JP2007210918A - Testosterone-increasing agent, treated material of plant belonging to the genus allium, and food additive containing them - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To specify an active ingredient as a testosterone-increasing agent and provide the testosterone-increasing agent, a treated material of a plant belonging to the genus Allium and a food additive containing the same. <P>SOLUTION: This testosterone-increasing agent is provided by containing an L-cysteine sulfoxide derivative expressed by formula (1) [wherein, R is a 1-7C alkyl, a 2-7C alkenyl, a 6-12C aryl, a 7-12 C arylalkyl or an 8-10C arylalkenyl group] as an active ingredient. The compound can be extracted from the plant belonging to the genus Allium after inactivating its C-S lyase. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to a testosterone increasing agent and the like, and more particularly, to a testosterone increasing agent useful for improving sexual function aging in men, a processed leek plant, and a food additive containing them.

Viagra (registered trademark) is well known as a male sexual function improving drug, but it is pointed out that this drug is not suitable for hypertensive patients.
On the other hand, the Allium genus plant (onion, garlic, ginger garlic, leek, leek, etc.) is one of the most consumed among many vegetables, and the physiological action of this genus plant A lot of research has been done.

  For example, Japanese Patent Application Laid-Open No. 9-169661 (Patent Document 1) discloses that an onion or processed product such as onion juice or onion vinegar is also used to increase testosterone (a type of steroid hormone) that is useful for improving male sexual function aging. And is expected to be applied to a wide range of patients, including hypertensive patients as described above.

However, an active ingredient as a testosterone increasing agent contained in an onion or a processed product thereof has not been specified.
JP-A-9-169661

An object of the present invention is to specify an active ingredient as a testosterone increasing agent, and to provide a testosterone increasing agent, a processed green onion plant, and a food additive containing the active ingredient.
Another object of the present invention is to efficiently extract an active ingredient as a testosterone increasing agent from an allium plant, and to provide a testosterone increasing agent, a processed leek plant product and a food additive containing this active ingredient.

As a result of intensive studies to solve the above problems, the present inventors have found that a specific L-cysteine sulfoxide derivative contained in the genus Allium plant has an effect of increasing testosterone, and completes the present invention. It came to.

The testosterone increasing agent of the present invention is
Containing an L-cysteine sulfoxide derivative represented by the following formula (1) as an active ingredient;

[In Formula (1), R is an alkyl group having 1 to 7 carbon atoms, an alkenyl group having 2 to 7 carbon atoms, an aryl group having 6 to 12 carbon atoms, an arylalkyl group having 7 to 12 carbon atoms, or An arylalkenyl group having 8 to 10 carbon atoms. ].

  The L-cysteine sulfoxide derivative is preferably a compound represented by the following formula (1A);

[In the formula (1A), R is CH ₃ , CH ₂ CH ₃ , CH ₂ CH ₂ CH ₃ , CH (CH ₃ ) ₂ , CH ₂ (CH ₂ ) _n CH ₃ (n is 2 to 2
It is an integer of 5. ), CH ₂ CH═CH ₂ , CH═CHCH ₃ , Ph, CH ₂ —Ph or CH ₂ CH═CH—Ph (where Ph is a phenyl group). ],
At least one compound selected from the group consisting of S-methyl-L-cysteine sulfoxide, S-propyl-L-cysteine sulfoxide, S-allyl-L-cysteine sulfoxide and S-1-propenyl-L-cysteine sulfoxide is particularly preferred preferable.

The L-cysteine sulfoxide derivative may be a compound extracted from an Allium plant.
The extraction is preferably performed after inactivating the CS lyase in the genus Leek.

The C-S lyase is preferably deactivated by heating the Allium plant at a pressure of 1 to 5 atmospheres, a temperature of 40 to 150 ° C., and a time of 5 to 120 minutes.
It is preferable that the heating is performed on the green onion plant that has not been cut.

The processed leek plant of the present invention is:
It is obtained by inactivating C—S lyase in the genus Allium plant by heating the Allium plant at a pressure of 1 to 5 atm, a temperature of 40 to 150 ° C., and a time of 5 to 120 minutes,
Containing an L-cysteine sulfoxide derivative represented by the following formula (1B) in an amount effective for increasing testosterone;

[In Formula (1B), R is an alkyl group having 1 to 3 carbon atoms or an alkenyl group having 2 to 3 carbon atoms. ].
Moreover, as the testosterone increasing agent, a testosterone increasing agent containing the processed green onion plant is also preferable.

