JPH0625081A - Beta-acid @(3754/24)lupulones) acyl derivative having antioxidation action - Google Patents

Abstract

PURPOSE:To obtain the subject derivative being stable, capable of exhibiting strong antioxidation activity in vivo and useful for medicines, beverages and foods, etc., by acylating beta acids (lupulones) obtained from hop. CONSTITUTION:beta-Acids (lupulones) obtained from hop are made to react with an acylating agent such as an acid chloride in a solvent such as pyridine or dichloromethane at ordinary temperature to 0 deg.C for 1-24hr to provide the objective compound of the formula [R is CH(CH3)2 or CH2CH(CH3)2, etc.; R1 is H, 1-20C alkyl, alkenyl, etc.].

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION The present invention is directed to various diseases that may impair health maintenance such as adult diseases, intractable diseases such as rheumatoid arthritis and Behcet's disease, trauma such as burns, and cosmetic disorders such as acne and spots. The present invention relates to a novel acyl derivative of hop β-acid (luprons) which has an effect of prevention and treatment and has an antioxidant effect, and a pharmaceutical product, a food and drink, and a cosmetic product containing this compound as an active ingredient.

[0002]

The β-acyl acyl derivative of the present invention is a novel substance which has not been known in the prior art. The present inventor has clarified that the hop extract, which is a raw material of beer, and the β-acids (luprons) contained therein have a strong active oxygen scavenging action, that is, an antioxidant action, and applied for a patent for the result and the production method ( Japanese Patent Application No. 2-329799).

However, β acid is known to be unstable to light and oxygen and easily decomposed. Therefore, the handling of β-acid is difficult, and its utilization range must be narrowed.

[0004]

The present inventor has found β-acid as a component having an excellent antioxidant effect in hops, but it is problematic in that it is unstable and easily decomposed.
Therefore, the present invention provides a stable β-acid which is obtained by using β-acid as a derivative and which exhibits a strong antioxidant effect in vivo.
It is intended to provide an acid acyl derivative.

[0005]

The present invention is an acyl derivative which is a stable β-acid (luprons) obtained from hops and which exhibits a strong antioxidant effect in vivo. The acyl derivative of the present invention preferably has the following formula (I):

[0006]

[Chemical 2]

(In the formula, R is --CH (CH ₃ ) ₂ or --CH ₂ CH (CH ₃ ).
₂ , —CH (CH ₃ ) CH ₂ CH ₃ , and R ₁ is hydrogen, a linear or branched alkyl or alkenyl group having 1 to 20 carbon atoms, or a phenyl group. ) Is a β-acid (ruprons) acyl derivative. β-acids may be subjected to silica gel chromatography, and if necessary, high performance liquid chromatography, to obtain a hop extract obtained by extracting a hop crushed product with an organic solvent such as n-hexane or ethyl acetate, either alone or as a suitable mixture with each other. It is obtained by purification using (Japanese Patent Application No. 2-329799). But on the other hand, DRJ Laws
Method by J. Inst. Brew., 76, 188 (1970), J. Ch.
em. Soc. (c), 3824 (1971)).

Acid chlorides and acid anhydrides can be used as the acylating agent used in the reaction. Further, pyridine, dichloromethane, chloroform or the like is used as a reaction solvent, and if necessary, triethylamine, dimethylaminopyridine or the like can be added. The reaction temperature is
The reaction is carried out at room temperature or 0 ° C., and the reaction time is preferably 1 to 24 hours.

The acylated product thus obtained can be isolated from the reaction mixture by a conventional separation and purification means such as extraction, concentration and neutralization.
It can be isolated and purified by using means such as filtration, recrystallization, silica gel chromatography, thin layer chromatography and, if necessary, high performance liquid chromatography. The obtained β-acid acyl derivative is a colorless to pale yellow oily substance or a crystallized powder, and has an active oxygen (superoxide, hydroxy radical, hydrogen peroxide, etc.) inhibitory action, lipid peroxide production inhibitory action, rat ventricular properties It has antiarrhythmic action and anti-inflammatory action.

