JP2012236820A - Composition for preventing or treating chronic kidney disease - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a composition high in safety to living body, excellent in uptake easiness such as swallowability, and effective for preventing or treating chronic kidney diseases.SOLUTION: The composition for preventing or treating chronic kidney diseases (CKD), containing an alginate, is provided, wherein the alginate is preferably is sodium or potassium salt. Chronic kidney diseases to be objects of prevention or treatment for this composition are involved in patients as subjects having the risks or diagnosed as CKD in no relation to the presence/absence of diabetes. For this composition, the alginate is preferably is to be administered at a dose prophylactically or curatively effective for CKD.

Description

The present invention relates to a composition for preventing or treating chronic kidney disease.

1. With respect to chronic kidney disease (CKD), the number of patients with kidney disease is becoming more serious worldwide every year. In 2002, the US Kidney Foundation newly proposed the concept of “chronic kidney disease (CKD)”, and an approach for prevention and improvement of CKD has begun (for example, Patent Document 1). For example, Patent Document 2 discloses a composition for preventing, ameliorating, and treating diabetes and / or diabetic nephropathy using a combination of dietary fiber and polyphenols.

CKD is a condition in which findings showing renal damage and a decrease in renal function continue chronically. Specifically, it is defined as a pathological condition satisfying either (1) or (2) below.
(1) Abnormal findings (particularly microalbuminuria and proteinuria) in kidney tissue and urine / biochemistry / imaging tests that last more than 3 months are suspected of kidney disease
(2) More than 3 months, glomerular filtration rate (GFR: unit expressing the function of the kidney) is less than 60 ml / min / 1 · 73 m ² (normal 100 ml / min / 1 · 73 m ² )

Although CKD does not have subjective symptoms in the early stages, if left untreated, it can lead to end-stage renal failure, which can lead to a serious condition where people cannot live without artificial dialysis or kidney transplantation. is there. End stage renal failure continues to increase worldwide, and the challenge is how to prevent and treat it at an early stage of CKD.

Furthermore, it has been clarified that CKD easily causes cardiovascular diseases such as heart disease and stroke, and how to treat CKD and prevent cardiovascular diseases is a big problem.

2. About alginate Alginic acid is a kind of polysaccharide contained in natural seaweeds, and has two monosaccharides, β-D-mannuronic acid and its C-5 epimer, α-L-guluronic acid. It is a substance. One of these salts, sodium alginate, has long been used as a food additive such as thickeners, gelling agents, and stabilizers.

In the pharmaceutical field, it is used as an agent for peptic ulcer and as a component for controlling the release of drugs and adjusting the solubility of tablets (for example, Patent Document 3). Moreover, sodium alginate which is a kind of dietary fiber is also known as a constipation improving agent (patent document 4 etc.).

Special table 2009-514986 specification International Publication No. 2006/082643 Japanese Patent Application Laid-Open No. 08-092105 Japanese Patent Application Laid-Open No. 2000-060487

The present inventors have found that sodium alginate, known as an additive to foods and medicines, has the effect of preventing and reducing chronic kidney disease (CKD) related symptoms. In particular, the ingestion of alginate has also been found to have an effect of preventing and reducing CKD-related symptoms by suppressing an increase in urinary total protein amount or urinary albumin amount and possibly reducing it.

It is an object of the present invention to provide a composition that is highly safe for living bodies, is excellent in ease of ingestion such as ease of use, and is effective in preventing or treating CKD.

That is, the present invention relates to a composition for preventing or treating chronic kidney disease (CKD), which contains alginate.

In certain preferred embodiments, the composition is a CKD prevention composition, and the prevention composition is administered to a subject at risk for CKD.
The subject having the risk of CKD is, for example,
(1) hematuria positive,
(2) hypertension,
(3) Impaired glucose tolerance (4) Diabetes,
(5) dyslipidemia,
The subject has at least one symptom or habit selected from the group consisting of (6) obesity and (7) smoking.

