JP2003012554A - Composition for alleviating invasion and wound treatment promotion - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a composition capable of alleviating invasion in an operation period and recovering a wound. SOLUTION: This composition for alleviating invasion and promoting wound treatment comprises an antioxidant, a metabolic auxiliary factor containing vitamin B1, B2, B6 and niacin and/or pantothenic acid, a cell growth promotion factor containing folic acid, vitamin B12 and/or vitamin A, a zinc-containing nucleic acid and protein synthesis auxiliary factor. By the composition containing such vitamins, zinc, etc., in vivo functions such as metabolism promotion, activation of cell growth, etc., are induced. In vivo activity and restoration action are improved by reinforcing an antioxidant action, etc. Aggression in an operation period is alleviated and recovery of a wound can be promoted.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a composition for reducing invasiveness / promoting wound treatment, and more particularly to a composition for reducing invasiveness / promoting wound treatment in the perioperative period.

[0002]

2. Description of the Related Art Generally, when undergoing surgery, anesthesia is administered prior to the surgery, and the effect of the anesthesia lowers the body temperature. This decrease in body temperature is accompanied by a decrease in cell activity, which also delays the recovery of the patient. In addition, for wounds left after surgery, measures to prevent wound infection are taken by administering antibiotics or applying antiseptic, but healing of the wound itself depends on the natural healing power of the patient. There is. Since such a perioperative invasion imposes a physical and mental burden on the patient,
There is a need for a drug that can be recovered early.

[0003]

However, it is difficult to suppress hypothermia during anesthesia during operation because the center of body temperature cannot be directly regulated by a drug or the like. Further, even if it is possible to improve the immunity with a drug such as immunoglobulin, it is difficult to improve the natural healing power of a patient.

On the other hand, various mechanisms for maintaining the activity of cells are provided in the living body. Energy is generated by these mechanisms to maintain body temperature. It has also been known that, due to the recent progress in cell biology, various factors having a healing power for wounds such as FGF (fibroblast growth factor) are present in the living body. Therefore, it is considered that by maintaining the homeostasis of the patient and improving the wound healing power through these intrinsic factors / mechanisms, perioperative hypothermia can be reduced and wound recovery can be promoted.

Therefore, the present invention reduces the perioperative invasion,
It is an object to provide a composition capable of healing a wound.

[0006]

[Means for Solving the Problems] In view of the above problems, as a result of intensive research, as a result of administering a substance capable of activating or assisting endogenous factors of the body such as vitamins and zinc to a patient, It was discovered that the hypothermia during the period can be reduced and the healing of the wound can be accelerated, and the present invention has been completed. That is, the present invention is a composition for reducing invasiveness and promoting wound healing, which comprises an antioxidant and a metabolic cofactor including vitamins B1, B2, B6, niacin or / and pantothenic acid,
It is characterized by containing a cell growth promoting factor containing folic acid, vitamin B12 or / and vitamin A, and a nucleic acid / protein synthesis cofactor containing zinc.

As described above, the composition containing vitamins and zinc induces functions in the living body, for example, promotion of metabolism, activation of cell growth, etc., and strengthens the antioxidant effect. It can improve the activity and repair action of the peritoneum, reduce perioperative invasion, and promote wound recovery.

Preferred embodiments of the above antioxidants include antioxidant vitamin agents such as vitamin C, vitamin E and β-
At least one of the carotenes can be included.

Further, according to one preferable aspect of the present invention,
Vitamin C, vitamin E, β-carotene, vitamin B
1, B2, B6, niacin, pantothenic acid, folic acid, vitamin B12, vitamin A, zinc, vitamin D3 and iron can be included.

Further, the dosage form of the present invention can be a liquid preparation in which the composition is dispersed in an ingestible liquid. In addition, fruit juice is used as this liquid, and it is possible to take it tastefully, and it is also possible to take other nutritional components at the same time.

[0011]

BEST MODE FOR CARRYING OUT THE INVENTION Embodiments of the present invention will be described in detail below.

The composition for reducing invasiveness / accelerating wound healing in the present embodiment broadly includes an antioxidant, a metabolic cofactor, a cell growth promoter, and a nucleic acid / protein synthesis cofactor.