The derivative having an antioxidant activity of the present invention can be formulated into a carrier with commonly used carriers, auxiliaries, additives and the like, and it can be used as an oral or parenteral product according to a conventional method as a drug or quasi drug. It can be used in the fields of products, foods, cosmetics and the like. Oral preparations include tablets, capsules, granules, fine granules, syrups, etc., and parenteral preparations include ointments, creams, external preparations such as liquid preparations, sterile solution preparations,
There are injections such as suspensions.

When these products are administered to a disease as a medicine, 20 mg to 500 mg is administered once to several times a day, that is, 20 mg to 1,
It can be administered at a total daily dose of 000 mg, and its effects can be sufficiently exerted. The derivative of the present invention is a physiologically acceptable vehicle as a medicine, carrier, excipient, integrator, preservative, stabilizer,
It is mixed with a flavoring agent or the like in a required unit dose form.

The adjuvants that are mixed in tablets, capsules, etc. are as follows. Tragant, gum arabic, corn starch, integrants such as gelatin, excipients such as microcrystalline cellulose, corn starch, pregelatinized starch, puffing agents such as alginic acid, lubricants such as magnesium stearate, sucrose. A mixture of lactose, a sweetener such as saccharin, a peppermint, a red oil, a flavoring such as cherry, and a capsule may further contain a liquid carrier such as a fat oil in the above materials. Also, other materials can be present as coatings or to otherwise modify the physical form of the formulation. For instance, tablets may be coated with shellac, sugar.
A syrup or elixir may contain the active compound, sucrose as a sweetening agent, methyl or propylparabens as preservatives, a dye and flavoring such as cherry or orange flavor.

Sterile compositions for injections include active substances in vehicles such as water for injection, naturally occurring vegetable oils such as sesame oil, coconut oil, peanut oil, cottonseed oil, etc., or synthetic fat vehicles such as ethyl oleate. Can be formulated by a conventional method of dissolving or suspending. Further, a buffering agent, a preservative, an antioxidant, etc. can be added as required.

As the external preparation, petroleum jelly, paraffin, oils and fats, lanolin, macrogol and the like are used as a base, and are made into ointments, creams and the like by a usual method. When the derivative of the present invention is added to a food, it may be in the form of the above-mentioned preparation, but it is processed and manufactured by a general manufacturing method by adding a necessary amount to each food material in the form of candy, rice cracker, cookies and the like. Since ingestion as a health food or a functional food is used for disease prevention and health maintenance, it is orally ingested several times a day and ingested as a processed product containing a total daily dose of 50 mg to 500 mg. Further, it can be used in combination with a compound having a partial antioxidant property such as vitamin C, vitamin E and coenzyme Qn. Further, these substances also have an action as a stabilizer of the present derivative, and it is useful to use them in combination. These antioxidants are used at sub-normal doses.

[0015]

EFFECTS OF THE INVENTION The β-acid derivative of the present invention obtained from β-acid of hops is chemically stable and has an antioxidant effect. Therefore, it is possible to prevent damage caused by active oxygen and lipid peroxides produced in vivo. Has the ability to suppress. Therefore, it is effective for the prevention and treatment of health disorders and beauty disorders, and can be applied and processed in medicines, foods and drinks, cosmetics and the like.

[0016]

EXAMPLES Next, examples of the derivatives of the present invention and test examples showing the effects of the derivatives will be described. This example shows a particularly preferred embodiment for the purpose of explaining the present invention in detail, and the present invention is not limited to this. Example 1 (Synthesis of β-Acetyl Acetyl Form) β-acid (0.82 g, 2 mmol, this β-acid is a mixture of colprone, lupron, and adolpron, and “β-acid” refers to this mixture in Example 2 and thereafter). Pyridine (10 ml)
And dissolve in acetyl chloride (2.4 mmol) under stirring at 0 ° C.
It was added little by little over the course of minutes. Furthermore, it stirred at room temperature for 1 hour. After completion of the reaction, the reaction solution was poured into 7% Na ₂ HCO ₃ (100 ml) to smash excess acetyl chloride. It was extracted with ethyl acetate (50 ml × 2), washed with 2N HCl (50 ml × 2) and saturated saline (50 ml × 2), and dried over Na ₂ SO ₄ . The oil obtained by concentration under reduced pressure was purified by silica gel chromatography (hexane: ethyl acetate = 40: 1) to obtain a β-acid acetyl derivative (580 mg) as an oil.