In another preferred embodiment, the composition is a therapeutic composition for CKD and is administered to CKD patients and exerts a therapeutic effect on chronic kidney disease regardless of the presence or absence of diabetes. .

With the above-mentioned CKD patient without depending on the presence or absence of diabetes, for example,
(1) high blood urea nitrogen (BUN),
(2) high urinary total protein,
(3) A patient having at least one symptom selected from the group consisting of high urinary albumin and (4) low glomerular filtration rate (eGFR).

The alginate is preferably a sodium salt or a potassium salt.

In a preferred embodiment, the alginate is administered in a prophylactically or therapeutically effective amount for chronic kidney disease. The preventive or therapeutically effective amount is, for example, an amount corresponding to 0.5% by mass or more in terms of the amount of sodium alginate powder in the daily intake of animals. Preferably, the upper limit is 5% by mass.

In a preferred embodiment, the composition is characterized in that 0.025 to 0.075 g / kg alginate per day is used for oral administration to humans.

By ingesting the composition of the present invention, the amount of total protein in urine can be reduced by the action of the alkali metal alginate. By reducing the amount of total protein in urine, the load on the kidney can be reduced, and as a result, the progression of CKD can be stopped and the prevention and treatment of CKD can be promoted.

It is the graph which compared the amount of albumin in urine of the diabetic nephropathy rat or mouse | mouth in an Example. It is the graph which compared the urinary total protein amount of the diabetic nephropathy rat or mouse | mouth in an Example. It is the graph which compared the blood glucose level of the diabetic nephropathy rat or mouse | mouth in an Example. It is the figure which showed the renal wet weight (at the time of the last sacrifice) of the diabetic nephropathy rat or mouse | mouth in an Example. It is the graph which compared the amount of urinary albumin of the adenine induction CKD rat in an Example, and the amount of total protein in urine. It is the graph which compared the blood glucose level (at the time of the last sacrifice) of the adenine induction CKD rat in an Example.

The present invention is described in detail below.
As described above, alginic acid is a substance having two monosaccharides, β-D-mannuronic acid and α-L-guluronic acid, which is its C-5 epimer, as structural units. The alginate contained in the composition for preventing or treating CKD of the present invention is a salt thereof.

Although the kind of alginate is not particularly limited, sodium salt or potassium salt is preferable, and sodium salt is particularly preferable. Sodium alginate and potassium alginate are also preferable because they are water-soluble and are commercially available and easily available. For example, sodium alginate and potassium alginate are commercially available from Food Chemifa Co., Ltd., Kimika Co., Ltd., Fuji Chemical Industry Co., Ltd., Kelco (UK), Sigma (US), PRONOVA biopolymer (Norway), etc. Yes.

In addition, the alginate used in the present invention can be appropriately used from low molecular weight to high molecular weight.

The subject of prevention or treatment of the composition is a subject who is at risk for CKD or a patient who has been diagnosed with CKD regardless of the presence or absence of diabetes.

The amount of alginate required for the prevention or treatment of CKD varies with the age and condition of the subject and patient, and is ultimately at the discretion of the physician or clinician.

Effective dosages of the agents of the present invention vary depending on, for example, the age, weight and general or clinical condition of the patient, the degree of symptoms being treated or the schedule of administration. The therapeutically effective dose can be determined empirically by conventional procedures known to those skilled in the art. See, for example, The Pharmaceuticals Basis of Therapeutics, Goodman and Gilman, et al. For example, effective doses can be estimated initially either in cell culture assays or in appropriate animal models. The animal model may also be used to determine the appropriate concentration range and route of administration. Such information can be used to determine useful doses and routes for administration in humans. The therapeutic dose can also be selected by analogy with the dosage for comparable therapeutic agents.

The particular mode of administration and dosing regimen of the composition of the present invention will take into account the details of the case (eg, the disease, the disease state involved, and whether the treatment is prophylactic) by the attending clinician. Selected. Treatment may include daily or multiple daily doses of alginate over a period of days to months or even years.

