KR101320485B1 - Compositions for anticancers containing decursin and/or decursinol angelate, or angelica extract containing decursin and/or decursinol angelate - Google Patents

Abstract

The present invention relates to an anticancer drug composition comprising a decancin and / or decosinol angelate, or a Angelica extract comprising the decansin and / or decosinol angelate as an active ingredient.

When the composition containing the decancin and / or decosinol angelate of the present invention, or the Angelica extract comprising the decansin and / or decosinol angelate as an active ingredient, bladder cancer, urinary tract cancer, kidney cancer, prostate cancer Genitourinary cancer, such as testicular cancer; Gynecological cancers such as breast cancer, cervical cancer, and the like; Digestive system cancers such as liver cancer, stomach cancer, rectal cancer, and pancreatic cancer; Lung cancer, lymph cancer, sarcoma, bone cancer, such as cancer patients can be provided with anti-cancer treatment with little side effects.

Angelica Extract, Decusin, Decusinol Angelate, Anticancer Drug

Description

Anticancer composition comprising a decancin and / or decosinol angelate, or an extract of Angelica g. DECURSIN AND / OR DECURSINOL ANGELATE}

The present invention relates to an anticancer drug composition comprising a decancin and / or decosinol angelate, or a Angelica extract comprising the decansin and / or decosinol angelate as an active ingredient.

There have been many studies examining the potential of anti-cancer agents in decancin and / or decusinol angelate, or as an active ingredient in Angelica extract, which contains decusin and / or decusinol angelate as an active ingredient.

Patent application No. 193-17935 discloses Decker against human uterine cancer cell line (HeLa S3), human chronic leukemia cell line (K-562), human liver cancer cell line (Hep G2), human colon cancer cell line (SNU-C4). The anticancer activity of the god has been confirmed, and the patent application No. 1996-30421 shows the growth of decansinol angelate against human lung cancer cell line (A-549), chronic leukemia cell line (K-562), liver cancer cell line (Hep G2). Patent application No. 1998-44340 confirmed the cancer cell differentiation-inducing effect of Decker's leukemia in the experiment using U-937 cells. In addition, Patent Application No. 2000-35749 discloses a method for synthesizing decosinol that exhibits selective lethal action on cancer cells compared to normal cells.

However, the above effects are only laboratory methods for cancer cell lines, and the types of cancer cell lines used are limited to lung cancer, liver cancer, uterine cancer, leukemia, and colorectal cancer. It is not known whether cancer is effective as an anticancer agent, and since no direct clinical trials have been conducted, there are questions about the anticancer effect on actual patients with complex physiological mechanisms.

In particular, even though the majority of anti-cancer drugs have been proved to be effective for certain cancer cell lines, many cases have been found to be ineffective or inadequate when applied in vivo. Moreover, the anti-cancer effects as well as the cytotoxic effects on normal cells are fatal. Frequently, there was no availability for enemy or industry.

Therefore, the inventors of the present invention, if the anti-cancer effect is clinically confirmed in the decancin and / or decusinol angelate, or the Angelica extract using the same as an active ingredient of Angelica, which has been widely used safely for a long time as a herbal medicine, The present inventors have determined that it is possible to provide safer and more widely available anticancer agents.

In accordance with the above object, the present invention provides an anticancer agent composition comprising a decancin represented by the following formula (1) or a decancin represented by the following formula (1) as an active ingredient.

(1)

(One)

In another aspect, the present invention provides an anticancer composition comprising a decansinol angelate represented by the following formula (2) or a decansinol angelate represented by the following formula (2) as an active ingredient.

(2)

(2)

In another aspect, the present invention provides an anticancer agent composition comprising the extract of Angelica mucus as an active ingredient of the decancin and / or decusinol angelate.

In addition, the composition of the present invention, the decansinol represented by the formula (3) to the sugar extracts containing the above-mentioned decusin and / or decusinol angelate, or decosin and / or decosinol angelate as an active ingredient It may further include a Angelica extract containing the decosinol represented by the formula (3).                     

