WO1986005094A1

WO1986005094A1 - Antiobesity agent and composition

Info

Publication number: WO1986005094A1
Application number: PCT/JP1985/000118
Authority: WO
Inventors: Takao Matsuo; Satoshi Horii; Nobuyuki Kitamori
Original assignee: Takeda Chemical Industries, Ltd.
Priority date: 1985-03-08
Filing date: 1985-03-08
Publication date: 1986-09-12

Abstract

An antiobesity agent comprising a combination of an alpha-glucosidase inhibitor and non-pathogenic, lactic acid-yielding bacteria, and an anti-obesity composition containing them. Obesity can be prevented or treated without temperance in eating, by oral administration of the agent or the composition. They are not substantially accompanied by diarrhea, meteorism, etc. which are induced by administration of an alpha-glucosidase inhibitor alone.

Description

Specification

Anti-obesity agent and anti-obesity composition

Technical field

The present invention relates to an anti-obesity agent comprising a combination of an α-glucosidase inhibitor which is an anti-obesity agent and a non-pathogenic live lactic acid-producing bacterium, and an anti-obesity composition comprising both of them.

Background art

In recent years, the number of people who become obese due to overnutrition has increased. The mechanism by which this obesity occurs is thought to be as follows. In other words, when carbohydrates contained in food are digested and become glucose, and absorbed into the body, the blood sugar level rises, and insulin stimulates the release of insulin from the kidney. The insulin acts on fat cells, and glucose in the blood is absorbed into fat cells and converted into fat, resulting in fat cell hypertrophy and abnormal accumulation of fat as the whole body, resulting in obesity. Occurs.

Therefore, administration of a drug that inhibits the digestion of carbohydrates in food into glucose will suppress the rise in blood sugar levels, thereby reducing insulin secretion and reducing the amount of fat synthesized from glucose. It can reduce or prevent obesity or treat it. Therefore, saccharolytic enzyme-inhibiting substances have been sought, and various drugs having the action have already been created.

However, when the above drugs are administered to animals, a large amount of undigested oligosaccharides and disaccharides stay in the intestinal tract and are not absorbed into the body from the intestinal tract, so that the osmotic pressure in the intestinal tract increases. The organism attempts to lower this to normal physiological osmotic pressure, and a large amount of water is secreted from the intestinal wall into the intestinal tract, resulting in osmotic diarrhea. In addition, various bacteria resident in the intestine use the above-mentioned retained oligosaccharides and disaccharides as an energy source and decompose them into carbon dioxide, hydrogen gas, methane gas, water, etc. Flatulence is also raw Cheating.

Disclosure of the invention

The present inventors have conducted intensive studies on a method for suppressing side effects such as diarrhea and flatulence resulting from the administration of the above-mentioned anti-obesity drug. It was found that the objective of the period was achieved. A In other words, the above-mentioned side effects such as diarrhea and flatulence do not occur because a large amount of oligosaccharides and disaccharides stay in the intestinal tract.I-Lactic acid-producing bacteria that utilize and remove these sugars to convert to lactic acid When lactic acid is administered, the lactic acid produced thereby is rapidly absorbed into the living body, so that the occurrence of osmotic diarrhea can be prevented. In this case, in particular, using a homo-lactic lactic acid fermentation bacterium produces only lactic acid without generating carbon dioxide gas, thereby preventing both diarrhea and flatulence at the same time. On the other hand, the produced lactic acid is absorbed into the living body through the intestinal tract wall, but unlike the case where glucose is absorbed, it does not stimulate insulin secretion, so that adipocyte hypertrophy does not occur. The original anti-fertility effect is maintained as it is.

Examples of -dalcosidase inhibitory substances used in the present invention include, for example, JP-A-57-200335, JP-A-58-59946, JP-A-58-162597, JP-A-58-216U5, JP-A-59-73549 and JP-A-59-95297.

General formula

[In the formula, A is a hydroxyl group, phenol, phenyl, phenyl, pyridyl, cyclohexyl, an optionally substituted phenyl-containing chain hydrocarbon group having 1 to ^ carbon atoms, a hydroxyl group, It represents a cyclic hydrocarbon group having 5 or 6 carbon atoms or a 锖 residue which may have a droxymethyl group, a methyl group or an amino group. Variolamine derivative represented by

Is raised.