In a preferred embodiment of the invention, 0.025 to 0.075 g / kg alginate per day is used for oral administration to humans. The administration period is not particularly limited depending on the medical condition of the patient, but is usually several weeks to several months.

In the case of experimental animals, the above-mentioned alginate needs to be administered in an amount of 0.5% by mass to 5% by mass as an effective amount, for example, in terms of the amount of sodium alginate powder in the daily intake of the animal. That is, in this case, 0.05 to 7.8 g / kg body weight is administered as alginate per day. On the other hand, in the prevention or treatment of chronic kidney disease (CKD) in humans, there is a tendency that the dose is lower than the effective dose in experimental animals.

It is clear that the effective amount, administration time and period of the above-mentioned alginate is that the active ingredient is of plant origin and has low toxicity (Food Safety Commission Additive Evaluation Report Alginic acid and its salts (sodium alginate, Ammonium alginate, potassium alginate, calcium alginate))), there is no particular limitation.

The composition of the present invention exhibits the effect of preventing or improving CKD without changing the blood glucose level. That is, it has the effect of suppressing the progress of CKD without changing the blood glucose level under the administration of sodium alginate. For example, as shown in the Examples, when the composition of the present invention was administered to diabetic nephropathy (diabetic (type I) nephropathy (severe)) or adenine-induced CKD rats, compared to the group not administered with alginate It was confirmed that the blood sugar level did not change. Further, when the composition of the present invention is administered to an animal model of diabetic nephropathy (diabetic (type I) nephropathy (mild) or diabetic (type II) nephropathy), during the alginate administration period, 20 It was confirmed that no decrease in blood glucose level of more than 10% was observed. From this, it is considered that the diabetic nephropathy or CKD pathological progression inhibitory effect observed in the Examples is not related to the fluctuation of blood glucose level.

Therefore, the composition of the present invention is effective not only for the prevention or treatment of diabetic kidney disease but also for the prevention or treatment of patients with non-diabetic kidney disease. Non-diabetic kidney disease refers to a case where the following criteria for diabetes are not satisfied, but the conditions for chronic kidney disease (CKD) are satisfied.

In the present specification and claims, whether or not the patient suffers from diabetes is determined according to criteria such as the Diabetes Society. For example, a fasting blood glucose level of 126 mg / dL or higher, a 75 g oral glucose tolerance test 2-hour value of 200 mg / dL or higher, and an occasional blood glucose level of 200 mg / dL or higher is confirmed twice or more in a test performed on another day. Refers to the patient.

Further, in the present specification and claims, as described above, a case where any one of the following conditions (1) and (2) is satisfied is referred to as chronic kidney disease (CKD).
(1) Abnormal findings (particularly microalbuminuria and proteinuria) in kidney tissue and urine / biochemistry / imaging tests that last more than 3 months are suspected of kidney disease
(2) The glomerular filtration rate (GFR: unit expressing the action of the kidney) is less than 60 ml / min / 1.73 m ² (normal 100 ml / min / 1.73 m ² ) for 3 months or more.

The composition of the present invention is useful for the prevention or treatment of chronic kidney disease. Specifically, the composition of the present invention shows an inhibitory effect on the increase in the amount of urinary albumin or the total protein in urine. For example, as shown in the Examples of the present application, in the case of a diabetic nephropathy model animal, the urinary albumin amount during the alginate administration period is 38% or more (maximum 75) when the non-administration group is 100%. %) Low or the total protein content in urine is 16% or more (maximum 75%) low. Further, for example, in the case of an adenine-induced CKD rat, the amount of urinary albumin during the alginate administration period is 32 to 35% lower than that in the non-administration group as 100%, or the total urinary protein amount is 34 to 34%. The effect is 36% lower.