(3)

(3)

The above-mentioned decusin, decosinol angelate or decosinol can be obtained by extracting, separating and purifying from Angelica gigas, and specific extraction and purification methods are described in the literature (Lee Ji-Joon et al., Biochemical Society, 1, 25-32). (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 decansin and / or decusinol angelate, or the decancin extract containing decusin and / or decosinol angelate, is a genitourinary cancer of men such as bladder cancer, urinary tract cancer, kidney cancer, prostate cancer, testicular cancer, etc. It shows a particularly preferable effect.

The decancin and / or the decosinol angelate, or the Angelica extract containing the decansin and / or decosinol angelate, exhibits particularly preferred effects on gynecological cancers such as breast cancer, cervical cancer and uterine cancer.

The decancin and / or decusinol angelate, or the Angelica extract containing decusin and / or decosinol angelate, exhibits particularly desirable effects on gastrointestinal cancers such as liver cancer, gastric cancer, rectal cancer and pancreatic cancer.

The decancin and / or decusinol angelate, or the Angelica extract containing decusin and / or decusinol angelate, exhibit particularly favorable effects on lung cancer.

The decancin and / or decusinol angelate, or the Angelica extract containing decusin and / or decusinol angelate, exhibits particularly preferred effects on lymph cancer.

Deucin and / or decusinol angelate, or Angelica extract containing decusin and / or decusinol angelate, exhibit particularly favorable effects on sarcoma and bone cancer.

The decancin and / or decusinol angelate, or the Angelica extract containing decusin and / or decusinol angelate, exhibits a desirable effect in the treatment of metastasized cancer.

The decancin and / or decusinol angelate, or the Angelica extract containing decusin and / or decusinol angelate, exhibits a desirable effect in the treatment of cancer having stage 3 or later, and preferably It is good to use in combination with chemotherapy.                     

The decancin and / or decusinol angelate, or the Angelica extract containing decusin and / or decusinol angelate, has a desirable effect in the monotherapy of cancers having stages prior to stage 2, resulting in anti-cancer Therapy can be used in combination.

In the case of using the decancin, the decosinol angelate, or the decosinol synthesized as the anticancer agent composition, all inorganic salts, organic salts, complexes, and the like, which are known to be incidental at the time of synthesis of the raw material, may be further included. .

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 An anticancer agent is provided.

In the present invention, the anticancer adjuvant further comprises a decancin and / or decosinol angelate, or a Angelica extract comprising the decansin and / or decosinol angelate as an active ingredient, and a pharmaceutically acceptable food additive. Food is 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.

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. The following clinical trials were performed by subjecting the following subjects to daily drinking at about 9 am and / or about 8 pm at about 50 ml of drinking water once or twice a day and once for three weeks.

Example 1

As shown in Tables 1 to 5, for urogenital cancer patients, the composition of the present invention is additionally administered to an existing anticancer agent according to the patient, or the composition of the present invention is administered alone, and is positive for anticancer effect and anticancer treatment. The effect which influenced was confirmed, and the result is shown to Tables 1-5.

Table 1 Anticancer Effects on Patients with Bladder Cancer

Patient ID gender age Metastasis ordnance cure result One south 68 Lymph nodes Four Use with anticancer drugs Reduction of white blood cell reduction, red blood cell recovery 2 south 40 Lymph nodes Four Use with anticancer drugs Reduction of white blood cell reduction, red blood cell recovery 3 female 65 Lymph nodes Four Use with anticancer drugs Reduction of white blood cell reduction, red blood cell recovery 4 south 75 brain Four Use with anticancer drugs Reduction of white blood cell reduction, red blood cell recovery 5 south 85 Lymph nodes Four Use with anticancer drugs Reduction of white blood cell reduction, red blood cell recovery 6 south 66 Lymph nodes Four Use with anticancer drugs Reduction of white blood cell reduction, red blood cell recovery 7 south 66 Lymph nodes Four Use with anticancer drugs Reduction of white blood cell reduction, red blood cell recovery 8 female 68 - Third Single dose Decrease in tumor size 9 south 66 liver Four Use with anticancer drugs Reduction of white blood cell reduction, red blood cell recovery 10 south 75 liver Four Use with anticancer drugs Reduction of white blood cell reduction, red blood cell recovery 11 south 75 liver Four Use with anticancer drugs Reduction of white blood cell reduction, red blood cell recovery 12 south 65 - Third Use with anticancer drugs Reduction of white blood cell reduction, red blood cell recovery 13 female 63 lungs Four Use with anticancer drugs Reduction of white blood cell reduction, red blood cell recovery

