JP6964960B2 - Nutritional composition to promote postoperative wound and / or anastomotic recovery - Google Patents

Description

The present invention relates to nutritional compositions for promoting postoperative wound and / or anastomotic recovery.

When surgery involving gastrointestinal anastomosis, such as total gastrectomy or duodenal resection, which requires gastrointestinal anastomosis, is performed, it may be fasted for a long period of time due to food leakage at the anastomotic site. You may be forced to extend your hospital stay.

Conventionally, it has been said that nutritional management is important as a response during the perioperative period (before and after surgery) (Non-Patent Document 1: Preoperative and postoperative nutritional management; Takashi Higashiguchi, Akihiro Ito, Fujita Health University School of Medicine) Surgery / Palliative Care Course MEDICAMENT NEWS (1912): 1-4, 2007.).

Among them, it has been reported that nutrients such as glutamine, ω-3 fatty acids, vitamins, and trace elements are required to enhance immunity and aim for early recovery after surgery, but collagen peptide has not been reported. ..

Preoperative and postoperative nutritional management; Takashi Higashiguchi, Akihiro Ito, Fujita Health University School of Medicine, Department of Surgery and Palliative Care MEDICAMENT NEWS (1912): 1-4, 2007.

An object of the present invention is to provide a nutritional composition for promoting the recovery of a wound and / or anastomosis after surgery.

The present inventor has found that the expression of collagen m-RNA, which is an index of collagen synthesis after surgery, is increased by giving a nutritional composition containing collagen peptide to an anastomotic surgery model animal. This suggests the possibility of early recovery after surgery with gastrointestinal anastomosis as well as conventional nutritional management with nutrients.

At the anastomotic site, the gastrointestinal tract is anastomosed and the tissue is reconstructed by expressing collagen synthesis. By orally administering a collagen peptide in order to increase the collagen synthesizing ability, it is considered that the collagen synthesizing ability is improved by the absorbed collagen decomposition product.

The gist of the present invention is as follows.
(1) A nutritional composition containing a collagen peptide for promoting the recovery of a wound and / or anastomosis after surgery.
(2) The composition according to (1), which is used so that 10 ± 3 g of collagen peptide is administered per day.
(3) The composition according to (2), which contains 10 ± 3 g of collagen peptide per administration unit and is used so as to be administered in one administration unit per day.
(4) The composition according to any one of (1) to (3), which is also used so that trace elements are also administered.
(5) The composition according to (4), wherein the trace element is at least one selected from the group consisting of iron, zinc and selenium.
(6) Used to administer at least one trace element selected from the group consisting of 5.0 ± 3.0 mg iron, 12 ± 6 mg zinc and 50 ± 25 μg selenium per day, (5). The composition described.
(7) The composition according to (6), which contains 5.0 ± 3.0 mg of iron, 12 ± 6 mg of zinc and 50 ± 25 μg of selenium per administration unit, and is used to be administered in one administration unit per day. thing.
(8) The composition according to any one of (1) to (7), which is also used so that vitamins are also administered.
(9) Vitamins include vitamin A and / or β-carotene, vitamin B ₁ , vitamin B ₂ , vitamin B ₆ , vitamin B ₁₂ , vitamin C, niacin, folic acid, vitamin D ₃ , vitamin E, biotin, and pantoten. The composition according to (8), which is at least one selected from the group consisting of acids.
(10) 300 ± 250 μg (equivalent amount of retinol activity) of vitamin A and / or β-carotene, 3.0 ± 1.5 mg of vitamin B ₁ , 3.0 ± 1.5 mg of vitamin B ₂ , 5.0 ± 2.5 mg of vitamin per day B ₆ , 10 ± 5 μg-Vitamin B ₁₂ , 500 ± 250 mg Vitamin C, 15 ± 7.5 mg Niacin, 550 ± 275 μg Folic acid, 5.5 ± 2.75 μg Vitamin D ₃ , 20 ± 10 mg Vitamin E, 50 ± The composition according to (9), wherein at least one vitamin selected from the group consisting of 25 μg of biotin and 10 ± 5 mg of pantothenic acid is administered.
(11) per dosage unit, vitamin A and / or β- carotene 300 ± 250 [mu] g (retinol activity equivalent), vitamin B ₁ of 3.0 ± _1.5mg, 3.0 ± 1.5mg of vitamin B _2, 5.0 ± 2.5 mg Vitamin B ₆ , 10 ± 5 μg-Vitamin B ₁₂ , 500 ± 250 mg Vitamin C, 15 ± 7.5 mg niacin, 550 ± 275 μg folic acid, 5.5 ± 2.75 μg Vitamin D ₃ , 20 ± 10 mg Vitamin E, The composition according to (10), which comprises 50 ± 25 μg of vitamin and 10 ± 5 mg of pantothenic acid and is used to be administered in 1-dose units per day.
(12) The composition according to any one of (1) to (11), wherein the dosage form is liquid, gel-like, powder, granule or tablet, and the dosage form is orally administered.