Specific examples of the N-substituted variolamine derivative represented by the general formula [I] include:

(1) N-phenethylvariamine,

(2) N— (3—Fenraryl) variolamine,

(3) N-furfurylvariolamine,

(4) N-thenyl variamine,

(5) N-(3-pyridylmethyl) variamine.

(6) N— (4—brobenzyl) variamine,

(7) N — [(R) — ^-hydroxyphenethyl] valiolamin,

(8) N — [(S) — ^ — hydroxyphenethyl] valiolamin, (9) N— (3—hydroxy-2-methoxyphenethyl) valiolamin, (10) N— (3,5) —Di-tert-butyl—4-hydroxybenzyl) valio—luamine,

(11) Ichi (sig σ-hexylmethyl) valiamine,

(12) Ν-geranylvario-lamin,

(13)-(1,3-dihydroxy-2-propyl) varioamine,

(14) Ν— (1, 3 —dihydroxy 1 1 phenyl 2 —propyl) valio—luamine,

(15) N-L (R) -α— (hydroxymethyl) benzyl] valiolamine,

(16) Ν-cyclohexylvariolamine, (Π) N- (2-hydroxycyclohexyl) valiamine,

(18) N-[(1 R, 2 R) —2—Hydroxink mouth] variolamine,

(19) N— (2-hydroxycyclopentyl) valiamine,

(20) Methyl 4- [US, 2S) — (2,4,5 (OH) / 3,5)-2,3,4,5—Tetrahydroxy-1-5-C— (Hydroxymethyl) cyclo Xyl] amino-4,6-dideoxy-1-D-glucopyranoside,

(21) Methyl 4 -— ((l S .2 S) — (2,4,5 (/ 3) / 3,5)-2,3,4,5—tetrahydroxy-1-5-C— (hydroxymethyl) Cyclohexyl] amino 4-didoxy-l-D-Darcopyranoside,

(22) [(1S, 2S) -C2,4,5 (OH) / 3,5) —2,3,4,5—tetrahydroxy—5—C— (hydroxymethyl) cyclohexyl] [(1 R,. 2 S) — (2, 6/3, 4) — 4.—amino 2.3—dihydroxy-16-C- (hydroxymethyl) cyclohexyl] amine,

(23) N-[(l R, 2 S)-(2,4 / 3 ₎ 5)-2,3,4-trihydroxy

5—C— (Hydroxymethyl) cyclohexyl] variolamine,

(24) N — [(1R, 2S) —2,6 / 3,4) —4-amino 2,3-dihydroxy 6-methylcyclohexyl] valiolamin,

(25) N-[(l R, 2 S)-(2,6 / 3,4) -2 ₍ 3,4-trihydroxy 6-methylhexyl hexyl) _varioamine

(26) N-[(1 R, 2 S) — (2, 4, 6/3) —2, 3, 4—trihydroxy

6—Methylcyclohexyl] pariolamin,

(27) 4-0-a-[4-[(1 S)-(l, 2, 4, 5 (0 H) / 3, 5) — 2.3,

4,5-Tetrahydroxy-5-C- (Hydroxymethyl) cyclohexyl) amino] -1,4,6-Dideoxy-1D-Darcopyranosyl-1D

-Dalkobiranose, 2 ^ I

5 5 1 5 1

(28) 1, 6—Unhidden draw 4— 0— α— [4-1 ((I S) — (1, 2, 4, 5 (0

H H) / 3,5) —2,3,4,5—Tetrahydroxyl 5—C— (Hydro o \

Xymethyl) cyclohexyl) amino] -1,4,6-dideoxy-1D-g

H

Rukopi_o o ■ —Norano syl] 1 ^ — D—Darcovyranoose

Such as NH NH.

A A

Above all, N— (1.3-dihydroxy-2-propyl) thiolamine, ie, 1 L (1 S) [1 (0H), 2,4,5 / 1,3] —5— [2— (2-Hydroquinone 1-hydroxyl i_tilleamino) 1-11 C— (Hydroxymethyl) 1,2,3,4-cyclohexyl -_— Santetol is an object of the present invention. Especially

10 It has come true.

Further, a general formula described in JP-A-57-64648, etc.