In healthy kidneys, the glomerulus, which is a constituent unit, functions as a barrier so that albumin or protein in blood does not leak into urine. On the other hand, when the glomerulus of the kidney is damaged and its barrier function is broken like CKD, a large amount of albumin or a protein having a higher molecular weight that does not normally leak out leaks. Next, albumin and protein that have passed through the glomeruli reach the tubule. The tubule has a function of reabsorbing and recovering a large amount of these proteins (albumin, transferrin / iron ion, complement, lipoprotein, etc.) into the blood. If this reabsorption continues in the tubules of CKD patients, tubule cell damage occurs, followed by tubulointerstitial damage, and the pathology of CKD is enhanced. That is, it is considered that the administration of alginate can be expected to prevent or treat CKD by suppressing the decrease in glomerular function or suppressing tubulointerstitial injury.

The composition of the present invention may be any of a solution, a suspension, a powder, a solid molding and the like. The dosage forms include liquids, tablets, capsules, troches, powders, granules, drinks, injections, patches, suppositories, inhalants, etc .; dietary supplements (supplements); foods, health foods It can be used for foodstuffs such as food materials, food additives, beverages, drinking water, soft drinks, taste beverages, alcohols, and the like; and feeds and feeds that require an improvement effect on biological functions.

When the composition of the present invention is a pharmaceutical product, other pharmaceutically acceptable additives (sweetening agents, flavoring agents, fragrances, emulsifiers, stabilizers, fillers, preservatives, etc.) It can mix | blend in the range which does not impair the effect of a composition. Although not particularly limited, examples of the additive include a sweetener such as stevioside and thaumatin, a corrigent such as citric acid and cocoa powder, a surfactant such as polyoxyethylene hydrogenated castor oil, polyoxyethylene sorbitan fatty acid ester, Examples include antiseptics such as methyl paraben, ethyl paraben, propyl paraben, and butyl paraben, stabilizers such as EDTA (ethylenediaminetetraacetate), erythorbic acid, and BHT (dibutylhydroxytoluene), and fillers such as light anhydrous silicic acid. These components may be blended singly or in combination of two or more.

When the composition of the present invention is a food or drink, other food-acceptable additives such as carbohydrates, carbohydrates, pigments, antioxidants, fragrances, sweeteners, emulsifiers, preservatives, seasonings Etc. can also be blended. It may also contain other nutritional supplements such as vitamins and minerals. The food can be eaten in any form, liquid or solid.

The composition of the present invention can also be used as a functional food, nutritional supplement, supplement or health food. Examples of dietary supplements or functional foods are not particularly limited, but liquid foods, semi-digested nutritional foods, ingredient nutritional foods, drinks, capsules containing sugars, fats, trace elements, vitamins, fragrances, etc. And processing forms such as an agent and enteral nutrient. In order to improve nutritional balance and flavor, the various foods may further contain nutritional additives and compositions such as amino acids, vitamins, and minerals, spices, fragrances, and pigments.

The composition of the present invention can be applied to feed for livestock, poultry and pets. For example, it can mix | blend with livestock feeds, such as dry dog food, dry cat food, wet dog food, wet cat food, semi-moist dock food, poultry feed, cattle, and pigs. The feed itself can be prepared according to a conventional method.
These therapeutic agents and prophylactic agents include non-human animals, for example, domestic mammals such as cattle, horses, pigs and sheep, poultry such as chickens, quails and ostriches, pets such as reptiles, birds and small mammals, It can also be used for farmed fish.

As a method for producing the composition of the present invention, a general food or pharmaceutical production method can be applied.

The composition of the present invention also functions as an inhibitor for increasing the total protein content in urine. The increase in the total urinary protein mass mainly reflects renal dysfunction associated with glomerular damage of the kidney, for example, when the protein is continuously excreted in the urine at 150 mg / day or more. Possible failure. As a method for quantifying the amount of total protein in urine, for example, pyrogallol red method or the like is used.

In addition, the effect of suppressing the increase in urinary total protein amount suggests suppression or improvement of the progression of renal dysfunction. Currently, as a first choice, a renin-angiotensin antagonist or a blood pressure control drug such as a diuretic is used. Can be administered to reduce the burden on the kidneys. In diabetic nephropathy, it is known that in addition to the above blood pressure control, blood glucose control by insulin administration or administration of various hypoglycemic drugs is important.