The composition of the present invention makes it possible to promote the recovery of the wound and / or anastomotic site after surgery.

Hereinafter, embodiments of the present invention will be described in more detail.

The present invention provides a nutritional composition containing a collagen peptide to promote postoperative wound and / or anastomotic recovery.

Collagen peptide is obtained by hydrolyzing gelatin to reduce its molecular weight, but it has a lower gelling effect when dissolved in water than gelatin, has excellent water solubility, and has the property of being easily dissolved in cold water. There is. In addition, collagen, which is the source of collagen peptide, can be extracted from pigs, cows, birds, fish skins and bones.

When the collagen peptide is administered using the composition of the present invention, the dose of collagen peptide is preferably 3 to 20 g and preferably 5 to 15 g per day, for example, administration per day. The composition containing the amount as one administration unit may be used so as to be administered once a day. In a preferred embodiment of the composition of the present invention, 10 ± 3 g of collagen peptide is administered per day, for example, a composition containing 10 ± 3 g of collagen peptide per administration unit. It should be used so that it is administered in 1-dose units per day.

The compositions of the present invention may also be used such that trace elements are also administered. The trace element may be at least one selected from the group consisting of iron, zinc and selenium. In postoperative patients, iron deficiency may occur, so it is advisable to add iron to the composition. In order to promote the recovery of the wound and / or anastomosis of the postoperative patient, it is preferable to add a nucleic acid / protein synthesis cofactor, for example, zinc. Zinc binds to albumin, globulin, etc. in the body and circulates throughout the body. It is known that in hypozincemia, zinc is mobilized into the liver from epithelial cells such as the skin and digestive tract, bones, etc., and deficiency in these epithelial tissues occurs early. In addition, zinc may be added as a cell growth promoting factor that can promote cell differentiation and proliferation. When zinc is used, it is preferable to use a zinc component (zinc yeast) produced by yeast that is permitted as a food additive and has a high bioavailability. Moreover, zinc sulfate may be used. Zinc is a constituent of superoxide dismutase, which is an antioxidant enzyme, and selenium is a constituent of glutathione peroxidase, which is an antioxidant enzyme. It may be added to the substance. Antioxidants have a strong reducing effect on the oxidative stress associated with surgery.

When a trace element is administered using the composition of the present invention, the daily dose is preferably 1.0 to 50.0 mg for iron, preferably 2.0 to 10.0 mg, and 1.0 to 45.0 mg for zinc. Suitable, 1.5 to 20.0 mg is preferable, 5.0 to 440 μg of selenium is suitable, 10 to 120 μg is preferable, and for example, a composition containing a daily dose as one administration unit is contained once a day. It should be used to administer. In a preferred embodiment of the composition of the present invention, at least one trace element selected from the group consisting of 5.0 ± 3.0 mg of iron, 12 ± 6 mg of zinc and 50 ± 25 μg of selenium is administered per day. So that, for example, a composition containing 5.0 ± 3.0 mg iron, 12 ± 6 mg zinc and 50 ± 25 μg selenium per dosing unit is administered in one dosing unit per day. It should be used.

