TWI332001B - Compound for treating hepatitis b and composition thereof - Google Patents

Description

1332001 IX. Description of the Invention: [Technical Field] The present invention is a compound for the treatment of type B liver (IV) compounds, pharmaceutical compositions and kits, and is a compound derived from natural plant-derived flavonoids. [Prior Art] About 5,000 people die of liver cancer every year in Taiwan, and more than 5,000 people die from cirrhosis and chronic hepatitis. Since the Republic of China in the past seventy-one years, 'the cancer is the top ten cause of death for the Chinese people. Among them, liver cancer is the first cause of cancer death among Chinese men and the second cause of cancer death among women. Therefore, liver disease can be said to be the most common local disease in Taiwan. Viral liver disease refers to liver diseases caused by disease, including acute and chronic hepatitis, liver cirrhosis, and liver cancer. In Taiwan, liver disease caused by viral liver disease is the most widespread. There are currently a variety of viruses that can cause hepatitis. The main changes in the liver are five PA B C D and hepatitis E viruses. Among them, b, c, and d hepatitis viruses can cause chronic hepatitis, cirrhosis, and even liver cancer. In Taiwan, the prevalence and mortality rate of hepatitis B is the highest. About 375 million people worldwide are infected with hepatitis B, mostly in Asia, and millions of them cause liver cancer. In the United States, the incidence of hepatitis B is mostly in the Chinese group, with a rate of up to 1%. Other Americans account for only 3%. Adults born in China, Taiwan, South Korea, and Vietnam have a hepatitis B rate of about 1.2%. Hepatitis B is infected by blood or body fluid containing hepatitis B virus that enters the body through the skin or the dead skin. The route includes ▲, injection, hemodialysis, acupuncture, ^月'", eyebrows, earbrews, sharing toothbrushes or knives, and sexual behavior. If pregnant, hepatitis B (four), it is possible to correct The virus is transmitted to the newborn and the vertical infection has been the most important way of infection of hepatitis 8 in China. After hepatitis B infection, there is no symptoms, so it is necessary to rely on blood tests to do positive. Hepatitis B virus surface antigen (10) heart) and Table 1332001 face antibody (Anti-HBs), if the blood HBsAg is positive, it may be the type B liver and inflammation band, and should be further traced. HBsAg is negative, and Anti-HBs is positive, indicating that the body has immunity against hepatitis B virus. HBsAg positive reaction, should be tested for hepatitis B virus e antigen (HBeAg) and e antibody (Anti-HBe). If the blood HBeAg is positive, it indicates that the hepatitis B virus in the patient is still vigorously produced, which is more likely to cause hepatitis and is highly contagious. Conversely, if the blood t HBeAg is negative, and Anti- HBe is positive, but the situation is reversed, but liver function should still be checked regularly. At present, interferon is better for the treatment of hepatitis B. Interferon can inhibit the activity of hepatitis B virus, improve liver inflammation and GOT, The GPT value is reduced. However, the surface antigen of hepatitis B virus still exists and will not disappear. And some patients will relapse after stopping the drug. The side effects of interferon, the most common is the appearance of a cold-like symptoms ( Fever, headache, body muscles, sore bones, usually appear in the first week of interferon injection, and then disappear. However, not all patients with hepatitis B are suitable for interferon therapy, and the effect of interferon therapy It is also different; in addition, there is a new therapeutic drug, "Zeffix", which is currently the only oral medication for the treatment of chronic hepatitis B. It is necessary to have restrictions on the use of this drug. Not all patients with hepatitis B and those with the original are suitable. It is necessary to be determined by a specialist to determine that the current hepatitis B is in the onset of the disease. Liver can improve liver inflammation and fibrosis. However, its shortcoming is that the emergence of drug-resistant viruses can cause dangerous acute hepatitis in patients. Furthermore, the use of this drug may also produce rare side effects that lead to skeletal muscle dissolution, which may lead to diaphragmatic lysis. To the respiratory function and so on. Therefore, there is still a great need to develop a more effective and low side effect hepatitis B treatment 1332001. SUMMARY OF THE INVENTION In view of the deficiencies of the prior art, the present invention aims to provide a compound for treating hepatitis B, including the following Compound of formula (1): Structural formula (I)

Wherein Us, R'i-R'5 is hydrogen (8), methoxy (〇Me) or ethoxy (1). It is still another object of the present invention to provide a humanized body for treating hepatitis B comprising a compound having the following structural formula (11): 〇 Structural formula (II)