However, any method is highly likely to cause serious side effects such as hyperkalemia, hypoglycemia or renal dysfunction. On the other hand, the treatment with alginate in the present invention is widely used as a food-derived component with few side effects in medicines, food additives and the like, and is considered to be a highly safe method.

The composition of the present invention also functions as an inhibitor for increasing the amount of urinary albumin. The increase in the amount of albumin in the urine mainly reflects renal dysfunction associated with glomerular damage of the kidney, for example, when albumin is continuously excreted in the urine for 30 mg / day or more. And is considered to be a kidney disorder. As a method for quantifying the amount of albumin in urine, for example, an immunoturbidimetric method using an anti-albumin antibody or an ELISA method is used.

Suppression of the increase in urinary albumin suggests suppression or improvement of progression of renal dysfunction. In humans, the method is generally the same as suppression of urinary total protein, and thus alginate. The treatment with is considered to be a method with few side effects as well.

In certain preferred embodiments, the composition is a composition for the prevention of chronic kidney disease and is administered to a subject at risk for chronic kidney disease. In the present specification and claims, “subject at risk of chronic kidney disease”
(1) hematuria positive,
(2) hypertension,
(3) impaired glucose tolerance,
(4) Diabetes,
(5) dyslipidemia,
It refers to a subject having at least one symptom or habit selected from the group consisting of (6) obesity and (7) smoking.

In the present specification and claims, “hematuria positive” refers to a state in which erythrocytes are mixed in urine. For example, when measured by the urine test paper method, hematuria is about 2+ or more. Hematuria 2+ means that the hemoglobin concentration in urine is 0.12 mg / dL or more. Hematuria is an important symptom for the diagnosis and treatment of renal and urological diseases and is a predictor of end stage renal failure. That is, hematuria is positioned as one of the risk factors for CKD.

In the present specification and claims, “hypertension” means, for example, a systolic blood pressure of 130 mmHg and / or a diastolic blood pressure of 80 mmHg or more, as shown in the “KKD Medical Guide” of the Japanese Nephrological Society. Say. The “hypertension” condition described in the present specification and claims progresses rapidly to end stage renal failure. That is, hypertension is one of the risk factors for CKD. The measurement method is performed by, for example, an arm band type mercury sphygmomanometer.

In the present specification and claims, the term “diabetic patient” means, for example, a fasting blood glucose level of 126 mg / dL or more, 75 g-oral glucose tolerance test 2 hour value as shown in the criteria of the Diabetes Society, etc. This refers to a case where any of 200 mg / dL or higher and blood glucose of 200 mg / dL or higher as needed is confirmed twice or more in a test performed on another day.

In the present specification and claims, “glucose intolerance” refers to a state that does not belong to either diabetes or normal type, and is susceptible to diabetes. The normal type means that fasting blood glucose satisfies 110 mg / dL or less and 75 g-oral glucose tolerance test 2 hour value 140 mg / dL or less.

In the present specification and claims, “dyslipidemia” refers to, for example, total cholesterol 220 mg / dL or higher, LDL cholesterol 140 mg / dL or higher, HDL, as shown in the 2007 edition of the Atherosclerotic Disease Prevention Guidelines, etc. It means that it is a case of less than 40 mg / dL of cholesterol or 150 mg / dL or more of triglycerides, and if combined with dyslipidemia, it is predicted that the onset of CKD will increase (the more urine protein increases, the more the lipid metabolism Abnormal mergers increase). That is, dyslipidemia is positioned as a risk factor for CKD.

In the present specification and claims, “obesity” means, for example, a body mass index (BMI) of 25 kg / m ² or more. According to a large-scale epidemiological survey, proteinuria is likely to appear in obesity, and obesity is positioned as a risk factor for CKD because it is a significant risk factor for the onset of proteinuria and CKD even if diabetes is excluded.