The compositions of the present invention may also be used such that vitamins are also administered. The vitamins are at least one selected from the group consisting of vitamin A, β-carotene, vitamin B1, vitamin B2, vitamin B6, vitamin B12, vitamin C, niacin, folic acid, vitamin D3, vitamin E, biotin, and pantothenic acid. It should be a seed.

Antioxidant vitamins such as vitamin A, β-carotene, vitamin C, and vitamin E are expected to act as antioxidants having a strong reducing action against oxidative stress associated with surgery. Since these antioxidant vitamins act at different stages, it is preferable to use them at the same time rather than using them alone. Vitamin C, which is one of the above antioxidant vitamins, not only acts as an antioxidant, but is also directly involved in cAMP enhancement and lipid solubilization action, and also causes collagen formation, xenobiotic detoxification, and induction of interferon production. It is preferable to include at least vitamin C as an antioxidant vitamin because it has various actions such as antihistamine action, immune function enhancement, antivirus, and antibacterial action. Vitamin A has not only a function as an antioxidant vitamin but also a function of promoting cell differentiation and proliferation. By promoting cell proliferation and differentiation, it is possible to promote proliferation of immune cells such as T cells, so that it is possible to improve immunity and enhance defense against infection.

Vitamin B ₁ , B ₂ , B ₆ , B ₁₂ , niacin, folic acid, and pantothenic acid are expected to act as metabolic cofactors. These vitamins that support metabolism have a role as coenzymes related to the metabolism of sugars, lipids, and amino acids, and are important components for life activities. For example, vitamin B ₁ as TPP (thiamine pyrophosphate) and B ₂ as FMN (flavin mononucleotide) and FAD (flavin adenine dinucleotide) are involved in the glycolytic system, TCA circuit, and regulation of β-oxidation. Vitamin B ₆ is involved in amino acid metabolism as such pyridoxal phosphate. Niacin is involved in glycolysis and lipid metabolism as NAD and NADP. In addition, pantothenic acid, as CoA, is involved in the TCA cycle, amino acid metabolism, and lipid metabolism. Folic acid, as FH4, is involved in amino acid metabolism and nucleic acid metabolism. Vitamin _{B 12} is as CoB12, involved in amino acid metabolism. Therefore, since these vitamin groups are components constituting different coenzymes, it is preferable to use all of the above-mentioned vitamin groups as the above-mentioned metabolic cofactors. In particular, the intake of these vitamins depends on the amount of energy and protein intake, and tends to be totally deficient in postoperative patients with low food intake. Therefore, it is preferable to add all the above vitamin groups to the composition in order to efficiently supply the intracellular energy required for the postoperative patient.

In addition, folic acid, vitamin B ₁₂ , β-carotene, zinc and the like can be expected to act as cell growth promoting factors that can promote cell differentiation and proliferation. By promoting cell proliferation and differentiation, it is possible to promote the proliferation of immune cells such as T cells, which are one of the lymphocytes, thus improving immunity and healing power from wounds and anastomosis due to surgery. It is possible to increase the defense against infection.

In addition to the above vitamins, vitamin D (for example, vitamin D ₃ ) for promoting the absorption of calcium can also be added. Alternatively, biotin may be added. Biotin is a coenzyme that has a fatty acid metabolism effect, and its deficiency may cause dermatitis and hair loss.