Table 2 Anticancer Effects on Patients with Urinary Tract Cancer

TABLE 3 Anticancer Effects on Kidney Cancer Patients

Patient ID gender age Metastasis ordnance cure result One south 42 goal Four Use with anticancer drugs Protective effect against edema and renal function hepatic function 2 female 54 lungs Four Use with anticancer drugs 3 south 52 lungs Four Use with anticancer drugs 4 female 59 lungs Four Use with anticancer drugs 5 south 46 lungs Four Use with anticancer drugs 6 south 60 lungs Four Use with anticancer drugs 7 female 63 lungs Four Use with anticancer drugs 8 south 46 lungs Four Use with anticancer drugs 9 female 43 - Four Alone No recurrence 10 south 49 - Second Alone No recurrence 11 south 46 - First Alone No recurrence 12 female 44 - First Alone No recurrence 13 south 47 - Second Alone No recurrence 14 south 47 - First Alone No recurrence 15 south 38 - Second Alone No recurrence 16 south 52 - Second Alone No recurrence 17 south 42 - Four Use with anticancer drugs Edema reduction, liver function, renal function protection 18 female 74 - First Alone No recurrence 19 south 51 - First Alone No recurrence 20 south 51 - Third Alone No revalidation 21 female 59 - Four Alone No recurrence 22 female 53 - First Alone No recurrence 23 female 63 - Four Use with anticancer drugs Edema reduction, liver function, renal function protection 24 south 70 - Four Alone No recurrence 25 south 45 - Four Use with anticancer drugs Edema reduction, liver function, renal function protection

Table 4 Anticancer Effects on Patients with Prostate Cancer

Patient ID gender age Metastasis ordnance cure result One south 72 goal Four Use with anticancer drugs Edema reduction, liver function, renal function protection 2 south 74 goal Four Use with anticancer drugs Edema reduction, liver function, renal function protection 3 south 72 goal Four Use with anticancer drugs White blood cell reduction, nausea 4 south 51 - Second Alone No progress 5 south 55 - Second Alone No progress 6 south 71 - First Alone No progress 7 south 56 - First Alone No progress 8 south 81 - Second Alone No progress 9 south 65 - Four Use with anticancer drugs Edema reduction, liver function, renal function protection 10 south 68 - Second Alone No progress 11 south 55 - Second Alone No progress 12 south 56 - First Alone No progress 13 south 74 - Second Alone No progress 14 south 56 - Four Use with anticancer drugs Edema reduction, liver function, renal function protection 15 south 73 - First Alone No progress 16 south 67 - Four Use with anticancer drugs Edema reduction, liver function, renal function protection 17 south 59 - Second Alone No progress 18 south 61 - First Alone No progress 19 south 71 - First Alone No progress 20 south 52 - Second Alone No progress 21 south 79 - Second Alone No progress 22 south 75 - Four Use with anticancer drugs Edema reduction, liver function, renal function protection 23 south 58 - Second Alone No progress 24 south 70 - Four Use with anticancer drugs Edema reduction, liver function, renal function protection 25 south 71 - Four Use with anticancer drugs Edema reduction, liver function, renal function protection

Table 5 Anticancer Effect on Testicular Cancer Patients

Patient ID gender age Metastasis ordnance cure result One south 38 lungs Four Use with anticancer drugs Edema reduction, liver function, renal function protection 2 south 23 - Four Use with anticancer drugs Edema reduction, liver function, renal function protection 3 south 35 - First Alone No recurrence 4 south 32 - Four Use with anticancer drugs Edema reduction, liver function, renal function protection

Example 2

As shown in Tables 6 to 7 below, the composition of the present invention is administered to patients with breast cancer, cervical cancer, and uterine cancer, and the effects of having a positive effect on anticancer effects and anticancer treatments are confirmed. 7 is shown.

