JPS60178818A - Pharmaceutical preparation of adriamycin - Google Patents

Abstract

PURPOSE:The pharmaceutical preparation having reduced cardiac toxicity induced by adriamycin, capable of manifesting its pharmaceutical effect sufficiently, obtained by blending adriamycin with an extract of crude drug having anti- oxidizing ability. CONSTITUTION:Adriamycin, an antitumor antibiotic, is blended with 0.01-2,000 times, preferably 0.1-500 times as much an extract of crude drug having anti- oxidizing ability as adriamycin by weight. An extract of crude drug selected from rosemary, sage, allspice, paprika, sesame, thyme, clove, ginger, nutmeg, Magnolia officinalis, and Schizandrae fructus is preferable as the extract of crude drug.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention is a novel drug aimed at alleviating cardiac dysfunction induced by adriamycin preparations, more specifically, the antitumor antibiotic adriamycin, and fully expressing its medicinal effects. Regarding adriamycin preparations.

Atriamycin is widely used as an excellent anti-Mm antibiotic, and depending on the method of application, it can cause cardiotoxicity, which has become a problem as a side effect.

The mechanism of cardiac toxicity caused by administration of adriamycin is presumed to be peroxidation of the lipid components that make up the cell membranes of the heart. Therefore, attempts have been made to pre-administer or simultaneously administer tocopherol, a free radical scavenger, as a method of preventing this peroxidation, but this method was not always satisfactory.

Furthermore, there is a report that when ascorbic acid, which is one of the antioxidants, is used in combination with adriamycin, the cardiac toxicity induced by adriamycin is significantly reduced (Japanese Patent Laid-Open No. 58-90512).

However, this method is not effective unless ascorbic acid or its salts are mixed 40 to 3,000 times as much as adriamycin, and is difficult or difficult to put into practical use.

As a result of various studies aimed at reducing the adriamycin-induced cardiac toxicity, the present inventor found that the combined use of a herbal medicine extract with antioxidant ability with adriamycin significantly reduces the cardiac toxicity induced by adriamycin. They discovered that it is possible to do this, and completed the present invention.

That is, the present invention provides an adriamycin preparation containing adriamycin and an extract of herbal medicine having antioxidant ability.

The herbal medicine extracts (hereinafter simply referred to as raw %% extracts) having antioxidant ability used in the present invention include allspice, anise (content: fennel), hasil, caraway, cardamom, cinnamon (cinnamon), clove ( Clove) coriander, fennel, garlic, ginger, radish, pepper, mustard, nutmeg, onion, hasher, pehar, saffron, rosemary, salvia , thyme, turmeric, vanilla, paprika, cloves, sesame, yokuinin, shibamei, chidatsu, schisandra, quince, raw materials, large quantities, sansho wholesale, peony skin, among others rosemary, Preferred are salvia, allspice, paprika, cloves, ginger, nutmeg, sesame, thyme, thick pear, and schisandra.

The crude drug extract is prepared by a conventional method by extraction using a solvent such as water, a hydrophilic organic heating medium, a hydrophilic organic heating medium containing water, other four solvents, or liquid edible oil or fat. Preferred solvents used for extracting crude drugs include:
Examples include ethanol, acetone, methanol, ethylene chloride, ethyl ether, propylene glycol, chrycerin, n-hexane, petroleum ether, petroleum benzene, water, and liquid edible fat blue, especially for safety and operability. From this point of view, ethanol, acetone, n-hexane, water, liquid edible fats and oils, etc. are preferable. These solvents can be used alone or in combination. For example, when using a mixed solution of a polar solvent and water, it is preferable that the concentration of the polar solvent is at least 40 mm (hereinafter referred to as H), particularly at least 60 mm. Further, when using a mixed solution of a polar solvent and a non-polar hot medium, it is preferable that the degree of locking of the non-polar solvent is 5φ or more.

In this extraction operation, a solvent is used in an amount equal to or more than the weight of the dried crude drug as a raw material, and the extraction is performed at room temperature for 1 hour or more, and if necessary, with heating. Usually, the extract is obtained by distilling off the solvent from this extract, or in the case of using the solvent used in the extraction process, ethanol, glycerin, propylene glycol, or a mixture of these and water. The liquid can also be used as is.

