JP4889854B2 - Bile pigment secretion promoter - Google Patents

Description

[0001]
BACKGROUND OF THE INVENTION
The present invention relates to secretion promoters bile pigments, more particularly, as an active ingredient a specific organic germanium compound, to a secretion promoters bile pigments exhibiting superior effects.
[0002]
[Prior art]
Formula (1)
[Chemical 2]
As for the organic germanium compounds represented by the compounds represented by formula (1), there are various effects on the human body such as interferon-inducing action (see JP-A-55-122717) and analgesic action (see JP-A-62-93293). It is known to have physiological activity.
[0003]
However, intensive research has been conducted on the mechanisms of the various physiological activities described above, and although some assumptions have been made, they have not been completely elucidated.
[0004]
Of the organogermanium compounds represented by the above formula, those in which R _{1 to} R ₃ are hydrogen atoms and X is a hydroxyl group are absorbed into the body only about 30% in the case of oral administration, and the remaining about 70% It is known that is discharged as it is. In addition, about 30% of the organic germanium compound absorbed in the body is also discharged to the outside after exhibiting various actions while circulating in the body by blood.
[0005]
Therefore, the action of about 70% of organogermanium compounds that are not absorbed in the body exerts in the gastrointestinal tract because if the gastrointestinal tract is deeply involved in the immune mechanism, It is considered that a useful application of the organic germanium compound can be newly provided.
[Problems to be solved by the invention]
[0006]
However, at present, no research has been conducted on the action of the organogermanium compound in the digestive tract.
[Means for Solving the Problems]
[0007]
The present invention has been made against the background of the above circumstances, and the formula (1)
[Chemical 3]
Wherein R _{1 to} R ₃ are a hydrogen atom or the same or different lower alkyl group or phenyl group having 1 to 4 carbon atoms, X is a hydroxyl group, an O-lower alkyl group having 1 to 4 carbon atoms, an amino group or OY. [Wherein Y represents a metal, lysozyme, or a basic amino acid.]
The present invention provides a secretory promoter for bile pigment , which comprises an organic germanium compound represented by the formula:
[0008]
BEST MODE FOR CARRYING OUT THE INVENTION
The present invention is described in detail below.
[0009]
The secretory promoter for bile pigment according to the present invention may be expressed as a specific organic germanium compound represented by the above formula (1) [hereinafter referred to as an organic germanium compound (1). As an active ingredient, this compound will be described first. This compound is based on germanylpropionic acid in which a propionic acid derivative having substituents R _{1 to} R ₃ and an oxygen functional group OX and a germanium atom are bonded. In this basic skeleton, germanium atoms and oxygen atoms are bonded at a ratio of 2: 3.
[0010]
The substituents R _{1 to} R ₃ are the same or different, and each represents a hydrogen atom, a so-called lower alkyl group such as a methyl group, an ethyl group, a propyl group, or a butyl group, or a substituted or unsubstituted phenyl group. The substituent X represents a salt of a carboxylic acid represented by a hydroxyl group, an O-lower alkyl group, an amino group, or OY. Y represents a basic compound represented by a basic amino acid such as a metal such as sodium or potassium (but not limited to a monovalent one), or lysozyme or lysine.
[0011]
Thus, the organic germanium compound (1) having the above structure is a known compound, and can be produced by various methods. For example, the substituents R _{1 to} R ₃ are hydrogen atoms and the substituent X is As for the hydroxyl group compound, trihalogermylpropionic acid such as trichlorogermylpropionic acid may be hydrolyzed as shown in the following reaction formula.
[Formula 4]
[0012]
The formula (1) representing the organic germanium compound corresponds to a state in which the organic germanium compound is isolated as a crystal. In an aqueous solution, the germanium-oxygen bond is hydrolyzed, and for example, the substituents R _{1 to} R ₃ are substituted. In a compound in which a hydrogen atom and substituent X is a hydroxyl group,
[Chemical formula 5]
The organic germanium compound (1) can also be represented by the following formula.
[Chemical 6]
[0013]
The secretion promoting agent for bile pigments of the present invention comprises the organic germanium compound (1) as an active ingredient, but there is no particular limitation on the administration method, and it is oral, parenteral or topical. Can be administered.
[0014]
