which contains an extract of an Asteraceae plant.
[2] キク科植物がナツシロギクである、請求項 1記載の飲食物。 [2] The food and drink according to claim 1, wherein the Asteraceae plant is feverfew.
[3] 腫瘍が転移性のものである、請求項 1または 2記載の飲食物。  [3] The food or drink according to claim 1 or 2, wherein the tumor is metastatic.
[4] サプリメントである、請求項 1〜3のいずれか 1項記載の飲食物。 [4] The food or drink according to any one of claims 1 to 3, which is a supplement.
[5] キク科植物の抽出物を含有する、腫瘍を抑制するための医薬組成物。 [5] A pharmaceutical composition for suppressing a tumor, comprising an extract of an Asteraceae plant.
[6] キク科植物がナツシロギクである、請求項 5記載の医薬組成物。 6. The pharmaceutical composition according to claim 5, wherein the Asteraceae plant is feverfew.
[7] 腫瘍が転移性のものである、請求項 5または 6記載の医薬組成物。 7. The pharmaceutical composition according to claim 5 or 6, wherein the tumor is metastatic.
[8] キク科植物の抽出物を摂食することを特徴とする、腫瘍を抑制する方法。 [8] A method for suppressing a tumor, which comprises feeding on an extract of an Asteraceae plant.
[9] キク科植物の抽出物が飲食物またはサプリメントとして提供される、請求項 8記載の 方法。 [9] The method according to claim 8, wherein the extract of the Asteraceae plant is provided as a food or drink or a supplement.
[10] キク科植物がナツシロギクである、請求項 8または 9記載の方法。  [10] The method according to claim 8 or 9, wherein the Asteraceae plant is feverfew.
[II] 腫瘍が転移性のものである、請求項 8ないし 10のいずれか 1項記載の方法。  [II] The method according to any one of claims 8 to 10, wherein the tumor is metastatic.
[12] キク科植物の抽出物を患者に投与することを特徴とする、患者における腫瘍の抑制 方法。  [12] A method for suppressing a tumor in a patient, comprising administering an extract of an Asteraceae plant to the patient.
[13] キク科植物がナツシロギクである、請求項 12記載の方法。  13. The method according to claim 12, wherein the Asteraceae plant is feverfew.
[14] 腫瘍が転移性のものである、請求項 12または 13記載の方法。  [14] The method of claim 12 or 13, wherein the tumor is metastatic.
[15] 腫瘍の抑制のための飲食物の製造における、キク科植物の抽出物の使用。  [15] Use of an extract of Asteraceae in the manufacture of food and drink for tumor suppression.
[16] 飲食物がサプリメントである請求項 15記載の方法。  16. The method according to claim 15, wherein the food or drink is a supplement.
[17] キク科植物がナツシロギクである、請求項 15または 16記載の方法。  [17] The method according to claim 15 or 16, wherein the Asteraceae plant is feverfew.
[18] 腫瘍が転移性のものである、請求項 15ないし 17のいずれか 1項記載の方法。  18. The method according to any one of claims 15 to 17, wherein the tumor is metastatic.
[19] 腫瘍の抑制のための医薬組成物の製造における、キク科植物の抽出物の使用。  [19] Use of an extract of Asteraceae in the manufacture of a pharmaceutical composition for tumor suppression.
[20] キク科植物がナツシロギクである、請求項 19記載の方法。  20. The method according to claim 19, wherein the Asteraceae plant is feverfew.
[21] 腫瘍が転移性のものである、請求項 19または 20記載の方法。  [21] The method of claim 19 or 20, wherein the tumor is metastatic.
PCT/JP2006/322571 2006-07-14 2006-11-13 Food, drink and medicinal composition having antitumor effect WO2008007450A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP2006549204A JPWO2008007450A1 (en) 2006-07-14 2006-11-13 Food / drink and pharmaceutical composition having tumor suppressive action

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2006194119 2006-07-14
JP2006-194119 2006-07-14

Publications (1)

Publication Number Publication Date
WO2008007450A1 true WO2008007450A1 (en) 2008-01-17

Family

ID=38923023

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2006/322571 WO2008007450A1 (en) 2006-07-14 2006-11-13 Food, drink and medicinal composition having antitumor effect

Country Status (2)

Country Link
JP (1) JPWO2008007450A1 (en)
WO (1) WO2008007450A1 (en)

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001045699A1 (en) * 1999-12-23 2001-06-28 Advanced Research And Technology Institute, Inc. Use of parthenolide to inhibit cancer
WO2002040017A1 (en) * 2000-11-15 2002-05-23 National University Of Singapore Cancer chemotherapeutical and chemopreventive agent
JP2002518456A (en) * 1998-06-25 2002-06-25 カート・ヘンドリクス Dietary supplements to support normal cerebrovascular conditions
WO2004093518A2 (en) * 2003-04-16 2004-11-04 The University Of Mississippi Immunostimulatory agents in botanicals
JP2004352626A (en) * 2003-05-28 2004-12-16 Asahi Breweries Ltd Anticholesterol agent containing plant-derived component
JP2005035951A (en) * 2003-07-17 2005-02-10 Akira Nai Inhibitor of tumor metastasis
JP2005538161A (en) * 2002-09-09 2005-12-15 ジョンソン・アンド・ジョンソン・コンシューマー・カンパニーズ・インコーポレイテッド Composition containing feverfew extract and method of use thereof

