KR20060066177A - Compositions for the hepatic function containing decursin and/or decursinol angelate, or angelica extract containing decursin and/or decursinol angelate - Google Patents

Abstract

The present invention relates to a therapeutic agent composition for liver function comprising a decancin and / or decosinol angelate, or a Angelica extract comprising the decansin and / or decosinol angelate as an active ingredient.

When using the composition comprising the decancin and / or decosinol angelate of the present invention, or the Angelica extract as the active ingredient decosin and / or decosinol angelate, having excellent effects on liver dysfunction, It is effective in preventing and treating liver function deterioration caused by drugs such as anticancer agents, and it is possible to provide safe liver function drugs, adjuvant drugs and health supplements without side effects even in long-term use.

Angelica Extract, Decusin, Decusinol Angelate, Liver Protection

Description

COMPOSITIONS FOR THE HEPATIC FUNCTION CONTAINING DECURSIN AND / OR DECURSINOL ANGELATE, OR ANGELICA EXTRACT CONTAINING DECURSIN AND / OR DECURSINOL ANGELATE}

The present invention relates to a therapeutic agent composition for liver function comprising a decancin and / or decosinol angelate, or a Angelica extract comprising the decansin and / or decosinol angelate as an active ingredient.

The liver is the center of metabolism, and functions to process various substances introduced into or produced in the body and to supply important substances, so that various problems occur when liver function is deteriorated by some cause.

Decreased liver function may cause mild fatigue, general weakness, nausea, vomiting, loss of appetite, weight loss, swelling, and, if chronic, can cause discomfort in the upper right abdomen, poor digestion, and gas You may feel pain or bloating when you are cold. If there is a disease in the liver or biliary tract, bilirubin, a metabolite of the human body, cannot be properly discharged, and it may cause yellowness of jaundice due to deposition on the sclera or skin of the eye, and bilirubin accumulated in the body is excreted in urine It is dark in color, and hepatic function decreases, so hepatic cells do not make enough blood coagulation factors, so often bleeding gums or nosebleeds. In addition, in the case of liver cirrhosis, symptoms such as bloating and swelling of the abdomen can be generally observed, and in severe cases, varicose veins are formed in the esophagus or stomach, and blood bleeding is caused by bleeding and bloody stools. It also causes black stools (黑色 便).

These liver dysfunction symptoms, further liver disease can be seen as the cause of the virus, drugs, alcohol, metabolic diseases, chronic cholestasis, hepatic-vein blood flow obstruction, the cause and symptoms, the degree of hepatic function Depending on the drug, hepatic transplantation, including surgical therapy may be selected.

However, due to the risk of surgery or side effects of drugs, there are some limitations in the treatment methods that are currently being introduced. Especially, no obvious cause is known, or other drugs, especially long-term drugs for the treatment of chronic diseases such as chemotherapy. There is a continuing need for preparations that can be safely and widely used in patients whose liver function is impaired or may be damaged due to administration.

In the pharmacological action of decursin, decursinol angelate, decurcinol, and / or two or more of the Angelica gigas extracts, which are the main components of Angelica gigas Nakai Many studies have been conducted on the disease, which is effective for leukemia cancer cells (Patent Publication No. 2001-0080265), for analgesic activity (Patent No. 10-0397950), for lung cancer, liver cancer, etc. (Patent registration notification) 10-0187881) and neuroprotective action (Patent Publication 2002-0078850).

However, a composition using decancin and / or decusinol angelate, or Angelica extract, which is an active ingredient of decusin and / or decosinol angelate, can be used pharmacologically or clinically for the effects related to liver function protection. Nothing was revealed.

Therefore, the inventors of the present invention are safer if hepatic function protection activity is confirmed in the decocin and / or decusinol angelate, or the extract of Angelica dulcis, as an active ingredient, which has been widely used safely for a long time as a herbal medicine. The present invention has been led to determine that the alternative drug can be widely used.

In accordance with the above object, the present invention provides a composition for treating liver function comprising a Angelica extract containing Decasin represented by the following Chemical Formula 1 or Decasin represented by the following Chemical Formula 1 as an active ingredient.