The dosage form is not particularly limited, and is formulated into an orally administered drug such as a tablet, powder or capsule, or a parenteral drug such as an injection, using a known carrier as necessary. It is.
[0015]
Further, the content of the organogermanium compound (1) in the secretion enhancer of the bile pigment of the present invention may be set as necessary, for example, about 1 to 1500 mg / l dosage unit. For example, it may be about 1 to 100 mg / Kg / day.
[0016]
【Example】
Hereinafter, the present invention will be described in detail based on examples, but this does not limit the present invention in any way.
[0017]
Synthesis of organic germanium compound Trichlorogermane (Cl ₃ GeH) is added to acrylic acid (CH ₂ CHCOOH) to obtain trichlorogermylpropionic acid (Cl ₃ GeCH ₂ CH ₂ COOH ) , and this is hydrolyzed. An organic germanium compound (1-1) [a compound in which R _{1 to} R ₃ are hydrogen atoms and X is a hydroxyl group in the formula (1)] was synthesized.
[0018]
Example 1
Using 3 weeks old experimental male Wistar rats, the rats were divided into 2 groups (5 animals each) of this drug administration group and control group so that the average body weights of both groups were equal after pre-breeding for 1 week. . The feed administered with 0.005% of the organic germanium compound (1-1) to the normal composition was freely fed to this agent-administered group, and the feed having the normal composition was freely fed to the control group. In addition, water was given freely.
[0019]
For both groups, the changes in food intake and body weight during breeding were measured, feces were collected in the late stage of the 18-day breeding period, decapitated on the final day and dissected. Whole blood was collected, serum was obtained by centrifugation, and the weights of major organs were measured. The contents of the cecum were removed after collection.
[0020]
Results 1) Appearance of feces From 2 to 3 days after the start of breeding, the feces of the rats in the control group were grayish white, whereas the administration group was clearly yellow. There was no difference in body weight change and food intake between the administration group and the control group.
[0021]
2) Changes in organs The cecum collected from rats in the administration group was clearly more yellowish than the cecum collected from rats in the control group. When the cecal contents were added to the diluent, this increased yellowness was found to be due to the cecal contents. There was no change in the appearance of other organs.
[0022]
3) Dye in cecal contents The contents of the cecum collected from the rats of the administration group and the control group were extracted with chloroform-methanol (2: 1). The yellow pigment was easily extracted from the cecum contents collected from the control group, and the final extract was obtained from the cecum collected from the administration group rats compared to the control group. It was remarkably yellow. Moreover, as a result of qualitative analysis by thin layer chromatography with silica, it was found that the main component of the yellow pigment was urobilin (stercobilin).
[0023]
4) Quantitative determination of the dye The solvent of the extract was distilled off, dissolved in a constant volume in 5 ml of chloroform, and filtered through a membrane filter to prepare a sample. This sample was quantitatively analyzed by HPLC. The results are shown in FIG. As can be seen in FIG. 1, the amount of pigment per unit weight (1 g) of cecal contents collected from rats in the administration group was significantly higher than that from the control group.
[0024]
Example 2
For 3 healthy adults, a capsule containing 250 mg of the organic germanium compound (1-1) was administered in 2 capsules twice a day, and the stool on the 5th and 7th days was collected. Two people had noticeable yellowing.
[0025]
【Effect of the invention】
As is clear from the above examples, the secretory promoter for bile pigments of the present invention provides a new type of abile agent mainly composed of an organic germanium compound.
[0026]
Further, since the organic germanium compound is a synthetic product, it can be stably supplied unlike crude drugs.
[Brief description of the drawings]
1 is a graph showing the results of quantitative analysis by HPLC of a dye in an extract in Example 1. FIG.

Claims (2)

Formula (1)
Wherein R _{1 to} R ₃ are a hydrogen atom or the same or different lower alkyl group or phenyl group having 1 to 4 carbon atoms, X is a hydroxyl group, an O-lower alkyl group having 1 to 4 carbon atoms, an amino group or OY. [Wherein Y represents a metal, lysozyme, or a basic amino acid.]
A secretory promoter for bile pigment , comprising an organic germanium compound represented by the formula: The secretion promoting agent for bile pigment according to claim 1, comprising an organic germanium compound in which R _{1 to} R ₃ are hydrogen atoms and X is a hydroxyl group in formula (1) as an active ingredient.