When vitamins are administered using the composition of the present invention, a daily dose of 20 to 2,700 μg (equivalent amount of retinol activity) of vitamin A and / or β-carotene is appropriate (for example, an equal amount of retinol activity). Vitamin A is 0 to 2,700 μg, β-carotene is 0 to 32.4 mg), 50 to 850 μg (retinol activity equal amount) is preferable (for example, vitamin A is 0 to 850 μg, β-carotene is 0 to 1.2 mg), Vitamin B ₁ is suitable for 0.1 to 20 mg and 0.5 to 10 mg, vitamin B ₂ is suitable for 0.1 to 20 mg and 0.5 to 10 mg, and vitamin B ₆ is suitable for 1.0 to 55. Mg is suitable, 1.5 to 20 mg is preferable, vitamin B ₁₂ is suitable for 2.0 to 100 μg, 5.0 to 30 μg is suitable, and vitamin C is suitable for 40 to 1,500 mg, 60 to 1,000 mg. For niacin, 2.0 to 350 mg is suitable, 5.0 to 30 mg is preferable, for folic acid, 100 to 1,000 μg is suitable, 150 to 900 μg is preferable, and vitamin D ₃ is 0.2 to 100 μg. 0.5 to 50 μg is preferable, vitamin E is 5 to 850 mg, 10 to 500 mg is preferable, biotin is 5.0 to 200 μg, 10 to 150 μg is preferable, and pantothenic acid is suitable. , 2.0 to 100 mg is suitable, 5.0 to 30 mg is preferable, and for example, a composition containing a daily dose as one administration unit may be used so as to be administered once a day. In a preferred embodiment of the composition of the present invention, 300 ± 250 μg (equivalent amount of retinol activity) of vitamin A and / or β-carotene (eg, 0 to 550 μg of vitamin A, 0 to 0 to β-carotene) per day. 6.6 mg), 3.0 ± 1.5 mg of vitamin B ₁ , 3.0 ± 1.5 mg of vitamin B ₂ , 5.0 ± 2.5 mg of vitamin B ₆ , 10 ± 5 μg of-vitamin B ₁₂ , 500 ± 250 mg of vitamin C, 15 ± 7.5 At least one selected from the group consisting of mg niacin, 550 ± 275 μg folic acid, 5.5 ± 2.75 μg vitamin D ₃ , 20 ± 10 mg vitamin E, 50 ± 25 μg biotin, and 10 ± 5 mg pantothenic acid. Vitamins are used to be administered, eg, 300 ± 250 μg (equivalent retinol activity) of vitamin A and / or β-carotene (eg, 0-550 μg of vitamin A, β-carotene) per dose unit. 0-6.6 mg), 3.0 ± 1.5 mg of vitamin B ₁ , 3.0 ± 1.5 mg of vitamin B ₂ , 5.0 ± 2.5 mg of vitamin B ₆ , 10 ± 5 μg of-vitamin B ₁₂ , 500 ± 250 mg of vitamin C, A composition containing 15 ± 7.5 mg niacin, 550 ± 275 μg folic acid, 5.5 ± 2.75 μg vitamin D ₃ , 20 ± 10 mg vitamin E, 50 ± 25 μg biotin, and 10 ± 5 mg pantothenic acid daily. It is preferable to use it so that it is administered in 1-dose units.

Further, the composition of the present invention may contain coenzyme Q10, galactooligosaccharide and the like. Since coenzyme Q10 has a strong antioxidant effect, it can be expected to act as an antioxidant having a strong reducing effect on oxidative stress associated with surgery. In addition, since it is a component involved in ATP production, it can be expected to have the effect of smoothly metabolizing nutrients by supplementing it. Galactooligosaccharide is a functional oligosaccharide that increases bifidobacteria in the digestive tract and exhibits an intestinal regulating effect, and by supplementing it, the state of the digestive tract can be kept normal and smooth absorption of nutrients can be expected.

When administered using the composition of the present invention, the daily dose of coenzyme Q10 is preferably 3 to 30 mg, preferably 5 to 25 mg, and the galactooligosaccharide is 10 to 10 g. Therefore, 0 to 5 g is preferable, and for example, a composition containing a daily dose as one administration unit may be used so as to be administered once a day.

Administration of the composition of the present invention may be performed orally. In some cases, enteral administration methods such as nasal tube, gastrostomy, and intestinal fistula may be used.

The composition of the present invention may be formed into a dosage form such as powder, granules, tablets, or liquid by mixing the above components, but in order to make it easily ingestible by postoperative patients, it is a liquid (drink). Type) or gel (jelly type), powdered product is preferable. If it is a liquid, gel, or powder product, it can be taken orally by postoperative patients who can take it orally.