In the present specification and claims, “having a habit of smoking” refers to smoking 20 or more cigarettes a day from a large-scale cohort study (NHANES II) conducted in the United States. The act of smoking is positioned as a risk factor leading to the introduction of dialysis.

By administering the composition of the present invention to a subject at risk of CKD, CKD associated with an increase in blood urea nitrogen, an increase in total urinary protein or urinary albumin, and a decrease in glomerular filtration rate (eGFR) The onset suppression can be expected.

In certain preferred embodiments, the composition is a composition for the treatment of chronic kidney disease and is administered to CKD patients. A chronic kidney disease patient to whom the composition of the present invention is administered may or may not suffer from diabetes. Further, in the present specification and claims, “chronic kidney disease patient” refers to the standards of the Japanese Society of Nephrology, for example,
(1) high blood urea nitrogen (BUN),
(2) high urinary total protein,
It refers to a patient having at least one symptom selected from the group consisting of (3) high urinary albumin and (4) low glomerular filtration rate (eGFR).

In the present specification and claims, “blood urea nitrogen (BUN) high value” is a finding suggesting impaired urinary BUN excretion due to renal dysfunction, for example, a case of exceeding 20 mg / dL. Say. BUN is measured by a method such as urease / glutamine dehydrogenase method.

In the present specification and claims, the “high urinary total protein value” is a finding suggesting renal dysfunction centering on glomeruli, for example, when it exceeds 150 mg / day. It is measured by a method such as the urinary total protein pyrogallol red method.

In the specification and claims of the present application, “high urinary albumin” is defined as microalbuminuria, and the findings suggesting renal dysfunction centering on glomeruli as well as urinary total protein levels. For example, it means a case where it exceeds 30 mg / day. Urinary albumin is measured by an immunoturbidimetric method or ELISA method.

In the present specification and claims, the “low glomerular filtration rate (GFR)” is a finding suggesting a glomerular disorder of the kidney, for example, less than 90 mL / min / 1.73 m ^2. Say. For example, the serum creatinine is calculated by the following formula by correcting the age and body surface area.
GFR (mL / min / 1.73 m ² ) = 194 × blood creatinine− ^1.094 × age− ^0.287
(Women multiply by 0.739)

The time course of the reciprocal serum creatinine level is used as an indicator of chronic renal failure progression. When looking at the transition of the serum creatinine that rises exponentially, a linear relationship can be obtained by plotting the reciprocal of the serum creatinine value against time, so that the slope is a measure of nephron decay, that is, the progression rate of CKD . Accordingly, when this value (inclination value) is negative and large, the progress of CKD is fast, and when it is small, the progress of CKD is slow.

EXAMPLES The present invention will be specifically described with reference to examples, but it goes without saying that the present invention is not limited thereto.

Example 1: Examination using diabetic (type I / type II) nephropathy model and non-diabetic progressive CKD model
In the manner shown in Table 1 below, two types of diabetic nephropathy model animals and one non-diabetic progressive CKD model animal were prepared, and sodium alginate (hereinafter referred to as AL-Na) for each model animal. A powdered mixed feed containing was administered.

Among the following animal models, type I diabetic nephropathy rats are pathological models in which insulin-dependent diabetes in humans is the primary disease. Type II diabetic nephropathy mouse is a pathological model in which non-insulin-dependent diabetes in humans is the primary disease. Adenine-induced CKD rats are a pathological model of human non-diabetic progressive CKD. In addition, the dosage is 0.9% by mass of the mixed diet for type I diabetic rats (severe or mild), 5% by mass of the mixed diet for type II diabetic mice, and the mixed diet for adenine-induced CKD rats. Of 0.5% by weight.

