JPH01294630A - Remedy for improving for hyperlipemia - Google Patents

Abstract

PURPOSE:To obtain improving agent of hyperlipemia effective for all cases containing remedy and preventive of arteriosclerosis, especially for I-type, containing phytic acid and salt of said acid as active ingredient. CONSTITUTION:Phytic acid and salt of said acid, e.g., non-toxic metal salt, non-toxic salt with organic base, non-toxic salt with basic amino acid or non- toxic salt with organic ester residue, is contained in the aimed agent as active ingredient. Dose of administration to human is suitably 1-100mg/kg for 1 day for one adult. In production of various preparations, various phytic acids or the mixtures in the range of pH6-8 is suitably selected in accordance with utilizing object such as drug, table luxuries or foods. Said composition is able to continuously use with a high safety and effect is further continued for improving of symptom, etc., by performing successive use or administration.

Description

DETAILED DESCRIPTION OF THE INVENTION (Industrial Field of Application) The present invention relates to a therapeutic agent for improving hyperlipidemia containing phytic acid and its salts as an active ingredient.

(Prior art) Hyperlipidemia refers to serum lipids, namely cholesterol,
It is a disease in which there is an abnormal increase in one or more of triglycerides, phospholipids, and free fatty acids, resulting in various disorders.

Pathological conditions are classified into type 1, in which endogenous triglycerides accumulate, type I, in which exogenous triglycerides accumulate, and type V, a combination of these.

Conventionally, various compounds have been known as hyperlipidemia improving agents; for example, glufibrate, dextran sulfate, nicotinic acid preparations, etc. are used for type III cases, and glogesterone nicotinate is used for type V cases. Hormone agents such as However, although some amylase inhibitors have been reported to be effective against type 1, there have been no reports of any drugs that are definitely effective.

On the other hand, phytic acids are widely distributed in the plant world as calcium, magnesium, and sometimes potassium salts.For example, rice bran contains 9.5 to 14.5X phytic acid, and industrial phytic acid or is the raw material for myo-inositol, which is derived from this.

Phytic acid and its salts have a wide range of uses. Calcium phytate has traditionally been used as a calcium reinforcing agent, rice bran itself and sodium phytate are used to prevent calcium stones, and potassium phytate is used to prevent hypercalcemia. It is used for treatment and to control hypercalciuria in sarcoidosis patients. It is also used in a variety of fields, including as a fermentation aid in the production of sake and wine, as a metal removal agent using the chelating action of phytic acid, as an antioxidant in the presence of iron and calcium ions, and as a corrosion-protective agent for metals. It's here.

However, there have been no reports of its hyperlipidemia-improving effect, especially as a preventive or therapeutic agent for arteriosclerosis.

(Problems to be Solved by the Invention) In view of the above-mentioned conventional techniques, the present invention aims to provide a hyperlipidemia improving agent that is effective in treating and preventing arteriosclerosis, especially in all cases including type 1. That is.

(Means for solving Section U) The present inventors discovered in the course of nutritional experiments with phytic acid that oral administration of phytic acid reduced body odor, bad breath, urine odor, and sweat odor, In particular, we investigated the effect of removing alcoholic halitosis, and found that this was due to the enzymatic inhibitory effect or biological metabolic effect of phytic acid, and furthermore, we found that phytic acid has a lipid-lowering effect.

Based on the above findings, the present invention proposes a therapeutic agent for improving hyperlipidemia, which contains phytic acid and its salt as an active ingredient.

The therapeutic agent for improving hyperlipidemia according to this invention can improve, treat, and prevent hyperlipidemia in humans when administered, and since phytate is odorless, it can be administered orally. It is easy to administer, and its effects can be expected by mixing phytic acid and its salts with food and drink, sprinkling or mixing them into dishes, or orally administering them in the form of powder or granules.

The dosage when administered to humans depends on the symptoms, dosage form, etc.;
he is appropriate.

In addition, in preparing various preparations, since phytic acid is a strong acid, various phytic acid salts in the range of I) 86 to 8 and mixtures thereof are generally used. Selected appropriately.

