WO1998006410A1 - Zinc-containing composition - Google Patents

Abstract

A zinc-containing composition comprising vitamin B6 and a zinciferous component, characterized in that the molar ratio of vitamin B6 to zinc contained in the component lies between 0.55:1 and 2.2:1. This composition is reduced in the side effects due to excessive intake of zinc and is therefore excellent in safety.

Description

 Description Zinc-containing composition Technology ffi hS

 INDUSTRIAL APPLICABILITY The present invention relates to a zinc-containing composition in which the risk of occurrence of excess zinc is reduced, and is applied to the fields of medicine, food, and the like. Background art

 Zinc is contained in all tissues and body fluids of humans and is the second highest-content trace element after iron. Trace elements are essential elements for living organisms that require a daily intake of 100 mg or less, and there are 15 types of substances other than zinc, such as iron and copper.

 Physiological effects of zinc include growth * skeletal development, activation of skin and its attached organs, maintenance of reproductive function, maintenance of taste and smell, effects on spirit and behavior, increased immune function, etc. can give.

 With the aging (aging) of zinc, the absorption rate decreases and urinary excretion increases, and the amount of zinc in the body decreases. In addition, zinc deficiency due to increased excretion due to exercise and sports, stress, etc. Is likely to occur. At present, daily oral dietary zinc intake is below 9 mg on average, well below the 15 mg daily requirement set in the United States. In particular, it has been reported that young women have recently consumed only 6 mg of zinc. Moreover, zinc is ubiquitous in food, making it difficult to secure the required amount. In addition, the amount of zinc required to prevent illnesses due to the effects of increased stress is often not obtained only by improving nutrition in daily diet, and sub-units are nutrients that may be deficient in vivo. It has been found.

On the other hand, with the prevalence of zinc preparations in the medical field, zinc overdose has recently become a concern. Excessive illness, such as a decrease in SOD activity in erythrocytes, has been reported following continuous administration of 50 mg daily in humans for 6 to 10 weeks. This set The dose is about 3 to 4 times the recommended daily allowance (RDA) prescribed in the United States, and the range of appropriate ft for zinc intake ft is narrow. Was a problem.

 An object of the present invention is to provide a highly safe zinc-containing composition in which the side effect of zinc due to excessive lead removal is reduced without impairing the physiological action of zinc. Disclosure of the invention

 The present inventors have conducted intensive studies in order to reduce the side effects caused by excessive intake of zinc. As a result, by combining vitamin B and zinc with a certain ratio, the physiological effects of zinc can be reduced. In particular, they have found that zinc excess can be prevented and zinc deficiency can be improved without impairing the skin beautiful effect of zinc, and the present invention has been completed.

That is, the present invention consists of vitamins and zinc-containing component, the proportion of zinc of vitamin B ₆ compound and zinc-containing component is 0.5 5: and characterized by a 1 molar ratio: 1 to 2.2 Is a zinc-containing composition.

 In the present invention, the effective dose of zinc is 1 to 50 mg per mouth, preferably 5 to 2 O mg for an adult.

The effective projecting amount of vitamin B ₆ such daily adult for zinc, the molar ratio 0.5 5: 1 to 2.2: 1, preferably 0.7 6: 1-2. 2: 1. If the zinc excess is used and the molar ratio of vitamin B ₆ to zinc is out of this range, the skin overgrowth caused by the zinc excess is deteriorated.

 The zinc-containing component in the present invention is a salt containing zinc, and any salt of an organic ion or an inorganic ion may be used as long as the anion is non-toxic. As an organic ion, for example,? Examples of ions of organic acids such as citrate, gluconic acid, cunic acid, malic acid, and tartaric acid, and examples of inorganic ions include ions of sulfuric acid, carbonic acid, chloride, phosphoric acid, and nitric acid. That is, examples of the zinc-containing component in the present invention include zinc dalconate, zinc quenate, zinc sulfate, zinc carbonate, zinc chloride, and zinc phosphate, with zinc gluconate and zinc sulfate being particularly preferred. These salts may be anhydrous or hydrated.

The vitamin B ₆ such as, for example, pyridinium Dokishin, pyridinium Dokisaru, pyridinium Dokisa Examples thereof include mine, pyridoxine phosphate, pyridoxal phosphate, pyridoxamine phosphate, and salts thereof. One or more of these vitamin B6s can be used.

 The zinc-containing composition of the present invention may contain other vitamins, for example, vitamin B group, vitamin C, vitamin A, vitamin D, vitamin E, and the like. One or more of these vitamins can be used.

 Further, the zinc-containing composition of the present invention may contain other minerals, for example, salts such as iron, copper, magnesium, and calcium. One or more of these minerals can be used.

 Crude drugs, crude drug extracts and the like can be blended as other medicinal ingredients.