Acquired data (1) Animal weight before and after the experiment, food intake, and daily intake of AL-Na in the AL-Na administration group (2) Urinary parameters (i) Total protein mass, (ii) Albumin content (3 ) Blood glucose concentration (4) Histological data

(Notes on Table 1)
1 Animal model in which urinary albumin excretion increases from one week after streptozotocin administration, and morphologically increases glomerular volume, glomerular basement membrane thickening and mesangial increase.
2. A model in which an Ay gene (a gene having multiple aspects such as obesity / hyperglycemia, body hair color, lethality (Ay / Ay)) is introduced into KK mice which are obese animals. An animal model in which marked microalbuminuria, glomerular basement membrane thickening, glomerular hypertrophy, and mesangial matrix increase are observed, but creatinine clearance does not decrease between 2 and 20 weeks of age (overfiltered state).
3. Oral intake of adenine causes accumulation of adenine metabolites (2,8-dihydroxyadenine) in the renal tubular lumen or stroma of the kidney, resulting in the formation of foreign body granuloma, tubule obstruction, or tubular epithelial cell An animal model in which necrosis occurs and kidney function is significantly reduced.

<Test results>
(1) Animal body weight at the start and end of the experiment, food intake, and AL-Na intake per day in the AL-Na administration group The intake of AL-Na is multiplied by the AL-Na mixed concentration. The numerical value obtained in this way was calculated by correcting it to a value per kg of animal body weight. As can be seen from Tables 2 to 5, no effect of AL-Na was observed on the animal body weight and food intake.

Tables 2 to 5 show animal weights before and after the experiment, food intake, and AL-Na intake per day in the AL-Na administration group in each example.

(2) Urinary parameters (FIGS. 1, 2, and 5)
In the case of type I diabetic rats, the urinary albumin and total protein levels in the AL-Na administration group were significantly lower than those in the control group in both severe and mild tests.
In the case of type II diabetic mice, the urinary albumin and total protein levels in the AL-Na administration group were clearly lower than those in the control group.
In the case of adenine-induced CKD rats, the urinary albumin showed a significantly lower value and the urinary total protein tended to be lower in the AL-Na administration group than in the control group.

(3) Blood glucose concentration (FIGS. 3 and 6)
In the case of type I diabetic rats (mild) and type II diabetic mice, the AL-Na administration group showed a slightly lower tendency compared to the control group, but in the case of type I diabetic rats (severe), the control group and AL-Na The administration group remained the same.
In the case of adenine-induced CKD rats, there was no difference between the untreated group, the control group and the AL-Na treated group at the end of the study.

(4) Histological data (Fig. 4)
<Wet kidney weight (at the time of final slaughter)>
In type I diabetic rats, the AL-Na administration group showed a lower tendency than the control group in both severe and mild cases. Also in type II diabetic mice, it was significantly lower in the AL-Na administration group than in the control.

Example 2: Effect of 5% by mass AL-Na solution on humans A 5% by mass solution of AL-Na was administered for a certain period of time to humans whose serum creatinine concentration was mild to moderately high. Obtained.

Patient No. 1
Age 64, male. The blood creatinine concentration for 3 months before administration of the AL-Na solution was successively changed at 1.18, 1.45, and 1.63 mg / dL at monthly intervals. When the AL-Na solution was administered at 80 mL per day for 3 months, the blood creatinine concentrations up to 3 months after the start of administration were 1.60, 1.83 mg / dL, and 1.37 mg / dL, respectively, at monthly intervals. It changed.

Patient No. 2
Age 61, male. The blood creatinine concentration for 3 months before administration of the AL-Na solution was successively changed at 1.09, 1.15, and 1.47 mg / dL at monthly intervals. When the AL-Na solution was administered at 90 mL per day for 3 months, the blood creatinine concentration until 3 months after the start of the administration was 1.83, 1.30 mg / dL, 1.28 mg / dL in order of one month. It changed.

Patient No. 3
Age 75, male. The blood creatinine concentration for 3 months before administration of the AL-Na solution was successively changed at 1.10, 1.11, and 1.27 mg / dL at monthly intervals. When the AL-Na solution was administered at 60 mL per day for 1 month, the blood creatinine concentration until 3 months after the start of administration was 1.04, 0.90 mg / dL, and 0.95 mg / dL in order of 1 month. It changed.

