JPH02255622A - Carcinostatic assistant - Google Patents

Abstract

PURPOSE:To provide a carcinostatic assistant containing specific herb drugs and Chinese drug preparations as active components, effective in reducing the side effects of carcinostatic agents and further promoting the carcinostatic action. CONSTITUTION:The objective carcinostatic assistant contains, as active components. at least one kind of herb drug selected from SAIKO (root of Bupleurum falcatum), TAKUSHA (bulb of Alisma plantagoaquatica), HANGE (rhizome of Pinellia ternata), OUGON (root of Scutellaria baicalensis), SOUJUTSU (rhizome of Atractylodes lancea). DAISOU (fruit of Zizyphus jujuba), CHOREI (sclerotium of Polyporus umbellatus), NINJIN (root of Panax ginseng), BUKURYO (sclerotium of Poria cocos), KANZOU (root of Glycyrrhiza glabra), KEIHI (bark of Cinnamomum cassia), SHOUKYOU (rhizome of Zingiber officinale), INCHINKOU (whole grass of Artemisia capillaris), gypsum, BOUI (root of Stephania tetrandra), JIOU (root of Rehmannia glutinosa), GOSHITSU (root of Achranthes bidentata). SANSHUYU (fruit of Coruns officinalis), SANYAKU (rhizome of Dioscorea batatas), SHAZENSHI (seed of Plantago asiatica). BOTANPI (root of Paeonia moutan), BUSHI (tuber of Aconitum carmichaeli). OUGI (root of Astragalus hliantchy), TOUKI (root of Angelica acutiloba), CHINPI (peel of Citrus unshu), SHOUMA (rhizome of Cimicifuga simplex), SHAKUYAKU (root of Paeonia albiflora) and SENKYU (rhizome of Cnidium officinale). Preferable combinations of the herb drugs are (A) SAIREI-TO composed of SAIKO, TAKUSHA, HANGE, SOUJUTSU, DAISOU, CHOREI, NINJIN, BUKURYO, KANZOU, KEIHI and SHOUKYOU, (B) CHINGOREISAN composed of TAKUSHA, SOUJUTSU, CHOREI, BUKURYO, KEIHI and INCHINKO and (C) a Chinese drug preparation selected from MOKUBOUI-SAN, GYLSHA-JINKIGAN and BOUFU-TSUSEISAN.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to an anticancer adjuvant that reduces the side effects of anticancer drugs and further enhances their anticancer effects.

[Prior Art and Section M] Many of the anticancer drugs currently used in clinical practice have serious side effects. However, are there any side effects?
Or, there are very few drugs that are more effective against cancer than existing drugs in clinical use.

For example, cisplatin is widely used clinically as an effective anticancer agent for lung cancer, gastrointestinal cancer, bladder cancer, prostate cancer, ovarian cancer, breast cancer, etc., and is also strongly associated with renal disorders, gastrointestinal disorders, etc. In particular, renal damage is significant, and this is a clinical dose-limiting factor.

[Means for Solving the Problems] The present inventors have been conducting research to solve the above problems, and have recently developed various herbal medicines and Chinese herbal preparations that enhance the anticancer effects of anticancer drugs such as cisplatin, and When we investigated synergistic effects to reduce side effects, we found that some crude drugs and/or certain Chinese herbal preparations have the effect of reducing the side effects of anticancer drugs such as cisplatin, and further enhancing their anticancer effects. The present invention has now been completed.

That is, the present invention is as shown below.

(1) Saihu, Sawatan, Hanxia, Huang■, Aomoto, Daito, Boar■, ginseng, burai, licorice, cinnamon, ginger, senchenba, gypsum, bokami, rhizogen, ox knee, mountain chestnut pod, An anticancer adjuvant containing at least one herbal medicine or an extract thereof selected from the group consisting of mountain medicine, chazenji, peony bark, fuzi, astragalus, danggui, chenpi, shuma, peony, and yogo, or an extract thereof as an active ingredient.

(2) The selected crude drugs are Saiko, Sawata, Hanka, Huang■, f■,
The anti-cancer adjuvant according to claim 1, which is Daito, boar, ginseng, turmeric, licorice, cinnamon, and ginger.

(3) The selected herbal medicines are Sawata, Ao■, Ojutsu, Boar■, and Bool.
The anticancer adjuvant according to claim 1, which is cinnamon and fungi.

(4) An anticancer adjuvant consisting of at least one Chinese herbal prescription selected from Mokuboto, Goshajinkigan, and Bofutsushosan.