(1)

(One)

In addition, the present invention provides a therapeutic agent for liver function comprising a Angelica extract containing the decosinol angelate or decosinol angelate represented by the formula (2) as an active ingredient.

(2)

(2)

In another aspect, the present invention provides a therapeutic composition for liver function comprising a Angelica extract as the active ingredient of the deckercin and / or decosinol angelate, or deckerin and / or decosinol angelate.

In addition, the composition of the present invention, the decosinol or decosinol represented by the above-mentioned Decusin and / or Decusinol Angelate, or a decansin extract containing Decasin and / or Decusinol Angelate represented by the formula (3) It may further include a Angelica extract containing.

(3)

(3)

The above-mentioned decusin, decosinol angelate or decosinol can be obtained by extracting, separating and purifying from Angelica gigas. (1970); and Korean J. Pharmacogn ., 21, 64-68 (1990)) and Patent Registration No. 10-2385092, but is not limited thereto, even if the solvent, extraction conditions, etc. are different Any extraction method can be used to obtain cine, decosinol angelate or decosinol.

The Angelica extract may further include all salts, organic salts, complexes, and the like, which are known to be incidental in the extraction process, in addition to the above-mentioned decusin, decosinol angelate or decosinol.

The above-mentioned decusin, decosinol angelate or decosinol can be synthesized and used as a specific method (Tetsuhiro Nemoto et al., Tetrahedron Letters , 41, 9569-9574 (2000); Lan Xie et al. J. Med) Chem ., 42, 2662-2672 (1999); Patent Application No. 2000-25749; and Patent Registration No. 10-0417624), but is not limited thereto, even if the synthesis conditions, such as the above decker Any synthetic method can be used to obtain cine, decosinol angelate or decosinol.

The decancin and / or decusinol angelate, or the Angelica extract containing decusin and / or decusinol angelate, have particularly favorable effects on liver failure, fatty liver, hepatitis or cirrhosis.

The decansin and / or decusinol angelate, or decansin extract containing decansin and / or decosinol angelate, is a virus, drug, alcohol, metabolic disease, chronic cholestasis, or hepatic-vein bleeding Exhibits a particularly desirable effect on lowering liver function.

The deucin and / or the decosinol angelate, or the decancin extract containing the decansin and / or decosinol angelate, is administered before or after the administration of an anticancer agent to prevent the desired liver cancer in cancer patients, and It has a therapeutic effect.                     

In the case of using the synthesized decomin, decosinol angelate, or decosinol as the composition for treating liver function, all inorganic salts, organic salts, complexes, and the like, which are known to be involved in the synthesis of the raw materials, may be further included. Can be.

The above compounds are inorganic salts selected from the group consisting of sodium salts, potassium salts, magnesium salts, calcium salts or organic salts selected from the group containing lysine, ethanolamine, N, N'-dibenzylethylenediamine, It may be in the form of a pharmaceutically acceptable salt.

In addition, the present invention comprises a decancin and / or Decusinol Angelate, or a Angelica extract as the active ingredient of Decusin and / or Decusinol Angelate, and further comprises a pharmaceutically acceptable carrier or pharmaceutical additive Treatment for liver function is provided.

In the present invention, hepatic function protection, which includes decancin and / or decosinol angelate, or Angelica extract as the active ingredient of decansin and / or decosinol angelate, further comprising a pharmaceutically acceptable carrier. An adjuvant therapeutic agent is provided.

In the present invention, hepatic function, which includes decansin and / or decusinol angelate, or Angelica extract as the active ingredient of decusin and / or decusinol angelate, further comprising a pharmaceutically acceptable food additive Protective foods are provided.

The composition comprising the decancin and / or decusinol angelate used in the present invention, or the Angelica extract, which is used as an active ingredient of the decusin and / or decusinol angelate, according to the target disease, the purpose and the condition of the patient. The dosage can be changed and used, and it is preferable to administer 1 to 100 mg, more preferably 3 to 30 mg once per day, usually 1 deg. In addition, the above dosage may be administered orally or parenterally formulated.

