JP2007016053A - Antineoplastic agent - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a means for improving the biodistribution and bioavailability of a substance having a pharmacologic action. <P>SOLUTION: This antineoplastic agent comprises the essences of one or more galenicals having a saliva action and adriamycin, wherein the galenical is selected from rhubarb, Cassia angustifolia, aloe, Prunus salicina, Pharbitidis Semen, Euphorbia kansui, Daphne genkwa, Euphorbiaceae, pokeweed root, Euphorbia lathyris, Draba nemorosa L, Hoelen, polyporus, Artemisiae capillaris, Cocculus trilobus, Sinomenii caulis, Coicis Semen, Benincasa cerifera, Dianthus chinensis L., Kochia scoparia L., Polygonus aviculare L., Pyrrosia lingua (Thunb.) Farw, whole grass of Plantago major, Malva verticillata, Dioscorea sativa. L., Inula Britannica L., seed of Phaseolus angularis, Crataegus cuneata, malt, Raphanus sativus L., Ephedra sinica, beefsteak plant leaf, flower of Schizonepeta tenuifolia, Seseli libanotis, Herba Elsholtziae, bardanae fructus, Spirodela polyrhiza, Equisetum hyemale, turmeric, Juglans regia L., Adenophora triphylla, Asparagus cochinchinensis, Ophiopogonis Tuber, Nerium indicum, Lilium makinoi, Loranthus parasiticus, Acorus calamus L., bezoar orientalis or the like. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

The present invention relates to an antineoplastic agent.

Kampo's philosophy includes the concept of qi, blood, and water, and it is said that a normal life can be maintained by maintaining a balance between these. Of these, the concept of water represents a metabolic system through water such as sweat and urine, and tsuyu is a concept that activates this metabolic system. Herbal medicines that improve the workings of such liquids are ascending drugs, laxatives, steep laxatives, diuretics, decongestants, anti-tabular medicines, gout moisturizers, active blood drugs, prosthetics, and prosthetics Those classified into medicines, fragrance-opening agents, anti-fogging cough agents, fragrance-opening agents and the like correspond to the following, and specific examples include the following. It is already known that taking these herbal medicines increases water metabolism, increases the secretion of sweat, urine, and various digestive juices, and enhances the action of carrying unnecessary substances from the human body to the outside. However, at present, nothing is known about the interaction between these liquid ameliorating agents and substances having various medicinal effects.
(Drugs, senna, aloe, icrinin, kengoshi, kansui, genka, tiger geese, shrimp, zokuzui, taleki, kyukoukonpi, bukuryo, chorei, ginseng, mokuboui, kanboui, yokuinin, toukaku, takuyaku Gyfushi, henchik, sekii, shazenshi, toki, hikai, kinsou, sekishozu, hanpen rei, gyokumaiish, hawthorn, bakuga, keinaikin, life sushi, maou, shisoyou, kei-gai, boufuu, koju, burdock, fuhei, mokzok, seikonoku, seikonoku, Shajin, Tenmondou, Bakumondou, Kyokuchiku, Hyakugou, Sakusei, Shobu, Bakugaishi, Gooh

On the other hand, when a substance having various pharmacological actions is used for treatment or the like, it is particularly important to know how the substances having these pharmacological actions are distributed in the body and the bioavailability. This is because in many drugs, the biodistribution and bioavailability are often not good, and the expected effect is not often obtained from the drug administration. That is, since the pharmacological action can be improved by improving the in vivo distribution and bioavailability of these substances having a pharmacological action, the advent of such a method has been awaited.

Furthermore, there is no known story that oral administration of a specific component improves the transdermal absorption and distribution in the body of a substance having a pharmacological action administered transdermally.

The present invention has been made in view of such circumstances, and an object of the present invention is to provide means for improving the biodistribution and bioavailability of a substance having a pharmacological action.

In view of such circumstances, the present inventors have sought a means for improving the biodistribution and bioavailability of substances having pharmacological effects, and as a result of earnest research, as a result of such actions on the essence of herbal medicines having a tsunami action. And found the invention. Hereinafter, the present invention will be described in detail focusing on the embodiment of the invention.

