JP5221094B2 - Regenerative agent for the subcutaneous muscle layer of pressure ulcers - Google Patents

Description

  The present invention relates to a pressure ulcer healing and / or prevention agent used for pressure ulcer prevention / treatment, which is administered to elderly or under-nutrient patients or surgical patients who need oral or tube feeding. Furthermore, the present invention relates to a whey protein nutritional supplement used for the prevention and treatment of pressure ulcers, which contains whey protein as a protein source and consists of carbohydrates, lipids, vitamins and minerals.

Pressure ulcer is a condition in which tissue is necrotized due to circulatory disturbance caused by prolonged pressure load on the bone protrusion. The direct cause is local ischemic necrosis due to continuous compression. Risk factors for the development of pressure ulcers include social factors such as decreased tissue durability, quality of nursing and care, as well as local physical pressure and circulatory disturbance. Regarding tissue durability, external factors (local factors) include friction, deviation, and incontinence, and internal factors (systemic factors) include basic diseases such as aging, diabetes and circulatory disorders, and malnutrition. Are listed.
As a standard for pressure ulcer treatment, there are “Guidelines for Prevention and Treatment of Pressure Sores”. There are conservative treatments and surgical treatments for pressure ulcers, but these guidelines are mainly conservative treatments. Pressure ulcers require treatment from many directions, and nursing and nursing care occupy a large percentage, including regular repositioning and wiping, body pressure dispersion devices, and nutrition management. In particular, nutritional management is important for enhancing the durability of tissues essential for pressure ulcer prevention and treatment and for promoting wound healing. Although pressure ulcers are difficult to cure once they develop, prevention has been important, but in recent years, comprehensive assessments have made it possible to cure them with appropriate care plans.
As a technique for the prevention and treatment of pressure ulcers with a nutritional composition, an amino acid nutrient for pressure ulcer prevention and treatment containing an amino acid having a specific composition is disclosed in JP-A-11-130669 (Patent Document 1). Because this is a mixture of amino acids, the taste is poor and continuous intake is considered difficult.

JP 2004-41006 (Patent Document 2) discloses a liquid nutritional composition characterized in that the weight ratio of copper to zinc is 1:10 or more. This provides an enteral-feeding liquid diet that can provide patients with the copper and zinc necessary to nutritionally prevent and treat pressure ulcers without causing problems such as overdose. To do. However, there is a report that the prevention of pressure ulcers cannot be expected even if zinc is administered to patients who are not in a deficient state of zinc (Guideline for pressure ulcers for doctors and nurses, Medical School, p88, Non-Patent Document 1).
JP-A-2004-284972 (Patent Document 3) discloses a therapeutic agent for enteral wounds containing wheat gluten and wheat gluten hydrolyzate. It is a therapeutic agent for enteral wounds containing wheat gluten, wheat gluten hydrolyzate and / or a polypeptide corresponding to the hydrolyzate. (Diameter) only decreases. Circulatory disturbance due to pressure load occurs in the order of intradermal venules, intramuscular veins, intramuscular arteries, and intradermal arterioles, so the subcutaneous muscle layer is more likely to be damaged than the epidermis and dermis. It is difficult to say that the reduction in area is a healing effect. In addition, pressure ulcers that remain in the shallow layer heal in the process of migration and progression of basal cells from the wound edge and wound surface, but those that extend to the deep layer require proliferation of granulation tissue (clinical nursing, 31: 1456). , 2005, non-patent document 2).
Therefore, a nutritional agent that is unlikely to become pressure ulcers if taken in advance and / or continuously, and promotes muscle layer regeneration of the affected subcutaneous tissue even if pressure ulcers occur, and has been desired.

Japanese Patent Laid-Open No. 11-130669 Japanese Patent Laid-Open No. 2004-41006 Japanese Unexamined Patent Publication No. 2004-284972 Guidelines for pressure ulcer treatment for doctors and nurses, School of Medicine, p88 Clinical Nursing, 31: 1456, 2005

    This invention is made in view of such a problem, The objective is to provide the nutrient which can prevent or treat pressure ulcer formation by continuous ingestion. In addition, the effect is not only to reduce the wound area of the skin epidermis, but also to promote the regeneration of tissue that extends to the subcutaneous muscle layer.

  The inventors of the present invention have conducted a intensive study on a nutrient that is easy to take continuously for pressure ulcer prevention / treatment and has a regeneration promoting effect on the subcutaneous muscle layer, and found that whey protein has such an effect. We found that this problem can also be solved by taking nutritional supplements containing whey protein as an active ingredient. That is, in the present invention, whey protein is included as an active ingredient, and if it is taken in advance and / or continuously, it is difficult to become a pressure ulcer, and even if a pressure ulcer occurs, it has an excellent effect on the regeneration of the muscle layer of the affected subcutaneous tissue.