The above antioxidant has a strong reducing action against oxidative stress associated with diseases and aging. Examples of such antioxidants include vitamin C, vitamin E,
Antioxidant vitamins such as β-carotene may be mentioned. Since these antioxidant vitamins have different stages of action, it is preferable to use one of them at the same time, rather than use them alone. In addition, vitamin C, which is one of the above-mentioned antioxidant vitamins, not only acts as an antioxidant, but is also directly involved in cAMP promotion and lipid solubilization action, and
Since it has various actions such as collagen formation, xenobiotic detoxification, induction of interferon production, antihistamine action, immune function enhancement, antivirus and antibacterial, it is preferable to include at least vitamin C as an antioxidant vitamin.

When the above-mentioned antioxidant vitamins are used, the daily dose is 100 to 2000 mg of vitamin C, and preferably 500 to 1000 mg for improving humoral immunity. . Vitamin E content is 5 IU-600 IU,
It is preferably 20 IU. The content of β-carotene is 3
It is mg to 30 mg, preferably 6.6 mg.

Although the above-mentioned antioxidant vitamin agent has been shown as a preferred embodiment as the above-mentioned antioxidant, the antioxidant is not limited to the antioxidant vitamin agent, and instead of or supplementing the above-mentioned antioxidant vitamin agent. , Antioxidants contained in foods such as polyphenols and catechins can be used.

As a metabolic cofactor contained in the present composition,
Any or all of vitamins B1, B2, B6, B12, niacin, pantothenic acid or folic acid can be added. These vitamins that support metabolism have a role as coenzymes for metabolism of sugars, lipids and amino acids, and are important components for life activity. For example, vitamin B1 acts as TPP (thiamine pyrophosphate) and B2 acts as FMN (flavin mononucleotide) and FAD (flavin adenine dinucleotide), which are involved in the regulation of glycolysis, TCA cycle, and β-oxidation. Vitamin B6 participates in amino acid metabolism as pyridoxal phosphate. Niacin is involved in glycolysis and lipid metabolism as NAD and NADP. Also, pantothenic acid is CoA and TC
Involved in A cycle, amino acid metabolism, lipid metabolism. Folic acid is F
As H4, involved in amino acid metabolism and nucleic acid metabolism. Vitamin B12 is involved in amino acid metabolism as C0B12.

Therefore, since these vitamins are components that constitute different coenzymes, it is preferable to use all of the above vitamins as the above-mentioned metabolic cofactor. In particular, the intake of these vitamins is dependent on the amount of energy and protein intake, and is generally affected in patients with low food intake such as perioperative patients and patients with low absorption or utilization. Tends to run short. Therefore, in order to efficiently perform intracellular energy supply required for wound healing and the like in these patients, it is preferable to add all the above vitamin groups to the composition.

The amount of the above vitamins added to the composition is 1
As a daily dose, vitamin B1 is 1.1 mg to 11.0 mg, which is a standard amount for daily intake, preferably 3
mg. Vitamin B2 is a daily intake of 1.2m
g to 12.0 mg, preferably 3 mg. Vitamin B6 is a daily intake of 1.6 mg to 16.0 mg,
It is preferably 5 mg. Vitamin B12 is a daily intake standard of 2.4 μg to 24.0 μg, preferably 10 μg
Is. Niacin is a daily intake of 16mg-30
mg, preferably 20 mg. Folic acid is 0.2 mg to 1.0 mg, preferably 1 mg, which is a daily intake standard. Pantothenic acid is a daily intake of 5 mg to 50 m
g, preferably 10 mg.

The cell growth promoting factor contained in the composition is a factor capable of promoting cell differentiation and proliferation. Examples of the cell growth promoting factor include folate and vitamin B1.
2. Any or all of vitamin A (β-carotene) and zinc can be used. The above-mentioned folic acid and vitamin B12 have not only a function as a metabolic cofactor in a living body, but also a function of promoting cell differentiation / proliferation. Also,
Vitamin A has a function as an antioxidant vitamin as well as a function of promoting cell differentiation / proliferation.

When these micronutrients are deficient, cells having a high rate of regeneration and shedding, for example, invasive sites, erythrocytes, gastrointestinal epithelial cells, etc., are easily damaged. It becomes possible to promote the healing of the invasive site. By promoting cell proliferation / differentiation, it is possible to promote the proliferation of immune cells such as T cells as well, thereby improving immunity and enhancing healing power of wounds and defense against infection. Become.