  The food additive of the present invention is characterized in that it contains the testosterone increasing agent or the processed green onion plant.

  According to the testosterone increasing agent, the processed green onion plant and the food additive of the present invention, testosterone can be increased. Therefore, the testosterone increasing agent of the present invention, the processed plant of the genus Allium plant and the food additive are used to prevent male sexual function aging, as well as breast cancer, endometrial cancer, ovarian cancer, thyroid cancer, menopausal function for which testosterone is effective. It is useful for preventing and treating diseases specific to women, such as disabilities.

Next, the testosterone increasing agent, the processed green onion plant and the food additive of the present invention will be described in more detail.
<L-cysteine sulfoxide derivative>
The testosterone increasing agent of the present invention contains an L-cysteine sulfoxide derivative represented by the following formula (1) as an active ingredient.

[In Formula (1), R is an alkyl group having 1 to 7 carbon atoms, an alkenyl group having 2 to 7 carbon atoms, an aryl group having 6 to 12 carbon atoms, an arylalkyl group having 7 to 12 carbon atoms, or An arylalkenyl group having 8 to 10 carbon atoms. The alkyl group and alkenyl group may be linear or branched, and the aryl group may have a substituent. ].

  The L-cysteine sulfoxide derivative is preferably a compound represented by the following formula (1A);

[In the formula (1A), R is CH ₃ , CH ₂ CH ₃ , CH ₂ CH ₂ CH ₃ , CH (CH ₃ ) ₂ , CH ₂ (CH ₂ ) _n CH ₃ (n is 2 to 2
It is an integer of 5. ), CH ₂ CH═CH ₂ , CH═CHCH ₃ , Ph, CH ₂ —Ph or CH ₂ CH═CH—Ph (where Ph is a phenyl group). ],
S-methyl-L-cysteine sulfoxide, S-propyl-L-cysteine sulfoxide, S-allyl-L-cysteine sulfoxide or S-1-propenyl-L-cysteine sulfoxide is included in the genus Allium plants such as onion and garlic It is particularly preferable from the viewpoint of being a component and highly safe for oral intake.

The testosterone increasing agent of the present invention may contain one or more L-cysteine sulfoxide derivatives represented by the above formula (1) (or formula (1A) or formula (1B)). Good.

In the present specification, “L-cysteine sulfoxide derivative” means “L-cysteine sulfoxide derivative represented by the formula (1)” unless otherwise specified.
The L-cysteine sulfoxide derivative may be an artificially synthesized L-cysteine sulfoxide derivative or a naturally-derived L-cysteine sulfoxide derivative (that is, obtained from a plant or the like).

  L-cysteine sulfoxide derivatives are described in du Vigneaud, V., Dyer, HM and Harmon, J., J. Biol. Chem. 101, 719 (1933). And Higuchi, O., Tateshita, K. and Nishimura, H. , J. Agric. Food Chem. 51, 7208-7214 (2003). Etc., specifically, it can be synthesized by the procedure shown in the following scheme 1.

[In the above scheme 1, X is Br or I, and R is the same as R in the above formula (1).
]
An example of a method for synthesizing the L-cysteine sulfoxide derivative (1) will be described in more detail with reference to Scheme 1 above.

L-cysteine and RX are reacted in 2N sodium hydroxide / ethanol at room temperature for about 15 minutes and then heated at reflux for 1 to 2 hours, and pure (A) is purified by recrystallization. obtain. Next, (A) is reacted at 0-5 ° C. in 30% -H ₂ O ₂ / glacial acetic acid or in water,
The reaction is stopped by confirming that A) has completely disappeared by thin layer chromatography, and the L-cysteine sulfoxide derivative (1) can be obtained by recrystallization.

On the other hand, a part of this L-cysteine sulfoxide derivative is also contained in the onion genus plants (Allium genus) such as onion, garlic, ginger garlic, leek, leek and the like. A preferred method for extracting L-cysteine sulfoxide derivatives from Allium plants will be described later.

<Testosterone increasing agent>
The testosterone increasing agent of the present invention contains the L-cysteine sulfoxide derivative as an active ingredient.