In this invention, the phytates include potassium phytate, sodium phytate, ammonium phytate,
Non-toxic metal salts and organic bases such as arginine phytate, ornithine phytate, lysine phytate, histidine phytate, monoethanolamine phytate, jetanolamine phytate, triethanolamine phytate, and glucamine phytate. non-toxic salts of
Examples include non-toxic salts with basic amino acids and non-toxic salts with organic ester residues.

The number of moles of various bases required to adjust 1 mole of phytic acid to DH of 6 to 8 is shown in Table 1, for example.

Phytic acid and its salts in Table 1 are tasteless and odorless and can be easily administered orally.
It can be mixed with the animal's drinking water, sprinkled or mixed into dishes, feed, etc., or administered in the form of powder or granules.

(Effects of the Invention) In summary, according to the present invention, since phytic acid and its salts are used as main components, a lipid-lowering effect on hyperlipidemia can be easily obtained by oral administration.

Furthermore, according to the present invention, phytic acid or its salt is solid;
Since it is effective regardless of its liquid form, it can be taken orally.

Furthermore, the composition of the present invention is highly safe and can be used continuously, and its effects in improving symptoms and the like can be sustained by continuous use or administration.

(Example) Further, the present invention will be explained in detail by giving examples.

Example 1 Test Example 1; Lipoprotein lipase (LPL) induction effect (a) Test animals, method Wistar rat body weight 190-200. using 1
After fasting for 2 hours or more, sodium phytate was administered to 4 groups in the range of 1 to 50 μm into the tail vein under anesthesia, and blood was collected from the descending vena cava 5 minutes after administration.

Sodium citrate was added to the collected blood to give a final concentration of 3 mg/ml, and the blood was centrifuged to obtain plasma.

(b) Test method The LPL activity in the obtained plasma was expressed by measuring the amount of released fatty acids.

Free fatty acids were measured using the NEFAC Test Wako Kit (manufactured by Wako Tsumugi Pharmaceutical Co., Ltd.).

(c) Test results (1) Changes in free fatty acids due to changes in dosage
As shown in the figure.

When measured in the range of 1 to 50 air/kg/body weight, it was found that free fatty acids were induced depending on the amount of sodium phytate, and doses of more than 50 air/kg/body weight were lethal. .

(2) Results of induction of free fatty acids over time When 20 kg/body weight was administered intravenously, the results showed that LPL was maximally induced 5 minutes after intravenous injection, as shown in Figure 2.
It lasted about 40 minutes.

From the following results, it was found that the product of the present invention has a lipid-lowering effect.

2; Cyphilophilicity test■ 0.5g of the garlic seasoning preparation according to Production Example 13 described below together with other seasonings <33■ as phytic acid)
was added to beefsteak meat and cooked, and a panel of 20 people tasted it together with the meat without phytic acid added.The quality of taste, texture, and smell were compared with the untreated meat, and a palatability test was conducted. The results shown in Table 2 were obtained.

Table 2 From the results, it has good taste and can be used as a food seasoning material.
It turned out to be effective.

3; Cyphilophilicity test■ Three patients with diabetic hyperlipidemia drank 30ml (100ml as phytic acid) of the drink prepared in Production Example 12, which will be described later, once a day for 7 consecutive days. A questionnaire survey was conducted regarding the feel of the soft drink and the feeling of taking it, and the results shown in Table 3 were obtained.

Table 3: The drug was administered to give an image of it as a health food, and although no comment can be made on the effects from this result, it was found to be effective in terms of its suitability as a food.