Table 6 Anticancer Effects on Breast Cancer Patients

Patient ID gender age Metastasis ordnance cure result One female 51 - Third Alone No side effects of chemotherapy,
No recurrence 2 female 52 - Third Alone No side effects of chemotherapy,
No recurrence 3 female 48 - Third Alone No side effects of chemotherapy,
No recurrence 4 female 48 - Third Alone No side effects of chemotherapy,
No recurrence 5 female 58 - Third Alone No side effects of chemotherapy,
No recurrence 6 female 51 - Third Alone No side effects of chemotherapy,
No recurrence 7 female 53 - Third Alone No side effects of chemotherapy,
No recurrence 8 female 42 - Third Alone No side effects of chemotherapy,
No recurrence 9 female 39 - Third Alone No side effects of chemotherapy,
No recurrence 10 female 44 - Third Alone No side effects of chemotherapy,
No recurrence 11 female 51 - Third Alone No side effects of chemotherapy,
No recurrence 12 female 41 - Third Alone No side effects of chemotherapy,
No recurrence 13 female 55 - Third Alone No side effects of chemotherapy,
No recurrence 14 female 62 - Third Alone No side effects of chemotherapy,
No recurrence

Table 7 Anticancer Effects on Cervical and Cervical Cancer Patients

Patient ID gender age Metastasis ordnance cure result One female 75 lungs Four Alone No side effects of chemotherapy,
No recurrence 2 female 48 lungs Four Alone Slow deterioration rate,
Liver function, new function protection 3 female 39 - Four Alone No side effects of chemotherapy,
No recurrence 4 female 68 - Four Alone No side effects of chemotherapy,
No recurrence 5 female 55 - Four Alone No side effects of chemotherapy,
No recurrence 6 female 35 - Four Alone No side effects of chemotherapy,
No recurrence 7 female 75 - Four Alone No side effects of chemotherapy,
No recurrence 8 female 50 - Four Alone No side effects of chemotherapy,
No recurrence 9 female 56 - Four Alone No side effects of chemotherapy,
No recurrence 10 female 51 - Four Alone No side effects of chemotherapy,
No recurrence 11 female 51 - Four Alone No side effects of chemotherapy,
No recurrence 12 * female 58 - Four Alone No side effects of chemotherapy,
No recurrence

(Patient 12 * is a uterine cancer patient; other patients 1-11 are cervical cancer patients)

Example 3

As shown in Table 8 below, for patients with gastrointestinal cancer, the composition of the present invention is additionally administered to an existing anticancer agent, or the composition of the present invention is administered alone, thereby positively affecting the anticancer effect and anticancer treatment. Confirmed the effect, and the results are shown in Table 8.

Table 8 Anticancer Effect on Gastrointestinal Cancer Patients

Patient ID gender age disease Metastasis ordnance cure result One south 64 Gastric cancer lungs Four Alone No progress 2 south 64 Gastric cancer - Four Alone No progress 3 south 74 Gastric cancer - Four Alone No progress 4 south 73 Gastric cancer - Four Alone No progress 5 south 74 Rectal cancer liver Four Use with anticancer drugs Chemo side effects,
Nausea, edema loss 6 south 50 Rectal cancer lungs Four Use with anticancer drugs Chemo side effects,
Nausea, edema loss 7 south 74 Rectal cancer - Four Alone No progression or recurrence 8 south 57 Rectal cancer - Four Alone No progression or recurrence 9 south 51 Rectal cancer - Four Alone No progression or recurrence 10 south 74 Rectal cancer - Four Alone No progression or recurrence 11 female 56 Rectal cancer - Four Alone No progression or recurrence 12 south 50 Rectal cancer - Four Alone No progression or recurrence 13 south 71 Rectal cancer - Four Alone No progression or recurrence 14 south 68 Rectal cancer - Four Alone No progression or recurrence 15 south 54 Rectal cancer - Four Alone No progression or recurrence 16 south 52 Rectal cancer - Four Alone No progression or recurrence 17 female 42 Rectal cancer - Four Alone No progression or recurrence 18 female 56 Pancreatic cancer - Four Alone No progression or recurrence 19 female 42 Pancreatic cancer - Four Alone No progression or recurrence 20 south 51 Liver cancer _ Third Use with anticancer drugs Chemo side effects,
Nausea, edema loss

Example 4

As shown in Table 9 below, for lung cancer patients, the composition of the present invention is additionally administered to an existing anticancer agent according to the patient, or the composition of the present invention is administered alone to have a positive effect on the anticancer effect and chemotherapy. The effect was confirmed and the result is shown in Table 9.