Further, in the case of making a gel-like product, it is preferable to dissolve the gelling agent in water, add each component of the composition to the gelling agent, fill the container, and cool the product. If necessary, the gelling agent may be heated to dissolve it in water, the container may be sealed, or the composition may be sterilized by heating or the like.

In order to improve the taste when taken orally, fruit juice or vegetable juice can be used instead of water. The amount added to the composition of the present invention is preferably 10 to 500 g, preferably 35 to 250 g, for water, fruit juice or vegetable juice, as the content per administration unit. Examples of fruit juice or vegetable juice include blueberry juice, grape juice, grapefruit juice, lemon juice, orange juice, carrot juice, apple juice, pineapple juice, peach juice, banana juice, and the like. Carrot juice, blueberry juice and grape juice are preferable because they can soften the acidity and odor of group B. For liquid products, the volume per dosing unit is preferably 20-250 ml, preferably 30-150 ml, more preferably 125 ± 25 mL. The water content of the liquid product can be, for example, about 110 ± 22.0 g per administration unit. In the case of a gel product, the mass per administration unit is preferably 20 to 250 g, preferably 30 to 150 g, and more preferably 80 ± 16 g. The water content of the gel product can be, for example, about 53 ± 10.6 g per administration unit.

As the gelling agent, thickening polysaccharides such as dextrin, agar, xanthan gum, locust bean gum, carrageenan and pectin, gellan gum, silium seed gum, tara gum, guagam, glucomannan alginic acid, tamarind seed gum, cellulose and the like can be used. It is possible, and it is preferable to use one kind or two or more kinds of thickening polysaccharides. The amount of the gelling agent added to the composition of the present invention is preferably 0.5 to 5.0 g, preferably 0.75 to 2.0 g, and more preferably 0.82 ± 0.16 g per administration unit.

The gel strength of the gel-like product is not particularly limited as long as it can be ingested by the postoperative patient, but the gel strength at 20 ° C. is preferably ^{7,200 ± 2,000 N / m 2.}

Further, when the gel strength is 7,200 ± 2,000 N / m ² , the adhesion energy is 50.3 ± 40 J / m ³ and the cohesiveness is more preferably 0.23 ± 0.5 J / m ^3. Such a gel having low adhesion and high cohesiveness has excellent swallowing suitability.

Gel strength can be measured as follows. As a gel strength measuring device, use a Yamaden texture meter and a plunger of φ20 mm x 8 mm, and measure at a measurement temperature of 20 ° C, a compression speed (speed of pushing the plunger) of 10 mm / s, and the number of times the plunger is pushed twice. I do.

In the above gel strength measurement, the adhesion energy is measured as negative energy when the plunger is pulled out after being pushed in once.

The cohesiveness is measured as the ratio of the energy of the first time and the energy of the second time when the gel is pushed twice in the above gel strength measurement.

Furthermore, glucose, sugar, flavors, acidulants, sweeteners (acesulfame K, sucralose, etc.) and the like may be added to the composition of the present invention. Also, if necessary, excipients, binders, bulking agents, disintegrants, surfactants, lubricants, dispersants, buffers, preservatives, coating agents, preservatives, colorants, plasticizers, etc. It may be added.

The amount of energy of the composition of the present invention is appropriately 10 to 200 kcal, preferably 20 to 125 kcal per administration unit. Regarding general ingredients, for example, the protein content is about 5 to 50 g, the carbohydrate content is about 3 to 30 g, the sodium content is about 1 to 500 mg, and the water content per administration unit. The amount should be about 30 to 150 g.

An example of the standard composition table of the composition of the present invention (in 125 mL ± 25 mL for one drink type or 80 g ± 16 g for one jelly type) is shown in Table 1 below.