In addition, the composition comprising the decancin and / or decusinol angelate used in the present invention, or the Angelica extract as the active ingredient deckercin and / or decosinol angelate, reduced uric acid during the clinical trial process of the present inventors Positive effects were observed for the clinical trials of the patient. Further investigation of the present inventors is further underway.

Hereinafter, the present invention will be described in more detail with reference to Examples. However, these examples do not limit the scope of the present invention.

Dosing method

A foam comprising 300 mg of a mixture of Decasin and Decusinol Angelate obtained by culturing and extracting a Korean Angelica extract as described in Patent Registration No. 10-0385092 was prepared. About 50ml of drinking water around 9 am and / or 8 pm daily was administered to the following subjects once or twice a day and once or three times per day for 8 weeks.

Example 1

As shown in Table 1, a total of 19 patients with liver dysfunction classified into three groups for each hospital which performed clinical experiments were checked for changes in SGOT / SGPT before and after administration of the composition of the present invention, and the results are shown in Table 1. Indicated.

Table 1

Severity Number of patients SGOT / SGPT Reduction Cases (%) No change (%) SGOT / SGPT increase cases (%) Ⅰ Ⅱ Ⅲ 4 4 11 3 (75.0%) 2 (50.0%) 8 (72.7%) 1 (25.0%) 0 (0%) 1 (9.0%) 0 (0%) 2 (50.0%) 2 (18.2%) Sum 19 13 (68.4%) 2 (10.5%) 4 (21.0%)

(%)

Example 2

As shown in Table 2 below, 10 cancer patients undergoing chemotherapy and / or radiation therapy were checked for changes in SGOT / SGPT before and after administration of the composition of the present invention, and the results are shown in Table 2.

TABLE 2

Patient ID Disease name gender SGOT change                                          SGPT change                                          result Before administration After administration Before administration After administration One Bladder cancer south 17 5 21 15 decrease 2 Lymphoma south 26 18 50 32 decrease 3 Rectal cancer female 33 29 51 37 decrease 4 Rectal cancer female 30 19 47 28 decrease 5 Breast cancer female 25 14 46 14 decrease 6 Rectal cancer south 35 28 70 58 decrease 7 Breast cancer female 38 33 72 64 decrease 8 Chronic liver abscess south 45 31 52 41 decrease 9 Prostate cancer south 34 25 66 28 decrease 10 Prostate cancer south 31 24 49 25 decrease

Example 3

Nine cancer patients were given the composition of the present invention for two weeks in advance, followed by administration of one or two anti-cancer drugs (16 times in total), and the average of the results obtained after confirming the change of SGOT before and after each anticancer drug administration. Table 3 shows.

TABLE 3

Number of doses SGOT Reduction (%) SGOT ascents (%) result 1 to 2 times for 9 people (16 times) 13 (81.3%) 3 (18.7%) Good

(%)

Example 4

A total of 38 patients with liver dysfunction diseases classified into two groups for each hospital where clinical trials were conducted were examined for the presence or absence of microscopic hematuria before and after administration of the composition of the present invention, and the results are shown in Table 4.

Table 4

Patient group Number of patients Normalization  decrease No change Increase I 12 4 (33.3%) 3 (25.0%) 4 (33.3%) 0 (0%) Ⅱ 26 3 (11.5%) 3 (11.5%) 14 (53.8%) 6 (23.0%) Sum 38 7 (18.4%) 6 (15.8%) 18 (47.4%) 6 (15.8%)

(%)

Example 5

Ten patients with liver dysfunction diseases were examined for the presence of proteinuria and bilirubinuria before and after administration of the composition of the present invention, and the results are shown in Table 5.

Table 5

Symptom Number of patients Normalization decrease No change increase Proteinuria 6 1 (16.7%) 1 (16.7%) 3 (50.0%) 1 (16.7%) Bilirubinino 4 3 (75.0%) 0 (0.0%) 1 (25.0%) 1 (25.0%)

(%)

According to Example 1 (Table 1), a decrease in SGOT / SGPT was observed in 68.4% of the patients with various stages of liver disease administered with the composition of the present invention, and only 21% of the cases were increased. As a result of transient increase, the administration was continued, and as in other cases, the decrease was confirmed.