(1) Herbal medicines having squeezing action used in the present invention The herbal medicines used in the present invention are, according to Kampo classification, a laxative drug, a laxative drug, a steep drug, a water-use drug, a decontamination drug, an answer table Drugs, gouty moisturizers, active agents, prosthetics, antidepressants, fragrance-opening agents, antifocal cough agents, and fragrance-opening agents. It has been known. Specific herbal medicines include Daio, Senna,
Aloe, Icrinin, Kengoshi, Kansui, Genka, Taikiki, Shorikiku, Zokuzuishi, Teirexi, Ukyukoupi, Bukuryo, Chorei, Inchinkou, Mokuboui, Kamboui, Yokuinin, Tokanin, Tsuyaku, Kakukaku, Difushi, Henchiku, Shichiki, Shiki Shiki Ginseng, Sekisho, Hanpen Rei, Gokumaishu, Hawthorn, Bakuga, Keinai Kin, Life Kushi, Maou, Shisoyo, Keigai, Bowfu, Kouju, Goboushi, Fuhei, Mokuzoku, Sekinanto, Turmeric, Kotonik, Shajin, Ginseng, Ginkgo Examples include shobu, scallops and gourd. In the present invention, these crude drugs can be used as they are, or can be used as an extract, a solvent-removed product thereof, or a fraction-purified product thereof. The essence in the present invention means a generic name of these. Particularly preferred are solvent extracts or solvent removal products thereof. An extract can be obtained by adding 1 to 10 times the amount of a solvent to a crude drug or a processed product thereof, and immersing it for several hours at a temperature near the boiling point or for several days at room temperature. The solvent used is preferably a polar solvent, for example, water, alcohols such as ethanol and propylene glycol, esters such as ethyl acetate and methyl formate, ethers such as diethyl ether and tetrahydrofuran, and ketones such as acetone and methyl ethyl ketone. One or two or more selected from halogenated hydrocarbons such as methylene chloride and chloroform can be preferably exemplified. Particularly preferred is a water extract or a solvent removal product thereof. In the present invention, these herbal medicines are administered orally. By this administration, the absorption of the pharmacologically active substance administered by a route different from the oral route into the living body and the arrival at the diseased site can be improved, and the bioavailability of the pharmacologically active substance can be increased. The preferred dosage of the essence of the herbal medicine having a sluice action, which is a distribution improving agent of these pharmacologically active substances of the present invention, is preferably 10 to 20000 g per day for each adult and divided into several times. is there. The administration is preferably performed prior to the administration of the pharmacologically active substance, and the timing is preferably 1 hour to 30 minutes before the administration of the pharmacologically active substance. Also particularly noteworthy is to improve the absorption of pharmacologically active substances from the skin with less blood influence and the arrival at the disease site. That is, this is because, in the skin where the metabolism, absorption and excretion by blood cannot be expected greatly, the tsuyu action referred to Kampo takes on this action instead. The distribution improving agent for pharmacologically active substances of the present invention includes excipients, binders, coating agents, lubricants, sugar coatings, disintegrants, extenders, flavoring agents, emulsifying / solubilizing / dispersing agents, stabilizing agents. It is also possible to formulate and use together with optional components such as an agent, a pH adjuster and an isotonic agent.

(2) Pharmacologically active substance used in the present invention The pharmacologically active substance that can be used in the present invention is not particularly limited as long as it is a substance having a physiological activity that is administered by a different administration route from the above-mentioned crude drug having a tsunami action. For example, if it is a pharmaceutical, it is administered by routes such as injection, suppository, topical skin, hypnotic / sedative, antipyretic / analgesic, stimulant / stimulant, antipruritic, mental Nervous drugs, silicicidal drugs, antihistamines, allergic diseases drugs, cardiovascular drugs, respiratory drugs, anti-ulcer drugs, laxatives, hormone drugs, antifungal drugs, vitamins, antibiotics, anti-inflammatory drugs, anti-neoplastic agents, etc. Examples of cosmetics include whitening ingredients, wrinkle-improving ingredients, skin-beautifying ingredients, hair-restoring ingredients, blood circulation promoting ingredients, dullness-improving ingredients, and cosmetic break-up preventing ingredients. When the distribution improvement of the pharmacologically active substance of the present invention is present, the uptake from the skin and the arrival at the diseased site are improved, and the bioavailability is improved. These substances having pharmacological activity may be administered according to usual examples.

ADVANTAGE OF THE INVENTION According to this invention, the means to improve the biodistribution and bioavailability of the substance which has a pharmacological action can be provided.

Hereinafter, the present invention will be described in more detail with reference to examples, but it is needless to say that the present invention is not limited to these examples.

<Example 1>
5 l of water was added to 1 kg of each of the following herbal medicines having a tsunami effect and boiled for 3 hours. This was filtered to remove insolubles and freeze-dried to obtain the distribution improving agent for pharmacologically active substances of the present invention. This was dissolved in 0.1 ml of physiological saline at a dose of 100 mg / Kg, and orally administered to ICR mice (three mice per group) previously depigmented. Minoxidil was dissolved in 100 μl of ethanol and administered transdermally. In the control group, 0.1 ml of physiological saline was administered instead of the physiological saline solution of the pharmacologically active substance distribution improving agent of the present invention. Two weeks after administration, hair growth is ++: much higher than the control group, +: more compared to the control group, ±: slightly higher than the control group, −: less than or equal to the control group Observed and judged according to the criteria. The results are shown in Table 1. From this, it can be seen that the hair growth effect of minoxidil, which is a hair restorer, is enhanced by the pharmacologically active substance distribution improving agent of the present invention.