CH ₂ 0H

HO

[In the formula, A is a hydroxyl group, a phenyl group, a phenyl group, a phenyl group, a cycloalkyl group, an optionally substituted phenyl group having 1 to 10 carbon atoms, a hydroxyl group, a hydroxymethyl group. Having a methyl group and an amino group

20 represents a cyclic hydrocarbon group or a sugar residue having 5 or 6 carbon atoms. Varienamine Ν-substituted derivatives represented by the general formula described in JP-A-57-114554, etc.

CH ₂ 0H [Wherein A is a hydroxyl group, phenoxy, phenyl, furyl, pyridyl, cyclohexyl, an optionally substituted phenyl hydrocarbon group having 1 to 10 carbon atoms, a hydroxyl group, a hydroxymethyl group, It represents a C5 or C6 cyclic hydrocarbon group or sugar residue that may have a methyl or amino group. The Ν-substituted derivative of validinin represented by the formula [1] is also suitably used as the α-dalcosidase inhibitory substance of the present invention.

In addition, acarbose [(acarbose) .BA Yg 5421, Naturwissenschaften, Vol. 64, pp. 535-537 (1977), Japanese Patent Publication 54-39474], Trestatin [(trestat in), The · Journal of Antibiotics, Vol. 36, pp. 1157–1175

(1983) and Volume 37, pp. 182 to 186 (1984); Japanese Patent Application Laid-Open No. 54-163511], Adiposins [(adiposins), The Journal of Antibiotics, J. Antibiotics] Vol. 35, pp. 1234-1236 (1982); Starch Chemistry (J. Jap. Soc. 'Starch Sci.), Vol. 26, pp. 134-144 (1979), Vol. 27, pp. 107-113 (1979) 1980); JP-A-54-106402; JP-A-54-106403; JP-A-55-64509; JP-A-56-123986; JP-A-56-125398]; Amylostatin

[(amylostatins), Agricultural and Biological Chemistry (Agri.c. Biol. Chem.), Vol. 46, pp. 11-1945 (1982); Kaisho 55-'71494; JP 55-157595], oligostatins [(oligostatins), SF-1130X, JP 53-26398; JP 56-43294, The Journal of Antibiotics (J. Antibiotics), Vol. 34, U24-1433 (1981)], amino sugar compounds (JP-A-54-929 (39), etc.). A review of α-darcosidase inhibitors is provided by E. Truscheit et al., Angewandte Chemie, Vol. 93, pp. 738-755 (1981)]. Have been. In addition, acarbose and oligostatin C

Methyl 4 -— [(1S, 6S)-(4,6 / 5)-, 5,6-trihydroxyl-3-3-hydroxymethyl-2-cyclo obtained by methanolysis of (oligostatins C) [Hexene 1-yl] Amino 1, 4,6-dideoxy α-D-darcopyranoside [182nd Annual Meeting of the American Chemical Society (182nd

AC Sational meeting Abstracts paper) ME DI 69, August 1981, New York; The Journal 'Ob' Antibiotics, 34, 1429-1433 (1981); 57-24397], 1-deoxyno jirimycin [(1—deoxyno rimycin), Natsuru Nitswijssenschaften, Vol. 66, pp. 584-585 (1979)] and N-substituted derivatives thereof, for example BAYm 1099 and BAYo 1248 [The Journal of Clinical Investigation (J. Clin. Invest), Vol. 14 (2-2), 47 (1984); Diabetologia Vol. 27 (2 ), 288A, 346A, 323A (1984)].

The non-pathogenic lactic acid-producing bacteria that can be used in the present invention include not only lactic acid bacteria in a narrow sense, but also lactic acid bacteria in a broad sense, for example, bacteria of the genus Sporolabacillus sp. Contains live bacteria of the genus if idobacterium. Those that do not generate gas that causes flatulence during growth and reproduction can be used more advantageously.

Lactic acid-producing bacteria that can be used in the present invention include Lactobacillus acidophilus (Lactobacillus acidophilus), L. salivarius (L.

salivalius), L. delbruecki, L. leic manni i, L. lactis, L. casei, Streptocco ': / Cas bacilli (Streptococc s faecalis) S. faecci (S. faeci), S. lactis (S. lactis) and the like are used. _ Bacterial microorganisms of the genus Bacillus are derived from two molecules of glucose by fermentation. Produces two molecules of lactic acid and three molecules of acetic acid to produce B. idobacterium um bif iduin, B. infantis, B. adolescent is, B. Longum (B. longum) and the like are used, but these are typical and not limited to these. These microorganisms are vulnerable to air, oxygen, high temperature, and humidity when they are dry, but Streptococcus microorganisms are generally more stable than other lactic acid-producing microorganisms and are easier to handle.