"中中4, is hydrogen (Η), methoxy (0Me) or ethoxy (howling. In addition to the present invention - the purpose is to provide a medical group for the (four) hepatitis B" line includes - effective A compound of the above formula (1) or (11). Another object of the present invention is to provide a kit for treating hepatitis B =: the aforementioned "' effective amount of the aforementioned structural formula (1) or (H) a compound; and i' ▲ an acceptable adjuvant, carrier or excipient. [Embodiment] The compound of the present invention is a main structure of a compound for treating hepatitis B having the following structural formula (i) Compounds: Structural Formula (I)

FU 〇 wherein R4-R5 and R'rR'5 are hydrogen (H), oxime (OMe) or ethoxy (OEt). The aforementioned compound of formula (I) is, for example, but not limited to, methylated lacquerin (Fisetin Me)

OMe methylated xanthophyll (Baicalein Me) OMe Ο

Methylated quercetin (Quercetin Me) 1332001 OMe Ο

OMe

MeO OMe OMe

Morin Me OMe O

OMe

MeO OMe

MeO methylated 7,8-di- flavonoids (7,8-0111^ 〇和>^3乂〇116) Ο

MeO OMe ; and

Cellulite (CPB, Tangeretin) OMe O

MeO

MeO

OMe OMe Another compound of the present invention for treating hepatitis B's main structure is a compound having the following structural formula: 1332001 Structural Formula (II) r2 r3

R4 ο wherein Ri-h and RVR'5 are hydrogen (oxime), oxime (OMe) or ethoxy (OEt). The aforementioned compound of formula (II) is, for example, but not limited to, thiolated naringenin (Naringenin Me)

