JPH0769879A - Antidiabetic - Google Patents

Abstract

PURPOSE:To obtain an antidiabetic agent capable of effectively preventing or improving especially complication of diabetes. CONSTITUTION:This antidiabetic agent contains 10-hydroxydecenoic acid, 10- hydroxydecanoic acid or 3,10-dihydroxydecanoic acid. These fatty acids have respectively a low 50% inhibition constant, i.e., IC50 for bovine lens-derived AR(aldose reductase) or human placenta-derived AR and this antidiabetic agent, therefore, can effectively prevent or improve complication of diabetes.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an antidiabetic agent used for treating or preventing diabetes.

[0002]

2. Description of the Related Art Aldose reductase (EC1.1.
1.21) is an enzyme involved in nicotinamide adenine dinucleotide phosphate (NADPH) -dependent glucose metabolism, and is deeply involved in complications of diabetes, especially peripheral neuropathy, retinopathy, cataract, renal disorder, etc. ing. That is,
In glucose metabolism during diabetes, aldose reductase (hereinafter referred to as AR) activates the conversion of glucose into sorbitol. Moreover, sorbitol has a low cell membrane permeability and is stored inside the cell and is hardly excreted. Therefore, osmotic pressure increase, cell swelling, etc. occur, and the above-mentioned diabetic complications are caused.

Since the abnormality of the polyol metabolic pathway is closely related to the onset of diabetes, many aldose reductase inhibitors (hereinafter referred to as ARI) have been recently developed (Metabolism Vol. 26, No 27, p. 629, 1989).
), Only the generic name Epalrestat was marketed in Japan as a prescription drug in 1992, the first in the world. This inhibitor has come to be commonly used in combination with the lack of a suitable drug for the treatment of diabetic complications.

Originally, it is widely known that flavonoids which are widely present in nature, such as leaves and resins of plants, have ARI action, but it is reported that foods contain ARI other than flavonoids. There is none.

By the way, as to the royal jelly, which is also said to be a treasure trove of physiologically active substances, Japanese Patent Laid-Open No. 4-279597
As disclosed in Japanese Patent Publication, various actions have been reported.

[0006]

However, there are few substances for which the action of royal jelly is specified. Regarding the antidiabetic effect of royal jelly, Kramer et al. Insect Physi
ol. , Vol. 23, 293-295, 1977, it is alleged to have confirmed insulin-like peptides in royal jelly.

However, it cannot be said that the conventional antidiabetic action is explained because the amount is very small and the royal jelly is orally administered. On the other hand, clinically effective reports have been made domestically and internationally, but it has not been clarified what substances in royal jelly exert an antidiabetic effect.

The present invention has been made by paying attention to the above conventional problems. The object of the invention is to provide an antidiabetic agent which can effectively treat or prevent complications of diabetes.

[0009]

In order to achieve the above object, the invention of the antidiabetic agent according to claim 1 is characterized by containing 10-hydroxydecenoic acid. The invention according to claim 2 is characterized by containing 10-hydroxydecanoic acid. Further, the invention according to claim 3 is characterized by containing 3,10-dihydroxydecanoic acid.

[0010]

The function of the present invention is 10-hydroxydecenoic acid, 10-
Hydroxydecanoic acid or 3,10-dihydroxydecanoic acid has an aldose reductase inhibitory function.
Therefore, in glucose metabolism, the conversion of glucose to sorbitol is suppressed, so that diabetes is effectively prevented or treated.

[0011]

EXAMPLES The present invention will be described in more detail with reference to the following examples. (Example 1) In this example, a method for preparing AR and a method for measuring activity are shown.

[0012] Fresh bovine lens was homogenized by adding 9 volumes of physiological saline containing 1 mM mercaptoethanol, subjected to ammonium sulfate fractionation by centrifugation at 3000 rpm for 10 minutes, and dialyzed against distilled water. I went. And DE
A linear gradient elution of sodium chloride was performed by AE cellulose column chromatography, and AR fractions were collected. Similarly, AR fractions derived from human placenta were collected.

Using these fractions, the coenzyme NADPH
Was used to measure the enzyme activity, and the enzyme inhibitory action of ARI was measured. (Example 2) In this example, a method for purifying ARI and an AR inhibitory activity will be described. The purification method and the identification method themselves are well known.

An equal amount of ethyl alcohol was added to fresh raw royal jelly, and the mixture was stirred and the supernatant was separated and concentrated under reduced pressure.
Fractions having a strong RI action were collected. Further, re-chromatography was carried out and elution was carried out by silica gel column chromatography (chloroform: methanol = 4: 1). The isolated ARI is N
It was identified by MR and mass spectrometry (MS). ARI identified
Were 10-hydroxydecenoic acid, 10-hydroxydecanoic acid and 3,10-dihydroxydecanoic acid.

Further, an ARI inhibition test was carried out to measure the sample concentration at a 50% inhibition rate with respect to the bovine lens-derived AR and human placenta-derived AR, that is, IC ₅₀ . The AR inhibitory activity is shown in Biochem. Pharm., 20, p1637-1648.
(1971) and Anal. Biochem., 84, p361 to 369 (1978), and a known method based on the rate of change in absorbance at 340 nm. The results are shown in Table 1. In addition, as a control example, the IC ₅₀ of quercetin which is a flavonol derivative is shown.

[0016]

[Table 1]

As shown in Table 1, the three fatty acids of Examples 1 to 3 have considerably small IC ₅₀ values, and they are derived from bovine lens A.
Regarding the IC ₅₀ for R, the fatty acids of Examples 2 and 3 are almost the same as the quercetin of Control Example 1. Further, IC ₅₀ is less than the IC ₅₀ of either the fatty acid of Examples 1 to 3 quercetin to human placenta-derived AR. Therefore, it is understood that these fatty acids are excellent in the enzyme inhibiting effect of ARI. Therefore, these fatty acids can effectively treat or prevent complications such as peripheral neuropathy, retinopathy, cataract, and renal disorder due to diabetes.

The present invention is not limited to the above-mentioned embodiments, but may be embodied by changing the configuration as follows, for example, without departing from the spirit of the invention. (1) 2 of 10-hydroxydecenoic acid, 10-hydroxydecanoic acid and 3,10-dihydroxydecanoic acid
Consists of a combination of at least one ingredient. (2) Use of the antidiabetic agent of the present invention as an oral feeding composition. (3) Mixing 10-hydroxydecenoic acid, 10-hydroxydecanoic acid or 3,10-dihydroxydecanoic acid in royal jelly or other foods such as health foods to prepare an antidiabetic agent.

[0019]

As described above in detail, the antidiabetic agent of the present invention has the excellent effect that the complications of diabetes can be effectively treated or prevented.

 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Takashi Nonogaki 1-1, Kano Sakurada-cho, Gifu City Api Stock Company

Claims (3)

[Claims] 1. An antidiabetic agent comprising 10-hydroxydecenoic acid. 2. An antidiabetic agent comprising 10-hydroxydecanoic acid. 3. An antidiabetic agent, which comprises 3,10-dihydroxydecanoic acid.