Agent for preventing or improving symptoms caused by imbalance of sex hormones

(Production of Lophenol Compound (Compound 1))

[0138]Mesophyll of aloe vera (transparent gel portion) (100 kg) was liquefied using a homogenizer, and 100 L of an ethyl acetate / butanol (3:1) mixed liquid was added thereto, followed by stirring. After allowing to stand overnight, the ethyl acetate / butanol mixed liquid and an aqueous layer were separated to recover the ethyl acetate / butanol mixed liquid. This ethyl acetate / butanol mixed liquid was concentrated under reduced pressure. The mass of the recovered ethyl acetate / butanol mixed liquid extract was 13.5 g.

[0139]A solution obtained by dissolving 13 g of the extract in 1 ml of a chloroform / methanol (1:1) mixed liquid was passed through a column filled with 400 g of Silica Gel 60 (manufactured by Merck & Co., Inc.), the extract was adsorbed thereon, then, eluted by a stepwise gradient method of stepwisely increasing the methanol concentration using a chloroform / methanol mixed liquid (each mixing ratio of chloroform:methan

(Production of Cyclolanostane Compound (Compound 2))

[0142]To 8.0 g of γ-oryzanol (manufactured by Oryza Oil & Fat Chemical Co., Ltd.) were added 250 ml of distilled water, 50 g of sodium hydroxide, 150 ml of isopropanol, 150 ml of ethanol, and 150 ml of methanol, and heating refluxing was performed for 2 hours using a mantle heater. After the reaction, the reaction liquid was added to 1300 ml of water, and the produced white precipitate was suction-filtered to obtain a solid. In order to wash the remaining alkali, the resulting residue was suspended in 1000 ml of water, and suction filtration was performed again. This operation was repeated two times, and the final residue was lyophilized under reduced pressure to obtain 5.91 g of an oryzanol hydrolysate. The hydrolysate was purified by HPLC to obtain 2435 mg of cycloartenol, and 1543 mg of 24-methylene-9,19-cyclolanostan-3-ol (Compound 2).

[0143]Then, using the resulting cycloartenol, 9,19-cyclolanostan-3-ol (Compound 2) was synthesize

(Preparation of Sample Containing Mixture of Lophenol Compound and Cyclolanostane Compound Added Thereto)

[0145]Using 4-methylcholest-7-en-3-ol, 4-methylergost-7-en-3-ol and 4-methylstigmast-7-en-3-ol which had been obtained by Production Example 1, and 9,19-cyclolanostan-3-ol and 24-methylene-9,19-cyclolanostan-3-ol which had been obtained by Production Example 2, a mixture in which the mass ratio of the lophenol compound and the cyclolanostane compound was lophenol compound (Compound 1):cyclolanostane compound (Compound 2)=1:1 was obtained.

[0146]Using carboxymethylcellulose (CMC: manufactured by DKS Co., Ltd.), a mixture of the lophenol compound and the cyclolanostane compound was dispersed to prepare a 10000-fold diluted powder and a 100000-fold diluted powder. These powders were added to the AIN93G feed at 2%, to prepare a test sample 1 and a test sample 2.

[0147]That is, a test sample 1 containing Compound 1 (lophenol compound) and Compound 2 (cyclolanostane compound) at a total amo