MeO OMe Ο

; and Flavanone Ο

Wherein the aforementioned compound can be obtained by natural plant extraction (for example: flavanone, CPB) or by flavonoids with bismuthylsulfate. The invention also encompasses a pharmaceutical composition for the treatment of hepatitis B comprising an effective amount of a compound of the above formula (I) or (II). The invention further relates to a kit for treating hepatitis B comprising: a compound of formula (I) or (II) having a 1332001 effect; and a pharmaceutically acceptable adjuvant, carrier or excipient . The aforementioned kits may further comprise, for example, but are not limited to: a instructions for use or a container for containment. Suitable pharmaceutical carriers may contain inert ingredients which do not substantially react with the compounds of the present invention. Standard pharmaceutical dosage form techniques can be utilized, as described in Remington's Pharmaceutical Sciences, Mack Publishing Company, Easton, PA. Suitable pharmaceutical carriers for parenteral administration include, for example, sterile water, physiological saline, bacteriostatic saline (salt containing about 0.9% mg/ml phenyl alcohol), phosphate buffer saline, Hank solution , forest format lactose solution and other similar carriers. The above-mentioned pharmaceutical composition may be subjected to a preparation, and may be powdered, granulated, ingot, liquid, gel or paste according to a conventional process. The aforementioned pharmaceutical composition may be provided in the form of a food, a drink, a medicine, a reagent or a nutritional supplement, and the aforementioned compound may be administered by intravenous, intramuscular, epithelial, intraperitoneal, inhalation, buccal, oral, transdermal, or the like. The manner of administration will depend on the type of disease, condition or condition being treated. By "effective amount" is meant that the dose of the compound will provide a beneficial result upon administration to a subject, or that the dose of the compound will provide the desired activity in vivo or in vitro. In the case of tumors, for example, beneficial clinical outcomes include reducing the number of hepatitis viruses, reducing the rate of hepatitis virus growth, reducing the severity of hepatitis-related symptoms, and/or prolonging lifespan and/or improving the subject's treatment. quality of life. The exact dose to be administered to a subject must be determined by the type, extent or symptom of the disease and the individual's constitution, such as general health, age, sex, weight, and tolerance to the drug. The dose is also related to the extent, severity and type of hepatitis. Those skilled in the art can determine the appropriate dosage based on the foregoing or other factors. The foregoing and other technical features of the present invention will be apparent from the following detailed description of the preferred embodiments. The following examples are intended to describe the advantages of the invention in one step, and are not intended to limit the scope of the invention. EXAMPLES Example 1 Preparation of Cellulite (CPB, Tangeretin) Commercially available 500 g of green skin was pulverized to a powder form, and 1500 liters of Zhengjixuan was added, heated to 60 ° C for stirring extraction, and filtered after two hours. The filter residue was further added with 1500 ml of n-hexane (twice) under the above conditions for the second extraction and the third extraction, and the filtrate was combined. Then, the n-hexane was distilled off by a reduced pressure rotary concentrator to obtain an oily extract of 19.2 g. After the extract was dissolved in 100 ml of n-hexane, it was extracted three times with 50 ml of 80% aqueous methanol solution, and the sterol aqueous solution was collected and combined, and then the solvent was distilled off under a reduced pressure rotary concentrator to obtain 4.1 g of the extract, and then added. 10 ml of the fermentation, dissolved in heat 'cooled and placed overnight to be crystallized, then filtered solid, washed with 5 ml of methanol and then dried to give 1.04 g of 85% pure CPB (Tangeretin) crystals, and then purified with a silica gel column Acetone: n-hexane = 1:1 was eluted to obtain 0.79 g of 99% pure hesperidin crystals. The structure was confirmed by nuclear magnetic resonance (NMR) (hydrogen spectrum 3_884 ppm 3H, 3.957 ppm 6H, 3.957 ppm 6H, 4.030 ppm 3H, 4.109 ppm 3H, 6.609 ppm lH, 7.023 ppm 2H, 7.876 ppm 2H) ° Example 2, Methylation Preparation of toxanthin (3,3,,4,5,7_卩61113|116*11〇\}^13¥〇116) Preparation of quercetin (Quercetin ' 3,3',4',5, 7-Pentahydroxyflavone) Add 0.3 ml of methanol to 0.3 ml, stir at room temperature 25 ° C, add 45% sodium