JP2002053481A - Anti-malignant tumor agent - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an effective anti-malignant tumor agent, carcinostatic agent or anticancer agent, capable of being orally ingested and having extremely high safety. SOLUTION: This anti-malignant tumor agent contains an extract of Rhinacanthus nasutus (L) Kurz with water and/or an organic solvent as a principal ingredient. The anti-malignant tumor agent has excellent anti-malignant tumor activities and no side effect, and is useful for inhibiting and preventing the cancer. Therefore, the anti-malignant tumor agent can be daily orally ingested, and is expected to have a wide use as a raw material for a medicine and a food with extremely high safety.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to an anticancer agent, an anticancer agent,
It relates to an anticancer agent. More specifically, the present invention relates to a novel anti-neoplastic agent, anti-cancer agent, and anti-cancer agent containing an extract of Hakutsuru Reishi as a main component.

[0002]

2. Description of the Related Art Anti-neoplastic, anti-cancer and anti-cancer drugs have been selected to act selectively on tumor cells and have relatively low toxicity to normal cells, but leukopenia due to myelosuppression, Fatal side effects such as thrombocytopenia and neutropenia, side effects of gastrointestinal disorders such as nausea and vomiting, and side effects such as hair loss, development of drug resistance,
In addition, since many drugs are difficult to administer orally, many problems in use such as restriction of the administration route remain unsolved. Therefore, there is a need for an anti-neoplastic agent, an anti-cancer agent, and an anti-cancer agent that selectively act on tumor cells, have extremely low toxicity to normal cells, and have a limited administration route.

[0003] Rinacanthus n
Asuta (L.) Kurz) is an evergreen small shrub belonging to the genus Linakanthus, which is native to the Deccan Plateau in southern India. Known (“Primary Color Makino Kazoku Encyclopedia”, p.492, Hokuryukan, 1
988), mainly used in China and Taiwan, and more recently in Japan. Others
In a previous application filed by the present applicant, this white cranes Reishi has the ability to scavenge active oxygen (Japanese Patent Application Laid-Open No. 9-143091; active oxygen scavenger) and has an excretion promoting action (Japanese Patent No. 3077).
No. 019, excretion enhancer) and that it has a lipid peroxide inhibitory action (JP-A-2000-16945, lipid peroxide inhibitor). However, it is not known that the water and / or organic solvent extract of Hakutsuru Reishi has antineoplastic activity.

[0004]

Many of the therapeutic agents that destroy cancer cells not only kill cancer cells but also act on normal cells, so they have strong side effects and are often difficult to use orally. Therefore, there were many problems in use, such as the restriction of the administration route. The present inventors have solved the above problems,
Oral ingestion is possible, extremely safe, with the aim of providing an effective antineoplastic agent, anticancer agent, anticancer agent, as a result of intensive research, water or organic solvent extract of Hakutsuru Reishi, The present invention has been completed based on the finding that it has an excellent effect on malignant tumors, and has extremely safe anticancer and anticancer effects without side effects.

[0005]

SUMMARY OF THE INVENTION The present invention relates to an anti-neoplastic agent comprising a water and / or organic solvent extract of Hakutsuru Reishi as a main component. The antineoplastic agent of the present invention can be obtained by extracting Hakutsuru Reishi with water and / or an organic solvent and distilling off the extraction solvent from the extract.

[0006] As the Hakutsuru Reishi used in the present invention, commercially available leaves, whole plants, roots or stems or a mixture thereof can be used. Preferably they are sun-dried and / or drum-dried and crushed by a mill.
It is pulverized to a mesh or less, preferably 12 mesh or less. If necessary, this Hakutsuru Reishi is sun-dried and / or
Alternatively, a drum-dried product roasted by a roaster may be used.

In the present invention, the solvent used for extraction includes water and an organic solvent, and these can be used alone or as a mixture of two or more. Water includes tap water, deionized water, distilled water, and the like.

In the present invention, the organic solvent used for the extraction includes lower alcohols having 1 to 4 carbon atoms, aliphatic ketones having 3 to 4 carbon atoms, and the like.
Lower alcohols are preferred, and ethanol, methanol and the like are particularly preferred.

In the present invention, the extraction is carried out by adding a 5-fold to 50-fold amount of a solvent to the ground white crane, and leaving, shaking or stirring. Extraction temperature from 0 ° C to 130
Although it can be carried out at a temperature of 0 ° C., it is preferably carried out at a temperature from room temperature to 110 ° C. The time required for extraction depends on the temperature and the grinding condition of Hakutsuru Reishi, but usually ranges from 30 minutes to 6 hours.
About an hour.

After the extraction, the extract of Hakutsuru Reishi is obtained as a liquid having an odorless or slight aroma and a unique rich taste by using conventional means such as decantation, centrifugation, and filtration under reduced pressure. This may be used as it is, but preferably, it is purified by filtration, centrifugation, or another method, and further concentrated appropriately to obtain a concentrated extract of Hakutsuru Reishi, which may be used after heat sterilization. it can. Heat sterilization can be performed at a temperature of 60 ° C to 100 ° C.
It is preferable to carry out at a temperature of 5 ° C.

[0011] The above-mentioned heat-sterilized concentrated extract is further concentrated under reduced pressure to dryness, spray-dried, freeze-dried, or the like, and dried as a fine powder having an odorless or slight aroma and a unique rich taste. An extract is obtained, which may be used.