Example 2 Composition Ifitic acid (as anhydride) 660. Add 29 g of sodium hydroxide and an appropriate amount of purified water to adjust the pH to 6. To 660 g of phytic acid (as anhydride), add 412 g of potassium hydroxide and an appropriate amount of purified water to adjust the pH to 6. Prepared liquid composition: 660 g of hafitic acid (as anhydride), add 177 g of lithium hydroxide and an appropriate amount of purified water, and adjust the pH to 6. Add ethanolamine to 660 g of diphytic acid (as anhydride). 581K and an appropriate amount of purified water were added to adjust the Ell to 8.To 660 g of phofitic acid (as anhydride), 979 g of jetanolamine and an appropriate amount of purified water were added to adjust the pH to 8.
Phytic acid (as anhydride) to a liquid composition adjusted to 660. and triethanolamine 1805. and an appropriate amount of purified water to bring the pN
To 660 g of tophytic acid (as anhydride), add 1657 N-methylglucamine and an appropriate amount of purified water, and add O
Liquid composition Tifitin i11 with H adjusted to 7! (as anhydride) 660g L-
Add 1,510 g of arginine and an appropriate amount of purified water, and
A liquid composition containing 66G of rifitic acid (as anhydride) and 1753G of L-histidine. and a liquid composition whose pH was adjusted to 6 by adding an appropriate amount of purified water Nufitic acid (as anhydride) eeog, sodium hydroxide 118sr, potassium hydroxide 478t, calcium chloride (dihydrate) 6.08f, phosphoric acid A solution prepared by adding 157 g of disodium hydrogen (as anhydrous) and an appropriate amount of purified water to adjust E)H to 9. can be converted into

In addition, regarding compositions made of these as liquids or powdered,
Pharmaceutical compositions can be prepared and formulated.

Example 3 A formulation composition was prepared from the composition obtained in Example 2, and various formulations were manufactured from it.

Formulation Composition A Lactose was added to Composition Nu (containing 200 ml of phytic acid) to make a total amount of 1000 ml.

Pharmaceutical composition B Composition N (contains 1oollIr as phytic acid)
Add lactose to make a total volume of 1000R.

Formulation Composition C Purified water was added to the composition (containing 100 μm of phytic acid) to make a total volume of 1000 μm.

Light silicic anhydride was added to the composition for formulation (containing 200 # of phytic acid) and dried to make a total amount of 1000 cm.

Preparation Example Preparation Example 1 (Elixir) Preparation Composition CIoog (10K as phytic acid) Fugata Orange Sei 24ml Ethanol 400ml Glycerin
400ml Purified water Total amount too+nl Collect a predetermined amount of the above ingredients and mix them uniformly to make a clear and colorless elixir. A single dose of 5 ml of this elixir contains 50 ml of phytic acid.

Production Example 2 (Capsule) Pharmaceutical composition A 200 rur (
Phytic acid: 40 ■) Lactose 20 ■ Corn starch 38 ■ Magnesium stearate 2. Collect a predetermined amount of the above ingredients and mix them uniformly.
Fill into No. 2 capsule. Incidentally, one capsule contains 40 μg of phytic acid.

Production example 3 (granules) Pharmaceutical composition A 6001. r (as phytic acid: 120 ■) Lactose: 140 mg Corn starch: 250 ■ Hydroxypropyl cellulose: 10 ■ A predetermined amount of the above components is collected, mixed uniformly, and wet-granulated using water and ethanol to form granules. Note that 1 g of this granule per dose contains 120 μg of phytic acid.

Production Example 4 (Powder) Pharmaceutical composition A was packaged in an aluminum heat seal package.
It is made into sachets of 1.5 g.

Production Example 5 (Tablets) Pharmaceutical composition A 100■ (20IIIr as phytic acid) Corn starch 19゜Crystalline cellulose 30゜Magnesium stearate 1■ Take a predetermined amount of the above ingredients, mix them uniformly, and then compression mold them to a diameter For 7 days, each tablet weighs 150 cm.

Furthermore, this one tablet contains 20 μg of phytic acid.

Production Example 6 (syrup) Pharmaceutical composition c sog (as phytic acid) White sugar 300g D-sorbitol (70g) 250g Methyl paraoxybenzoate 03t Propyl paraoxybenzoate 015g Sodium citrate
1G.

Citric acid 1.5 as fragrance
2g purified water
A predetermined amount of the above components (10,100 O in total) was collected, dissolved and mixed to form a colorless and clear syrup. In addition, 100 ml of phytic acid is added to each dose of 20 ml of this syrup.
■Contains.