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2002518456A (en) * 1998-06-25 2002-06-25 カート・ヘンドリクス Dietary supplements to support normal cerebrovascular conditions
WO2001045699A1 (en) * 1999-12-23 2001-06-28 Advanced Research And Technology Institute, Inc. Use of parthenolide to inhibit cancer
WO2002040017A1 (en) * 2000-11-15 2002-05-23 National University Of Singapore Cancer chemotherapeutical and chemopreventive agent
JP2005538161A (en) * 2002-09-09 2005-12-15 ジョンソン・アンド・ジョンソン・コンシューマー・カンパニーズ・インコーポレイテッド Composition containing feverfew extract and method of use thereof
WO2004093518A2 (en) * 2003-04-16 2004-11-04 The University Of Mississippi Immunostimulatory agents in botanicals
JP2004352626A (en) * 2003-05-28 2004-12-16 Asahi Breweries Ltd Anticholesterol agent containing plant-derived component
JP2005035951A (en) * 2003-07-17 2005-02-10 Akira Nai Inhibitor of tumor metastasis

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
CALTAGIRONE S. ET AL.: "Flavonoids apigenin and quercetin inhibits melanoma growth and metastatic potential", INT. J. CANCER, vol. 87, no. 4, 2000, pages 595 - 600, XP003020508 *
WU C. ET AL.: "Antiproliferative Activities of Parthenolide and Golden Feverfew Extract Against Three Human Cancer Cell Lines", JOURNAL OF MEDICINAL FOOD, vol. 9, no. 1, March 2006 (2006-03-01), pages 55 - 61, XP003020507 *

Also Published As

Publication number Publication date
JPWO2008007450A1 (en) 2009-12-10

Similar Documents

Publication Publication Date Title
JP2008542300A (en) Compositions and methods for preventing and treating conditions associated with inflammation
WO2006033412A1 (en) Alleviator for radiation disorder
JP3988168B1 (en) Composition having brain cell activity effect by ginkgo biloba leaf nanoparticle
US20180353540A1 (en) Pharmaceutical composition for treating leukemia and preparation method thereof
CN107569608B (en) Pharmaceutical composition for reducing blood sugar
KR101731859B1 (en) A composition for the prevention or treatment of abnormal weight loss comprising Citrus Unshiu Peel extract
KR101989739B1 (en) Composition for preventing or treating diabetes mellitus comprising Rorippa globosa extracts
WO2008010335A1 (en) Plant extract having arthritis-preventive effect
WO2014134833A1 (en) Edible composition, preparation method therefor, and food product comprising the composition
KR101898891B1 (en) Composition for Suppressing Side effects of Apoptosis-inducing Anti-cancer Drugs Using Ginsenoside Compound K
WO2011095095A1 (en) Medicinal composition comprising alcohol-soluble and water-insoluble licorice extract, pharmaceutical preparation, pharmaceutical application, therapeutic method, and preparative method thereof
WO2008007450A1 (en) Food, drink and medicinal composition having antitumor effect
JP2016537428A (en) Ephedra arata extract and method of use
JP2003104901A (en) Composition for health promotion
KR20150018167A (en) A pharmaceutical composition comprising fermented Eastern prickly pear
CN112353837B (en) Flos puerariae extract and its use
WO2008075649A1 (en) Food or drink, quasi drug and medicinal composition for promoting hair growth and method of promoting hair growth
JP4681246B2 (en) Immunostimulator
JP2003286181A (en) Improving agent for constitution easily inducing atopic dermatitis
JPH02279629A (en) Antitumor agent adaptive to pulmonary carcinoma
CN104800686A (en) Medicine composition for treating overeating sequelae and preparation method and purpose of medicine composition
JP2016108265A (en) Persistent antioxidant
Kemper Shark cartilage, cat's claw, and other complementary cancer therapies
JP2004115420A (en) Therapeutic agent for bronchial tube and pulmonary disease and food and beverage containing the same
JP5233177B2 (en) Oral composition containing Anchu powder and Shigyakusan extract

Legal Events

Date Code Title Description
ENP Entry into the national phase

Ref document number: 2006549204

Country of ref document: JP

Kind code of ref document: A

121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 06823345

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

NENP Non-entry into the national phase

Ref country code: RU

122 Ep: pct application non-entry in european phase

Ref document number: 06823345

Country of ref document: EP

Kind code of ref document: A1