JPH0733678A - Prevention and therapy of urolithiasis, tea leaf extract having preventive and therapeutic effect therefor and preventive and therapeutic agent therefor containing the same extract - Google Patents

Abstract

PURPOSE:To obtain the extract capable of dissolving uroliths composed mainly of a phosphate and of discharging them outside the body, excellent in the safety and useful for a livestock, a pet animal, etc., by extracting tea leaves, e.g. with water alone. CONSTITUTION:The extract can be obtained by extracting tea leaves such as oolong tea leaves with water alone or a mixture of water and an organic solvent such as ethanol. In addition, this extract is administrated preferably in an amount of 5 to 30g/100kg in the case of oral administration and a livestock.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a tea leaf extract having a preventive and / or therapeutic effect on urolithiasis, a preventive / therapeutic agent for urolithiasis in livestock and pet animals, and the urine of livestock and pet animals to which it is administered. Related to stone disease prevention and treatment methods.

[0002]

2. Description of the Related Art In recent years, in livestock production, the productivity per unit area has been increased and the fattening technique has been modified. In order to carry out more efficient breeding management, it has become common for livestock to be fed a large amount of standardized feed such as concentrated feed such as bran over a long period of time. With the changes in feeding conditions such as such a rich feeding of concentrated feed, urinary stone disease has frequently occurred in livestock.

Urolithiasis is a disease in which inorganic salts dissolved in urine form calculi due to changes in urinary components, which enter the urinary tract to cause various disorders. Of this,
What a calculus is formed in the urinary system is called a urinary calculus or urinary calculus, which causes urethral obstruction and is accompanied by clinical symptoms such as dysuria is called urolithiasis or urolithiasis. In addition, depending on the location of the stone, it is called renal stone disease, bladder stone disease, urethral stone disease, etc. As a general clinical finding, fine gray-white stones attached to the pubic area, decreased appetite,
Diarrhea, etc. are seen. In severe cases, hematuria, urine drip, urinary retention,
Some may present with colic symptoms, limb open posture, etc., and may die from uremia, bladder rupture, etc.

This disease is a typical urological disease that frequently occurs in castrated fattening cattle in Japan. The mechanism of its onset has not been clarified yet, but it is considered that the stone formation is promoted especially by the change of the metabolism of phosphorus when the concentrated feed is supplied in large amounts.

The main component of calculi found in urolithiasis is magnesium phosphate in Japan, but urate and silicate are also included.

[0006] Conventionally, for the treatment and prevention of this disease, it has been effective to lower the pH of urine and continuously administer ammonium chloride for the purpose of diuretic effect. May cause poisoning. In general, fattening cattle have low levels of carotene and vitamin A in blood, and a deficiency or deficiency state has been observed particularly in the urolithiasis multi-incidence group, and deficiency of vitamin A is a factor of urolithiasis. Therefore, administration of a mixture of vitamins A and D ₃ is said to be effective, but the effect varies considerably depending on the nature and composition of the stone.

Japanese Unexamined Patent Publication (Kokai) No. 50-12217 discloses a method for treating / preventing urolithiasis in cattle, which comprises orally administering a magnesium salt to cattle. This method
Phosphoric acid in the feed reacts with the administered magnesium salt in the digestive tract to form insoluble magnesium phosphate, which inhibits the absorption of phosphate in the intestinal tract, and phosphorus in the urine due to excessive intake of phosphate To prevent the excretion of.

Japanese Unexamined Patent Publication (Kokai) No. 58-67624 discloses a veterinary drug composition comprising a green leaf powder, a urine acidifying agent, a mild diuretic and a calcium chelating agent for preventing the urological system of cats. It is disclosed. In this method, no green leaf powder has been identified at all, and substitution with synthetic chlorophyll is also possible, and it is stated that these result in carotene and other minor elements contained in the plant. This veterinary composition serves to acidify urine, help prevent inflammation of the urinary system, reduce the amount of dry substances in urine, and help prevent urinary diseases such as urolithiasis.

Japanese Unexamined Patent Publication (Kokai) No. 63-87948 discloses a feed additive for livestock which contains an extract of Vladimir oedum and cyclodextrin. Vladimir beetle has been folklorely effective for a long time in promoting human urinary stone excretion and preventing the increase of stones. However, since the dried leaves or the extract thereof are repelled by cattle violently as they are, the extract is mixed with cyclodextrin so that the cow does not repel it.

