JPS6312848B2 - - Google Patents

Description

[Detailed description of the invention] The present invention relates to a novel anticancer agent.

Recently, cancer has become a major cause of death in humans, and therefore research and development of anticancer drugs is being actively carried out both in Japan and abroad. As a result, many anticancer drugs have been discovered and are now in clinical use, but they have not yet been able to completely treat cancer.

The present inventors conducted various studies to obtain an anticancer agent, and as a result, they discovered an anticancer agent with excellent effects and almost no toxicity.

That is, the present invention relates to an anticancer agent comprising a shark liver extract having an iodine value of 385 or more and a boiling point of about 350° C. or more (30 mmHg).

The anticancer agent of the present invention is an extract from shark liver. Target sharks include all sharks,
In other words, it refers to the Elasmobranchii, excluding middle rays. Examples of sharks include Squalidae, such as Centrophorus and Acanthidium.
elegantia), Lepidorhinus (Lepidorhinus
foliaceus), tallow shark (Centrophorus aus),
Catulidae, such as Parmaturus pilosus; carcharidae, such as Carcharias owstoni; Echinoshinidae, such as Echinorhinus brucus; among these, the merganser shark is particularly preferred.

In producing the anticancer agent of the present invention, the liver is removed from these sharks, the contents of the liver are fractionally distilled, and then treated with a solvent. As an example of the manufacturing method, for example, at about 300℃ (30mmHg) for about 30 minutes to about 90 minutes
Heat for about 30 minutes to about 90 minutes at about 330℃ (30mmHg), saponify to remove unsaponifiables,
It is then heated to about 350° C. (30 mm Hg) and the distillate is treated with an organic solvent such as ethanol to remove impurities and then the organic solvent is removed. The iodine value of the obtained extract is 385 or more, preferably 385 to 395
It is. The calculated value of the iodine value of squalene contained in the liver of sharks is 371.1, and past literature values are 340-380, but compared to this, the iodine value of this extract is extremely high. Extracts with a high iodine value of 385 or higher have a more significant anticancer effect than extracts with a lower iodine value. Other physical properties of this extract include, for example, n ²⁵ _D 1.494 and acid value 0.02 to 0.01. In addition, the boiling point of this extract is approximately 350℃ at 30mmHg.
The temperature is preferably about 350 to 370°C.

The anticancer agent of the present invention can enhance the host organism's resistance to cancer, and its therapeutic effect is extremely excellent. Furthermore, the anticancer agent of the present invention has extremely low toxicity. In other words, the acute toxicity in rats is LD ₅₀ of 35 g/Kg or more when administered orally.
No adverse effects were observed pathologically or histopathologically when 8 g/Kg was orally administered to rats every day for one consecutive month. Such low toxicity has never been seen with conventional anticancer drugs.

The anticancer agent of the present invention is effective when administered orally or parenterally, but the effect is particularly remarkable when administered orally. For oral administration, various conventional dosage forms for oral administration can be used, and for example, those encapsulated in soft gelatin capsules can be used. The unit dosage form for oral administration of the anticancer agent of the present invention is 50 to 500 mg of the active ingredient, that is, an iodine value of 385 or higher and a boiling point of approximately 350°C or higher (30 mm
Examples include shark liver extracts of Hg) encapsulated in capsules. For example, 300 to 1250 mg of the active ingredient is orally administered 1 to 3 times a day, depending on age and symptoms.

The anticancer agent of the present invention can enhance the anticancer effect when used alone or in combination with other anticancer agents or anticancer therapy.

The anticancer agent of the present invention has a more remarkable anticancer effect than conventionally used anticancer agents, has extremely low toxicity, has no side effects even when used repeatedly, and has extremely high practical value.

Examples regarding anticancer effects are shown below.

Example 1 200,000 leukemia cells L-5178Y were planted in RPMI1640 medium, and the boiling point extracted from the liver of a shark was added to the RPMI1640 medium.
An extract of 350-370°C (30 mmHg) and an iodine value of 386 was added at 500 γ/ml. After 48 hours of addition, the number of proliferating cells on the supplemented medium was compared to that on the unsupplemented medium. As a result, the number of proliferating cells in the non-supplemented medium was 1,190,000, while that in the supplemented medium was 488,000, indicating an inhibition rate of 59%.

Example 2 9.7 million cells of Sarcoma 180 were subcutaneously transplanted into 10 ICR mice (female). 24 hours after transplantation, boiling point 350 ~
85 mg of the liver extract of merganser liver at 370° C. (30 mmHg) and an iodine value of 388 was administered orally or intraperitoneally to each mouse once a day for 10 days.

Four weeks after sarcoma cell transplantation, mouse sarcoma 180
A solid tumor was cut out, its weight was measured, and its tumor growth inhibition rate was determined.

In this experiment, a tumor growth inhibition rate of 48.2% was obtained by oral administration and 31.7% by intraperitoneal administration.

On the other hand, PS-K, which is used as an anticancer drug,
The experiment described above was repeated, except that 500 mg/Kg was orally administered once a day for 10 days. The tumor growth inhibition rate in this case was 7.8%. Therefore, the anticancer agent of the present invention is far more effective than conventional anticancer agents.

Example 3 20 BDF ₁ mice (female) were divided into 2 groups, and each group (10 mice) was given a boiling point of 350 to 370°C (30 mm
Hg) and iodine value 386 liver shark liver extract was orally administered at a dose of 8.5 mg per mouse once a day for 5 days.
Next, 100,000 leukemia cells L-1210 were intraperitoneally transplanted into each animal in both groups, and 24 hours later, the whole body was irradiated with 600 rad of radiation.

Next, to the group that received the merganser liver extract,
For another 5 days, the same amount of the same amount of the same amount of the same liver extract as before was orally administered.

The average survival time for the group receiving only radiation was
It was 9.33 days, whereas it was 12.51 days in the group that was also administered with the liver extract of Merganser liver extract.

Example 4 BDF ₁ 10 mice (female) were given a boiling point of 350 to 370°C.
(30 mmHg) and an iodine value of 386, the liver extract of merganser liver was administered orally every other day in an amount of 85 mg per mouse. After 3 administrations, Lewis lung cancer was subcutaneously transplanted into the spinal column 24 hours later.

1 mouse every other day 24 hours after transplantation
It was orally administered 5 times at a dose of 85 mg per animal.

Mice treated with shark liver extract showed a 143% longer survival rate than mice not treated with it.

Comparative Example 1 A boiling point of 350-370℃ (30
The method described in Example 2 was repeated, except using a crab liver extract with an iodine value of 376 mmHg) and an iodine value of 376. The tumor growth inhibition rate in this case was 38.2%.

Comparative Example 2 Boiling point 330-345℃ (30
mmHg) and iodine value of 378.
The method described in Example 2 was repeated. The tumor growth inhibition rate in this case was 35.4%.

Example 5 Erhlich ascites carcinoma was intraperitoneally transplanted into 10 ICR mice (female), and the boiling point was 350-370 from 24 hours after transplantation.
C. (30 mmHg) and an iodine value of 386, 0.1 ml/mouse of the liver extract of merganser liver was orally administered daily for 15 days.

Mice given merganser liver extract had a 71% longer survival rate than mice not given the drug.

Claims (1)

[Claims] 1. An anticancer drug consisting of a shark liver extract with an iodine value of 385 or higher and a boiling point of approximately 350°C or higher (30 mmHg).