Thin Layer Chromatography (TLC): Rf = 0.49
(Developing solvent n-hexane: ethyl acetate = 10: 1, detection
UV) Infrared absorption spectrum (IR, cm ^-1 , neat): 1760 Proton nuclear magnetic resonance spectrum (NMR) δ (ppm, CDCl ₃ ): 1.55 (s, 12H), 2.22 (s, 3H), 1.65 (s) , 6
H), 2.30-2.70 (m, 4H), 2.80-3.15 (m, 2H), 4.70-5.20 (m, 3
H), 18.00-18.20, 18.90-19.20 (1H).

Example 2 (Synthesis of β-acid n-caprylyl compound) β-acid (0.82 g, 2 mmol) was dissolved in pyridine (10 ml), and 0
Under stirring at 0 ° C, n-caprylyl chloride (2.4 mmol) was added little by little over 30 minutes. Furthermore, it stirred at room temperature for 1 hour.
After completion of the reaction, the reaction solution was poured into 7% Na ₂ HCO ₃ (100 ml) to smash excess caprylyl chloride. Ethyl acetate (50
It was extracted with ml × 2). It was washed with 2N HCl (50 ml × 2) and saturated saline (50 ml × 2), and dried with Na ₂ SO ₄ . The oily substance obtained by concentration under reduced pressure was purified by silica gel chromatography (hexane: ethyl acetate = 40: 1) to obtain a β-acid caprylyl compound (550 mg) as an oily substance.

Thin layer chromatography (TLC): Rf = 0.73
(Developing solvent, detection is the same as in Example 1) Infrared absorption spectrum (IR, cm ^-1 , neat): 1770 Proton nuclear magnetic resonance spectrum (NMR) δ (ppm, CDCl ₃ ): 1.35 (m, 9H), 1.55 (s, 12H), 1.65 (s, 6
H), 2.0-2.3 (m, 2H), 2.30-2.70 (m, 4H), 2.80-3.15 (m, 2
H), 4.70-5.20 (m, 3H), 18.00-18.20, 18.90-19.20 (1H).

Example 3 (Synthesis of β acid palmitoyl compound) β acid (0.82 g, 2 mmol) was dissolved in pyridine (10 ml), and the mixture was added at 0 ° C.
Under stirring, palmitoyl chloride (2.4 mmol) was added portionwise over 30 minutes. Furthermore, it stirred at room temperature for 1 hour. After completion of the reaction, the reaction solution was poured into 7% Na ₂ HCO ₃ (100 ml) to crush the excess palmitoyl chloride. It was extracted with ethyl acetate (50 ml × 2). 2N HCl (50ml x 2), saturated saline solution (50ml x 2)
It was washed with and dried over Na ₂ SO ₄ . The oily substance obtained by concentration under reduced pressure was subjected to silica gel chromatography (hexane:
The product was purified with ethyl acetate = 40: 1) to obtain a palmitoyl β-form (650 mg) as an oil.

Thin layer chromatography (TLC): Rf = 0.80
(Developing solvent, detection is the same as in Example 1) Infrared absorption spectrum (IR, cm ^-1 , neat): 1770 Proton nuclear magnetic resonance spectrum (NMR) δ (ppm, CDCl ₃ ): 1.30 (s, 29H), 1.55 (s, 12H), 1.65 (s, 6
H), 2.0-2.2 (m, 2H), 2.30-2.70 (m, 4H), 2.80-3.15 (m, 2
H), 4.70-5.20 (m, 3H), 18.00-18.20, 18.90-19.20 (1H).