Further, Japanese Patent Application Laid-Open No. 4-208227 also discloses a urinary stone preventive and therapeutic agent containing ammonium chloride and an extract of Vladivost.

[0011]

[Problems to be Solved by the Invention] Administration of ammonium chloride, which has been conventionally carried out as a drug therapy for the prevention and treatment of urolithiasis, does not have a desired therapeutic effect and may further impair the health of cattle. In addition, Vladimir oak is not practical because it is difficult to obtain in large quantities.

[0012] Further, removal of calculi by surgical operation leads to a decrease in productivity, and there is a high possibility of recurrence, so it cannot be said to be an appropriate treatment method. In order for fattening farmers to cultivate international competitiveness, it is urgently necessary to establish a therapeutic and preventive method for urolithiasis for stable management with the aim of improving productivity and meat quality.

Further, urolithiasis is a urinary tract disease not only in fattening cattle but also in dairy cows, pigs, lamb, other domestic animals, dogs, cats and other pet animals, and has the same problem as fattening cattle. Has occurred.

Therefore, the first object of the present invention is to have a urolithiasis-preventing / treating effect obtained from tea leaves, which is a raw material that is highly safe for domestic animals or pet animals and can be easily obtained in large quantities. A tea leaf extract is provided.
A second object of the present invention is to provide a preventive and / or therapeutic agent for urolithiasis of livestock and pet animals, which comprises the above extract of tea leaves. Further, a third object of the present invention is to prevent urolithiasis by administering the above-mentioned urolithiasis preventive / therapeutic agent to livestock and pet animals.
It is to provide a treatment method.

[0015]

Means for Solving the Problems The inventors of the present invention have conducted various searches in order to find a substance containing a component having a urolithiasis-preventing / treating effect. Therefore, the present invention has been completed and the present invention has been completed.

That is, the first object of the present invention is to provide a tea leaf extract having a preventive and therapeutic effect on urolithiasis obtained by extracting tea leaves with water alone or a mixture of water and an organic solvent. The second object of the present invention is to provide a prophylactic / therapeutic agent for urolithiasis of livestock and pet animals, which comprises the tea leaf extract alone or the tea leaf extract and a physiologically acceptable excipient. These have been achieved by the methods for preventing and treating urolithiasis of livestock and pet animals, which administer the above-mentioned agents for preventing and treating urolithiasis.

The present invention will be described in detail below. The tea leaves used in the present invention are unfermented green tea such as sencha, gyokuro, and matcha, and fermented tea leaves such as Toryu tea, black tea, and Puer tea.
The tea leaves may be used alone or in combination of two or more.

The solvent used for extracting the tea leaf extract is one or two selected from water alone or water and lower organic alcohols such as methanol, ethanol, propanol and isopropanol, and lower organic solvents such as acetone and methyl ethyl ketone. It is a mixture of two or more species. The polar solvent alone cannot efficiently extract the active ingredient of the present invention, so that it must be a mixture with water, and the mixing ratio is
The polar solvent content is preferably 90% by volume or less.

The ratio of the tea leaf to the extraction solvent at the time of extraction is not particularly limited, but 20 to 100 times by weight of the solvent is preferable to 1 weight of the tea leaf.

The extraction temperature is conveniently in the range of room temperature to the boiling point of the solvent under normal pressure, and the extraction time is preferably in the range of 10 minutes to 24 hours, although it depends on the extraction temperature.

The obtained tea leaf extract is provided in a liquid or jelly-like wet state or in a dry state such as powder, granules or blocks.

The preventive and / or therapeutic agent for urolithiasis of the present invention comprises the tea leaf extract obtained as described above alone or the tea leaf extract and a physiologically acceptable excipient. Examples of physiologically acceptable excipients include sucrose, starch,
Excipients such as mannitol, sorbitol, lactose, glucose, cellulose, talc, calcium phosphate, calcium carbonate, such as cellulose, methyl cellulose, hydroxymethyl cellulose, polypropylpyrrolidone,
Binders such as gelatin, gum arabic, polyethylene glycol, sucrose, starch, etc., such as starch, carboxymethyl cellulose, hydroxypropyl starch, sodium hydrogen carbonate, calcium phosphate, calcium citrate, etc. disintegrants, such as magnesium stearate, aerosyl, talc, lauryl. Lubricants such as sodium sulfate, eg, preservatives such as sodium benzoate, sodium bisulfite, methylparaben, propylparaben, etc., stabilizers such as citric acid, sodium citrate, acetic acid, eg methylcellulose, polyvinylpyrrolidone, aluminum stearate. And the like, dispersants such as hydroxypropylmethyl cellulose, and diluents such as water.

