Renal function protecting agent for cats with impaired renal function, and cat food and cat medicine containing the same

Abstract

To provide renal function protectants and cat feed and cat medicines for cats whose kidneys have different characteristics from those of other mammals.SOLUTION: A renal function protectant for cats containing an ester of docosahexaenoic acid (DHA) is used. As the ester, a glyceride ester is preferable. The dose is preferably 125 mg / kg / day or more as the amount of DHA. In addition, oral administration is preferable as the administration form. In addition, a cat feed and a cat medicine that contain the renal function protectant for cats are provided.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to a renal function protector for cats with reduced renal function, a cat feed containing the same, and a cat medicine.

Background Art

[0002] Conventionally, cats have a lower intake of water compared to other animals, while they ingest proteins such as meat as the main nutrient source, imposing a large burden on the kidneys. It is said that about 30% of cats over 15 years old develop kidney diseases.

[0003] In the clinical symptoms of kidney diseases in animals other than cats, mainly a decrease in urine volume, edema, and proteinuria due to damage to glomeruli responsible for the filtration function of the kidneys are observed, and glomerular lesions caused by immune-mediated, diabetic, hypertensive, etc. are observed pathologically.

[0004] And, as an anatomical feature of the kidneys of animals other than cats, in the cortex, the interlobular veins of the renal lobules adjacent to the interlobular arteries shunt around the renal tubules. Therefore, these renal lobules are connected to each other by blood vessels, and it is considered that the renal function functions not in the lobule unit but in the lobe unit. Therefore, the renal function will decrease overall in the kidneys.

[0005] On the other hand, in the clinical symptoms of feline kidney diseases, mainly polydipsia and polyuria, dehydration symptoms are observed, and proteinuria is not often recognized. Since cats are originally animals with low water intake, the renal tubules are developed to enhance water reabsorption in the kidneys. And it is said that damage to the renal tubules (tubulointerstitial lesions) affects kidney diseases.

[0006] Based on various renal pathological findings in cats, although local aggravation is observed, it does not necessarily reflect the overall function. Therefore, it is said that the renal function of cats functions at the lobular unit, and the structure of the cat's kidney is different from that of other animals (Non-Patent Document 1). In addition, among feline diseases, many cases related to polycystic kidney disease (PKD) have been reported. The incidence of PKD is estimated to be 1 in 1000 cats. PKD is a slowly progressive and irreversible genetic kidney disease, and it is known to be frequently found in Persian cats and cats related to Persians by blood.

[0007] Regarding the general protection of renal function in mammals, it has been known from some descriptions that the administration of DHA (docosahexaenoic acid) and EPA (eicosapentaenoic acid) has been useful. For example, the requirement for long-chain highly unsaturated fatty acids in the life stages of cats is extremely small, being 0.06 g / kg as EPA+DHA during the growth period, 0.0016 g / kg for the maintenance of adult animals, and 0.0028 - 0.0034 g / kg during late pregnancy and peak lactation (Non-Patent Document 2). Also, as the dosage required for the suppression of proteinuria, it has been reported that as omega-3 fish oil, it is at least 1 g / 4.55 kg BW (Non-Patent Document 2). However, in this report, on the premise that the content of DHA / EPA contained in omega-3 fish oil is unknown, and there is no data on cats in the annotation, and it is described that it is based on the author's empirical value from human data, and the effect of DHA / EPA on actual cats has not been proven (Non-Patent Document 3).

[0008] Furthermore, regarding dogs, it is described that the upper limit of the tolerable intake of omega-3 fatty acids (Omega-3) is 2,080 mg / 10 kg, but here it is also described that the upper limit of the tolerable intake of omega-3 fatty acids for cats is unknown (Non-Patent Document 4).

[0009] Furthermore, from the perspective of safety, there is some discussion about platelet aggregability. In healthy cats, there is a report (Non-Patent Document 5) indicating a correlation between the n-6 / n-3 ratio and platelet aggregation ability. On the other hand, there is also a report (Non-Patent Document 6) stating that no change in platelet aggregation ability was observed even when cats (age, gender, weight, etc. unknown) were given 1.75 g / day or 2.625 g / day of the total amount of EPA + DHA. Thus, the current situation is that the discussion is divided.

[0010] Regarding the effect of DHA in animals other than cats, there is a known technique (Patent Document 1) in which, for renal impairment model rats, by administering DHA-rich triglyceride (H-DHA-TG) at 2,000 mg / kg or more (1,200 mg / kg or more as DHA), the increase in blood pressure, the onset of stroke, and the leakage of proteinuria are suppressed.

Prior Art Documents

Patent Documents

[0011]

Patent Document 1

Non-Patent Documents

[0012]

Non-Patent Document 1

Non-Patent Document 2

Non-Patent Document 3

Non-Patent Document 4

Non-Patent Document 5

Non-Patent Document 6

Summary of the Invention

Problems to be Solved by the Invention

[0013] The present invention aims to provide a renal function protecting agent for cats having characteristics different from those of other mammals in the kidneys. It also aims to provide a cat feed and a cat medicine containing the renal function protecting agent.

