Zinc supplementation after bypass surgery

Abstract

To provide an agent for improving the prognosis of bypass surgery.SOLUTION: An agent for treating peripheral circulatory disturbance after bypass surgery contains zinc acetate as an active ingredient and is orally administered to a subject having hypozincemia after bypass surgery, twice a day after meal at a dosage of 50 mg in terms of zinc.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] The present invention relates to zinc supplementation therapy after bypass surgery, particularly after lower limb bypass surgery. More specifically, the present invention relates to a protective agent for peripheral circulatory disorders after bypass surgery, which is characterized by administering zinc at a certain dosage to a subject exhibiting hypozincemia after bypass surgery, and an agent for improving the healing of wounds, ulcers, or gangrene caused by peripheral circulatory disorders after bypass surgery. [Background technology]

[0002] In recent years, coupled with the aging population and the rise in lifestyle-related diseases, the incidence of peripheral diseases of the lower limbs, such as critical limb ischemia caused by arteriosclerosis obliterans, has been increasing. In particular, critical limb ischemia can develop into ulcers and gangrene in the feet as it progresses, and in severe cases, amputation may be necessary, significantly affecting the patient's quality of life.

[0003] Treatments for ischemic diseases such as critical limb ischemia include drug therapy using antiplatelet agents and peripheral vasodilators, intravascular treatment using stent placement or balloon catheters in the affected area, and bypass surgery in severe cases. Bypass surgery is a surgical procedure that bypasses the lesion, connects the central artery and peripheral artery using artificial blood vessels or the patient's own blood vessels, and delivers blood to tissues distal to the occluded lesion. Because bypass surgery delivers blood to the periphery, bypassing the lesion, it is said to have the advantage of longer-term patency compared to intravascular treatment (Non-Patent Document 1). [Prior art documents] [Non-patent literature]

[0004] [Non-Patent Document 1] Azuma Nobuyoshi, Heart, vol.45, No.1, p16(2013) Summary of the Invention [Problem to be solved by the invention]

[0005] However, even among patients who have undergone bypass surgery, there are some who have a poor prognosis, such as those who experience restenosis after surgery. Poor prognosis after bypass surgery not only requires treatment such as reoperation, but in severe cases may lead to ulcers, gangrene, and various other complications, necessitating amputation. Therefore, the development of technology to improve the prognosis of bypass surgery has been desired.

[0006] The present invention has been made in view of the above circumstances, lower limbs Improving the prognosis of bypass surgery The purpose of this invention is to provide a drug for [Means for solving the problem]

[0007] The present inventors have conducted research using many cases and confirmed that serum zinc concentration affects the prognosis of bypass surgery. Specifically, they found that patients with serum zinc deficiency after bypass surgery have a relatively lower graft patency rate than patients with sufficient serum zinc. As a result of further intensive research, they found that administering a certain amount of zinc to patients with serum zinc deficiency after bypass surgery can improve the prognosis of bypass surgery, and thus completed the present invention.

[0008] That is, the present invention is a protective agent for peripheral circulatory disorders after bypass surgery, which contains zinc acetate as an active ingredient and is orally administered to subjects with hypozincemia after bypass surgery at a dose of 50 mg twice a day after meals.

[0009] The present invention also provides an agent for improving the healing of wounds, ulcers, or gangrene caused by peripheral circulatory disorders after bypass surgery, which contains zinc acetate as an active ingredient and is orally administered to a subject with hypozincemia after bypass surgery at a dose of 50 mg of zinc twice a day after meals. [Effects of the Invention]

[0010] According to the present invention, it is possible to provide a therapeutic agent for peripheral circulatory disorders caused by hypozincemia after bypass surgery, or an agent for improving the healing of wounds, ulcers, or gangrene caused by hypozincemia after bypass surgery. [Brief explanation of the drawings]

[0011] [Figure 1] Photographs of the affected area in cases where ulcers that developed after bypass surgery were cured by administration of the peripheral circulatory disorder protective agent according to the present invention (A: 2 weeks after the start of administration, B: 1 month after the start of administration, C: 2 months after the start of administration). DETAILED DESCRIPTION OF THE INVENTION

[0012] The present invention will be described in detail below.

[0013] The present invention relates to an agent for protecting peripheral circulatory disorders after bypass surgery and an agent for improving healing, which contains zinc acetate as an active ingredient and is characterized by being orally administered 50 mg of zinc twice a day after meals to subjects who exhibit hypozincemia after bypass surgery, particularly after lower limb bypass surgery.

[0014] Here, the peripheral circulatory disorder protective agent means a drug that heals and improves the condition of an affected area, such as a wound, ulcer, or gangrene, caused by peripheral circulatory disorder, and protects the subject (patient) from damage. Since it heals and improves the condition of the affected area of ​​the patient, it can also be defined as a wound, ulcer, or gangrene healing and improving agent.

[0015] The agent for protecting peripheral circulatory disorders and the agent for improving healing according to the present invention are defined by the active ingredient, the dose, and the method of use.

[0016] The peripheral circulatory disorder protective agent of the present invention can be provided in various oral dosage forms containing zinc oxide as an active ingredient. Preferred forms include tablets, orally disintegrating tablets, capsules, and granules containing zinc acetate as an active ingredient. In any form, it is desirable that the dissolution rate be at least a certain level. Specifically, a formulation that exhibits a dissolution value of 85% or more at 15 minutes according to Method 2 of the Japanese Pharmacopoeia dissolution test (paddle method, water, test solution volume 900 mL, 50 rpm) is preferably used. By using a formulation satisfying these conditions, it is possible to effectively increase serum zinc concentration.