In addition to the L-cysteine sulfoxide derivative, the testosterone increasing agent of the present invention is used for excipients, preservatives, solubilizers, stabilizers, wetting agents, emulsifiers, sweeteners, coloring agents, flavoring agents, osmotic pressure changing agents. It may further contain a salt, a buffering agent, a coating agent and the like.

Examples of the testosterone increasing agent of the present invention include extracts containing L-cysteine sulfoxide derivatives, dry powders, granules, tablets, capsules, emulsions, ointments, injectable drugs and the like. The testosterone increasing agent may be added as a food additive to various seasonings such as drinks, sauces and dressings. Other uses include pharmaceuticals made from L-cysteine sulfoxide derivatives.

<Extraction of L-cysteine sulfoxide derivatives from Allium plants>
[Leek plant]
As described above, the L-cysteine sulfoxide derivative used in the testosterone increasing agent of the present invention may be extracted from a genus Allium plant.

Since the Allium plant contains a large amount of the L-cysteine sulfoxide derivative and can be obtained in large quantities at low cost, it is preferable as a source of the L-cysteine sulfoxide derivative. As the onion plant, onions, garlic, ginger garlic, leeks, leeks, rakkyo, shallot, chives, nobil, etc. can be used. Among them, onion, garlic, leek, rakki have many L-cysteine sulfoxide derivatives. Contains,
In addition, it is particularly preferable because it is highly consumed at home and abroad and is inexpensive.

[Deactivation by heat treatment of CS lyase]
When extracting an L-cysteine sulfoxide derivative from an Allium plant, it is necessary to inactivate C-S lyase contained in the Allium plant before cutting the Allium plant.

Here, “cutting the genus Leek plant” means cutting (dividing, or simply damaging) an edible part of the genus Leek plant (for example, a phosphorus stem in an onion). Means. However, it may be cleaved as long as the degradation of the L-cysteine sulfoxide derivative described below is slightly caused.

This C-S lyase is one of the enzymes of the genus Allium contained in the genus Allium and is also referred to as allinase. When it is mixed in the extracted L-cysteine sulfoxide derivative,
As described in [0024] to [0025] of 003-210132, the L-cysteine sulfoxide derivative is decomposed by the action of C—S lyase, and R—S—S (→ O) —R ( R is a methyl group, a propyl group, an allyl group, or a propenyl group.) Volatile disulfide, trisulfide, propanethiol S-oxide (tearing component) and the like are generated.

Therefore, by deactivating the action of CS lyase in this way, the L-cysteine sulfoxide derivative represented by the above formula (1) can be extracted without changing to a volatile sulfur-containing compound, Testosterone in serum can be increased by this L-cysteine sulfoxide derivative.

The means for inactivating C-S lyase is not particularly limited, but from the viewpoint of cost, a method of heating an Allium plant (hereinafter also referred to as “heat treatment”) is preferable.
Specific conditions for the heat treatment of the genus Allium (hereinafter also simply referred to as “heat treatment”) include a pressure in the range of 1 to 5 atmospheres, a temperature in the range of 40 to 150 ° C., and a time It is preferably in the range of 5 to 120 minutes, the pressure is in the range of 1 to 2 atmospheres, the temperature is in the range of 100 to 120 ° C., and the time is more preferably in the range of 20 to 40 minutes. When the above conditions are satisfied, C—S lyase can be efficiently deactivated and decomposition of the L-cysteine sulfoxide derivative can be avoided.

Moreover, if the hulls are removed without removing the hulls of the genus Leek, or the hulls are removed so as not to damage the edible part (eg, phosphorus stems in the onion), a part of the L-cysteine sulfoxide derivative is obtained. Or it is preferable at the point which avoids all decomposition | disassembly.

[Extraction of L-cysteine sulfoxide derivative]
By extracting the L-cysteine sulfoxide derivative after the inactivation of the C-S lyase by heat treatment or the like, the L-cysteine sulfoxide derivative can be used as an active ingredient of the testosterone increasing agent.