The zinc-containing composition of the present invention may be used as it is or as necessary with other known additives such as a shaping agent, a disintegrant, a binder, a lubricant, an antioxidant, a coating agent, a coloring agent, and a fragrance. , Flavoring agents, surfactants, plasticizers, preservatives, sweeteners, pH regulators, and other substances commonly used in pharmaceutical technology are blended, and granules, powders, capsules, tablets, tablets, dry syrups, syrups, best Katachi嗨for implementing the _c invention may be oral preparations such as solutions

 Hereinafter, the present invention will be described in more detail based on examples and test examples.

 Example 1

 (Prescription example)

 70 mg of zinc gluconate (equivalent to 10 mg of zinc metal) Pyridoxine hydrochloride 24 mg

 Purified white sugar 5 g

 pH adjuster qs

 Purified water (total) 50 ml (pH 3.0)

 60% of the above ingredients at room temperature? After dissolving in purified water of (4) and adjusting the pH to a predetermined value, the volume of the solution was adjusted with purified water to prepare a drink.

 Example 2

(Prescription example) Zinc sulfate7-hydrate 22 mg (equivalent to 5 mg of gold-zinc) Pyridoxine hydrochloride 20 mg

 Purified white sugar 5 g

 PH preparation appropriate amount

 Purified water (total) 50 ml (H3.5)

 Prepared in the same manner as in Example 1.

 ^ Example 3

 (Prescription example) in 4 capsules

 Zinc gluconate 35 mg (equivalent to 5 mg zinc metal) Pyridoxine hydrochloride 20 mg

Vitamin B ₂ 24 mg

 Nicotinic acid amide 60 mg

 Vitamin C calcium 1 80 mg

 DH A oil 1 500 mg

 Magnesium aluminate metasilicate 1 65 mg

 Polysorbate 6 0 9 5 mg

 Wheat germ oil 1 6 1 mg

 After the above components were weighed and uniformly mixed, the resulting mixed powder was filled into soft capsules or soft capsules at 560 mg each to obtain four force busel agents.

 Test example

 (Experimental materials)

① Adjustment of experimental diet

 Ten kinds of experimental diets having the compositions shown in Table 1 were prepared by a conventional method. The zinc concentration was set to 2 mg for normal diet, 100 g for deficient diet, 0.3 mg / 100 g for deficient diet, and 6 mg for excess diet, and 100 g for 100 mg of vitamin. For vitamins, pyridoxine hydrochloride was used. 0.4 mg

100 g (No. l to 3) and pyridoxine hydrochloride: zinc = 0.22: 1 to 3.30

: 1 (iDol / niol ratio: No. 4 to 10). Table 1 Composition of experimental diet

Vitamin B _h concentration B β: Z n

 (iDg /! OOg) (mg / 100g) (mol / raol)

1 0.30 .4 0 .5 7: 1

 2 2 0. 4 0. 0 9: 1

 3 6 0. 4 0. 0 3: 1

 4 6 3 .1 0.2 2: 1

 5 6 7 .7 0 .5 5: 1

 1 0. 7 0. 7 6: 1

 7 6 1 5.5. 5 1.10: 1

 8 6 3 1 .0 2.2 0: 1

 9 6 4 6 .5 3.30: 1

 1 0 2 4 .7 1.00: 0: 1

(experimental method)

 (1) The 4-week-old male hairless rats were divided into 10 groups, and each group consisted of 8 animals. Each animal was bred for 4 weeks on 10 different diets (N 0.1 to 10), and the transepidermal water loss (TE WL) (No.

1-10) and erythrocyte Cu, Zn-S0D (Superoxide dismutase) activity (No.

2 to 10) were measured.

 (Measurement and quantification method)

 ① Measurement of transepidermal water loss (TEWL)

 Under shallow ether anesthesia, transepidermal water loss (T EWL) in the abdomen was measured using EvaPolymer Ichiichi EP-1 (ServoMed AB).

 ② Quantification of Cu.Zn—SOD activity in red blood cells

Under ether anesthesia, red blood cells were separated and washed from heparin blood collected from the inferior vena cava, lysed with water, hemoglobin was removed with ethanol / chloroform, water-ethanol layer was removed, water was added, and test samples (blood conversion) In 1/1000 dilution, The final ethanol content was 0.25%).

This sample: 0.1 ml, Reagent A (substrate solution): 0.2 ml (0.2 mM hydroxyxamine, 0.2 mM hypoxanthine, plI 7.0) 0.5 ml (water the KC NZ final concentration of 1 mM), reagent B (reaction start solution): 0. 2 ml (1. 2 5 mU Kisanchi Nokishide ^{Ichisu, 1 0- 4 MED TA- 2 N} a), buffer: 0. 5 ml (4 1.6 mM ,, P 3 1.2 mM Na ^ BO?) Was stirred with 37 for 30 minutes, and then reagent C (coloring solution): 2.0 ml (300 ml) g / m 1 sulfanilic acid, 5 ii g / m 1 N—1—naphthylenediamine, 16.7% acetic acid) and left at room temperature for 20 minutes, then absorbance at 550 nm The activity value of SOD was determined from the measured value of.

 (Result)

 The experimental results are shown in Tables 2, 3 and 4.