The amount of each component added to the composition is a daily dose of folic acid, vitamin B12, vitamin A.
(Β-carotene) is as described above, zinc is 1.2 mg
˜30 mg, preferably 10 mg.

Zinc can also be used as a cofactor for nucleic acid and protein synthesis. In the body, this zinc binds to albumin, globulin, etc., and circulates throughout the living body. In hypozincemia, it is known that zinc is mobilized to the liver from epithelial cells such as skin and digestive tract, bone, etc., and deficiency in these epithelial tissues occurs quickly. Therefore, in order to improve the wound healing power, it is preferable to add a nucleic acid / protein synthesis cofactor such as zinc. When zinc is used, it is preferable to use a zinc component (zinc yeast) produced by yeast, which is permitted as a food additive and has a high bioavailability.

As described above, the constituent components of the present composition are the antioxidant, the metabolic cofactor, the cell growth promoting factor, and the nucleic acid / protein synthesis cofactor, but one component has an overlapping action. In some cases, it is not necessary to use different substances for each of these constituent elements, and one substance can be used as a plurality of constituent elements.

In addition to the above constituents, other additive substances can be supplemented. For example, iron may be added to the composition because iron deficiency or the like occurs in a patient having a low food intake such as perioperative period. Further, calcium and vitamin D for promoting absorption of calcium can be added. Furthermore, an intestinal substance such as raffinose can be added.

The above composition can be formed into a dosage form such as powder, granules and tablets by mixing the above components.
In order to make it easily ingestible by patients during the perioperative period, it is preferable to use a liquid preparation. With a liquid preparation, it is possible to take it orally for patients who can take it orally and for patients who cannot take it by tube.

In the case of a liquid preparation, the liquid that disperses or dissolves the composition may be a liquid that can be taken without diminishing the action of each organism, for example, water, physiological saline, or the like. To improve the taste when ingested, fruit juice or the like can be used.

The present invention will be specifically described below with reference to examples, but the present invention is not limited to these examples.

[0028]

[Example] As a composition for reducing invasiveness and promoting wound healing,
A liquid agent having the following composition was prepared. β-carotene
6.6mg, vitamin B1 3mg, vitamin B2 3
mg, Vitamin B6 5mg, Vitamin B12 10μ
g, vitamin C 500 mg, niacin 20 mg,
Folic acid 1 mg, Vitamin D3 150 IU, Vitamin E
20 IU, 10 mg of pantothenic acid, 10 mg of zinc (as zinc yeast), 70 mg of calcium, 20 mg of phosphorus, 5 mg of iron, 30 mg of sodium, 70 mg of potassium, 2 g of raffinose were mixed and dispersed and mixed in a fruit juice liquid containing 20% of ginseng extract.

The above composition solution was administered to a patient undergoing elective anesthesia for general anesthesia. Specifically, 45 patients undergoing general anesthesia waiting surgery (3 hepatectomy, 4 duodenal resection, 3 thoracic esophagectomy, 9 total gastrectomy / pyloric gastrectomy, 15 colon / rectal resection, and other 1
1) randomly divided into a composition liquid administration group (n = 22) and a non-administration group (n = 23), and the composition liquid was orally or orally administered to the administration group for 3 days before surgery and 7 days after surgery. It was administered once a day by tube.

In the administration group and the non-administration group, (1) the rectal temperature as the intraoperative invasion degree, and (2) the change in the postoperative invasion degree as blood I
L-6 level, CRP (C-reaction-peptide), (3) Wound healing process, period until suture removal, presence of wound complications,
Decrease rate of decubitus, (4) Vitamin A, E and zinc as in-vivo changes of micronutrients, (5) Total protein, albumin, retinol binding protein (RBP), b as wound healing related substances, b
FGF (basic fibroblast growth factor) was measured.

Intraoperative Invasiveness: The rectal temperature difference (° C) between the start and end of surgery was 1.03 + 0.58 in the non-administration group.
In contrast, 0.48 + 0.45 in the treated group, which was significantly lower than that in the non-treated group. Therefore, it was shown that intraoperative hypothermia was reduced in the administration group.