Example 4 (Synthesis of β-acid stearoyl compound) β-acid (0.82 g, 2 mmol) was dissolved in pyridine (10 ml),
With stirring, n-stearoyl chloride (2.4 mmol) was added little by little over 30 minutes. Furthermore, it stirred at room temperature for 1 hour. After completion of the reaction, pour the reaction solution into 7% Na ₂ HCO ₃ (100 ml),
Crush excess stearoyl chloride. Ethyl acetate (50 ml
Extracted with × 2). 2N HCl (50ml × 2), saturated saline solution (50
It was washed with ml × 2) and dried with Na ₂ SO ₄ . The oil obtained by concentration under reduced pressure was purified by silica gel chromatography (hexane: ethyl acetate = 40: 1) to obtain a β-acid stearoyl derivative (600 mg) as an oil.

Thin Layer Chromatography (TLC): Rf = 0.78
(Developing solvent, detection is the same as in Example 1) Infrared absorption spectrum (IR, cm ^-1 , neat): 1770 Proton nuclear magnetic resonance spectrum (NMR) δ (ppm, CDCl ₃ ): 1.30 (s, 31H), 1.55 (s, 12H), 1.65 (s, 6
H), 2.0-2.2 (m, 2H), 2.30-2.70 (m, 4H), 2.80-3.15 (m, 2
H), 4.70-5.20 (m, 3H), 18.00-18.20, 18.90-19.20 (1H).

Example 5 (Synthesis of β acid pivaloyl derivative) β acid (0.82 g, 2 mmol) was dissolved in pyridine (10 ml),
With stirring, pivaloyl chloride (2.4 mmol) was added portionwise over 30 minutes. Furthermore, it stirred at room temperature for 1 hour. After completion of the reaction, the reaction solution was poured into 7% Na ₂ HCO ₃ (100 ml), and excess pivaloyl chloride was crushed. It was extracted with ethyl acetate (50 ml × 2). It was washed with 2N HCl (50 ml × 2) and saturated saline (50 ml × 2), and dried with Na ₂ SO ₄ . The oily substance obtained by concentration under reduced pressure was purified by silica gel chromatography (hexane: ethyl acetate = 40: 1) to give a β-acid pivaloyl compound (54
0 mg) was obtained as an oil.

Thin layer chromatography (TLC): Rf = 0.73
(Developing solvent, detection is the same as in Example 1) Infrared absorption spectrum (IR, cm ^-1 , neat): 1760 Proton nuclear magnetic resonance spectrum (NMR) δ (ppm, CDCl ₃ ): 1.35 (s, 9H), 1.55 (s, 12H), 1.65 (s, 6
H), 2.30-2.70 (m, 4H), 2.80-3.15 (m, 2H), 4.70-5.20 (m, 3
H), 18.00-18.20, 18.90-19.20 (1H).

Example 6 (Synthesis of benzoyl β-acid compound) β-acid (0.82 g, 2 mmol) was dissolved in pyridine (10 ml),
With stirring, benzoyl chloride (2.4 mmol) was added portionwise over 30 minutes. Furthermore, it stirred at room temperature for 1 hour. After completion of the reaction, the reaction solution was poured into 7% Na ₂ HCO ₃ (100 ml) to smash excess benzoyl chloride. It was extracted with ethyl acetate (50 ml × 2). It was washed with 2N HCl (50 ml × 2) and saturated saline (50 ml × 2), and dried with Na ₂ SO ₄ . The oily substance obtained by concentration under reduced pressure was purified by silica gel chromatography (hexane: ethyl acetate = 40: 1) to give a β-benzoic acid derivative (520 m
g) was obtained as an oil.