Raw materials include collagen peptide (gelatin), galactooligosaccharide, sugar, glucose, fruit juice (orange, apple, pine apple, peach, banana), dried yeast, coenzyme Q10, vitamin C, lactic acid Ca, fragrance, acidulant, vitamin E. , Thickening polysaccharide, Na citrate, Sweetener (Acesulfam K, Sclarose), Niacin, Ca pantothenate, Vitamin B ₆ , Vitamin D, Vitamin A, Vitamin B ₂ , Vitamin B ₁ , β-carotene, Folic acid, Vitamin B _{12 and the} like can be mentioned.

The composition of the present invention may contain electrolytes such as potassium, calcium, magnesium and phosphorus derived from raw materials. It is desirable to include electrolyte components such as potassium, calcium, magnesium, and phosphorus in an amount that does not exceed the Japanese dietary intake standard (male 50-59 years old level).
Sodium (target amount (sodium chloride equivalent): less than 8 g)
Potassium (approximate amount: 2500 mg, target amount: 3000 mg or more)
Calcium (recommended amount: 700 mg)
Magnesium (recommended amount: 350 mg)
Phosphorus (upper tolerable amount: 3000 mg, standard amount: 1000 mg)

Hereinafter, the present invention will be described in detail based on Examples, but the present invention is not limited to these Examples.
[Example 1] Preparation of a wound healing model of a rat gastrointestinal (small intestine) anastomosis and evaluation of the wound healing effect of CP10-Measurement of gene expression intensity by real-time PCR-
Purpose A group in which the m-RNA gene expression intensity of collagen expressed in the process of repairing the anastomotic site was measured using a rat gastrointestinal anastomosis model, and a beverage containing 10 g of collagen peptide "CP10; manufactured by Nutry Co., Ltd." was administered (hereinafter referred to as "Nutry"). , CP10 group) and the non-administered group (hereinafter referred to as Cnt group) were compared and examined for the expression intensity of various collagen genes.
Test method
Six-week-old rats (Slc: SD (SPF) 6-week-old male; obtained from Nippon SLC Co., Ltd.) were received and bred on a low-protein diet (purchased from Oriental Yeast Co., Ltd.). The test substance (CP10 containing 10 g of collagen peptide) was orally administered to 7-week-old rats twice daily for 7 days (2.5 mL / kg x 2 / day (0.2 g / kg x 2 / day as collagen peptide)). ). The control and untreated groups received the same volume of water for injection orally (2.5 mL / kg x 2 / day). The animals were fasted from the 7th day. The abdomen was opened under mixed solution anesthesia (intravenous administration) of medetomidine hydrochloride 0.15 mg / kg, midazolam 2 mg / kg, and butorphano 2.5 mg / kg, and anastomotic surgery was performed on the small intestine. After abdominal closure, a 5% sugar solution was orally loaded at a rate of 5 mL / kg. Feeding was performed the day after surgery. After the operation, the cleavage pressure was measured by the following method. That is, rats were lethal under anesthesia with a mixture of medetomidine hydrochloride 0.15 mg / kg, midazolam 2 mg / kg, and butorphano 2.5 mg / kg, and the tissue around the anastomotic site was peeled off to remove the surrounding adhesion tissue. Photographs were taken of all surgical sites. The intestine including the surgical site was removed, and air was injected into the intestine at a rate of 150 mL / hr using a syringe pump (Terfusion Syringe Pump STC-525, Terumo Corporation) to directly pressurize the small intestine. The pressure in the intestinal tract is measured via a pressure transducer (Nihon Kohden Co., Ltd., DX 360) and a blood pressure measurement amplifier (Nihon Kohden Co., Ltd., AP 641G), and a recorder (Nihon Kohden Co., Ltd., Thermal Array Recorder RTA) 1200) Recorded on. The pressure immediately before the anastomotic site was cleaved was defined as the cleft pressure. In the untreated group, the abdomen was closed immediately after the abdomen was opened. The cleavage pressure was measured 120 hours after the operation. Administration of the test substance continued after surgery as well. The administration on the day of measurement of the cleavage pressure was performed only on the first administration on that day. Animals were bred individually and body weight and food intake were measured twice a week. The tissue was removed and stored frozen.