Further, it can be used in combination with other conventionally used preventive / therapeutic agents for urolithiasis, nutrients and the like.
For example, a mixture of the tea leaf extract and ammonium chloride and / or salt, vitamin A, vitamin D ₃ , calcium, and various other diuretics can be considered.

The dosage form is not particularly limited, and liquids, powders, granules, tablets, pills, bolers and the like can be mentioned. The content ratio of the tea leaf extract in the preparation is generally 5 to 7
It is 0% by weight, preferably 40 to 50% by weight.

When the preventive and / or therapeutic agent for urolithiasis of the present invention is administered to livestock or pet animals, it generally varies depending on the animal species, age (monthly age), sex, degree of symptoms, dosage form, administration system, etc. Oral administration in livestock animals: Tea leaf extract 5-30g
/ 100Kg, 50-300 by oral administration in pet animals
mg / 1 Kg is preferred.

The oral administration includes a method of administering the tea leaf extract itself or a preparation containing the tea leaf extract directly, or by mixing with the drinking water or the feed, and the like.

In the present invention, livestock includes cattle, pigs, goats, sheep and the like, and pet animals include dogs, cats and the like.

[0028]

EXAMPLES The present invention will be described in more detail with reference to examples. Example 1 (Extraction of tea leaf extract) 10% of 45% ethyl alcohol per 100 kg of Choryu tea leaf
00 liters were added, and extraction was performed at room temperature for about 20 hours. The extract was filtered through diatomaceous earth and concentrated under reduced pressure (60 ° C, 150 ° C).
The solid content concentration was adjusted to 30 to 40% by means of a torr), and the powder was pulverized by a spray dryer to obtain 18 kg of a bird dragon tea leaf extract (hereinafter sometimes referred to as UE).

Formulation Example 1 (Liquid) Toryur Tea Leaf Extract Extract Prepared in Example 1 50 g Saccharin 1 g Methylcellulose 50 g Distilled Water Appropriate amount 500 ml

Formulation Example 2 (powder) Goryu tea leaf extract extract prepared in Example 100 100 g Lactose 620 g Carboxymethylcellulose sodium 200 g Hydroxypropylcellulose 30 g Talc 50 g 1000 g

Test Example 1 (Therapeutic effect test by administration to cattle with urolithiasis) 4-month-old Holstein male fattening cow 1 diagnosed with urolithiasis
0 animals were tested and divided into 2 groups of 5 animals each. The bird dragon tea leaf extract extract (powder) prepared in Example 1 had a weight of 100 k.
What was suspended in water at 5 g or 10 g per g was forcibly orally administered to each group, and urine was collected before administration, 3 days, 7 days, and 13 days after administration, respectively. As a method for diagnosing the degree of urolithiasis, urine pH and urinary phosphate crystal value (U
PV) was measured. The obtained results are shown in Table 1 below. In addition, pH and phosphate crystal value (UP
The transition of V) is shown.

Table 1 Days after administration 0 3 7 13 (5 g / 100 kg administration group) Urine pH 8.5 8.3 8.0 6.8 UPV in urine UPV 3 6 10 18 (10 g / 100 kg administration group) Urine pH 8.5 7.3 7.2 7.0 Urine UPV 18 22 24 10

The phosphate crystal value (UPV) in Table 1 and FIGS. 1 and 2 was measured as follows. 2 ml of 1M ammonia water was added to 2 ml of the collected urine supernatant,
After standing for 1 minute, this was centrifuged at 3000 rpm for 15 minutes. After discarding 3.6 ml of the supernatant and shaking the residue well, it was put in a hematoclick capillary tube and centrifuged at 3000 rpm for 10 minutes. The crystal height was measured relative to the height of the entire sample in the hematoclick capillary and this was expressed as "%" as the phosphate crystal value (UPV).