Postoperative invasiveness: There was no difference in the CRP value produced during inflammation between the administration group and the non-administration group. On the other hand, regarding IL-6, which mediates an acute phase inflammatory response, when blood IL-6 levels (pg / ml) on the 3rd and 7th days after surgery were measured, 61.8 + 63.8, It was 40.0 + 40.7. In contrast, in the administration group, 48.8 + 34.1, 3 respectively
The value was 3.7 + 19.3, which was lower than that in the non-administration group. Therefore, it was shown that the administration of the composition solution reduces postoperative acute inflammation.

Wound healing process: The period (days) until thread removal is
In the non-administration group, it was 8.72 + 2.69. On the other hand, it was 7.31 + 2.54 in the treated group, which was shorter than that in the non-treated group. In addition, wound complication (wound infection) was 2 in the non-administration group.
This was seen in 1 case (8.7%), whereas 1 case (4.5%) in the administration group.
%) Only. The incidence of pressure sores was 9 in the non-administration group (39.13%), whereas it was 6 in the administration group.
This was an example (27.3%), which was significantly lower than the non-administration group. From this, in the administration group, the progress of wound healing was better than in the non-administration group, and since complications and the like were suppressed, the administration of this composition solution improved the wound healing power and immunity in patients. It has been shown that it can be improved.

Changes in micronutrients: Zinc (μg / dl) was 55.5 + 18.1 and 68.3 + 11.7 in the non-administered group, respectively, when blood levels were measured 3 and 7 days after surgery, whereas The values in the treated groups were 63.0 + 20.4 and 87.9 + 18.7, respectively, which were significantly higher.

Substances related to wound healing: total protein, albumin,
Retinol-binding protein showed no significant difference between the two. On the other hand, bFGF (pg / ml) was 3
It was 5.93 + 5.12 on the day, compared to 3 postoperatively in the administration group.
On the day, it was 14.01 + 11.08, which was significantly higher than that in the non-administered group. From this, it is possible to promote the production of bFGF showing a high wound healing effect in the administration group,
It was suggested that this resulted in the favorable wound healing process described above.

In this example, the administration period of the composition was set to 3 days before surgery and 7 days after surgery, but it is easy for those skilled in the art to change the administration period. Further, based on various perioperative indexes in the above patients, the increase / decrease in the dose of the composition per day, the supplementation, replacement, deletion of the components in the composition can be easily performed by those skilled in the art. Is.

[0037]

EFFECTS OF THE INVENTION As described above, the composition of the present invention can reduce the invasion during the perioperative period (intraoperative period and postoperative period) and can bring about a high wound healing effect.

Front page continuation (51) Int.Cl. ⁷ Identification code FI theme code (reference) A61K 31/375 A61K 31/375 31/409 31/409 31/4415 31/4415 31/51 31/51 31/525 31 / 525 31/593 31/593 31/7088 31/7088 33/26 33/26 33/30 33/30 47/46 47/46 A61P 17/02 A61P 17/02 (72) Inventor Shin Kawaguchi Yokkaichi, Mie Prefecture 2-2-4 Ichi-Hatsunaka F-term in Sankyo Pharmaceutical Co., Ltd. (reference) 4C076 AA16 CC19 CC23 CC24 4C084 AA24 MA21 MA63 ZA89 4C086 AA01 BA09 BA18 BC18 BC83 CB04 CB09 DA14 HA03 HA11 MA03 MA05 MA21 MA63 NA05 ZA89 ZC75 4C206 AA01 CA09 FA44 KA03 KA05 MA03 MA05 MA41 MA83 NA05 ZA89 ZC75

Claims (5)

[Claims] 1. A composition for reducing invasiveness and promoting wound healing, which comprises an antioxidant, a metabolic cofactor including vitamin B1, B2, B6, niacin or / and pantothenic acid, folic acid, vitamin B12 or / and. And a cell growth promoting factor containing vitamin A, and a nucleic acid / protein synthesis cofactor containing zinc. 2. The composition according to claim 1, wherein the antioxidant is an antioxidant vitamin. 3. Vitamin C, vitamin E, β-carotene,
The composition according to claim 1 or 2, comprising vitamins B1, B2, B6, niacin, pantothenic acid, folic acid, vitamin B12, vitamin A, zinc, vitamin D3 and iron. 4. The composition according to claim 1, which is dispersed in a liquid that can be taken. 5. The composition according to claim 4, wherein the liquid is fruit juice.