① Assuming that vitamin B 6 is -constant and the zinc concentration is changed, as is clear from Table 2, the TEWL value is low at a zinc concentration of 2 mg / 100 g and a zinc-deficient diet (zinc concentration 0%). 3 mg Z l 0 0 g) causes a worsening of skin conditions due to zinc deficiency, and a zinc overdose (zinc concentration 6 mg Z 100 g) causes a worsening of skin conditions due to excess zinc, and zinc ingestion The dosage range was very narrow. If only zinc is administered to remedy zinc deficiency, the risk of subhyperplasia is very high. Table 2 Effect of dietary zinc concentration on transepidermal water loss (TEWL)

(Vitamin B _B concentration is constant at O. Mg Z l OO g) Diet Zinc concentration BZ n Abdominal TE WL

 N o (mg / 100g) (iDol / mol) (g / m2h)

1 0.3 0.57: 1 56.3 ± 3.1

 2 0.09: 1 2 0.6 ± 1.4

 3 6 0.03: 1 39.7 ± 1.7

* TEWL values are indicated by average soil SEM ② From Table 3, it can be seen from Table 3 that when the zinc concentration of 6 mgZ, which causes hyperzincism, is 100 g, the molar ratio of vitamin B _fi to the zinc amount is 0.55: 1 to 2.2: 1. At (No. 4 to 8), the TEWL value was the normal control value (No. 2), and no zinc excess occurred.

Zinc hyperkinesia against zinc content the amount of vitamin B _beta zinc concentration of normal 2 m gZ 1 0 0 g to not cause, 1. molar ratio 00:. 1 if (N o 1 At 0), the TEWL value was not different from the normal control value (No. 2) fed on a normal diet, and even at the optimum zinc concentration, increasing vitamin Be did not adversely affect zinc absorption. Table 3 Transepidermal water root loss (TEWL) for zinc and vitamin B concentrations

 Effect Zinc Concentration B Z n Abdominal Ding EWL

 N 0 (nig / IOOg) ol / mo 1) (g / m2h)

2 2 0. 0 9: 1 2 0.6 ± 1.4

 3 6 0.03: 1 39.7 Sat 1.7

 4 6 0.22: 1 2 0.5 ± 0.4

 5 6 0.55: 1 16.7 ± 2.4

 6 6 0.76: 1 17.0 ± 1.4

 7 6 1.10: 1 17.0 Sat 1.3

 8 62.20: 1 18.0 ± 1.1

 9 63.30: 1 95.0 ± 1.6

1 0 2 1. 0 0: 1 2 0.7 ± 0.6

* TEWL values are shown as average soil SEM

③ Table 4 based, zinc causing hyperkinesia 6 mg / 1 00 0. 7 in a molar ratio amount against the amount of zinc addition of g vitamin B ₆ in the zinc concentration of 6:. 1-2 20: 1 in the case (N o. In 6 to 8), the SOD value became the normal normal control value (No. 2), and no zinc excess occurred.

In addition, at a zinc concentration of 2 mg / 100 g, which does not cause excessive zinc, and the addition of bismuth _{B in} a molar ratio of 1.0: 1 to the amount of zinc (N o 10)), the SOD value was not different from the normal control value (No. 2) fed with a normal diet, and even at the optimal zinc concentration, increasing vitamin な か っ did not adversely affect zinc absorption.

 Table 4 Measurement results of erythrocyte Cu, Zn-S OD activity Diet Zinc concentration B Z n S OD activity

 N o (rag / 100g) (mo 1 / mo]) (UNIT¾)

2 2 0. 0 9 1 1 0 0 ± 3

 3 6 0. 0 3 1 8 7 ± 2

 4 6 0.2 2 1 8 4 ± 3

 5 6 0.5 5 1 9 0 ± 5

 6 6 0.7 6 1 1 0 2 ± 4

 7 6 1. 1 0: 1 1 1 0 Sat 1

 8 6 2. 2 0: 1 1 0 3 ± 4

 9 6 3. 3 0: 1 9 5 ± 3

1 0 2 1. 0 0: 1 1 0 1 Sat 3

* S OD activity is based on the average value of dietary No. 2 as 100%.

 Average Soil SEM

Industrial applicability

According to the present invention, there is provided a highly safe zinc-containing composition in which side effects of zinc due to excessive intake of zinc are reduced without impairing the physiological action of zinc. By adjusting the compounding ratio of the vitamin B _6, zinc excess even dose rather difficulty appeared nitrous ^ excess symptoms, thus to be able to take zinc composition with confidence wide appropriate amount range of zinc intake It has become.

Claims

The scope of the claims 1. Vitamin B ₆ compounds and consists of zinc-containing component, vitamin B ₆ compound and zinc-containing component in proportions of zinc 0.5 5: 1 to 2.2: zinc, characterized in that the molar ratio of 1 Containing composition. 2. bi evening Min B ₆ compound and zinc-containing zinc ratio 0.7 in the component 6: 1 to 2. 2: 1 molar ratios claim 1, wherein the zinc-containing composition.