As the extraction method, a conventionally known method can be employed. For example, after the C-S lyase is inactivated by the above heat treatment, the Allium plant is ground with a mixer or the like, and is then washed with a 70% aqueous ethanol solution. After extracting the L-cysteine sulfoxide derivative, ethanol is further removed from the filtrate by a rotary evaporator to obtain an extract containing the L-cysteine sulfoxide derivative.
This extract may be further concentrated under reduced pressure to be processed into a concentrated extract.

<Processed onion plant>
The processed leek plant of the present invention has a pressure of 1 to 5 atmospheres, a temperature of 40 to 150 ° C., and a time of 5 to 120 minutes. Obtained by inactivating the C—S lyase of the formula (1B);

[In Formula (1B), R is an alkyl group having 1 to 3 carbon atoms or an alkenyl group having 2 to 3 carbon atoms. ].
The L-cysteine sulfoxide derivative represented by the formula (I) is contained in an amount effective for increasing testosterone. Preferred embodiments of the L-cysteine sulfoxide derivative, preferred conditions for inactivating the C—S lyase, and the like are the same as described above. In addition, in the case of a mouse (30 g body weight), the effective amount of the L-cysteine sulfoxide derivative in the processed plant of the genus Leek for testosterone is, for example, 0.2 g or more in terms of dry weight of onion, preferably Is 0.4 to 0.8 g.

  Since this processed green onion plant itself contains a component that increases testosterone, one preferred embodiment of the testosterone increasing agent of the present invention is a testosterone increasing agent containing this processed green onion plant.

The processed green onion plant is preferably used as a food alone or mixed with other food. Examples of the food product include powders made from the processed products of the genus Allium plant, processed food products such as pastes, drinks, and confectionery, and the embodiments described in [0023] of JP-A-2003-210132. It is done.

〔Example〕
Next, preferred embodiments of the present invention will be described in more detail with reference to examples, but the present invention is not limited thereto.

Onion concentrate extract production:
10 kg of onion (Hokkaido non-standard onion (scientific name: Allium cepa) Sapporo yellow)
Without removing the outer skin, it was put in a pressure cooker, heated at a pressure of 1.2 atm and a temperature of 120 ° C. for 30 minutes. The heat-treated onion was subjected to a mixer after removing the outer skin to obtain an onion paste. A 70% aqueous ethanol solution was added to the onion paste and stirred, and then the solid was removed by suction filtration using celite and filter paper to obtain an onion filtrate. The onion filtrate was concentrated under reduced pressure using a rotary evaporator to obtain a concentrated onion extract having an extract concentration of 834 mg / ml.

In addition, the presence of S-propyl-L-cysteine sulfoxide and S-methyl-L-cysteine sulfoxide in this onion concentrate extract was analyzed by various chromatographic methods, followed by analysis of nuclear magnetic resonance (NMR) spectra and chemistry. It was confirmed by the coincidence of the spectrum with the synthesized product, and the concentration was quantified by high performance liquid chromatography (HPLC).

Changes in serum testosterone levels:
This onion concentrate was diluted 30-fold to give a 27.8 mg / ml solution, and was freely given to aging-promoting model mouse SAMP1 (20 animals, 6 months of age at the start of intake, average body weight 31 g) for 4 months. Thereafter, the amount of testosterone (ng / dl) in the serum of this mouse was measured. The results are shown in FIG. In addition, the alteration was prevented by storing the diluted solution at a low temperature.

In addition, Fig. 1 shows the amount of testosterone in the category (control) in which tap water was freely given for 4 months.
As shown in Figure 1, serum testosterone levels were clearly increased in the mice that were allowed to freely drink the onion concentrate (diluent) compared to the category (control) that was allowed to drink tap water freely. .

S-propyl-L-cysteine sulfoxide (hereinafter also referred to as “PCSO”), which is abundant in onions, was synthesized by the method described in Scheme 1 above.
An aqueous solution prepared from synthesized PCSO (PCSO concentration = 0.31 mg / ml) can be freely given to aging-promoting model mouse SAMP1 (20 animals, 6 months old at the start of intake, average body weight 34 g) for 4 months. After that, the amount of testosterone (ng / dl) in the serum of this mouse was measured. The results are shown in FIG.

In addition, Fig. 2 shows the amount of testosterone in the category (control) in which tap water was freely given for 4 months.
As shown in FIG. 2, the amount of testosterone in the serum was clearly increased in the mice that were allowed to freely drink PCSO aqueous solution, compared with the category that was allowed to drink tap water freely (control).