Thin layer chromatography (TLC): Rf = 0.64
(Developing solvent, detection is the same as in Example 1) Infrared absorption spectrum (IR, cm ^-1 , neat): 1750, 700 Proton nuclear magnetic resonance spectrum (NMR) δ (ppm, CDCl ₃ ): 1.55 (s, 12H ), 1.65 (s, 6H), 2.30-2.70
(m, 4H), 2.80-3.15 (m, 2H), 4.70-5.20 (m, 3H), 7.30-7.77,
7.95-8.25 (5H), 18.00-18.20, 18.90-19.20 (1H).

Example 7 (further purification of β-acetyl acetyl compound) 200 mg of β-acetyl acetyl compound obtained in Example 1 was further purified by high performance liquid chromatography (HPLC) under the conditions shown below to obtain a colprone acetyl compound. (56 mg), lupron acetyl form
(62 mg) and adolprone acetyl derivative (26 mg) were obtained as oils.

HPLC: column (Shim pack prep-ODS- (H) -k
it (20mmφ)), detection 302nm, flow rate 10ml / mim, sample concentration 20mg / ml, injection volume 1ml, mobile phase 90% CH ₃ CN 10% H ₂ O instrumental analysis data of colprone acetyl compound mass spectrum (M ⁺ ). : 442 Infrared absorption spectrum (IR, cm ^-1 , neat): 1640, 1770 Proton nuclear magnetic resonance spectrum (NMR) δ (ppm, CD ₃ OD): 1.10 (d, 6H), 1.54 (s, 6H), 1.56 (s, 6
H), 1.66 (s, 6H), 2.26 (s, 3H), 2.39 (m, 2H), 2.72 (m, 2H),
2.96 (d, 2H), 4.01 (m, 1H), 4.89 (m, 2H), 4.99 (t, 1H)

Instrumental analysis data of lupron acetyl body Mass spectrum (M ⁺ ): 456 Infrared absorption spectrum (IR, cm ^-1 , neat): 1640, 1770 Proton nuclear magnetic resonance spectrum (NMR) δ (ppm, CD ₃ OD): 0.95 (d, 6H), 1.55 (s, 6H), 1.57 (s, 6
H), 1.67 (s, 6H), 2.07 (m, 1H), 2.27 (s, 3H), 2.44 (m, 2H),
2.74 (m, 2H), 2.90 (m, 2H), 2.95 (d, 2H), 4.88 (m, 2H), 4.
96 (t, 1H) Adolpron Acetyl-form instrumental analysis data Mass spectrum (M ⁺ ): 456 Infrared absorption spectrum (IR, cm ^-1 , neat): 1640, 1770 Proton nuclear magnetic resonance spectrum (NMR) δ (ppm) , CD ₃ OD): 0.88 (t, 3H), 1.09 (d, 3H), 1.38 (m, 2
H), 1.56 (s, 6H), 1.60 (s, 6H), 2.25 (s, 6H), 2.39 (m, 2H),
2.71 (m, 2H), 2.97 (m, 2H), 3.93 (m, 1H), 4.89 (m, 2H), 4.
96 (t, 1H)

Example 8 (Tablets, Capsules) [beta] -Acetyl derivative of Example 1 10 Lactose 75 Magnesium stearate 15 The above parts by weight were uniformly mixed to give tablets and capsules.

Example 9 (powder, granules) β-acetylate of Example 1 20 Starch 30 Lactose 50 The above parts by weight were uniformly mixed to obtain a powder and granules.

Example 10 (Injection) β-Acetyl acetylate of Example 1 1 Surfactant 9 Physiological saline solution 90 The above parts by weight were mixed by heating and sterilized to give an injection.

Example 11 (Cookie) Wheat flour containing 2% by weight of the β-acetylated product of Example 1 seasoned with salt, sucrose, butter, etc. was well stirred with an appropriate amount of water and heated at 190 to 200 ° C. at 30 ° C. Bake for minutes to make cookies. Example 12 (jelly) 13 g of agar was dissolved by heating in 1 liter of water, and sucrose was further added.
After adding 0 g, 150 g of starch syrup and a little salt and heating to dissolve with stirring, 2% by weight of the acetyl β-acid form of Example 1,
Fruit juice, colorants, flavors, etc. were added and cooled to form a jelly.