Patient No. 4
Age 67, male. The blood creatinine concentration for 3 months before administration of the sodium alginate solution was successively changed at 0.85, 0.88, and 0.97 mg / dL at monthly intervals. When sodium alginate solution was administered at 60 mL per day for 2 months, the blood creatinine concentration up to 2 months after the start of administration was successively changed at 1.02 and 1.02 mg / dL at monthly intervals.

Patient No. 5
Age 84, female. The blood creatinine concentration was 1.72 mg / dL three months before administration of the AL-Na solution and 3.39 mg / dL one month before administration. When the AL-Na solution was administered at 30 mL per day for 2 months, the blood creatinine concentration up to 3 months after the start of the administration was sequentially changed at 1.66, 1.93, and 1.88 mg / dL at monthly intervals. .

Patient No. 6
Age 82, female. The blood creatinine concentration for 3 months before administration of the AL-Na solution was successively changed at 1.15, 1.11, and 1.05 mg / dL at monthly intervals. When the AL-Na solution was administered at 30 mL per day for 1 month, and the blood creatinine concentration up to 2 months after the start of the administration, the concentration gradually changed at 1.11 and 1.05 mg / dL at monthly intervals.

The slope of the plot (reciprocal value of creatinine minus time slope) of the above six subjects with the reciprocal value of blood creatinine concentration as the vertical axis and the time as the horizontal axis was calculated between 3 months before administration and 2 months after administration. In comparison, an increase in slope was observed. That is, when the AL-Na solution was administered, a result of improving the pathological condition of chronic kidney disease (CKD) was obtained.

Conclusion derived from Example 2-It was suggested that even when alginate was administered to humans, an effect of improving the pathological condition of chronic kidney disease could be obtained.
Assuming that a general human body weight is 60 kg, the dose of AL-Na administered in the additional examples is calculated as 25 to 75 mg / kg body weight / day.
The effective dose of alginate described in the specification of the prior document (Patent Document 2) is 100 mg / kg body weight / day. Therefore, in Example 2 above, it was suggested that even a dose lower than the amount described in the prior literature is effective.

The composition of the present invention is a composition having a prophylactic or therapeutic effect on chronic kidney disease regardless of whether it is diabetic or non-diabetic, and regardless of the pathology of diabetes.

Claims (7)

A composition for preventing or treating chronic kidney disease, comprising an alginate. The composition is a composition for preventing chronic kidney disease,
The prophylactic composition is administered to a subject at risk of chronic kidney disease,
The subject at risk of chronic kidney disease is
(1) hematuria positive,
(2) hypertension,
(3) impaired glucose tolerance,
(4) Diabetes,
(5) dyslipidemia,
The composition according to claim 1, wherein the composition has at least one symptom or habit selected from the group consisting of (6) obesity and (7) smoking. The composition is a composition for the treatment of chronic kidney disease,
The composition is administered to a patient with chronic kidney disease and exerts a therapeutic effect on chronic kidney disease regardless of the presence or absence of diabetes,
The chronic kidney disease patient does not depend on the presence or absence of diabetes,
(1) high blood urea nitrogen level,
(2) high urinary total protein,
The composition according to claim 1, which has at least one symptom selected from the group consisting of (3) high urinary albumin and (4) low glomerular filtration rate. The composition according to claim 1, wherein the alginate is a sodium salt or a potassium salt. The composition according to any one of claims 1 to 4, wherein the alginate is administered in an amount effective for preventing or treating chronic kidney disease. The composition according to claim 5, wherein the prophylactically or therapeutically effective amount is an amount corresponding to 0.5% by mass or more in terms of the amount of sodium alginate powder in the daily intake of animals. 7. Composition according to any one of the preceding claims, characterized in that 0.025 to 0.075 g / kg alginate per day is used for oral administration to humans. .

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