hydroxide and dimethyl sulfate in a cross-cycle, and control the pH between pH 11 and 13, and use high efficiency. The liquid chromatography was monitored and analyzed until the reaction was completed. After decanting and concentrating to remove the sterol, 5 ml of water and 50 ml of ethyl acetate were added to extract the phases, and the ethyl acetate layer was taken, dehydrated with anhydrous sodium sulfate, filtered, and concentrated. For the crude product, the rubber column was washed with ethyl acetate: hexane = 2:1 mixed solution to obtain the product 3 '3', 4', 5,7-Pentamethoxyflavone 0.34 g (92 ° /. yield) . The structure was confirmed by NMR 1332001 (hydrogen spectrum 3.887 ppm 3H; 3.899 ppm 3H; 3.953 ppm 3H; 3.959 ppm 3H; 3.965 ppm 3H; 6.324 ppm 1H; 6.486 ppm 1H; 6.971 ppm 1H; 7.692 ppm 2H). Example 2: Preparation of methylated morin (2,3,4',5,7-?61^311^11〇\5^13¥〇116) Preparation of morin (Morin ' 2', 3, 4',5,7- Pentahydroxyflavone) 0.3 g of methanol 10 ml, stirred at room temperature 50 ° C, and then added dropwise 45% sodium hydroxide and dimethyl sulfate 'and control the pH value at pH 11 to 13 And the reaction was monitored by high performance liquid chromatography until the reaction was completed. The methanol was removed by concentration under reduced pressure. Then, 50 ml of water and 50 ml of ethyl acetate were added to extract the phases, and the ethyl acetate layer was added to anhydrous sodium sulfate for dehydration. A crude product was obtained, which was purified by chromatography on ethyl acetate: n-hexane = 2:1 to give the product 2',3,4',5,7-Pentamethoxyflavone 0.31 g (84% yield). The structure was confirmed by NMR (hydrogen spectrum 3.809 ppm 3H; 3.833 ppm 3H; 3.847 ppm 3H; 3.867 ppm 3H; 3.958 ppm 3H; 6.338 ppm 1H; 6.431 ppm 1H; 6.582 ppm 2H; 7.372 ppm 1H). Example 4 Preparation of methylated flavin (Sj'j'^-Tetramethoxyflavone) Take flavin (Fisetin, 3,3', 4', 7-Tetrahydroxyflavone) 0.03 g of methanol 4 ml, room temperature 5 〇 . (: stirring, cross-circulation addition of 45% sodium hydroxide and dimethyl sulfate) and control the pH value between pH 11 and 13, and monitored by high performance liquid chromatography until the reaction is complete, concentrated under reduced pressure After removing the methanol, 30 ml of water and 30 ml of ethyl acetate were added to extract the phases, and the ethyl acetate layer was added to anhydrous sodium sulfate for dehydration, and the filtrate was concentrated to give a crude product, which was then taken from ethyl acetate: n-hexane = 2: Purified product 3,3',4,,7-Tetramethoxyflavone 0.031 g (86% yield). The structure was confirmed by nuclear magnetic resonance (hydrogen spectrum 3.929 ppm 3H; 3.973 ppm 3H; 332001 4.017 ppm 6H; 6.956 ppm 1H) 7.042ppm 2H; 7.771ppm 2H; 8.207ppm 1H). Example 5 Preparation of methylated baicalein (5,6,7-Trimethoxyflavone) Take Baicalein '5,6,7-Trihydroxyflavone 0.03 g of sterol 4 ml, stirring at 50 ° C at normal temperature, adding 45% sodium hydroxide and dimercaptosulfate in a cross-cycle, and controlling the pH between pH 11 and 13, and performing high performance liquid chromatography Monitor and analyze until the reaction is complete. Concentrate under reduced pressure to remove methanol, then add 30 ml of water and 30 ml of acetic acid. The phase was taken, and the ethyl acetate layer was added to anhydrous sodium sulfate for dehydration, filtered, and concentrated to obtain a crude product, which was purified by ethyl acetate: n-hexane = 2:1 to obtain a product 5,6,7. -Trimethoxyflavone 0.032 g (92% yield). The structure was confirmed by nuclear magnetic resonance (hydrogen spectrum 3.970 ppm 3H; 4.032 ppm 3H; 4.044 ppm 3H; 6.718 ppm 1H; 6.861 ppm 1H; 7-561 ppm 3H; 7.934 ppm 2H). Preparation of methylated 7,8-dimethoxyflavone 7.10-Dihydroxyflavone 0.3 g of methanol 10 ml, stirred at 50 ° C at room temperature 45% sodium hydroxide and dimethyl sulfate were added dropwise, and the pH value was controlled between pH 11 and 13, and the reaction was monitored by high performance liquid chromatography until the reaction was completed. After the leaven, 50 ml of water and 50 ml of ethyl acetate were added to extract the phases, and the ethyl acetate layer was added to anhydrous sodium sulfate for dehydration, filtered, and concentrated to give a crude product, and then ethyl acetate: n-hexane = 2: 1 Purification of the product 7,8-Dimethoxyflavone 0.33 g (98% yield). Confirmation of structure by nuclear magnetic resonance (hydrogen 4 .010 ppm 3H; 4_052 ppm 3H; 6.770 ppm 1H; 7.054 ppm 1H; 7.535 ppm 3H; 7.965 ppm 3H). Example 7. Preparation of methylated naringenin (4',5,7-Trimethoxyf丨avanone) Take naringenin (Naringenin, 4',5,7-Trihydroxyflavanone) 0_3 