Example 13 (candy) 20 parts by weight of sucrose, 10 parts by weight of candy (75% solid content) and 10 parts by weight of water
After adding 1 part by weight and mixing, heating and stirring at 150 ° C., 2% by weight of the acetyl β-acid form of Example 1, the coloring agent and the fragrance were added and cooled to obtain a candy. Example 14 (Hand lotion) Carbowax 1500 (15 parts by weight), alcohol (8 parts by weight) and propylene glycol (90 parts by weight) were thoroughly mixed and dissolved,
A hand lotion was prepared by adding 52.5 parts by weight of water, 2 parts by weight of the β-acetylated product of Example 1, an appropriate amount of perfume and preservative.

Example 15 (External preparation) Ethyl paraoxybenzoate 0.1 Butyl paraoxybenzoate 0.1 Lauromacrogol 0.5 Cetanol 18 White petrolatum 40 Water 37.3 β-Acetyl acetylate of Example 1 4 Using each component of each of the above weight parts An ointment was prepared according to a conventional method.

Test Example 1 (Rat Brain Homogenate Lipid Peroxide Production Inhibition Test) Rat brain homogenate lipid peroxidation inhibition test was carried out on 3 compounds of α-tocopherol, β acid, and β acid acetylated body obtained in Example 1. It was The method is the method of Uchiyama et al. (Uchiyama, M. & Mihara, M . : Anal. Biochem. 86,
271 (1978)) and Kato et al.'S method (Kaneyoshi Kato, Norio Shimamoto:
Takeda Research Institute, 47, 27 (1988)) was referred to. 1 g (wet) of rat brain was homogenized in 50 mM phosphate buffer (pH 7.4, 4.9 ml), centrifuged at 2,500 rpm for 15 minutes, the supernatant was diluted 3 times, and an antioxidant was added to the diluted solution. 10 μl of the dimethyl sulfoxide solution (10 ⁻⁴ to 10 ⁻⁶ M / ml) was added and incubated at 37 ° C. for 1 hour. The amount of lipid peroxide produced in these reaction solutions was measured by the TBA (thiobarbituric acid) method.

The results are shown in FIG. The measurement is performed four times or more for each compound, and the average of the inhibition rate (% inhibition) at each concentration of the test substance is obtained and plotted. All the three compounds were found to have lipid peroxidation inhibitory activity in the range of 10 ⁻⁴ to 10 ⁻⁶ M. In particular, the β-acid acetylated form showed activity comparable to that of α-tocopherol.

Test Example 2 (Rat Brain Homogenate Lipid Peroxidation Production Inhibition Test) Three compounds of lupron purified from α-tocopherol and β acid by a method similar to that in Example 7, and the lupron acetyl derivative obtained in Example 7 A rat brain homogenate lipid peroxide production inhibition test was performed. The method is the method of Uchiyama et al. (Uchiyama, M. & Mihara, M .: Anal.Biochem . 86, 271
(1978)) and Kato et al.'S method (Kaneyoshi Kato, Norio Shimamoto: Takeda Research Institute, 47, 27 (1988)). Rat brain 1
Homogenize g (wet) in 50 mM phosphate buffer (pH 7.4, 4.9 ml), centrifuge at 2,500 rpm for 15 minutes, dilute the supernatant 3 times, and add the dimethyl antioxidant solution to the diluted solution. Add 10 μl of sulfoxide solution (10 ^-4 to 10 ^-6 M / ml),
Incubated at 37 ° C for 1 hour. The amount of lipid peroxide produced in these reaction solutions was measured by the TBA (thiobarbituric acid) method.

The results are shown in FIG. The measurement is carried out three times or more for each compound, and the average of the inhibition rate (% inhibition) at each concentration of the test substance is obtained and plotted. All the three compounds were found to have lipid peroxidation inhibitory activity in the range of 10 ⁻⁴ to 10 ⁻⁶ M. In particular, the lupron acetyl form is α
-Showed better activity than tocopherol and lupron.