Means for Solving the Problems

[0014] The present inventors have found that by containing an ester of docosahexaenoic acid (DHA), it has an effect of protecting the renal function of cats. That is, the present invention is as follows. [1] A cat renal function protecting agent containing an ester of docosahexaenoic acid (DHA). [2] The cat renal function protecting agent according to [1], which is a glyceride ester. [3] The cat renal function protecting agent according to [1] or [2], wherein the dosage is 125 mg / kg / day or more in terms of the amount of DHA. [4] The cat renal function protecting agent according to any one of [1] to [3], which is an oral administration agent. [5] A cat feed containing the cat renal function protecting agent according to any one of [1] to [4]. [6] A cat medicine containing the cat renal function protecting agent according to any one of [1] to [4].

Effects of the Invention

[0015] According to the present invention, it is possible to provide a renal function protecting agent for cats having characteristics different from those of other mammals in the kidneys, and also to provide a cat feed and a cat medicine containing the renal function protecting agent.

Modes for Carrying Out the Invention

[0016] As the renal function protector for cats used in the present invention, esters of DHA can be used. Here, there are no particular restrictions on the esters of DHA, and examples include ethyl ester, glyceride ester, glycerophospholipid, etc. Among these, glyceride ester is preferred.

[0017] Further, when the ester is a glyceride ester, DHA may be ester-bonded to any of the α-position, β-position, and γ-position of the glyceride. That is, it may be mono-, di-, or tri-glyceride of DHA, or a mixed glyceride ester of DHA and other fatty acids. In this case, there are no particular restrictions on the content of DHA in the glyceride ester. For example, the ratio of DHA to all fatty acids constituting the glyceride ester can be, for example, 20 to 99% by mass, 50 to 99% by mass, 60 to 95% by mass, 65 to 90% by mass, etc.

[0018] There are no particular restrictions on the dosage of the renal function protector administered to cats, but in terms of the amount of DHA, it is preferably 125 mg / kg / day or more. For example, it can be 125 to 2000 mg / kg / day, 150 to 1800 mg / kg / day, 250 to 1500 mg / kg / day, etc.

[0019] There are no particular restrictions on the administration method of the renal function protector, and examples include oral administration.

[0020] The cat feed of the present invention contains the above-mentioned renal function protector for cats. There are no particular restrictions on the form of the cat feed, and examples include paste-like, solid, liquid, etc. The pharmaceutical for cats of the present invention contains the above-mentioned renal function protector for cats. There are no particular restrictions on the form of the pharmaceutical for cats, and examples include tablets, powders, granules, liquids, injections, etc.

Examples

[0021] Hereinafter, the present invention will be described with reference to examples, but the present invention is not limited to the examples.

[0022] <Example 1> Setting the dosage of DHA using healthy cats Five healthy cats were administered 0.45 mL / kg / day (250 mg / kg / day as DHA) or 0.9 mL / kg / day (500 mg / kg / day as DHA) of DHA-rich triglyceride (H-DHA-TG: manufactured by Maruha Nichiro Corporation) directly before evening feeding or mixed with a commercially available pet food (paste) for 28 days. During the intake period, free drinking water was provided, and 25 g / piece of general feed was given in the morning and evening. General physical examination findings and blood tests (general biochemistry tests, coagulation system tests) were performed before the start of intake and 28 days after intake.

[0023] As a result, the general physical examination was within the normal range. In the blood test, when administered at a dose equivalent to 250 mg / kg / day of DHA, a significant change in blood glucose level (decrease) was observed, and when the dose was gradually increased to 500 mg / kg / day of DHA, a significant change in TG (decrease) was observed, but it was within the normal range and was judged to be no problem. DHA is known to improve lipid metabolism, and a dose-dependent response was confirmed with a decrease in blood neutral lipids when administered at 250 mg / kg / day of DHA (p = 0.19) and 500 mg / kg / day of DHA (p = 0.04). Regarding the coagulation system (PT, APTT), no significant change was observed, and it was judged that there was no problem related to aggregability up to a dose equivalent to 500 mg / kg / day of DHA.

[0024] The fatty acid composition of the used DHA-rich triglyceride (H-DHA-TG: manufactured by Maruha Nichiro Corporation) is shown in Table 1.

[0025]

Table 1

[0026] <Example 2> Administration of DHA-rich triglyceride to cats with reduced renal function Five female cats with reduced renal function were administered DHA-rich triglyceride (H-DHA-TG; manufactured by Maruha Nichiro Corporation) directly before the evening feeding or mixed with a commercially available pet food (paste) at a dose of 0.23 mL / kg / day (125 mg / kg / day as DHA) or 0.45 mL / kg / day (250 mg / kg / day as DHA) for 28 days. Among the five cats subject to the test, three were administered a vasopressin V2-receptor antagonist (tolvaptan, trade name: Samsca, manufactured by Otsuka Pharmaceutical Co., Ltd.) at 3 - 4 mg / kg / day in combination. During the intake period, free drinking water was provided, and 20 g of potassium-restricted feed per cat was given in the morning and evening. General physical examination findings, blood tests (general biochemistry tests, SDMA), and urine tests were performed before the start of intake and 28 days after the start of intake.