[0012] In addition to the Hakutsuru reishi extract of the present invention, if necessary, various components generally used in foods, quasi-drugs, pharmaceuticals, etc., ie, aqueous components, as long as the effects of the present invention are not impaired, By blending powder components, oils, surfactants, moisturizers, thickeners, antioxidants, fragrances, pigments, etc., foods mainly composed of Hakutsuru Reishi extract, quasi-drugs,
Various compositions such as pharmaceuticals can be manufactured.

Next, the present invention will be described more specifically with reference to examples and test examples, but the present invention is not limited to these examples.

EXAMPLE 1 1 kg of ground roasted Hakutsuru Reishi was extracted twice with 25 liters of hot water at 90 ° C. for 2 hours, and the obtained extracts were combined to obtain 55-60.
After concentrating to about 1/10 volume under reduced pressure at ℃, it is filtered under pressure.
The filtrate was sterilized by heating at 90 to 95 ° C. and concentrated to dryness under reduced pressure to obtain 310 g of Hakutsuru Reishi leaf hot water extract.

Example 2 1 kg of ground Hakutsuru Reishi root was crushed with 10 L of 90% ethanol.
For 2 hours under reflux for 3 hours.
After concentrating to about 1/10 under reduced pressure at 5 to 60 ° C, the mixture is filtered under pressure. The filtrate was heat-sterilized at 90 to 95 ° C., concentrated to dryness under reduced pressure, and 85.5 g of a white crane Reishi root 90% ethanol extract.
I got

[0015] The anti-malignant tumor effect of the Hakutsuru reishi extract of the present invention was evaluated by an in vivo antitumor activity test using mice and an in vitro cancer cell growth inhibitory activity test using prostate cancer and bladder cancer cell lines.

[Test Example] Test Example 1 Measurement of In Vivo Antitumor Activity 0.1 ml of the cell suspension of Sarcoma 180 was Jc
Implantation was performed into the right thigh muscle of 1-ICR mice (female, 4 weeks old). The number of each drug administration group, positive control group, and control group was 10 per group. The Hakutsuru Reishi extract was orally administered once a day for 14 days from 7 days before tumor implantation to 7 days after transplantation. The Hakutsuru Reishi leaf extract prepared in Example 1 and the Hakutsuru Reishi root extract prepared in Example 2 were each suspended in 0.5% CMC and administered at 500 mg / kg / day. As a positive control, Mitomycin C was intraperitoneally administered once a day for 7 days from the day after tumor implantation. M
Itomycin C is dissolved in sterile distilled water and 1mg / k
g / day was administered intraperitoneally. The dose volume is 1 body weight.
The volume was 0.1 ml per 0 g. On day 10 after tumor implantation, the mice were sacrificed, and the weight of each tumor was measured. Then, the average tumor weight of the drug-administered group and the control group was determined, and the tumor growth inhibition rate (IR) was determined by the following equation. IR (%) = [1− (average tumor weight of control group / average tumor weight of drug administration group)] × 100 Further, T-test was performed on the average tumor weight between the control group, the drug administration group, and the drug administration group, The case where the tumor weight was significantly reduced compared to the control group was regarded as effective. Table 1 shows the results. As is clear from Table 1, the tumor growth inhibition rate with respect to the control group was 52.5% in the Hakutsuru reishi root extract produced in Example 2, and 44.44 in the Hakutsuru reishi leaf extract produced in Example 1. 2%. Mito used as a positive control
The tumor growth inhibition rate of mycin C was 52.7%,
From these comparisons, a remarkable tumor growth inhibitory effect was confirmed for the Hakutsuru Reishi extract.

Test Example 2 Measurement of In Vitro Cancer Cell Growth Inhibitory Activity As an in vitro evaluation system, a prostate cancer cell line (5
637, KK47) and a bladder cancer cell line (PC-3, L
NCaP) was used to evaluate the inhibitory effect of Hakutsuru Reishi extract on cancer cell growth. Cancer cell line 5637, KK47, PC-
3 and LNCaP were placed in each well of a 96-well culture dish.
0 cells were inoculated, cultured in a culture solution containing a certain concentration of Hakutsuru Reishi extract, and the number of viable cells after a certain time was measured using Alamar Blue. The measurement results were totaled to evaluate the cancer cell growth inhibitory effect of the Hakutsuru Reishi extract. As a result, in each of the cell lines, the concentrations of the Hakutsuru Reishi leaf extract produced in Example 1 and the Hakutsuru Reishi root extract produced in Example 2 both ranged from 0.1 to 0.001%. In the culture days,
In the range from day 1 to day 5, a cell growth inhibitory effect was observed in a concentration- and time-dependent manner. When each concentration was 0.1%, the cancer cell growth inhibition rate was almost 100%.

From the above test results, it is clear that Hakutsuru Reishiba root and leaf extract show a marked inhibitory effect on malignant tumor growth. In addition, since the effect was observed by continuous administration before tumor transplantation, it was revealed that the antineoplastic agent of the present invention exerts a cell growth inhibitory effect by activating the immune function of the host.

No side effects such as weight loss were observed by continuous oral administration of the anti-neoplastic agent of the present invention, confirming that the anti-neoplastic agent of the present invention is a highly safe substance that can be taken orally. .

[0019]

Industrial Applicability The antineoplastic agent of the present invention has excellent antitumor activity and has no side effects, and is therefore useful for suppressing and preventing cancer. Therefore, the antineoplastic agent of the present invention can be taken orally on a daily basis, and is expected to be widely used as a highly safe drug and food material.

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Claims (1)

[Claims] 1. An antineoplastic agent comprising a water and / or organic solvent extract of Hakutsuru Reishi as a main component.