Hereinafter, the drugs (1) to (4) are collectively referred to as the drug of the present invention.

The herbal medicines mentioned above do not exhibit anticancer effects by themselves, and the Chinese herbal medicines described below do not exhibit anticancer effects by themselves. but,
As described in the present invention, when administered in combination with cisplatin, the anticancer effect of cisplatin is enhanced and its toxicity is reduced. This was completely unknown before.

Among the drugs of the present invention, those in which the selected herbal medicines are Saiku, Zawata, Hanka, Huang, Aono, Daito, Boar, Ginseng, Boului, Licorice, Cinnamon, and Namiyaki are known as Saireito. It is a traditional Chinese medicine prescription, and the selected herbal medicines are Sawatari, Fukisei, Ino■, Chiya■,
The one containing cinnamon and fungi is a Chinese herbal formula known as Sensatsu Goreisan.

In addition, the constituent herbal medicines and composition ratios of Saireito, Senchin Goreisan, Mokhobito, Gosha Ikukigan, and Bofutsu are determined according to the classical Chinese medicine; There is a wide range of ratios, and the amount of ingredients contained in crude drugs changes depending on the place of production, the time of collection, and natural conditions such as weather, so it is necessary to increase or decrease the mixing ratio of each constituent crude drug as appropriate.

Therefore, the drug of the present invention may be mixed at any ratio as long as it satisfies the following mixing ratio.

■4 to 7 parts by weight of Saireito Saiko, 1 part of Sawatou 5 to 6 parts, 4 to 5 parts by weight of Hanka, 3 parts by weight of Huangrei, 3 to 4.5 parts by weight of Fukigami, 2 to 3 parts by weight of Daito
Parts by weight: 3 to 4.5 parts by weight of boar, 2 to 3 parts by weight of ginseng, 3 to 4.5 parts by weight of turmeric, 2 parts by weight of licorice, 2 to 3 parts by weight of cinnamon, and 1 to 4 parts by weight of ginger.

■4.5 to 6 parts by weight of Senchen Gorei Sanzawa, 3 to 4.5 parts by weight of Fukusei, 3 parts of Irei
~4.5 parts by weight, 3 to 4.5 parts by weight of Fuyeon, 2 to 3 parts by weight of cinnamon, and 3 to 4 parts by weight of Cinnamon.

■10 parts by weight of Kibohama gypsum, 4 parts by weight of Kibohama gypsum, 3 parts by weight of cinnamon, 3 parts by weight of carrot
Weight part.

■ 5 to 6 parts by weight of Gyushuma Jinkimaru Jiko, 2 to 3 parts by weight of Ushihi, 3 parts by weight of Sannaiya, 3 parts by weight of Yamayaku, 2 to 3 parts by weight of Kurumaeko, 3 parts by weight of Sawatara,
3 parts by weight of Kia Ling, 3 parts by weight of Mudanpi, 1 part by weight of cinnamon bark, and 0.5 to 1 part by weight of Shuji Fuzi powder.

■2 parts by weight of Bofutsusho Sankorei, 2 parts by weight of licorice, 2 parts by weight of Kikyo, 2 parts by weight of plaster
3 parts by weight, 2 parts by weight of Shiro JIt, 1.2 parts by weight of Rhubarb [, Siffm part, 1.2 parts by weight of Peony, 1.2 parts by weight of Paeonia japonica, 1.2 parts by weight of Peony
Severely injured area, 1.2 parts by weight of calyx, 1.2 parts by weight of toki, 1 part by weight
．． 2 parts by weight, windbreak 1.27Ii yatebu, 1.2 parts by weight of ephedra, 1.2 parts by weight of renryo, 0.3 to 1.2 parts by weight of ginger, 3 to 5 parts by weight of talcum, 0.7 to 1 part by weight of Glauber .5 parts by weight.

In addition, among the drugs of the present invention, Saiko, Zawata, Hanxia, Huang■, Aomoto, Daito, Ino■, ginseng, Boului, licorice, cinnamon, ginger, Fungus I
s, gypsum, bulwark, rhizome, ox knee, wild vegetable pod, wild medicine, kuramaenji,
It is preferable to use crude drugs listed in the Japanese Pharmacopoeia and the Japanese Pharmacopoeia Non-Japanese Pharmacopoeia Standards Collection for the herbal medicines listed in the Japanese Pharmacopoeia and the Standard Collection of Non-Japanese Pharmacopoeia.