gram plus 1332001 methanol 10 ml '50 ° C stirring 45% sodium hydroxide and dimethyl retinate were added dropwise in a cross-cycle, and the pH value was controlled between pH 11 and 13, and the reaction was monitored by high performance liquid chromatography until the reaction was complete. After adding 50 ml of water and 50 ml of ethyl acetate, the phases were extracted, and the ethyl acetate layer was added to anhydrous sodium sulfate for dehydration, filtered, and concentrated to give a crude product, which was then washed with ethyl acetate: n-hexane = 2:1. The purified product 4',5,7-Trimethoxyflavanone 0.21 g (61% yield) was identified by NMR (hydrogen spectrum 3.691 ppm 2H; 3.780 ppm 3H; 3.822 ppm 3H; 3.878 ppm 3H; 6.304 ppm 1H; 6.884 Ppm 3H; 7.322 ppm 1H; 7.472 ppm 2H). Example 8 Preparation of methylated quercetin (3,3',4',5,7-卩611 (36|110\5^丨3¥0116) Take quercetin (Quercetin, 3, 3' , 4', 5, 7-Pentahydroxyflavone) 0-lg plus ethanol 6 ml, stirring at room temperature 25 ° C, cross-circulation dropwise 45 ° / sodium hydroxide and diethyl sulfate, and control the pH value at 11- Between 13 and monitored by high performance liquid chromatography until the reaction was completed. After concentration and concentration of ethanol to remove ethanol, 10 ml of water and 15 ml of ethyl acetate were added to extract the phases, and the ethyl acetate layer was added to add anhydrous sulfuric acid. The sodium is dehydrated, filtered, and concentrated to give a crude product. The product is purified by ethyl acetate: n-hexane = 1; 1 and purified to give the product 3,3',4',5,7-Pentaethoxyflavone 0.11 g (75%) Nuclear NMR spectrum (1.2-1.7 ppm 15H; 4.0-4.3 ppm 10H; 6.324 ppm 1H; 6.486 ppm 1H; 6.971 ppm 1H; 7.64 ppm 1H; 7.801 ppm 1H) Example IX, methylated morin (2 Preparation of ',3,4',5,7-Pentamethoxyflav〇ne) Morin, 2',3,4',5,7- Pentahydroxyflavone 〇ig plus 6 ml of ethanol, stirred at 50 ° C, cross Add 45% sodium hydroxide and diethyl sulfate to the ring, and control the pH value between 11-13, and monitor the analysis by high performance liquid chromatography until the reaction is complete. Water and 15 ml of 1332001 ethyl acetate were extracted and separated, and the ethyl acetate layer was added to anhydrous sodium sulfate for dehydration, filtered, and concentrated to give a crude product, which was purified by ethyl acetate: n-hexane = 1:2 The product 2,3,4',5,7-Pentaethoxyflavone 0.12g (82% yield) nuclear magnetic resonance spectrum (11-1.7ppm 15H; 4.0-4.3ppm 10H; 6.358ppm 1H; 6.422ppm 1H; 6.591ppm 2H 7.401ppm 1H) Example 10. Preparation of methylated laccase (3,3,,4,,7_Tetramethoxyflavone) Take flavin (Fisetin, 3,3',4',7-Tetrahydroxyflavone) O.Olg Add 1 ml of ethanol, stir at 50 ° C, add 45% sodium hydroxide and diethyl sulfate in a cross-cycle, control the pH value between 11 and 13, and monitor and analyze with high performance liquid chromatography until the reaction is complete. Concentrated under reduced pressure to remove ethanol, then add 1 ml of water and 1 ml of ethyl acetate to extract the phases, and take ethyl acetate. The ester layer was dehydrated by adding anhydrous sodium sulfate, filtered, and concentrated to give a crude product, which was purified by ethyl acetate: n-hexane = 1:2 to obtain product 3,3',4',7-Tetraethoxyflavone 〇.〇 12 g (86% yield) nuclear magnetic resonance hydrogen spectrum (1.2-1.7 ppm 12H; 4.1-4.4 ppm 8H; 6.912 ppm 1H; 7.052 ppm 2H; 7.783 ppm 1H; 7.822 ppm 1H; 8.194 ppm 1H) Example XI, A Preparation of 5,6,7-Trimethoxyf丨avone, Baicalein' 5,6,7-Trihydroxyflavone 0_01g, 1 ml of ethanol, 50 ° C, stirring, and 45% dropwise Sodium hydroxide and diethyl sulphuric acid vinegar, and control the acid value between 11-13, and monitor and analyze the reaction to the reaction element by high performance liquid chromatography, reduce Μ > The mixture was extracted with water and 10 ml of ethyl acetate. The ethyl acetate layer was dried over anhydrous sodium sulfate, filtered and concentrated to give a crude product, which was purified by ethyl acetate: n-hexane = 1:2. Product 5,6,7-Triethoxyflavone 〇.〇1 lg (84% yield) Nuclear magnetic resonance hydrogen spectrum (1.2-1.8ppm 9H; 4.1-4.3ppm 6H; 6.682ppm 1H 6.821ppm 1H; 1332001 7.583ppm 3H; 7.943ppm 2H) Example 12, Preparation of methylated 7,8-dimethoxyflavone 7,8-dimethoxyflavone 7,8-Dihydroxyflavone) 0.06g Add 4ml of ethanol, stir at 50°C, add 45% sodium hydroxide and diethyl sulfate in a cross-cycle, and control the pH between 11-13, and efficiently The liquid chromatography was monitored and analyzed until the reaction was completed. The ethanol was concentrated under reduced pressure, and then 10 ml of water and 10 ml of ethyl acetate were added to extract the phases, and the ethyl acetate layer was added to anhydrous sodium sulfate for dehydration, filtered, and concentrated to give a crude product. Then, the product was purified by ethyl acetate: n-hexane = 1:1 with a ruthenium tube column. 