JPH01163128A - Liver function improver - Google Patents

Abstract

PURPOSE:To obtain a liver function improver useful for long-term administration, preventing or improving deterioration of disease state by administration during hepatic diseases, having no side effects, comprising a fermented metabolite of a bacterium belonging to the genus Lactobacillus as an active ingredient. CONSTITUTION:An liver function improver containing a fermented metabolite of Lactobacillus bifidus as an active ingredient. Lactobacillus longus may be cited as the bacterium belonging to the genus Lactobacillus. A fermented metabolite of a bacterium belonging to the genus Lactobacillus obtained by inoculating and cultivating the bacterium in a medium containing de-fatted powdered milk is used. The active ingredient is used alone or combined and directly administered. For example, the active ingredient is administered as a preparation composition such as solution or capsule. A dose is 1-10g per adult daily in oral administration and 100-2,000mg in intramuscular or blood administration.

Description

DETAILED DESCRIPTION OF THE INVENTION A. Field of Industrial Application The present invention relates to an agent for improving renal function, and more particularly to an agent for improving renal function containing fermented Bifidobacterium thoracotomy as an active ingredient.

BACKGROUND OF THE INVENTION Conventional Techniques In drug therapy for renal function decline, adrenocortical hormones, immunosuppressants, non-steroidal anti-inflammatory drugs, antihypertensive diuretics, etc. are used depending on the ingredients and symptoms of the disease. There is no particularly effective drug therapy for renal failure, where renal function is severely impaired, and patients with renal failure undergo painful hemodialysis, which affects 9,000 patients each year. It also affects people, and the total number of dialysis cases has now reached 70,000 nationwide.

In addition, it is well known that these treatments require high costs, are long-term, and place a severe burden on patients, both mentally and physically. Many of the renal function-improving drugs currently available have strong side effects and have limited therapeutic efficacy, and there are only a few drugs that are effective for renal failure.

8. Problems to be solved by the invention Therefore, with the aim of providing a renal function improving agent with few side effects and a wide range of therapeutic effects, as a result of intensive research, it was discovered that fermented metabolites of bifidobacteria can be used to treat renal diseases, particularly renal failure. For,
They discovered that it has a significant effect and completed the present invention.

21 Means for Solving Problems Accordingly, the present invention provides a renal function improving agent containing a fermented metabolite of Bifidobacterium as an active ingredient.

The bifidobacterium referred to in the present invention is Blfidobacterium.
There are no particular limitations on bacteria as long as they belong to the genus Bifidobacterium, for example, Bifidobacterium.
-dobacteria+ longum (Bifidobacterium longum), Bifidobacte
rlum breve (Bifidobacterium breve), BLfidobacterium 1nfan
-tis (Bifidobacterium infantis), Bifidobacterium bifl
dum (Bifidobacterium bifidum)-Bi
fidobacterium adole-scent
is (Bifidobacterium adrecusentis), Bifidobacterium pseudo
longum (Bifidobacterium pseudolongum) and the like.

As for the culture conditions, bifidobacteria are inoculated into a bifidobacteria growth medium containing skim milk powder, lactose, glucose, peptone, yeast extract, etc., and the temperature is, for example, 20 to 40°C, preferably 35 to 39°C. The culture time also varies depending on the amount of inoculated bacteria, but for example, when the amount of inoculated bacteria is 1 to 50%, the culture time is 2 to 60 hours, preferably 3 to 50%.
-5% and culture time for 20-48 hours.

Regarding the medium, the medium components include skim milk powder, lactose, glucose, peptone, yeast extract, etc., but there are no particular limitations on these medium components, and there should be no problem as long as the medium can grow bifidobacteria. do not have.

The bifidobacterium fermentation metabolite referred to in the present invention is a bifidobacterium fermentation metabolite after culturing under the above-mentioned conditions. It may also be sterilized or dried to solidify, including methods such as freeze-drying.

Next, the administration method and dosage of the renal function improving agent of the present invention containing fermented metabolites of Bifidobacterium as an active ingredient will be described.The renal function improving agent of the present invention may be administered either singly or in combination directly. However, to be more specific about the composition for administration, the composition will be as shown in the formulation examples below.

Examples include liquids, capsules, tablets, granules, powders, emulsions, injections, etc., but there is no need to limit them to these forms, and as long as they are in an administrable form, there is no need to worry about the onset of effects after administration. It's not a hindrance.