As is clear from Table 1 and FIGS. 1 and 2, the urine of cattle with urolithiasis having calculi with phosphate as the nucleus shows high alkalinity, but the ginger tea extract is extracted. By administration of urine, the urine collected 3, 7, and 13 days after the administration was compared with that before administration, and the pH was shifted from the alkaline range to the neutral to weakly acidic range, and the phosphate crystal value (UPV)
Was gradually increased compared to before administration. From these results, when the tea leaf extract was administered to cattle with urolithiasis, the urinary phosphate-based stones were dissolved and eluted in the urine, resulting in an increase in phosphate crystal values. it is conceivable that. Along with that, it is considered that the pH of the urine was in the normal range and the condition in which calculi were hard to occur was improved. Test Example 2 (calculus dissolution test) A solubilization test was carried out using the ginseng tea leaf extract prepared in Example 1 by using a calculus mainly containing ammonium magnesium phosphate collected from the bladder of a cow with urolithiasis. .

After urinary stones were crushed in a mortar, 1 each was put in a test tube.
20 mg each of water, 1% Goryu tea leaf extract and extract solution (1% UE) and 0.1% Goryu tea leaf extract and extract solution (0.1% UE) were added at room temperature. . The magnesium and phosphorus concentrations (mg / dl) in the solution were measured 0, 15, 30, 60 and 120 minutes after the addition. The obtained results are shown in Table 2 below and FIGS. 3 and 4.

Table 2 Elapsed time (min) 0 15 30 60 120 (Mg elution amount water 0 0.3 0.4 0.5 0.5 mg / dl) 1% UE 0 1.3 2.0 2.3 2.5 0.1% UE 0 0.9 1.4 1.8 2.0 (P elution Water 0 0.3 0.5 0.6 0.7 mg / dl) 1% UE 0 1.6 2.5 2.8 3.1 0.1% UE 0 1.2 1.9 2.2 2.3

The magnesium concentration (mg / dl) is
The xylidine blue method and phosphorus concentration (mg / dl) were measured by the p-methylaminophenol reduction method.

As a result of this test, when the dragon stone extract extract solution was added to a urinary stone sample containing magnesium ammonium phosphate as the main component, the magnesium and phosphorus concentrations in the solution rapidly increased. Are believed to dissolve. That is, it is clear that the tea leaf extract has a function of dissolving phosphate stones. The results of this test support the results of Test Example 1.

[0039]

EFFECTS OF THE INVENTION According to the present invention, urinary stones containing phosphate as a main component can be dissolved and discharged to the outside of the body, which is highly safe for living organisms and can be easily and mass-produced. A tea leaf extract having advantages such as being obtained and having excellent urolithiasis-preventing / treating effect, a urolithiasis-preventing / treating agent for livestock and pet animals, and a method for preventing / treating urolithiasis are provided. .

[Brief description of drawings]

FIG. 1 is a bird's-tea leaf extract 5 g / 100 kg.
It is a figure which shows the time transition of pH and phosphate crystal value (UPV) of urine collected from the urolithiasis cattle which administered the.

[Fig. 2] Fig. 2 is an extract of the bird dragon tea leaves 10g / 100k.
It is a figure which shows the time transition of pH and phosphate crystal value (UPV) of the urine extracted from the urolithiasis cattle which administered g.

[Fig. 3] Fig. 3 is a graph showing the time course of magnesium elution amount in the case of adding water and an extract solution of Choryu tea leaves to crushed urinary stones.

[Fig. 4] Fig. 4 is a diagram showing the time course of the amount of phosphorus elution when water and a bird dragon tea leaf extract solution are added to crushed urinary stones.

 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Hisaya Suda 3-4-10 Nihonbashihonmachi, Chuo-ku, Tokyo Kaken Pharmaceutical Co., Ltd.

Claims (6)

[Claims] 1. A tea leaf extract having a preventive and therapeutic effect on urolithiasis obtained by extracting tea leaves with water alone or a mixture of water and an organic solvent. 2. The tea leaf extract according to claim 1, wherein the tea leaf is Goryu tea leaf. 3. A preventive and / or therapeutic agent for urolithiasis of livestock and pet animals, which comprises the tea leaf extract extract according to claim 1 alone or the tea leaf extract extract and a physiologically acceptable excipient. 4. The preventive and / or therapeutic agent for urolithiasis according to claim 3, which contains the tea leaf extract in an amount of 5 to 50% by weight. 5. A method for preventing and treating urolithiasis of livestock and pet animals, which comprises administering the agent for preventing and treating urolithiasis according to claim 3. 6. The method for preventing and treating urolithiasis according to claim 5, wherein the livestock is bovine.