[0017] The patient to whom the agent for protecting peripheral circulatory disorder and the agent for improving healing according to the present invention are administered is a patient who has hypozincemia after bypass surgery. Here, hypozincemia refers to a state in which serum zinc concentration is reduced and zinc in the body is insufficient.

[0018] The normal range for serum zinc is 80-130 μg / dL. According to the 2018 Guidelines for the Treatment of Zinc Deficiency, a serum zinc concentration between 60 μg / dL and 80 μg / dL is considered to be latent zinc deficiency, and a serum zinc concentration below 60 μg / dL is considered to be zinc deficiency.

[0019] The peripheral circulatory disorder protective agent of the present invention is particularly preferably used for patients with zinc deficiency. Specifically, it is orally administered to patients confirmed to have a serum zinc concentration of less than 60 μg / dL after bypass surgery. However, even if a patient is classified as having potential zinc deficiency based on the above criteria (a serum zinc concentration of 60 μg / dL or more but less than 80 μg / dL), if the patient's condition is poor and, for example, signs of restenosis are observed based on the ABI (ankle brachial pressure index) value, the agent may be administered at the same dose.

[0020] The peripheral circulatory disorder protective agent and healing improving agent of the present invention is orally administered at a dose of 50 mg of zinc twice a day, morning and evening, after meals. Administration is continued while monitoring the patient's condition, and discontinued when the serum zinc concentration reaches 100 μg / dL or higher. After discontinuation of administration, if the serum zinc concentration decreases to less than 60 μg / dL, administration is resumed at the same dosage. [Example]

[0021] The present invention will be described below with reference to specific embodiments, but it will be understood that the present invention is not limited to these embodiments, and that various changes and modifications therein can be made by those skilled in the art without departing from the scope or spirit of the present invention as defined in the appended claims.

[0022] Reference example Forty-four patients who underwent infrainguinal bypass surgery for severe limb ischemia were divided into a zinc-deficient group (serum zinc concentration less than 60 μg / dL, 23 patients with 24 limbs, 74±8 years old) and a zinc-sufficient group (serum zinc concentration 60 μg / dL or more, 21 patients with 21 limbs, 70±7 years old), and the graft patency and limb salvage rates 12 months after bypass surgery were compared.

[0023] The 1-year primary and secondary graft patency rates were 18±10% and 36±12%, respectively, in the zinc-deficient group, and 53±12% and 53±12% in the zinc-sufficient group, showing significantly higher values ​​in the zinc-sufficient group. The 1-year limb salvage rate was 47±12% in the zinc-deficient group and 95±5% in the zinc-sufficient group, also showing significantly higher values ​​in the zinc-sufficient group. The 1-year wound healing rate was also examined, and was 48±12% in the zinc-deficient group and 86±9% in the zinc-sufficient group, showing significantly higher values ​​in the zinc-sufficient group.

[0024] Example 1 This is a case in which postoperative zinc supplementation was successful in salvaging a patient who underwent bypass surgery (proximal anastomosis: popliteal artery above the knee, peripheral anastomosis: dorsalis pedis artery) due to severe lower limb ischemia in the left leg artery. This patient's initial progress after bypass surgery was uneventful, but two months later, intimal hyperplasia along the entire length of the graft caused graft occlusion and an ulcer developed in the heel. Revascularization and local negative pressure wound therapy were performed, but the condition did not improve. When serum zinc levels were measured, they were found to have fallen to 49 μg / dL.

[0025] Therefore, one zinc acetate tablet (Nobelzin (registered trademark) 50 mg tablets, manufactured by Nobelpharma Co., Ltd., 50 mg zinc per tablet) was orally administered after breakfast and dinner. As a result, after the start of administration, the ulcer site gradually recovered and was healed two months later (Figure 1). These results demonstrate that the use of the peripheral circulatory disorder protective agent according to the present invention can improve the condition of patients with hypozincemia after bypass surgery. [Industrial Applicability]

[0026] According to the present invention, it is possible to provide an agent for protecting peripheral circulatory disorders caused by hypozincemia after bypass surgery, or an agent for improving the healing of wounds, ulcers, or gangrene caused by hypozincemia after bypass surgery.

Claims

1. This product contains zinc acetate as an active ingredient and is used in patients with hypozincemia after lower limb bypass surgery. A method for treating post-bypass surgery characterized by administering 50 mg of lead twice a day orally after meals. Protects against peripheral circulatory disorders.

2. This product contains zinc acetate as an active ingredient and is used in patients with hypozincemia after lower limb bypass surgery. A method for treating post-bypass surgery characterized by administering 50 mg of lead twice a day orally after meals.

2. An agent for improving the healing of wounds, ulcers, or gangrene caused by peripheral circulatory disorders.

3. The subject has been confirmed to have a serum zinc concentration of less than 60 μg / dL after lower limb bypass surgery. The therapeutic agent for peripheral circulatory disorders according to claim 1 or the therapeutic agent for improving peripheral circulatory disorders according to claim 2, Good medicine.

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