<Example 2>
5 l of water was added to 1 kg of each of the following herbal medicines having a tsunami effect and boiled for 3 hours. This was filtered to remove insolubles and freeze-dried to obtain the distribution improving agent for pharmacologically active substances of the present invention. This was dissolved in 0.1 ml of physiological saline at a dose of 100 mg / kg, and 10 ⁴ Erich's ascites tumors were dispersed in 0.1 ml of physiological saline 10 days in advance and administered into the back skin. Then, it was orally administered to ICR mice (3 mice per group) in which cancer had been transplanted, and adriamycin 10 mg / Kg was intravenously administered 30 minutes after the administration. In the control group, 0.1 ml of physiological saline was orally administered instead of the physiological saline solution of the pharmacologically active substance distribution improving agent of the present invention. Two weeks after administration, the size of the cancer was measured, ++: very small compared to the control group, +: small compared to the control group, ±: slightly smaller than the control group, whether the same as the control group Judgment was made on the basis of more criteria. The results are shown in Table 2. This shows that the anticancer effect of adriamycin, which is an anticancer agent, is enhanced by the pharmacologically active substance distribution improving agent of the present invention.

<Example 3>
Carrageenan edema (3 mice per group) was created on the foot pad of Wistar male rats, and the above-mentioned pharmacologically active substance distribution improving agent was dissolved in 0.1 ml of physiological saline at a dose of 100 mg / Kg and orally administered. The control group received saline alone. The carrageenin edema rat was applied with an ointment containing 1% by weight of indomethacin in petrolatum, and 24 hours later, the size of the edema was determined according to the following criteria. ++: Significantly smaller edema compared to the control group, +: Obviously smaller edema than the control group, ±: Slightly smaller edema than the control group,-: The size of the edema is the same as the control group Was judged on the basis of large. The results are shown in Table 3. This table shows that the anti-inflammatory action of indomethacin is enhanced by the administration of the pharmacologically active substance distribution improving agent of the present invention.

<Example 4>
Using 20 female panelists aged 21 to 34 who suffer from darkness, a use test was conducted to improve the darkness of the following lotion. The panelists were randomly divided into two groups, one group taking 0.5g of lyophilized water extract of persimmon 30 minutes before using lotion, and the other group using lotion only I was asked to. After using the skin lotion for 3 months, the black-and-white improvement was answered on the basis of ++: markedly improved, +: clearly improved, ±: slightly improved,-: not improved or corrupted. It was. The results are shown in Table 4 as the number of appearance examples. From this, it can be seen that the group taking the essence of acupuncture, which is a distribution improving agent for the pharmacologically active substance of the present invention, has an excellent color blackness improving effect.

Claims (5)

An anti-neoplastic agent comprising a combination of a herbal essence having a tsuyu action and adriamycin, wherein the herbal medicine is diou, senna, aloe, icrinin, kengoshi, kansui, genka, taigaki, shorikiku, zokuzuishi, taylexi, ukuyu kopi , Bukuryu, Chorei, Inchinkou, Mokuboui, Kamboui, Yokuinin, Tokanin, Tsuyaku, Kukukaku, Djifushi, Henchiku, Sekii, Shazenshi, Toki, Hikai, Ginseng, Sekishozu, Hampeirei, Gokumaiish, Hawthorn, Bamboo moth, Berry , Keigai, Bofuu, Kouju, Burdock, Fuhei, Mokuzoku, Sekinanto, Turmeric, Kotonik, Shajin, Tenmondou, Bakumondou, Gokuchiku, Zingou, Ukisei, calamus, selected Bakugaishi, and Goou, antineoplastic agents. The herbal medicine is selected from the following: 1. The antineoplastic agent according to 1. The antineoplastic agent according to claim 1, wherein the herbal medicine is selected from Diou, Aloe, Zokuzuishi, Bukkyou, Chorei, Tokanin, Toki, Hawthorn, Perilla, Goboushi, Turmeric, Shajin, and Gou. The antineoplastic agent according to claim 1, wherein the crude drug is gou. The antineoplastic agent according to any one of claims 1 to 4, wherein the adriamycin is administered by an intravenous administration route, and the essence of a crude drug having a lysing action is administered by an oral administration route.