JPS5832823A - Cancer eliminating agent - Google Patents

Abstract

PURPOSE:A cancer eliminating agent containing a vitamin D having no hydroxyl group at the 1alpha-positon as an active constitutent. CONSTITUTION:A cancer eliminating agent containing a vitamin D as an active constituent. The vitamin D has a very powerful differentiation inducing ability against the human myelocytic leukemia HL-60 call in a low concentration. Vitamin D2, vitamin D3, 25-hydroxyvitamin D3, 2alpha-hydroxyvitamin D3, 2beta-hydroxyvitamin D3 and the corresponding 5,6-trans derivatives, tachysterol, etc. may be cited as the vitamin D. 5, 6-cis-Vitamin D, tachysterol, etc. in the vitamin D derivative are prepared by the well-known method. The 5, 6-trans-vitamin D is obtained by reacting the corresponding 5, 6-cis-vitamin D with iodine in an inert solvent. The aimed substance is formulated into a desired form by the conventional method and administered. The dose thereof is 20pg-10mug/ml, and administered as a soft capsule, etc.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a cancer-removal agent containing vitamin Ds as an active ingredient.

As a result of recent research on the isolation of metabolic products of vitamin b1 and the metabolic pathway of vitamin b1 by DeLuca and Kodicek et al., 25-hydroxyvitamin D3.1α and 25-dihydroxyvitamin n3 were found as metabolites.
, lαr24.25- trihydroxyvitamin D3
Vitamin Ds such as these have come to be known. It is well known that these metabolites and the many derivatives that were subsequently synthesized promote the ability to transport calcium from the intestinal tract and the ability to mobilize bone minerals, and are useful as therapeutic agents for various diseases based on abnormalities in calcium metabolism. ing.

The present inventors conducted separate research on the drug 111j effects of these vitamin Ds, and found that, surprisingly, without exception, most vitamin Ds were found to be effective against human myeloid leukemia HL-60 cells. We discovered an extraneous fact that it has a very strong ability to induce differentiation into macrophages. This person's ability to induce differentiation into cancer cells has nothing to do with the previously known effects of vitamin N 1F (4) on regulating calcium metabolism, and vitamin D, such as 9.1 - This is a property unique to compounds having a secoergostane skeleton.The present invention was completed through further research based on this new knowledge, and excludes vitamin D derivatives (however, vitamin I having a hydroxyl group at the 1α position) derivatives. ) is an invention for cancer removal and removal as an active ingredient.

In the present invention, vitamin Ds are, for example, compounds having a 9,1°-secocholestane skeleton and a 9,10-seconylgostane skeleton, specifically vitamin D2, vitamin D3.25-hydroxyvitamin D3.25-hydroxy Vitamin D2.22-dehydro25-and droxyvitamin D3.24.25-dihydroxyvitamin D3.24-hydroxyvitamin D3.25.26-dihydroxyvitamin D3.24-oxovitamin C,2
5-Hydroxy-24-oxovitamin D3.24.2
4-difluoro-25-hydroxyvitamin D3,24
-Fluoro-25-hydroxyvitamin D3.2α-hydroxyvitamin D3.2β-hydroxyvitamin D3
．． 1β-hydroxyvitamin D3.1β, 25-dihydroxybizy9,10-secocholester-5(10), ?
-Diene-3β, 25-diol, etc. are praised.

Among these vitamin D derivatives, 5,6-cis vitamin Ds, tachysterols, and dihydrotachysterols are all known compounds, such as those disclosed in JP-A-5O-4.
osSt No. 50-100043, No. 50-100
No. 04.4, No. 51-26858, No. 51-2685
No. 9, No. 51-100055, No. 54-63058, No. 54-3-103855, No. 55-11460, No. 55-72
No. 185, No. 55-76858, No. 56-22763
No. 3,565,924, US Pat. No. 3,585,221, US Pat. No. 3,607,888, US Pat. No. 3,702,810, US Pat.
It is manufactured according to the description in each patent publication of No. 5374 and No. 3739001. Note that 5,6-transvitamin T) 61 contains some new compounds, which can be easily obtained by treating the corresponding 5,6-cis vitamin D with iodine in an inert solvent. .

These compounds of the present invention are formulated and administered in a desired form according to conventional methods. The dose is extremely small, and the blood concentration varies depending on the compound, but is 20p2 to 10μf/rttl.
It is effective and can be administered as a soft capsule.

Experimental example "'ji" 1 part human bone complement leukemia HT, -60 cells suspended in RPMI-1640 medium (medium containing penicillin and streptomycin, supplemented with 10% FBS)/d concentrated f
Dispense 0.1 to each of the four parts of a Falcon Microtest Plate-4 (96-well flat bottom) at 37°C.
The mixture was incubated overnight in an air:carbon dioxide (95:5) stream. The next day, the ethanol and solution of each sample was added to RPMI-1.
The solution was diluted 40 times with 640 medium, and then diluted stepwise by 4 times to prepare solutions with 5 concentrations, and 0.1 ml of each solution was added to each of the four parts of the microplate. 37℃
After culturing for 3 days in an air: carbon dioxide (Umame 95:5) airflow with dust incorporation, the cells extending on the bottom of each four parts were observed under an inverted phase contrast microscope, and the adherent cells were observed. The minimum effective dose of each analyte was determined as an index. The results are shown in the table below for Example 1゜0. D, O (manufactured by Nisshin Oil Co., Ltd., triglyceride of medium chain fatty acids) 60? 25-hydroxyvitamin D3”, (]
After adding 391 ng of sorbic acid as a stabilizer, soft capsules containing 25-hydroxyvitamin D3'fI: 1.0 μm per capsule were prepared using a gelatin-coated soft capsule machine according to a conventional method. Manufactured.

Example 2゜In place of 25-hydroxyvitamin D3 in Example 1, Il:61't)-6,19-evidioxy-9゜1
0-secocholester-5(10), 7-ginine-3β
.

[6R)-6,19-evidioxy-9 per capsule was prepared in the same manner using 25-diol 1.0'Q k.
, 10-secocholester-5(10), 7-renin-3
β,25-diol 1.0μ? Soft capsules containing the following ingredients were obtained.

Applicant: Chugai Pharmaceutical Co., Ltd. 17 = Procedural amendment (spontaneous) September 2-3, 1980 Commissioner of the Japan Patent Office Shima 1) Mr. Haruki ■, Indication of the case 1982 Patent 1ifi No. 129426 2, Invention Name Decancer Drug 3, Relationship with the Amendment Case Patent Applicant 5-5-1 Ukima, Kita-ku, Tokyo (331) Chugai Pharmaceutical Co., Ltd. Representative Kimio Ueno Detailed description of the invention in the specification Column 6, Supplementary 0 contents Delete 1- as shown in the attached sheet.

Procedural amendment (formality) %formula%) 1.Display of the incident 1981 Patent Application No. 129426 2. Name of the invention cancer removal agent 3. Person who makes corrections Relationship to the case Patent applicant 5-5-1 Ukima, Kita-ku, Tokyo (331) Chugai Pharmaceutical Co., Ltd. Representative Kimio Ueno 4. Agent 3-41-8 Takada, Toshima-ku, Tokyo Inside Chugai Pharmaceutical Co., Ltd. January 5, 1982 (Shipping date: January 2611, 1982) 6. Subject of correction Specification 7. Contents of correction As per attached sheet Specification 1j (no change in content) 156-

Claims (1)

[Claims] A cancer removal agent containing vitamin D'M (excluding vitamin D derivatives having a hydroxyl group at the 1α position) as an active ingredient.