In addition, the tissue stored frozen was pulverized and genetically analyzed. A bead-type cell crusher Micro SmashTM (TOMY Seiko Co., Ltd.) was used for crushing. A portion of the extracted total RNA was used to measure the concentration and RIN value of the total RNA solution.

After that, a reverse transcription reaction was performed, and the gene expression analysis of collagen I and III was performed by real-time PCR. Based on the obtained data, the Ct value was calculated using the analysis software ABI PRISM SDS 2.1. Furthermore, the relative value was calculated from the obtained Ct value.
Results The cleavage pressure in the control group was 94.3 mmHg 120 hours after surgery. In the CP-10 administration group, the value was 106.3 mmHg, which was higher than that in the control group. At that time, the gene expression results of collagen I and III at the anastomotic site were 14.26 for collagen I and 15.27 for CP10 group, 9.84 for collagen III and 11.86 for CP10 group, and both collagen I and III. Gene expression was high in the CP10 group.

The present invention can be used to promote recovery of a wound and / or anastomosis after surgery.

Claims (10)

A nutritional composition containing collagen peptide for promoting the recovery of a postoperative wound and gastrointestinal anastomosis. The composition according to claim 1, wherein 10 ± 3 g of collagen peptide is administered per day. The composition according to claim 2, which contains 10 ± 3 g of collagen peptide per administration unit and is used so as to be administered in one administration unit per day. The composition according to any one of claims 1 to 3 , wherein a trace element, which is at least one selected from the group consisting of iron, zinc, and selenium, is also used to be administered. The composition according to claim 4 , wherein at least one trace element selected from the group consisting of 5.0 ± 3.0 mg of iron, 12 ± 6 mg of zinc and 50 ± 25 μg of selenium is administered per day. thing. The composition according to claim 5 , which comprises 5.0 ± 3.0 mg of iron, 12 ± 6 mg of zinc and 50 ± 25 μg of selenium per dosing unit and is used to be administered in one dosing unit per day. In addition, at least one selected from the group consisting of vitamin A and / or β-carotene, vitamin B1, vitamin B2, vitamin B6, vitamin B12, vitamin C, niacin, folic acid, vitamin D3, vitamin E, biotin, and pantothenic acid. The composition according to any one of claims 1 to 6 , wherein the vitamins which are seeds are also used to be administered. 300 ± 250 μg (equivalent retinol activity) of vitamin A and / or β-carotene, 3.0 ± 1.5 mg of vitamin B1, 3.0 ± 1.5 mg of vitamin B2, 5.0 ± 2.5 mg of vitamin B6, 10 ± 5 μg per day -Vitamin B12, 500 ± 250 mg of vitamin C, 15 ± 7.5 mg of niacin, 550 ± 275 μg of folic acid, 5.5 ± 2.75 μg of vitamin D3, 20 ± 10 mg of vitamin E, 50 ± 25 μg of biotin, and 10 ± 5 mg The composition according to claim 7 , wherein at least one vitamin selected from the group consisting of pantothenic acid is administered. 300 ± 250 μg (equivalent amount of retinol activity) of vitamin A and / or β-carotene, 3.0 ± 1.5 mg of vitamin B1, 3.0 ± 1.5 mg of vitamin B2, 5.0 ± 2.5 mg of vitamin B6, 10 ± per unit of administration 5 μg-Vitamin B12, 500 ± 250 mg Vitamin C, 15 ± 7.5 mg Niacin, 550 ± 275 μg Folic Acid, 5.5 ± 2.75 μg Vitamin D3, 20 ± 10 mg Vitamin E, 50 ± 25 μg Biotin, and 10 ± The composition according to claim 8 , which contains 5 mg of pantothenic acid and is used to be administered in 1-dose units per day. The composition according to any one of claims 1 to 9 , wherein the dosage form is a liquid, gel, powder, granule or tablet, which is orally administered.