Production example 7 (dry syrup) Pharmaceutical composition 8100■ (10■ as phytic acid) Sodium citrate 2.4° Anhydrous citric acid 2.2M tragacanth powder
2.7g white sugar suitable
Quantity Hydroxypropylcellulose 3.0 ■Fragrance
A predetermined amount of the above components was sampled and mixed uniformly, followed by wet granulation using water and ethanol to form a dry syrup. This dry syrup contains 1 G of phytic acid per 1 ton of single dose.

Production Example 8 (lozenge) Pharmaceutical composition A 100 ■ (2ONt as phytic acid) White II 87G ■ Lactose
20m Magnesium Stearate 10 ■ 100g of Composition A and 870g of white sugar among the above ingredients are collected, mixed uniformly, wet granulated using water and ethanol, and dried at 35°C or lower. To this, 20 g of lactose and 10 g of magnesium stearate are added and mixed to form a lozenge with a diameter of 15III, 11ii:1r.

One tablet of this lozenge contains 20 mg of phytic acid.

Production example 9 (candy) Pharmaceutical composition 8 100 ■ (10+w as phytic acid) White sugar 2400 ■ Starch syrup 15
00mg Fragrance Trace Amount of the above ingredients Mix 240t of medium white sugar, 1sog of starch syrup, and 100g of purified water, heat and melt, filter for 6 minutes to remove foreign substances, concentrate this liquid under reduced pressure under heat to remove moisture, ℃Moisture 2-3
% candy dough was made.

The composition siog and a small amount of fragrance were added to this dough, mixed, and molded into a candy weighing 4 g each.This candy contained 10+w of phytic acid.

Production example 10 (limonade agent) Pharmaceutical composition C3+r (300μ as phytic acid) Simple syrup 2.5ml purified water
Total amount: 30a+1 Collect a predetermined amount of the above ingredients and mix them uniformly to make a limonade agent. A single 30 ml dose of this limonade contains 30 Gm of phytic acid.
Contains g.

Production Example 11 (granules) Pharmaceutical composition D500■ (as phytic acid 100■) Garlic powder 750■Lactose
Collect an appropriate amount of the above ingredients,
After uniformly mixing, the mixture was wet-granulated using water and ethanol to obtain granules. A single dose of 1.5 g of this granule contains phytin a100.

Production example 12 (drink) Pharmaceutical composition Cig.

(100■ as phytic acid) Honey 0.5g white sugar
2.0g citric acid
Appropriate amount of sodium citrate
Amount of varmint water
A predetermined amount of 1Mi of the above ingredients was taken and mixed uniformly to form a clear, colorless liquid for internal use. A single dose of 30 ml of this solution contains 100 μl of phytic acid.

Production Example 13 (Garlic seasoning) Pharmaceutical composition D 0.285 g (0.1 g as phytic acid) Avicel 0.18r! Garlic powder 0.75 f Light silicic anhydride 0.156 g Cornstarch
A predetermined amount of the above ingredients was taken and made into granules using a conventional method.

L Garden Yu Star 1 A stability test was carried out for the above-mentioned Production Examples 1 to 10, and the residual amount of phytic acid was measured. The results are shown in Table 4.

Table 4: Residual phytic acid X in stability test of production example < vs. indicated content (X))

[Brief explanation of the drawing]

FIG. 1 shows changes in blood free fatty acids with changes in phytic acid dosage, and FIG. 2 shows the results of a time-course induction test for free fatty acids after phytic acid administration. Patent applicant Sanwa Kagaku Institute Co., Ltd. Figure 1 Changes in free fatty acids due to changes in dosage (■/kg) Figure 2 til113 fllin)

Claims (2)

[Claims] (1) A therapeutic agent for improving hyperlipidemia containing phytic acid and its salt as an active ingredient. (2) Claim 1, wherein the salt of phytic acid is a non-toxic metal salt, a non-toxic salt with an organic base, a non-toxic salt with a basic amino acid, or a non-toxic salt with an organic ester residue. A therapeutic agent for improving hyperlipidemia.