In addition, the use of microorganisms resident in the intestine, such as Streptococcus faecalis, Lactobacillus acidophilus, and Bifidobacterium bifidobacter, as lactic acid-producing bacteria, disrupts the intestinal bacterial flora. There is no advantage.

In accordance with the present invention, when a single glucosidase inhibitor is administered in combination with a non-pathogenic lactic acid-producing bacterium, the dose of the single glucosidase inhibitor is 0.05-500 mg / adult Z, preferably ^. ~ ^! ^ Adults / time, usually 2 or 4 times daily, preferably between 1 hour before meals and 2 hours after meals. In particular, when the dalcosidase inhibitor is a variolamine derivative represented by the general formula [I], it is recommended that 1.0 to 20 tngZ of an adult be administered 2 to 4 times a day, preferably 1 hour before a meal to 2 hours after a meal. It is effective to administer it orally at an appropriate time.

On the other hand, the number of viable non-pathogenic lactic acid-producing bacteria used in combination with the above inhibitor is 10 ³ to 10 ¹² cells / adult / time, preferably 10 ⁵ to 丄 01 ^{1 in} terms of the number of viable cells. It is effective to take a preparation containing Z doses per adult, usually 2 to 4 times a day, preferably 1 hour before meals to 2 hours after meals.

-As a method of administering a combination of a glucosidase inhibitor and a non-pathogenic lactic acid-producing bacterium, a preparation containing the inhibitory substance and a preparation containing the lactic acid-producing bacterium are separately prepared, and both preparations are simultaneously prepared. Or at a different time There is a method of administering the active ingredient and a method of administering a composition containing both the inhibitory substance and the lactic acid-producing bacterium. It is often more convenient to administer a composition containing both components.

The dosage form of a glucosidase-inhibiting substance, a preparation containing lactic acid-producing bacteria alone, and a composite preparation containing both at the same time, take into account the physicochemical properties, biological properties, etc. of each component. Dosage forms convenient for administration may be tablets, pellets, granules, granules, powders and capsules. In addition, in each preparation, besides the hair dalcosidase inhibitor and the lactic acid-producing bacteria, there are appropriately selected excipients, coloring agents, fragrances, stabilizers, brighteners, etc., which are commonly used in the preparation. May be used.

An anti-obesity composition containing a glucosidase-inhibiting substance and a non-pathogenic lactic acid-producing bacterium can be prepared by mixing both components according to a conventional method of preparation. In the above, the compounding ratio of the a-dalcosidase inhibitory agent and the non-pathogenic lactic acid-producing bacterium is preferably 10 ³ to 10 ^{12 in} the former case and 5 to 500 mg in the former case, and 1.0 to 10 in the latter case. 50mg

ΙΟ ⁵ ^) ^{1 0} pieces are especially desirable.

In addition, lactic acid-producing bacteria are generally anaerobic and are susceptible to air or oxygen when dry, and are susceptible to high temperatures and humidity. It is preferable to process at low temperature.

When the composition of the present invention is formed into a solid preparation, the powder may be simply mixed together by a drying method, or the powder may be compressed into granules or tablets. When granules and tablets are produced by a wet method, they can be kneaded using an aqueous solution of a binder and dried to obtain a target solid preparation. Further, the powder or granules thus obtained can be filled into capsules to give capsules. In order to mix a small amount of the active ingredient with a large amount of other powders to obtain a uniform mixture, it is better to employ a so-called stepwise mixing method. For example, the active ingredient

A uniform powder is obtained by mixing with 100 to 200 times the volume of powder, and a uniform powder is obtained by mixing this with the remaining powder.

Drying from hydrated materials can be performed by L-drying, freeze-drying, spray drying, or other means.

In order to obtain the lactic acid-producing bacteria, the cells can be suspended in a neutral buffer solution containing an appropriate stabilizer, for example, monosodium glutamate salt, adnitol, etc., and dried by a method known per se. Is preferred.

The composition of the present invention is effective in preventing obesity by using a small amount thereof, and the administration method is simple and has almost no side effects.