The adriamycin preparation of the present invention is prepared by preparing a mixture of adriamycin and the above-mentioned crude drug extract into tablets by a conventional method.
It is manufactured by making oral preparations such as pills, granules, and capsules; parenteral preparations such as injections and suppositories. The blending ratio of adriamycin and crude drug extract can be selected depending on the symptoms, application method, etc. Generally, the blending ratio of the crude drug extract to adriamycin is 0.01 to 2000 times the amount, especially 0.
It is preferable to use 5 to 5 oo times the weight, and the best effect can be obtained at this time.

The acute toxicity (L Dso ) of adriamycin is 13.7 ■/Kg when administered intraperitoneally to male mice. remains almost unchanged.

The method of administering the adriamycin preparation of the present invention varies depending on the nature of the disease, the dosage form of the preparation, and the administration method, but for example, administering the preparation of the present invention in an amount equivalent to 10 to 30 cm of adriamycin once a day for 4 to 6 days. A method of continuous intravenous administration followed by a 7-10 day rest period is adopted. In order to further improve the effects of the present invention, it is preferable to use the above-mentioned intravenous administration in combination with the administration of crude drug extracts.

Furthermore, it is also possible to adopt a method in which only adriamycin is administered intravenously and the crude drug extract is orally administered.

Next, the present invention will be explained with reference to Examples. The materials used in this example are as follows.

Test compound Niadriamycin (manufactured by Kyowa Hakko Kogyo) Rosemary extract (acetone extract of commercially available rosemary powder) Test hub: Mouse (male BDF, mouse, 11 weeks old, average physical size 302) Example 1 Mice (20 mice per group) were given adriamycin (5my/
Kp ) and rosemary extraction
, 1 mg/Kg, or xo+w/Kf) with 5
It was administered intraperitoneally every other day. The dosage per animal is 0η/Kq, 1 mg/Kg, or ioq/Icy.
amounts of rosemary extract and adriamycin (
51q/I<f) was added with N. triglyceride to give a total volume of 110.5 ml, and an injection was used.

After administration, the cherry blossoms were observed every day to examine the survival rate. The result is the first
As shown in the figure.

Example 2 Mice (15 mice per group) were given Adriamycin (20 Da/7 days) intraperitoneally once, and rosemary extract was given to Adriamycin/24 hours before, 2 hours before, and 2 hours after administration. A total of 4 doses were administered 24 hours later. The rosemary extract was administered by adding medium-chain fatty acid phototriglyceride to the rosemary extract, which gave a dosage of 5 my/KSI or so++y/Ky per animal, to give a total volume of 5 ml of injection. was used. After administration, the animals were observed every day to examine the survival rate. The results are shown in FIG.

Example 3 Mice (20 mice per group) were used, and 0 rosemary extract was used.
After one week of feeding on a diet containing 20 g of adriamycin, the mice were fed once intraperitoneally with 20 kg of adriamycin, and the animals were continued to be fed with the same diet. After administration of adriamycin, the animals were observed every morning to determine the survival rate.

The results are shown in FIG.

Feed composition: Soybean oil 10 (%) Casein 20 α-Starch 59.6 Cellulose 4 Vitamin (herbal combination) 2 Minerals (//　//)　4 Coria chloride 0.2 0-zumary extract 0.2

[Brief explanation of drawings]

FIG. 1, FIG. 2, and FIG. 3 are graphs showing oral changes in survival rate of mice. l...Adriamycin (5rq/Kr) 2...Adriamycin (5■/Ky) + rosemary extract (1 scrap y/Kg) 3...Adriamycin (5my
/ Kri) 10 rosemary extract (1 or 7)
4... Adriamycin (2011W/Oan) 5.
...Adriamycin (20Tng/l<9) + rosemary extract (5+=+y/Kg)6...Adriamycin (20'y/1;v)+rosemary extract (50hq/h)7...・Adriamycin (
20hv/h) 8... Adriamycin (20”t/
Ky)+Rosemary extract 062% or higher-containing diet Fig. 1 Number of 1 after administration of Adriamycin Fig. 2 Number of days after administration of Adriamycin Fig. 3 Number of days after administration of Adriamycin

Claims (1)

[Scope of Claims] (1) An adriamycin preparation containing adriamycin and a herbal medicine extract having antioxidant ability. 2. The adriamycin preparation according to claim 1, wherein the herbal medicine is selected from the group of rosemary, salvia, allspice, paprika, sesame, thyme, globe, ginger, nutmeg, koboku, and schisandra. .