In other words, when preparing these oral solid preparations, after adding excipients to the main drug, and further adding binders, disintegrants, lubricants, coloring agents, preservatives, and flavoring agents as necessary,
Form into tablets, coated tablets, granules, powders, capsules, etc. by conventional methods. Examples of excipients include lactose, cornstarch, white sugar, glucose, sorbitol, crystalline cellulose, etc., and binders include polyvinyl alcohol, polyvinyl ether, ethyl cellulose, methylcellulose, gum arabic, tragacanth, gelatin, etc.
Hydroxypropyl cellulose with Shellat, hydroxypropyl starch, polyvinyl pyrrolidone, etc. are used as disintegrants, starch, agar, gelatin powder, crystalline cellulose, calcium carbonate, sodium bicarbonate, etc.
Calcium citrate, dextrin, pectin, etc.
Examples of lubricants include magnesium stearate,
Coloring agents such as talc, polyethylene glycol, silica, and hydrogenated vegetable oil are permitted to be added to pharmaceutical products, while preservatives such as sodium dehydroacetate, benzoic acid, epinephrine, and ascorbic acid are used as flavoring agents. As the flavoring agent, base syrup, cocoa powder, peppermint, aromatic acid, peppermint oil, dennou, cinnamon powder, etc. are used. These tablets and granules may be coated with sugar coating, gelatin coating, or other coatings as appropriate.

In addition, when preparing injections, the pH of the crude drug should be adjusted as necessary.
11 preparations, solubilizers, suspending agents, buffers, stabilizers, preservatives, etc. are added, and prepared as subcutaneous, intramuscular, or intravenous injections by conventional methods.

Possible administration methods include oral, intramuscular, and intravascular, but the daily dose for adults is 1 to 10 per day for bifidobacteria fermented metabolites obtained by freeze-drying.
g, 100-2,000 mg intramuscularly and intravascularly
Although it is desirable to administer the same amount, the dose can be increased or decreased as appropriate depending on the symptoms.

Examples will be described below, but the present invention is not limited to these in any way.

Example 1゜Bifidobacterium++tongue (
Bifidobacterium longum) and skim milk powder (10,
0%), milk N (1.5%), peptone (1.5%), yeast extract (0.5%), sodium chloride (0.5%),
Inoculated into a medium containing cysteine (002%) and at a temperature of 37
The culture solution cultured at ℃ for 20 hours was sterilized and filtered using a membrane filter to prepare bifidobacteria fermented metabolites.

Example 2 Bifidobacterium breve was inoculated onto a BL agar medium (Eiken Chemical Co., Ltd.) and cultured at a temperature of 37°C for 24 hours. The culture solution was sterilized using a membrane filter. The bacterial fermentation metabolite was further freeze-dried to prepare a bifidobacterial fermentation metabolite.

Example 3゜Bjfidobacterium 1nfantis
(Bifidobacterium infantis), skim milk powder (10.0%), lactose (1.5%), yeast extract (0.0%),
5%), sodium chloride (0,5%), cysteine (0
, 02%) and cultured at 37°C for 20 hours, the culture solution was sterilized using a membrane filter.
The bifidobacterium fermentation metabolite thus obtained was further freeze-dried to prepare a bifidobacterium fermentation metabolite.

Example 4゜Bifidobactertum bifidum
(Bifidobacterium bifidum) was inoculated onto a BL agar medium (Eiken Chemical Co., Ltd.) and cultured at a temperature of 37°C for 24 hours. Prepared.

Example 5゜Bifidobacterium adolescen
tis (Bifidobacterium adressentis), skim milk powder (10.0%), glucose (1.0%),
Yeast extract (0.5%), sodium chloride (05%),
Inoculated into a medium containing cysteine (0.02%) and at a temperature of 3.
After culturing at 7°C for 20 hours, filter the culture solution through a membrane filter.
The bifidobacterium fermentation metabolite was further freeze-dried to prepare a bifidobacterium fermentation metabolite.

Example 6゜Bifidob & cterium pseudolong
um (Bifidobacterium pseudolongum)
Skimmed milk powder (10,0%), glucose (2,0%), peptone (1,5%).

Yeast extract (0.5%), sodium chloride (0.5%)
, cysteine (0.02%) was inoculated and cultured at a temperature of 37° C. for 20 hours. The culture solution was sterilized using a membrane filter to prepare bifidobacteria fermented metabolites.

Example 7 Liquid fermentation metabolite of Bifidobacterium *l 20. Oif simple syrup 8.0g Sodium dehydroacetate 0.01g Make the total amount to 1001 with purified water, and use 1 or more as a miscible solution.

Book 1: Bifidobacterium fermentation metabolites prepared under the culture conditions of Example 1.

Example 8. Capsules Fermented metabolites of bifidobacteria *2 500. OH(
Lactose 500.0 mg
Starch 150.0 B Talc 25. Omg Magnesium Stearate 25.0 mg These ingredients are mixed through a sieve and placed in a hard capsule.