Generally, diarrhea is caused by indigestion, abnormal intestinal fermentation, or disturbance of the intestinal flora. Depending on the cause, antibiotics, herbal medicines, lactic acid bacteria, and medicinal charcoal are used. ·

In other words, compounds such as antibiotics and creosote are used to kill intestinal bacteria or cause bacteriostasis that cause diarrhea, and Chinese medicine uses tannin, the main component of which is not necessarily clear. Astringent action is said to be the main drug effect.

In addition, lactic acid bacteria have been claimed to be effective for normalizing intestinal bacteria that have been disrupted by diarrhea or for treating indigestion, but the mechanism of action is well understood. Not.

In addition, medicated charcoal is used in anticipation of adsorption of gas produced by abnormal fermentation in the digestive tract, adsorption of harmful substances in self-poisoning, and detoxification.

According to the present invention, as described above, diarrhea and flatulence are prevented by blending a lactic acid-producing bacterium which selectively assimilates saccharides retained in the intestinal tract by inhibiting the digestion of carbohydrates by the antifertilizer. Can be prevented, and this milk Acid-producing bacteria are resident in the intestine and are harmless, and the lactic acid produced by their reproduction is completely harmless to humans, so it is extremely safe. BEST MODE FOR CARRYING OUT THE INVENTION

Example 1

To 88 g of potato flour, add bifidobacterium bifidum (IF 0

— 14252) is a powdered lg of 10 ¹² cells (iOg as cell powder) and N- (1,3-dihydroxy-2-propyl) paliolamine (hereinafter referred to as AO-128). In addition, mix well in a mortar for 10 minutes. Further, magnesium stearate powder lg was added and mixed well for 3 minutes to obtain a powdery composition.

Example 2

To carbonochloridate written order starch 84 g, Bifi Dobakuteriumu Bifi DOME. (IF 0 - U ²⁵²⁾ of viable cells by the addition of flour powder 5 g of the bacterial cell number 10 ¹² (10 g as bacteria ^) and AO -I ^28. Mix well in mortar for 10 minutes. Further, a powder lg of magnesium stearate was added thereto and mixed for 3 minutes to obtain a powdery composition. Each 100 g of this powdery powder composition was tableted at a compression pressure of 500 kg / cm ² to produce flat tablets having a diameter of 6.5 mm. This tablet was administered to 6 Beagle dogs (weight 9.1 ~

10.7 Kg) of each dog was orally administered one break immediately before the lined diet, and observed up to 48 hours after administration. No diarrhea was observed in any dog.

On the other hand, using a potato starch 94g, AO-128 5g and magnesium stearate lg, the same operation as above was carried out to obtain a compressed tablet containing AO-128 5mg per iOOmg (hereinafter referred to as AO-128 tablet). . )made.

In addition, from potato starch 89 g, Bifidobacterium bifidum (IF 0-14252) 10 ¹² viable bacteria (10 g as bacterial cell powder) and 1 g of magnesium stearate in the same manner as described above, 10 ³ tablets per IOOmg Tablets containing bacteria

(Hereinafter referred to as a bacterial tablet). One AO-128 tablet was orally administered to each of three beagle dogs 30 minutes before feeding, and one microbial tablet was orally administered immediately before feeding, and diarrhea was observed in all dogs observed for 24 hours. Did not.

In contrast, only three A-128 tablets were orally administered 30 minutes before feeding to each of the three beagle dogs, and observations were made without feeding the bacterial tablets after feeding. Flatulence and cat diarrhea were observed over a period of time. Example 3

Lactose 20g, corn starch 54 g, easy Tobachirusu azide Dofirusu (IF 0- 13951) viable bacterial cells Number 10 ^{1 Two} (10 g as bacteria powder), Streptomyces aureus off We - Cullis of (IF 0- 12580) Raw The bacteria were placed in a mortar with 10 ¹² cells (10 g as cell powder) and 5 g of AO-128 powder, and mixed well for 10 minutes. Further, magnesium stearate (lg) was added thereto, and the mixture was thoroughly mixed for 3 minutes. Each 10 Omg of this mixture was formed into a flat surface having a diameter of 6.5 mm under a pressure of 500 kg / cm ² . The tablets prepared in this way were orally administered to each of six beagle dogs immediately before the lined diet, and observed up to 48 hours after the administration. No diarrhea was observed in any dog. The same tablets were administered to 3 healthy boys, 1 tablet each, just before lunch, and observed for 10 hours. As a result, some flatulence was observed and no diarrhea was observed.