S-allyl-L-cysteine sulfoxide (hereinafter also referred to as “ACSO”), which is abundant in garlic and ginger garlic, was synthesized by the method described in Scheme 1 above.
An aqueous solution (ACSO concentration = 0.31 mg / ml) prepared from synthesized ACSO was freely given to aging-promoted model mouse SAMP8 (20 mice, 6 months old at the start of intake, average body weight 33 g) for 4 months. After that, the amount of testosterone (ng / dl) in the serum of this mouse was measured. The results are shown in FIG.

In addition, Fig. 3 shows the amount of testosterone in the category (control) in which tap water was freely given for 4 months.
As shown in FIG. 3, in the mice that freely drank ACSO aqueous solution, the amount of testosterone in serum was clearly increased compared to the category (control) that freely drank tap water.

  The testosterone increasing agent of the present invention, the processed plant of the genus genus plant and the food additive include not only male sexual function aging prevention by increasing testosterone, but also breast cancer, endometrial cancer, ovarian cancer, where testosterone is effective, Expected to be effective in preventing and treating diseases peculiar to women such as thyroid cancer and menopausal dysfunction.

FIG. 1 shows changes in the amount of serum testosterone in mice due to onion concentrate (diluted solution). FIG. 2 shows changes in the amount of serum testosterone in mice due to an aqueous PCSO solution. FIG. 3 shows changes in the amount of serum testosterone in mice due to the ACSO aqueous solution.

Claims (10)

A testosterone increasing agent comprising an L-cysteine sulfoxide derivative represented by the following formula (1) as an active ingredient;

[In Formula (1), R is an alkyl group having 1 to 7 carbon atoms, an alkenyl group having 2 to 7 carbon atoms, an aryl group having 6 to 12 carbon atoms, an arylalkyl group having 7 to 12 carbon atoms, or An arylalkenyl group having 8 to 10 carbon atoms. ]. The testosterone increasing agent according to claim 1, wherein the L-cysteine sulfoxide derivative is a compound represented by the following formula (1A);

[In the formula (1A), R is CH ₃ , CH ₂ CH ₃ , CH ₂ CH ₂ CH ₃ , CH (CH ₃ ) ₂ , CH ₂ (CH ₂ ) _n CH ₃ (n is 2 to 2
It is an integer of 5. ), CH ₂ CH═CH ₂ , CH═CHCH ₃ , Ph, CH ₂ —Ph or CH ₂ CH═CH—Ph (where Ph is a phenyl group). ]. The L-cysteine sulfoxide derivative is selected from the group consisting of S-methyl-L-cysteine sulfoxide, S-propyl-L-cysteine sulfoxide, S-allyl-L-cysteine sulfoxide and S-1-propenyl-L-cysteine sulfoxide. The testosterone increasing agent according to claim 1 or 2, wherein the testosterone increasing agent is at least one kind of compound. The testosterone increasing agent according to any one of claims 1 to 3, wherein the L-cysteine sulfoxide derivative is a compound extracted from a genus Allium plant. 5. The testosterone increasing agent according to claim 4, wherein the extraction is performed after inactivating C—S lyase in the genus Allium plant. The C-S lyase is deactivated by heating the Allium plant at a pressure of 1 to 5 atmospheres, a temperature of 40 to 150 ° C., and a time of 5 to 120 minutes. Claim 5
Testosterone increasing agent as described in.   7. The testosterone increasing agent according to claim 6, wherein the heating is performed on the uncut genus plants. It is obtained by inactivating C—S lyase in the genus Allium plant by heating the Allium plant at a pressure of 1 to 5 atm, a temperature of 40 to 150 ° C., and a time of 5 to 120 minutes,
An L-cysteine sulfoxide derivative represented by the following formula (1B) in an amount effective for increasing testosterone;

[In Formula (1B), R is an alkyl group having 1 to 3 carbon atoms or an alkenyl group having 2 to 3 carbon atoms. ]. The testosterone increasing agent according to any one of claims 1 to 7, which comprises the processed plant of the genus Allium according to claim 8.   A food additive comprising the testosterone increasing agent according to any one of claims 1 to 7 or 9, or the processed product of the genus Allium plant according to claim 8.

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