Book 2. This is a bifidobacteria fermented metabolite prepared under the culture conditions of Example 2.

Example 90 Tablet Fermented metabolite of Bifidobacterium *3 100. Og lactose 90.0 g starch 5.0 g talc
4.0 g Magnesium stearate 10 g or more were thoroughly mixed in a blender and tableted to produce 400 0.5 g tablets containing 0.25 g of bifidobacterium fermentation metabolites.

*3 Bifidobacterium fermentation metabolite prepared under the culture conditions of Example 3.

Example 10. Injection Fermented metabolites of Bifidobacterium *4 20. Og glucose 14.0 g Sodium chloride 5.6 g Epinephrine
1.0g phosphate buffer (0, IN,
pH6.0>1110.0 ml purified water,
Make the total volume 1.000ml, and sterilize it after passing.

*4: Bifidobacterium fermentation metabolite prepared under the culture conditions of Example 4.

Point 1: Effects of the Invention The renal function improving agent of the present invention exhibits a remarkable improvement effect on renal diseases, particularly renal failure, and has no side effects.

The effects of the present invention will be shown below using experimental examples.

Experimental Example 1゜Effect in renal disease model Adenine induces renal failure in rats〈Journal of Japanese and Chinese Medicine Society Vol. 1.3. No. 2.1986. P83-88
), therefore, rats were given adenine (400 mg/kg/
We investigated the improvement effect on renal function decline when administered orally. For the experiment, a Wlstar weighing around 150g was used.
Using rats, oral administration of adenine and intraperitoneal administration of the test substance were conducted in parallel for 5 consecutive days.The test substance used in the Yamanao experiment was the old f
Idobacterium Iongum (Bifidobacterium longum) with skim milk powder (10.0%),
A culture solution inoculated into a medium containing lactose (1.5%), yeast extract (0.5%), sodium chloride (0.5%), and cysteine (0.02%) and cultured at a temperature of 37°C for 20 hours. Fermented metabolites of bifidobacteria that have been sterilized using a membrane filter and the effect of improving renal function have been reported (Journal of the Japanese and Chinese Pharmaceutical Society Vol. 12. No. 2. 1985. P
365-371) The effects of Onpaito extract (an extract whose main components are Oga, medicinal ginseng, licorice, and Tsushi) were compared and studied.

``In addition, physiological saline was administered to the control group, and the dose to each individual was 10 1/kg. The renal function-improving effects of fermented metabolites of bifidobacteria were compared and studied using blood urea nitrogen content (BUN) and kidney weight as indicators.

Table 1 shows the BtlN values before and after administration, and the inhibition rate of the BUN value in the test substance administration group when the BUN value in the control group was taken as 100%.

Table 1 Effect of fermented metabolites of bifidobacteria on renal function of kidney disease model rats*: Significant difference was observed with a risk rate of 5% or less compared to the physiological saline administration control group.

As a result, blood urea nitrogen concentration was significantly lowered in the group treated with the fermented metabolite of Bebifidus Kan compared to the control group administered with physiological saline, and furthermore, the inhibition rate was higher than that of Onpai-to extract, a known substance. The results showed that the drug prevented and even improved renal function deterioration.

Next, Table 2 shows the left and right kidney weights of the bifidobacterium fermentation metabolite administration group, the Onpaito extract administration group, the physiological saline administration control group, and the untreated control group.

Table 2. Effect of fermented metabolites of bifidobacteria on kidney weight of kidney disease model rats*: Significant difference was observed with a risk rate of 5% or less compared to the physiological saline administration control group.

As shown in Table 2, the group treated with Onpai-to extract showed similar kidney weights and renal enlargement to the control group treated with physiological saline, whereas the group treated with thoracotomy as a substitute for fermentation of bifidobacteria. showed a significant difference in renal menstrual volume compared to the control group administered with physiological saline, suppressed renal swelling associated with exacerbation of renal failure, and exhibited a superior effect to Onpai-to extract.

Note that similar renal function improving effects were observed in Examples 2 to 10 as well.

Experimental Example 2゜Acute toxicity test As an acute toxicity test of fermented metabolites of bifidobacteria, W
5.000 mg/kg was administered orally and intraperitoneally to istar rats. As a result, no deaths or any toxic findings were observed.

As is clear from the above results, fermented metabolites of Bifidobacterium are effective in preventing or ameliorating the worsening of renal disease by administering them at the time of renal disease, and are effective in treating various renal diseases that require long-term administration. Since no side effects are observed,
It is extremely useful as a renal function improving agent.

Claims (1)

[Claims] A renal function improving agent whose active ingredient is a fermented metabolite of bifidobacteria.