On the other hand, lactic acid-producing bacteria-free tablets (1 tablet lO) obtained by the same procedure as above using 20 g of lactose, 74 g of corn starch, 5 g of AO-128 powder and 1 g of magnesium stearate were used. Containing 5 mg of A0-128 in Omg). When one tablet was administered to the same person under the same conditions, flatulence and diarrhea were observed for 5 to 8 hours after administration.

Example 4 '

A powder obtained by mixing lactose and corn starch in a weight ratio of 8 to 2,

Using AO-128 powder, hydroxypircellose and distilled water Then, granules containing 5 mg of AO-128 and 3 mg of hydroxypropyl cellulose in 100 mg (hereinafter referred to as A0-128 granules) were prepared by a wet kneading method. 100 g of AO-128 granules obtained in this way, viable bacteria of Bifidobacterium bifidium (IF 0-14252) were 9.5 x 10 ¹¹ cells (9.5 g as cell powder) and magnesium stearate. G.5g) was thoroughly mixed and formed into a flat tablet having a weight of liOmg and a diameter of 6.5 mm using a tableting machine. One tablet each was orally administered to each of three beagles immediately before feeding and observed for 48 hours. No diarrhea was observed.

On the other hand, AO-128 granules]; 00 g and magnesium stearate (1 g) were mixed to form a flat tablet having a weight of 101 mg and a diameter of 6.5 dragons in the same manner as described above. When one tablet of each of these tablets was orally administered to each of three beagle dogs immediately before feeding, diarrhea was observed in all dogs, albeit with a slight difference between 4 and 10 hours after administration.

Example 5-Lactose-corn starch mixed powder used in Example 4, AO-128, Streptococcus ♦ Huecaris (IF-I 12580), 1 kg by wet kneading using polyvinylpyridone AO—128 mg, 10 ¹ bacteria. Granules containing 30 mg of polyvinylpyrrolidone were prepared.

Reference example 1

1 g of the mixture obtained in Example 1 or a mixture containing other cells obtained in the same manner as in Example 1 was mixed with 99 g of a commercially available powdered feed (CE-2) to prepare a test mixture. Feed was prepared. This diet was fed to male J cl: SD rats (6 animals per group) at the age of 7 weeks, and the state of feces after 36 to 48 hours was observed. The control group was fed a diet mixed with 10 mg of AO-128 and 100 g of powdered diet. Table 1 shows the results. Table 1

^ +: The droppings are broken (watery stool)

Soil: Feces are observed, but water diffusion is observed on the absorbent paper. -: Feces are observed, and no water diffusion is observed on the absorbent paper.

Reference example 2

A test feed was prepared using two or more types of bacteria according to the method of Reference Example 1. However, the amount of potato starch was reduced by an amount corresponding to the increase in the amount of cells, to prepare a composition containing AO-128 and the cells, and this was mixed with the feed. The diet was fed to a 7-week-old Jci: SD rat (5 mice per group), and the state of feces was observed 36 to 48 hours later. The control group received a diet in which 10 mg of AO-128 was mixed with 100 g of powdered diet. Table 2 shows the results. Table 2

The results show that diarrhea caused by AO-128 was significantly reduced by the single and combined administration of lactic acid producing bacteria.

Reference example 3

Although the composition of the present invention reduces diarrhea, on the other hand, it is also possible that changes in hyperglycemia and hyperinsulinemia inhibitory action and antifertilization action after ingestion of diet may occur. Was considered.

Effect on the control of erythrocyte hyperglycemia and hyperinsulinemia An 8-week-old male fed a diet prepared in the same manner as in Reference Example 1 for 24 hours' Jcl: SD rats (6 rats per group) In addition, we examined how the inhibitory effect of AO-128 on hyperglycemia and hyperinsulinemia caused by feeding was affected by the administration of lactic acid-producing bacteria.