The above object can be achieved by the present inventions (1) to (8) below.
(1) A pressure ulcer healing and / or prevention agent containing whey protein as an active ingredient.
(2) The pressure ulcer healing and / or prevention agent according to (1), wherein 1.25 to 2.0 g / kg (body weight) per day is administered as a whey protein via the digestive tract. .
(3) A whey protein-containing nutrient containing the pressure ulcer healing and / or prevention agent according to (1) as a protein component.
(4) The whey protein nutrient according to (2) above, comprising a carbohydrate, a lipid, a vitamin, and a mineral.
(5) The whey protein nutrient according to (4), wherein the vitamin contains at least vitamin A and vitamin C.
(6) The whey protein nutrient according to (4) or (5) above, wherein the mineral contains at least calcium, iron, zinc, and copper.
(7) The whey protein nutrient according to any one of (3) to (6) above, wherein the content of whey protein is 2 to 13.5 g per 100 kcal.
(8) The whey protein nutrient according to any one of (3) to (7), which is liquid.
(9) The whey protein nutrient according to (8), which is sterilized under high pressure steam.

  As described above, pre- and / or continuous intake of the pressure ulcer healing and / or development preventive agent or whey protein nutrient containing the same according to the present invention can prevent or treat pressure ulcer formation and improve the patient's QOL. It can also contribute to reducing the burden on nursing and caregivers and reducing medical costs.

The pressure ulcer healing and / or prevention agent of the present invention is described in detail below. The pressure ulcer healing and / or prevention agent of the present invention is effective by itself, but is generally more effective when used in the form of a nutritional composition together with other nutritional components.
The agent for preventing and / or preventing the development of pressure ulcer according to the present invention has the effect of preventing / treating pressure ulcer in any commonly used dosage form as long as it is absorbed into the digestive tract. Specifically, the dosage form may be liquid, solid, gel, or powder, and the administration method may be oral administration, or nasal, gastric fistula, intestinal fistula administration .

As the whey protein used in the regenerating agent for the subcutaneous muscle layer of the pressure ulcer affected by the present invention, those produced by conventional methods can be used. For example, whey obtained as a by-product in the manufacturing process of cheese and casein is spray-dried, vacuum concentrated, osmotic membrane, reverse osmosis (RO), ultrafiltration (UF), ultrafiltration, electrodialysis It can be obtained by separating the protein component by a method such as a method, an ion exchange method or a crystallization method.
Moreover, the whey used as a raw material can be appropriately selected from cheese whey (acid whey), sweet whey, delactose whey, desalted whey, and the like.
Moreover, a whey protein concentrate (WPC) and a whey protein isolate (WPI) can be used .

The dosage of the pressure ulcer healing and / or prevention agent of the present invention is preferably 1.25 to 2.0 g / kg per day as a whey protein. Within this range, pressure ulcer prevention and treatment effects can be sufficiently exerted.
The whey protein content in the whey protein nutrient of the present invention is preferably 2 to 13.5 g / 100 kcal. Below 2 g / 100 kcal, the prevention and treatment effects of pressure ulcers cannot be fully exerted, and the protein content of general nutrients is low, making it unsuitable for administration to elderly or undernourished patients. In addition, at 13.5g / 100kcal or more, the protein content becomes excessive and the effect on the blending amount becomes relatively small, and when taking into consideration the intake of other nutritional components, it tends to deviate from a favorable nutritional balance.
The dosage of the whey protein nutrient of the present invention is preferably 750 to 2000 kcal per day. The dose of whey protein is preferably 37.5-100g per day.

In general, there is no clear basis for formulating the upper limit of protein due to the risk of toxicity (Ministry of Health, Labor and Welfare, Japanese dietary intake 2005 version). On the other hand, for amino acids, the human equivalent allowance is estimated from LD ₅₀ using rats (New Nutrition of Proteins and Amino Acids, Kodansha). Amino acids administered intraperitoneally rapidly move into the blood and rapidly increase the blood concentration, causing tissue damage specifically for each amino acid. In contrast, orally administered amino acids are modified by absorption in the small intestine, portal blood, and liver, respectively, and the increase in blood concentration is slow. When taken orally as a protein rather than as a free amino acid, the blood level rises more slowly because of the digestive process in the digestive tract, so there is no abnormal increase in serum levels that would cause tissue damage it is conceivable that. These results suggest that there is no acute toxicity when whey protein is taken orally or enterally.