The drug of the present invention can also be prescribed as a Chinese herbal medicine by decocting each of the mixed herbal medicines in the proportions mentioned above with 600% water to make 300%, and then taking the extract after removing the dregs in three doses as an anticancer adjuvant. However, in consideration of ease of administration and portability, a dry extract powder or a formulation of a Chinese herbal medicine extract can also be used as an anticancer adjuvant.

To formulate a dry extract powder, the extract obtained by the method described above is filtered, and then the extract is spray-dried or freeze-dried to obtain an extract powder. By adding excipients, adjuvants, etc., it can be made into preparations such as powders, granules, tablets, and capsules according to conventional methods for manufacturing preparations.

Extraction, powdering, and formulation of the crude drug are the same as described above, and the crude drug may be directly powdered and administered without extraction. Powderization can be performed by a commonly used powderization method.

Specific examples of manufacturing the drug of the present invention are shown below.

Specific example 1 Saiku 7g, Sawatan 59, Hanka 59, Huangrei 39, Ao/139
, Daito 39, 3g of boar, 3g of carrot, 3g of chili, 2g of licorice
, 2g cinnamon, ginger! Add 40 times the amount of purified water to 9,
Extraction was carried out at 0° C. for about 60 minutes, solid-liquid separation was carried out, and the resulting separated liquid was concentrated to one-half volume, and the concentrated liquid was spray-dried to obtain a dry extract powder.

Specific example 2 26 times the amount of purified water was added to Sawa 69, Ao Ac 4, 5 g, Irei 4.59, Horei 4,5V1 cinnamon 2.59, and Senchenman 49, and extracted at 100°C for about 60 minutes. , solid-liquid separation was performed, and the resulting separated liquid was concentrated to 1/2 of its volume, and the concentrated liquid was spray-dried to obtain a dry extract powder.

Specific example 3 Add 20 times the amount of purified water to 10 g of gypsum, 49 Bom, 3 g of cinnamon, and 3 g of carrot, extract at 100°C for about 60 minutes, separate solid and liquid, and the resulting separated liquid is 1/2 the amount The concentrated liquid was spray-dried to obtain a dry extract powder.

Specific example 4: 5 g of rhizome, 3 g of cow knees, 3 g of sasancha pods, 39 wild herbs, 3 kumasaneko
9. Add 28 times the amount of purified water to 39 sardines, 3 g of kare, 39 peony bark, 1 g of cinnamon bark, and 1 g of Shujitsushi powder, and boil at 100℃ for 60 minutes.
Extraction was carried out for about a minute, followed by solid-liquid separation, and the resulting separated liquid was concentrated to one-half volume, and the concentrated liquid was spray-dried to obtain a dry extract powder.

Specific example 5 2 g of Ori, 2 g of licorice, 29 bellflowers, 2 g of gypsum, 29 white circles,
1.59 rhubarb, 1.29 hisheng, 1.2 g of cypress, 1 peony
．． 29, 1.2g for use, 1.29 for return, light load! , 2g,
Windproof 1.29, Ephedra 1.2g, Liancho 1.29, Ginger 0.
39. Add 26 times the volume of purified water to 3 g of talcum and 0.79 g of Glauber's salt, extract at 100°C for about 60 minutes, separate solid and liquid, concentrate the resulting separated liquid until it weighs 2 minutes, and concentrate. The liquid was spray dried to obtain a dry extract powder.

Next, the fact that the drug of the present invention reduces the side effects of cisplatin, further enhances its anticancer effect, and is useful as an anticancer adjuvant will be explained using experimental examples.

Experimental Example 1 Using BALB/C mice implanted with female A (Meth-^), cisplatin and the drug obtained in the specific example were administered, and the weight of the tumor was measured 14 days later to determine the growth inhibition rate. The control group was a group to which only cisplatin was administered.

In addition, cisplatin was administered intraperitoneally at 0.5Q/ky.
The drug obtained in the specific example was orally administered at 0.597 to 9.

The results are shown in Table 1.

Experimental Example 2 The tumor weight and growth inhibition rate were determined in the same manner as in Experimental Example 1, except that the administered concentration of the drug obtained in the specific example was changed as follows.

The results are shown in Table 2.

Tumor weight and growth inhibition rate were determined in the same manner as in Experimental Example 1 except for the following.

The results are shown in Table 3.

Experimental Example 3 The administration concentration of cisplatin was 1.5 mg/ky, and the administration concentration of the drug obtained in the specific example was varied as follows. Experimental Example 4 Five-week-old female ICR mice implanted with Sarcoma 180 were administered. Cisplatin and the drug obtained in the specific example were administered, and the weight of the tumor was measured after 5 weeks to determine the growth inhibition rate.

