JPH0134203B2 - - Google Patents

Description

[Detailed description of the invention]

[1] Background Technical Field of the Invention The present invention relates to a drug absorption aid for rectal administration containing a triterpenoid saponin as an active ingredient. This triterpenoid saponin can be extracted and isolated from the pericarp (hereinafter referred to as Enmeihi) of Sapindus mukurossi Gaertn. PRIOR ART Saponins have only made progress in research over the past decade due to the difficulty in purifying and isolating them and the complexity of their structures. The characteristics of saponin are represented by foaming properties in aqueous solutions, red blood cell destruction activity (hemolytic activity), toxicity to fish, and ability to form complexes with cholesterol (steroids). In addition to inflammation, central depression, anti-fatigue, anti-ulcer, promotion of cholesterol metabolism, promotion of lipid metabolism, promotion of synthesis of nucleic acids and proteins, pharmacological effects such as protection against infection and antitumor have been discovered in recent years. The saponin-containing herbal medicines that have a relatively high saponin content and are still listed in the Japanese Pharmacopoeia include Senega, Onji, Kikiyo, Licorice, Goshitsu, Saiko, Chikusetsu Ginseng, Carrot, Bakumondo, and Osmanthus. Saponins are classified into steroid saponins and triterpenoid saponins depending on the chemical structure of their sapogenin moieties. Enmeihi saponin, one of the triterpenoid saponins, had not been used for medical purposes until now, but its anti-inflammatory effect was investigated due to the similarity of its chemical structure, and it was found to have a suppressive effect on carrageenin edema and adjuvant ostitis in rats. There are reports that it showed. Various pharmacological effects of saponins have been discovered as described above, but full-scale pharmacological research has just begun, and there is a possibility that new pharmacological effects not found in conventional drugs will be discovered in the future. is hidden. In addition, triterpenoid saponins containing hederagenin as genin include, for example, Akebia
guinata Decne.) (Chem.Pharm.Bull. 24 , 1021
(1976)), Caulophyllum
robustum Maxim.) (CA 85 , 106644h (1976)),
Fatsia japonica Decne.
(Phytochemistry 15 , 781 (1976)), Sapindus mukurossi Gaertn. (CA 73 ,
77544, 110062m, 110071p (1970) and CA 74 ,
13384f (1971)), Lecaniodiscus cupanioides
Planch.ex Benth. (Phytochemistry 20 , 1939
(1981)), but full-scale pharmacological research has not yet progressed. On the other hand, in the administration of antibacterial preparations, a minimum effective blood concentration is known, and drug blood concentrations below this are not effective no matter how long the drug remains in the body. For this reason, the absorption and utilization rate of drugs during rectal administration is extremely important, and from a pharmaceutical standpoint, conventional methods that increase the absorption efficiency of drugs and maintain effective blood concentrations with smaller amounts of drugs are Alternatively, consideration has been given to methods of administration. However, there would be great benefits if the absorption utilization rate could be increased by administering a conventional rectal drug using the conventional rectal administration method. Recently, the present inventor discovered that a herbal medicine extract containing saponin components has the effect of promoting the absorption of orally administered pharmacologically active substances (JP-A-57-145816 and JP-A-58-57400; 28th Annual Meeting of the Japanese Society of Herbal Pharmaceutical Sciences). [] Summary of the Invention The present invention is based on the discovery that this crude drug extract containing saponin components is also effective in promoting the absorption of pharmacologically active substances administered rectally. Therefore, rectally administered β-
A drug absorption aid for rectal administration for aiding the absorption of lactam-type antibiotics is characterized by containing a saponin component-containing crude drug extract as an active ingredient. [] Detailed Description of the Invention 1 Crude Drug Extract The crude drug extract used in the present invention is an extract of a crude drug containing a saponin component. 1. Herbal medicine A large number of herbal medicines containing saponin components are known, and any of them can be used in the present invention. Specific examples of saponin component-containing herbal medicines suitable for use in the present invention are as follows. In the present invention, the term "crude drug" is used synonymously or interchangeably with the corresponding "plant." (1) (Akebia quinata Decne.) or its congener plants (Akebiaceae) (2) Fatsia japonica Decne.et
Pianch) (3) Caulophyllum robustum
Maxim.) (4) Ivy (Hedera rhombea Bean) (5) Clematis chinensis
Osbeck) (6) Pulsatilla cernua Spreng. (7) Sapindus mukurossi Gaertn. (8) (Panax japonicum)
CAMeyer) (9) (Bureau) Daylily (Glycyrrhiza glabra L.)
var.glandulifera Regel et Herder,
Polygala senega L. var.
Latifolia Torrey et Gray) (11) (Bureau) Platycodon grandiforum
ADC) (12) (Polygala tenuifolia)
Willd.) (13) (Bureau) Achyranthes
fauriei Lev.et Van.) or Achyranthes
bidentata Blume (14) Cyclamen (Cyclamen europaeum) (15) Primula (Primula)
officinalis) (16) (bureau) Mishima Saiko (Bupleurum)
falcatatum L.) or its varieties (Umbelliferae) (17) (Panax ginseng)
(18) Panax notoginseng
Burkill) (19) American ginseng (Panax quinquefolium)
L.) Notes (1) Plants 1 to 7 contain saponin whose genin is hederagenin. (2) (bureau) indicates that it is a source plant for crude drugs listed in the 9th revised Japanese Pharmacopoeia. (3) The peel of the Sapindium japonica is called Enmeihi, and the root of the Mishimasaiko is called Saiko, and they have been famous as herbal medicine since ancient times. 2 Extraction The saponin-containing crude drug extract used in the present invention is
It can be obtained from herbal medicines using plants such as those mentioned above as raw materials by conventional methods. That is, for example, after the raw herbal medicine is defatted without being defatted or by using a common fat-soluble organic solvent, water or a lower aliphatic alcohol, especially a C ₁ to C ₄ monohydric alcohol,
or a mixture of water and lower aliphatic alcohol;
is used as an extractant to extract its active ingredients. In addition to these extractants, lower ketones such as acetone, lower ethers such as diethyl ether,
Esters of lower monocarboxylic acids and lower alcohols such as ethyl acetate and others may also be used. In the present invention, this extract can be used as it is or after being concentrated, but it is usually used after being purified to some extent. One example of purification consists of suspending the concentrated extract in water, adding n-butanol and shaking, separating the n-butanol layer and evaporating it to dryness. The plant does not necessarily have to be naturally produced, and may be obtained by tissue culture of cells from the raw material plant. Furthermore, if the tissue culture is in an undifferentiated state and already contains saponin components, this culture may be subjected to an extraction operation. 3. Extract The extract thus obtained contains saponin components. Preferred extracts for use in the present invention are triterpenoid saponins of the formula: The saponins used in the present invention are of three types, saponins A, B and C, depending on the type of group R in the above general formula.