Blood was collected from the tail vein immediately before the lined feed and at 30 minutes, 60 minutes, and 120 minutes after feeding, and the plasma glucose level and insulin level were measured. The results are shown in Tables 3 and 4. Table 3

Plasma glucose level

O-128 lactated plasma _course value mg / dl

K) Les Hes' 0 min 30 min 60 min 1 2 0 min

Iris,

Streb

Tococca

Su Hue

One squirrel

, Hinoi

Dhbakte

Lithium ·

Fido

(Cells

(%) Number / g)

0 0 101 Sat 6 179 ± 13 184 6 6 189 ± 11

0 each 10 ⁸ 98 ± 10 186 ± 13 182 = 13 178 ± 11

0.01 0 101 ± 10 141 Sat 8a 154 = ll ^a 152 ± ll ^a

0.01 Each I0 ^8. 96 Sat 2 146 ± 10 ^a 155 two 10 ^a 147 Sat 8 ^a

Table 4

Plasma insulin level

Mean standard deviation (n = 6) ·.-Significant difference from the first group (a: P <0.001,: P <0.01) · As shown by these results, dietary hyperglycemia and high levels of AO-128 The insulin-linemia inhibitory effect was not affected at all by the administration of bacterial cells. Reference example 4

A diet prepared in the same manner as in Reference Example 1 was fed to a 3-week-old male (Ziicker) fertilizer rat for 28 days, and changes in body weight gain, food consumption, dietary efficiency, and body fat were observed. Table 5 shows the results. · Table 5

Mean soil standard deviation (ii = 6) Significant difference from the first group (a: F <0.001, b: P <0.01, c: P <0.02) For body fat analysis, liver, epididymal fat tissue A sample from which the digestive tract and its contents were removed was used. The diet containing the cells was prepared and given every two days. There were no significant differences in any of the items between groups 2 and 3.

Reference example 5

Acute toxicity test for rat

In acute toxicity studies in rats, there were no deaths after oral administration of A0-128 at 10 g / Kg body weight. The three lactic acid bacteria used in the present invention were mixed with each other so as to contain 10 ^{11, and} were orally administered simultaneously with AO-128 (10 g / Kg body weight). There was no effect when given.

Industrial applicability

The anti-obesity agent and the anti-obesity composition according to the present invention prevent or treat the fertilization of humans and animals by oral administration without substantially reducing side effects such as diarrhea without reducing food consumption. It is useful as an agent for preventing and treating obesity in humans and animals.

Claims

The scope of the claims

1. Antifertilizer consisting of a combination of α-dalcosidase inhibitor and non-pathogenic lactic acid-producing bacteria

2. One glucosidase inhibitor

General formula

[In the formula, A represents a hydroxyl group, phenyl, phenyl, phenyl, cyclohexyl, a linear hydrocarbon group having 1 to 10 carbon atoms which may have a phenyl group which may be substituted, a hydroxyl group, a hydroxy group. It shows a cyclic hydrocarbon group or a sugar residue having 5 or 6 carbon atoms which may have amino group> methyl. Variol amine derivative represented by

2. The composition according to claim 1, wherein the composition is:

3. The composition according to claim 1, wherein the a-glucosidase inhibitory substance is N- (1,3-dihydroxy-2-monopropyl) valiolamin.

4 -.. Glucosidase inhibitory agent and set viewing combined ratio of non-pathogenic lactic acid-producing producing bacteria is, Q l~400mg to 10 ³ to 10 ^{1 2} a is Claims anti-obesity agent as set forth in claim 1, wherein .

An anti-obesity composition comprising a δ.-dalcosidase inhibitor and a non-pathogenic lactic acid-producing bacterium.

6. One glucosidase inhibitor

General formula

o one

[In the formula, A is a hydroxyl group, phenyl, phenyl, furyl, pyridyl, cyclohexyl, a linear hydrocarbon group having 1 to 10 carbon atoms which may have an optionally substituted phenyl group, It represents a C5 or C6 cyclic hydrocarbon group or sugar residue that may have a hydroxyl group, a hydroxymethyl group, a methyl group, or an amino group. Variol amine derivative represented by

6. The composition according to claim 5, wherein the composition is:

7. The composition according to claim 4, wherein the -glucosider inhibitory substance is N- (1,3-dihydroxy-21-propyl) valiolamin. · ·

5 8. A one Darukoshidaze inhibitory agent and Blend ratio of non-pathogenic lactic acid-producing producing bacteria is, Q. L~400mg pair 10 ³ to 10 ¹ claims a ^binary fifth term set Narubutsu . 0