The control group was a group to which only cisplatin was administered.

The dose of cisplatin was 0.5yzv/9, and this was administered intraperitoneally. The drugs obtained in the specific examples were orally administered at the concentrations shown below.

The results are shown in Table 4.

Table 4 They were grouped and their survival days were compared.

The dose of cisplatin was 25.0 R9/9, which was administered intraperitoneally, and the drug obtained in the specific example was orally administered at the concentrations shown below.

The results are shown in Table 5.

Table 5 Experimental Example 5 5-week-old female IC transplanted with Sarcoma 180
R? Cisplatin and the drug obtained in the specific example were administered using mice.

In addition, control experiment example 6 5-week-old female IC implanted with Sarcoma 180 was administered with only cisplatin.
R7 mice were used to administer cisplatin and the drug obtained in the specific example.

In addition, the control group was those administered only cisplatin.
Tumor weight and growth inhibition rate were determined 14 days after transplantation.

Also, the dose of cisplatin is 0.5m97,
This was administered intraperitoneally, and the drug obtained in the specific example was administered orally at the concentrations shown below.

The results are shown in Table 6.

Table 6 Furthermore, among the drugs of the present invention, an acute toxicity test was conducted on the Chinese herbal extract powders obtained in Examples 1 to 6 using ddY mice, and the results were 15g/&9 (dose limit).
There were no deaths after oral administration.

The safety of drugs other than Chinese herbal extract powder was also confirmed.

From the above results, it was confirmed that the drug of the present invention reduces the side effects of anticancer drugs and enhances the anticancer effect, and furthermore, from the results of the acute toxicity test, it is confirmed to be useful as an anticancer adjuvant.

Considering the experimental data and the results of acute toxicity tests in the present invention, the effective administration of the drug of the present invention is as follows:
Although it varies depending on body weight and degree of disease, the weight of dry extract powder of each prescription and herbal medicine and its extract is 1
[For Efil ~109 and other drugs, it is considered appropriate to take doses of 0.1 to 39 in three divided doses a day, depending on the symptoms.

EXAMPLES Next, the present invention will be described in more detail with reference to Examples, but the present invention is not limited thereto.

Example I 200 g of the dry extract powder obtained in Example I was mixed with 899 and magnesium stearate, and this mixture was used in a single-shot tablet machine to make slug tablets with a diameter of 20xx and a weight of 2.39, and this was applied to an oscillator. The mixture was pulverized, sized, and sieved to obtain good granules of 20 to 50 mesh particles. This granule is available in the same amount as 0.5 to 4.5 depending on the symptoms.
9 (equivalent to 0.34 to 3.10 y as dry extract powder weight) 3 times a day.

Example 2 200 g of the dry extract powder obtained in Example 2 was mixed with 20 g of microcrystalline cellulose and magnesium stearate,
This mixture was compressed using a single-shot tablet machine to produce tablets with a diameter of 7 mm and a weight of 225 mm.

This tablet contains 200 R9 of the drug of the present invention.

Take 2 to 16 tablets of the same amount three times a day, depending on your symptoms.

Example 3 The dry extract powder 50019 obtained in Example 3 was filled into hard capsules. This capsule is divided into 2 to 20 doses three times a day and taken depending on the symptoms.

Claims (4)

[Claims] (1) Saihu, zechu, half summer, yellow, blue, large jujube, boar, ginseng, boulangerie, licorice, cinnamon, ginger, 茵蒿, gypsum, boi, rhizogen, ox-knee, yam, mountain An anti-cancer adjuvant containing at least one herbal medicine or its extract as an active ingredient selected from the group consisting of Yakushu, Cheqianzi, Mudanpi, Fuzi, Astragalus, Danggui, Chenpi, Shengma, Paeonia and Chuan. (2) The selected herbal medicines are Saiko, Sawata, Hanka, Huang■, Ao■,
The anti-cancer adjuvant according to claim 1, which contains Japanese jujube, boar ginseng, ginseng, turmeric, licorice, cinnamon, and ginger. (3) The anticancer adjuvant according to claim 1, wherein the selected herbal medicines are sagebrush, sangol, swine, shulin, cinnamon, and 茵 and shuang. (4) An anticancer adjuvant consisting of at least one Chinese herbal prescription selected from Mokuboto, Goshajinkigan, and Bofutsushosan.