Test Example 3 (Erythrocyte hemolysis inhibition test) An erythrocyte hemolysis inhibition test was carried out on the lupron purified from α-tocopherol and β acid by the method according to Example 7, and the three compounds of the lupron acetyl derivative obtained in Example 7. went. The method is the method of Toda et al. (Toda, S. et al J. Enthno
pharmacol. 23, 105 (1988)) was referred to. Sheep red blood cells 1
A mixed solution of 0.50 ml of 0% suspension, 1.40 ml of 50 mM isotonic phosphate buffer and 0.05 ml of ethanol solution of antioxidant was prepared, and 0.05 ml of ethanol dilution of t-butyl hydroperoxide was further added to the mixture solution. Incubated at 30 ° C for 30 minutes. To these reaction solutions, add 4 ml of physiological saline, and add 3,000 rp
After centrifugation at m for 10 minutes, the absorbance of the supernatant at 540 nm was measured.

The results are shown in FIG. The measurement is carried out twice or more for each compound, and the average of the inhibition rate (% inhibition) at each concentration of the test substance is determined and graphed. α-Tocopherol and lupron were found to have erythrocyte hemolytic activity in the range of 10 ^-4 to 10 ^-6 M, and lupron acetyl compound in the range of 10 ^-5 to 10 ^-7 M. In particular, the lupron acetyl derivative showed superior activity to α-tocopherol.

[Brief description of drawings]

FIG. 1 is a graph showing the results of a rat brain homogenate lipid peroxide production inhibition test, in which the vertical axis represents the inhibition rate (%), in which the shaded portion is 10 ⁻⁶ (M) and the dotted portion is 10
^-5 (M), solid area is 10 ^-4 (M).

FIG. 2 is a graph showing the results of a rat brain homogenate lipid peroxide production suppression test, in which the vertical axis represents the inhibition rate (%), where ● represents α-tocopherol, lupron,
△ shows the case of a lupron acetyl body.

FIG. 3 is a graph showing the results of an erythrocyte hemolysis inhibition test, in which the vertical axis represents the inhibition rate (%), where ● represents the case of α-tocopherol, is lupron, and Δ is the lupron acetyl form.

Claims (8)

[Claims] 1. β-acid (Luprons) obtained from hops
An acyl derivative that is stable and exhibits strong antioxidant activity in vivo. 2. The following formula (I): (Wherein, _{R, -CH (CH 3) 2,} -CH 2 CH (CH 3) 2 or -C,
H (CH ₃ ) CH ₂ CH ₃ , R ₁ is hydrogen and has 1 carbon atom
~ 20 straight or branched chain alkyl or alkenyl groups, phenyl groups. ) The derivative according to claim 1, which is represented by 3. R in the formula (I) is —CH (CH ₃ ) ₂ (colplone form), —CH ₂ CH (CH ₃ ) ₂ (lupron form), or —CH (CH ₃ ).
CH ₂ CH ₃ (adolpron form), wherein R ₁ is hydrogen, a straight chain or branched chain alkyl or alkenyl group having 1 to 20 carbon atoms, a phenyl group colprone derivative, a lupron derivative, an adolprone derivative The derivative according to claim 2, which is any one of the above or a mixture of two or more thereof. 4. The derivative according to claim 3, which is any one of a β-acid acetyl derivative, a β-acid n-caprylyl derivative, a β-acid palmitoyl derivative, a β-acid stearoyl derivative, a β-acid pivaloyl derivative and a β-acid benzoyl derivative. 5. The derivative according to claim 3, which is one of a colprone acetyl body, a lupron acetyl body, and an adolpron acetyl body, or a mixture of two or more thereof. 6. A drug containing the acyl derivative according to claim 1. 7. A food or drink containing the acyl derivative according to claim 1. 8. A cosmetic containing the acyl derivative according to claim 1.