In addition, in Example 2 (Table 2) for patients with other relatively severe diseases such as various cancers, the overall decrease in SGOT / SGPT was also confirmed, impaired liver function of cancer patients due to surgery and chemotherapy, and liver function of other diseases. It was also found that it showed remarkable protection against damage. More interestingly, the composition of the present invention was pretreated for 2 weeks for cancer patients in this Example 3 (Table 3), which showed an 81.3% reduction in SGOT, thereby not only restoring liver function impairment in cancer patients, but also a prophylactic effect. It is confirmed to have an effect as an adjuvant treatment before and after the chemotherapy of cancer patients.

 As predicted from the recovery of the liver function values of the above examples, the administration of the composition of the present invention has been shown to provide therapeutic benefits in the recovery of hematuria, proteinuria, bilirubinuria (Examples 4 and 5, Tables 4 and 5). ).

A total of 23 cases (11.7%) were reported in 21 of 196 patients with various syndromes receiving the composition of the present invention. In addition, adverse events such as cerebral nervous system side effects and urinary system side effects were reported, but in all cases, they were transient side effects, and there were no side effects that required discontinuation of experiments or continuous changes in clinical values.

Claims (15)

Hepatic function therapeutic composition comprising a decancin represented by the formula (1) or a decansin represented by the following formula (1) as an active ingredient.

(One) A therapeutic agent for liver function comprising a Angelica extract containing Decusinol Angelate represented by the following Chemical Formula 2 or Decusinol Angelate represented by the following Chemical Formula 2 as an active ingredient.

(2) The therapeutic agent composition for liver function according to claim 1, further comprising a sugar ear extract containing a decosinol angelate represented by the following Chemical Formula 2 or a decosinol angelate represented by the following Chemical Formula 2.

(2) The therapeutic agent composition for liver function according to any one of claims 1 to 3, further comprising a decansinol represented by the following general formula (3) or a sugar extract containing the decosinol represented by the following general formula (3): .

(3) The liver disease therapeutic composition according to any one of claims 1 to 3, wherein the target disease of the liver cancer therapeutic composition is liver failure, fatty liver, hepatitis or cirrhosis. The disease according to any one of claims 1 to 3, wherein the disease of the liver function therapeutic composition is a virus, a medicament, an alcohol, a metabolic disease, a chronic cholestasis, or a hepatic-vein blood flow occlusion. Liver function therapeutic composition. The liver function therapeutic composition according to any one of claims 1 to 3, wherein the liver function therapeutic composition is administered before or after administration of the anticancer therapy. The method according to any one of claims 1 to 3, wherein the Angelica extract further contains inorganic salts, organic salts and complexes which are known to be incidental to the extraction process in addition to the above-mentioned decusin, decosinol angelate or decosinol. Hepatic function therapeutic composition comprising a. The method according to any one of claims 1 to 3, wherein the decusin and dekersinol angelate are synthesized, and further include inorganic salts, organic salts and complexes known to be incidental at the time of synthesis. Liver function therapeutic composition. The therapeutic agent composition for treatment of liver function according to any one of claims 1 to 3, wherein the decusin and decusinol angelate are in the form of a pharmaceutically acceptable salt. The method for treating liver function according to claim 10, wherein the salt is an inorganic salt selected from the group consisting of sodium salt, potassium salt, magnesium salt and calcium salt. The composition of claim 10, wherein the salt is an organic salt selected from the group consisting of lysine, ethanolamine, and N, N'-dibenzylethylenediamine. Deucin and / or decusinol angelate, or a decancin and / or decansinol angelate extract containing the extract as an active ingredient, characterized in that it further comprises a pharmaceutically acceptable carrier or medicament additive Liver function therapeutic composition. Hepatoprotective support comprising a decancin and / or decusinol angelate, or a Angelica extract comprising the decansin and / or decusinol angelate as an active ingredient, and further comprising a pharmaceutically acceptable carrier. remedy. Hepatic function protective action comprising a decancin and / or decusinol angelate, or Angelica extract as the active ingredient deckersin and / or decusinol angelate, and further comprises a pharmaceutically acceptable food additive Supplements.