0.08-Dimethoxyflavone 0.064 g (88% yield) NMR spectrum (1.4-1.6 ppm 6H; 4.2-4.4 ppm 4H) 6.801ppm 1H; 7.205ppm 1H; 7.592ppm 3H; 7.945ppm 3H) Example XIII, Preparation of methylated naringenin (4',5,7-Trimethoxyf丨avanone) Take naringenin (Naringenin, 4 ',5,7-Trihydroxyflavanone) O.lg plus ethanol 6 ml, stirred at 50 ° C, cross-circulation dropwise addition of 45% sodium hydroxide and diethyl sulfate Ester, and control the pH value between 11-13, and monitored by high performance liquid chromatography to complete the reaction, concentrated under reduced pressure to remove ethanol, then add 50 ml of water and 50 ml of ethyl acetate to extract the phase. The ethyl acetate layer was dried over anhydrous sodium sulfate, filtered and concentrated to give a crude product, which was purified by ethyl acetate: n-hexane = 1; 2 to give product 4',5,7-triethoxyflavanone 0.11 g (83) % yield) Nuclear magnetic resonance hydrogen spectrum (1.2-1.6 ppm 9H; 3.9-4.2 ppm 6H; 6.195 ppm 2H; 6.924 ppm 3H; 7.345 ppm 1H; 7.492 ppm 2H) Example 14. Compound of the present invention against hepatitis B Efficacy of the present invention is a cell test for detecting the efficacy of the above-mentioned eight compounds of the present invention for inhibiting hepatitis B virus 1332001, and the embodiment is as follows: (1) selecting a cell strain containing hepatitis B virus (HePG2.215) in DMEM medium. (Gibco) was cultured at 37 ° C and 5% CO 2 ; (2) different concentrations of the compound of the present invention were added to the cell line of step (1) for culture for four days; (3) for the second , for four days, collect the cell culture solution of step (2) Centrifugation (2000 x g for 2 minutes); and (4) centrifugation of the supernatant portion of step (3) using a commercially available kit for testing for hepatitis B virus surface antigen (HBs) and e antigen (HBe) inhibition, As a result, as shown in the first figure, it was found that the guanidine of the compound of the present invention can effectively inhibit hepatitis B virus surface antigen (HBs) and e antigen (HBe), among which hesperidin (CPB, Tangeretin), methylation The results of 7,8-di-based yellow steel and thiolated yellow baicale were the best (the results of methylated flavin and flavanone are not shown). It can be known from the above experimental results that the compound of the present invention does have the effect of inhibiting hepatitis B virus, and thus can be used for treating hepatitis B. The compound of the present invention is extracted by natural plant or by flavonoid with dimercaptosulfate. It is made by the base, has low side effects on the human body, is easy to obtain, and has a potential for development of a new generation of hepatitis B drugs. While the present invention has been described above in terms of the preferred embodiments thereof, it is not intended to limit the invention, and the invention may be modified and modified without departing from the spirit and scope of the invention. The scope of protection of the invention is defined by the scope of the appended claims. 1332001 [Simplified Description of the Drawings] The first figure shows the efficacy of the compounds of the present invention in inhibiting hepatitis B virus. [Component Symbol Comparison Description]

Claims (1)

1332001 The preparation of the compound for the treatment of hepatitis B or the compound of (II) is as follows: "Notice 10", the patent application is _: - 1. A compound composition of the compound of the formula (I) or (π) Use of the above structural formula: Structural formula (I) Structural formula (II) Wherein R^R5, R^-R'5 is hydrogen (oxime) or methoxy (〇Me), but is not at the same time 11 ' and the compound of the formula (I) or (II) is not hesperidin. • The use of the first aspect of the patent application, wherein the aforementioned compound is methylated lacquerin (FisetinMe) 0 20 1332001 3. The use of the aforementioned compound in the form of Baicalein Me, wherein the aforementioned compound is methylated OMe 0 MeO MeCT^^^^Cr 4. The use of the above-mentioned compound is the methylation OMe 0 as claimed in the patent application quercetin (Quercetin Me). OMe MeO OMe OMe 5. The use according to claim 1, wherein the compound is methylated morin (Morin Me) OMe Ο OMe MeO^^^OMe 6. The use according to claim 1, wherein the compound is methylated 7, 8-dimethoxyflavone 1332001 7. The use according to claim 1, wherein the compound is methylated naringenin (Oringenin Me) OMe Ο OMe 22