〔experimental method〕

Rats (weighing 180-220 g) are anesthetized with pentobarbital sodium (30 mg/Kg) and fixed supine on a metal waterbed in which constant-temperature water at 39°C is circulated. Insert the suppository through the anus and push with a glass rod until the tip of the suppository reaches the symphysis pubis.
The suppositories are based on Witepsol H-15 (Dynamik Nobel), which contains ampicillin sodium and saponin A or saponin B.
Alternatively, it was formulated by mixing saponin C, and the dosage was 1 g/Kg. Immediately after suppository administration, for control and saponin A, for 5 minutes,
10 minutes, 15 minutes, 35 minutes, 60 minutes, and 100 minutes; for saponin B and saponin C, 10 minutes, 20 minutes;
Blood was collected from the jugular vein of the rats at 30 minutes, 30 minutes, 50 minutes, and 100 minutes, and the active concentration was measured by a biological assay. In other words, in accordance with the Japanese Antibiotic Drug Standards, Bacillus subtilis (B.
subtilis) using the paper disc method at 37℃/
The cells were cultured and assayed for 15 to 20 hours. The composition of the administration suppository is as follows. Ampicillin sodium 50mg/rat 1Kg Saponin A or B or C
0.5-2 mg/1Kg of rat Examples according to the above experimental method are shown in the following table as Examples 1-5. In any case, no abnormalities such as damage to the rectal mucosa (for example, mucosal detachment) or bleeding spots were observed. [Example 1] Saponin A 0.5mg/Kg [Example 2] Saponin A 1mg/Kg [Example 3] Saponin A 2mg/Kg [Example 4] Saponin B 1mg/Kg [Example 5] Saponin C 1mg/Kg Kg

【table】

【table】

Claims (1)

[Scope of Claims] 1. A drug absorption adjuvant for rectal administration for assisting the absorption of a β-lactam antibiotic administered rectally, characterized in that the active ingredient is a crude drug extract containing a saponin component. 2. The drug absorption aid for rectal administration according to claim 1, wherein the saponin component-containing crude drug is obtained from Sapindus mukurossi Gaertn. 3. The drug absorption aid for rectal administration according to claim 1, wherein the saponin component-containing herbal drug is Enmeihi (the peel of Sapindium sapinata). 4. The drug absorption aid for rectal administration according to claim 1, wherein the saponin component-containing crude drug is a triterpenoid saponin represented by the following formula. 5. The drug absorption aid for rectal administration according to any one of claims 1 to 4, wherein the β-lactam antibiotic is ampicillin or ampicillin sodium. 6. Drug absorption for rectal administration according to any one of claims 1 to 5, which is in the form of a suppository comprising a β-lactam antibiotic, a herbal medicine extract containing a saponin component, and an excipient. Auxiliary agent.