  Whey protein accounts for about 20% of cow's milk protein and is richer in essential amino acids and cysteine than casein (Milk and dairy products in human nutrition, p90). In addition, since the flavor is good, even under continuous intake of nutrients containing this whey protein, the malnutrition is improved without impairing the patient's QOL. Furthermore, by taking this whey protein nutrient, the regeneration of necrotic subcutaneous muscle cells caused by circulatory disturbance by pressure load can be promoted.

(Example 1) A nutritional composition (Table 1) using whey protein as a protein source was prepared. The whey protein contained in this nutritional composition is 5.36 g per 100 kcal.
(Comparative Example 1) A nutritional composition was prepared in the same manner as in Example 1, except that sodium caseinate was used instead of whey protein in Example 1. The casein contained in this nutritional composition is 5.36 g per 100 kcal.
(Test Example 1) Animal experiments were conducted using the nutritional compositions prepared in Example 1 and Comparative Example 1. Rats were divided into two groups. One group was given the nutritional composition of Example 1 and the other group was given free access for 2 weeks. Using these rats, a pressure ulcer model was prepared by the method of Skalak et al. (Wound Rep Reg 8: 68-76, 2000). Furthermore, the intake of the nutritional composition was continued for one week, and the skin of the pressure ulcer formation was collected.

(Evaluation Example 1) The skin of the pressure ulcer formation area was fixed with formalin and then stained with HE (hematoxylin and eosin). Histological findings are shown in Table 2. In the group ingested the nutritional composition of Example 1 using whey protein as a protein source, the degree of scab, edema and cell infiltration were mild, and a good regenerative image was observed in the subcutaneous muscle layer. On the other hand, in the group ingested the nutritional composition of Comparative Example 1 with casein as the protein source, the degree of scab, edema and cell infiltration were mild to moderate, and no good regenerative image was observed in the subcutaneous muscle layer. It was.
(Evaluation Example 2) The number and area of regenerated myocytes in a single field of view of a strongly enlarged pathological specimen were measured using image analysis software (Scion Image). Specifically, cells that were polynuclear and highly stained with HE staining were regarded as regenerative muscle cells and were selected. The threshold value was set by the Threshold function, binarization processing was performed, and the cell number and area were measured. The area of one visual field was measured, and the area ratio was calculated by the formula {(area of regenerative muscle cells) / (total area of visual field)} × 100 (%). As a result, in Comparative Example 1, the number of cells was 20 and the area ratio was 4.50%, whereas in Example 1, the number of cells was 32 and the area ratio was 6.73%. It was revealed.
Skalak et al.'S pressure ulcer model is a model that well reflects the clinical pathology with histologically necrosis of the subcutaneous muscle layer. Muscle cells that have undergone circulatory disturbance due to pressure overload and invade macrophages, then become mature muscle fibers through the activation, differentiation and proliferation of muscle satellite cells. Among these processes, whey protein is thought to have an effect of activating muscle satellite cells and promoting differentiation and proliferation.

(Example 2) After mixing whey proteins, carbohydrates, lipids, vitamins and minerals in the blending ratios in Table 3 and stirring using a stirrer, the resulting solution was filled into a plastic container 500 mL at a time, sealed, Whey protein nutrient was prepared by heat sterilization at 121 ° C for 10 minutes. The obtained whey protein nutrient had good tube fluidity and could be administered by tube. In addition, it had a good taste and palatability and was easy to ingest.
(Comparative Example 2) An egg white protein nutrient was prepared in the same manner as in Example 2, except that egg white protein was added instead of whey protein in Example 2. The egg white protein nutrient obtained was clogged in the tube and could not be administered continuously. In addition, the taste was poor and oral intake was difficult.
(Comparative Example 3) A soy protein nutrient was prepared in the same manner as in Example 2 except that soy protein was added instead of whey protein in Example 2. The soy protein nutrient obtained was clogged in the tube and could not be administered continuously. In addition, the taste was poor and oral intake was difficult.

  Pre- and / or continuous ingestion of a pressure ulcer healing and / or development prevention agent or whey protein nutrient containing the whey protein of the present invention as an active ingredient can prevent or treat pressure ulcer formation and improve the patient's QOL In addition, it can contribute to reducing the burden on nursing and caregivers, and to reducing medical costs, and it can be used industrially.

Claims (2)

A regenerative agent for the subcutaneous muscle layer of a pressure ulcer affected part, comprising whey protein as an active ingredient . The regenerative agent for the subcutaneous muscle layer of an affected pressure ulcer according to claim 1, wherein 1.25 to 2.0 g / kg (body weight) per day is administered as a whey protein via the digestive tract.