[0027] The five female cats with reduced renal function showed normal values in general physical examinations and blood tests. In addition, the amount of the diet containing the actual H-DHA-TG consumed by the five cats was, on average, from half to the full amount. Regarding symmetric dimethylarginine (SDMA) in blood, urine protein creatinine ratio (UPC), and N-acetylglucosaminidase (NAG), which is a proximal tubule injury marker, when H-DHA-TG was administered at 0.23 mL / kg / day (125 mg / kg / day as DHA), no statistically significant decrease was observed. However, for SDMA, 3 out of 5 cases showed a decrease, and for UPC, all 5 cases showed a tendency to decrease overall. In addition, a significant improvement was observed in 1 case where NAG had severely deteriorated. Furthermore, when H-DHA-TG was administered at 0.45 mL / kg / day (250 mg / kg / day as DHA), all of SDMA, UPC, and NAG showed a decrease without exception in all 5 cases, and a significant decrease was observed overall before and after the administration of H-DHA-TG. The results are shown in Tables 2 and 3.

[0028]

Table 2

[0029]

Table 3

[0030] <Comparative Example 1> Comparison with Renal Impairment Model Rats After acclimating 4-week-old spontaneously hypertensive stroke-prone rats (SHR-SP / Izm, Japan SLC, Inc.) for 1 week, they were allowed free access to a solid diet containing 8% salt (AIN-93G, Oriental Yeast Co., Ltd.) and drinking water, and the following composition in Table 4 was orally administered for 4 weeks.

[0031]

Table 4

[0032] Serum SDMA, urinary UPC, and NAG after 4 weeks are shown in Table 5.

[0033]

Table 5

[0034] In renal impairment model rats, compared with the control group, when the DHA dosage was 1,200 mg / kg / day or more, suppression of proteinuria leakage and a significant decrease in SDMA were observed, but no change was observed in the NAG value.

[0035] On the other hand, as shown in Example 2, in cats, compared with non-administration, a decrease in SDMA, UPC, and NAG was observed even at a low dose of DHA administration (125 - 250 mg / kg / day), which is a lower dose compared to the DHA dosage for rats described above (Table 2, Table 3). Therefore, it was shown that in cats, the effect is exerted at a low dose and through different mechanisms of action. Also, in the above-mentioned test, considering the actual food intake, the estimated DHA intake is considered to be 62.5 - 250 mg / kg / day. As a DHA dosage that exhibits a more certain effect, preferably, it is ingestion in the range of 125 mg / kg / day or more, more preferably 150 mg / kg / day or more, and even more preferably 250 mg / kg / day or more. Therefore, it has the effect of protecting renal function at a low dosage and a realistic dosage compared to other animal species.

[0036] As described above, in cats with reduced renal function (mild renal impairment), administration of 125 mg / kg / day or more of DHA resulted in a decrease in blood SDMA, suppression of urinary protein leakage, and improvement of proximal tubular injury. Also, this dosage was about 1 / 5 of the effective amount in rats and humans.

Claims

1. A feline renal function protecting agent for administration to a subject, comprising: The subject is a cat with reduced renal function accompanied by renal tubular damage, Contains glyceride ester of docosahexaenoic acid (DHA), The ratio of DHA to the total fatty acids constituting the glyceride ester is 20 to 99% by mass, The glyceride ester is administered in an amount of 125 mg / kg / day to 250 mg / kg / day inclusive as DHA; administration reduces urinary N-acetylglucosaminidase concentration in a subject; Protects renal function in cats.

2. A feline renal function protecting agent as described in claim 1, administered in combination with a vasopressin V2-receptor antagonist.

3. The feline renal function protecting agent according to claim 1 or 2, which is an orally administered agent.

4. A feline renal function protecting agent described in any one of claims 1 to 3, which, upon administration, reduces the subject's urinary N-acetylglucosaminidase concentration compared to when the agent is not administered.

5. A feed for protecting the renal function of cats, comprising the agent for protecting renal function of cats according to any one of claims 1 to 4.

6. A pharmaceutical for protecting the renal function of cats, comprising the feline renal function protecting agent according to any one of claims 1 to 4.

7. A method for reducing urinary N-acetylglucosaminidase concentration in a subject, comprising: The subject is a cat with reduced renal function accompanied by damage to the proximal tubules, administering to the subject a glyceride ester of docosahexaenoic acid (DHA); The ratio of DHA to the total fatty acids constituting the glyceride ester is 20 to 99% by mass, The glyceride ester is administered in an amount of 125 mg / kg / day to 250 mg / kg / day in terms of DHA. method.

8. An N-acetylglucosaminidase reducer for cats for administration to a subject, comprising: The subject is a cat with reduced renal function accompanied by damage to the proximal tubules, Contains glyceride ester of docosahexaenoic acid (DHA), The ratio of DHA to the total fatty acids constituting the glyceride ester is 20 to 99% by mass, The glyceride ester is administered in an amount of 125 mg / kg / day to 250 mg / kg / day in terms of DHA. N-acetylglucosaminidase reducer for cats.

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