Table 9 Anticancer Effect on Lung Cancer Patients

Patient ID gender age Metastasis ordnance cure result One south 67 - Four Alone No progression or recurrence 2 south 55 - Four Alone No progression or recurrence 3 south 48 - Four Alone No progression or recurrence 4 south 84 - Four Alone No progression or recurrence 5 south 53 - Four Alone No progression or recurrence 6 south 68 - Four Alone No progression or recurrence 7 south 55 goal Four Use with anticancer drugs Shortening leukocyte reducer,
Erythrocyte Recovery, Nausea Reduction

Example 5

For various cancer patients as shown in Table 10 below, by additionally administering the composition of the present invention to an existing anticancer agent according to the patient, or by administering the composition of the present invention, having a positive effect on the anticancer effect and chemotherapy The effect was confirmed, and the result is shown in Table 10.

Table 10 Anticancer effect on various cancer patients

Patient ID gender age disease Metastasis ordnance cure result One south 41 Lymph cancer Relapse Four Use with anticancer drugs Reduction of edema, liver function, and renal function protection
2 south 41 Lymph cancer Relapse Four Use with anticancer drugs 3 south 65 Lymph cancer - Four Use with anticancer drugs 4 south 73 Lymph cancer - Four Use with anticancer drugs 5 south 61 Lymph cancer - Four Use with anticancer drugs 6 south 41 Lymph cancer - Four Use with anticancer drugs 7 south 39 Lymph cancer - Four Use with anticancer drugs 8 south 45 sarcoma - Four Use with anticancer drugs 9 south 82 Bone cancer - Four Alone No recurrence

According to Example 1 (Tables 1 to 5), in the case of urogenital cancer patients, even when the composition of the present invention is administered alone or in combination with an anticancer agent, the overall anticancer effect, prevention of recurrence, prevention of exacerbation, or anticancer treatment Positive effects such as the prevention of side effects were observed. In particular, the fact that the tumor size was reduced by administering the composition of the present invention to elderly female bladder cancer patients alone and the recurrence or metastatic urinary tract cancer patients were notable was the remarkable case, especially clinical cases. In patients with urinary tract cancer, kidney cancer, and prostate cancer, which had a relatively large number, administration of the composition of the present invention in stage 2 or less showed excellent anti-cancer effects alone, thereby inhibiting cancer progression and preventing recurrence.

Example 2 (Tables 6 to 7) relates to breast cancer, cervical cancer, and uterine cancer, in particular, where the anticancer effect of the composition of the present invention is excellently demonstrated. Results were shown for 14 cases in which all of the patients had stage 4 or later breast cancer patients who received the composition of the present invention alone, and all the side effects and recurrences of the existing chemotherapy were prevented. In addition, when the composition of the present invention was administered to 12 patients with cervical cancer and cervical cancer at the end of the day, excellent anticancer effects were observed in all of them, including patients with lung metastases.

Examples 3 to 4 (Tables 8 to 9) generally target gastric cancer, rectal cancer, lung cancer, etc., which have a significantly lower cure rate after stage 3, although the stage 4 patients were administered alone. It was confirmed to prevent recurrence.

In addition, bladder cancer, urinary tract cancer, renal cancer, prostate cancer, which have been administered in combination with the composition of the present invention to an existing anticancer agent to patients after stage 3 with respect to medical ethical issues, problems with metastatic cancer, and parental consent. In patients with testicular cancer, rectal cancer, and lymph cancer, it was theoretically impossible to confirm the anticancer effect due to the composition of the present invention. The reduction in was moderated. Although only one case, the composition of the present invention was administered alone to elderly bone cancer patients, it was also possible to confirm the effect of preventing recurrence.

In addition, four out of 33 patients who received the composition of the present invention reported a total of four (12.1%) side effects, including one gastrointestinal side effect, one sleep disorder, and one urinary system side effect. One other case has been reported, but since it was targeted to patients undergoing chemotherapy, no direct association with the composition of the present invention was confirmed, but in any case, it was a transient side effect. It was confirmed that no.

Claims (19)

As an active ingredient, a mixture of decusin represented by the following general formula (1) and decosinol angelate represented by the following general formula (2), or decosin represented by the following general formula (1) and decosinol angelate represented by the following general formula (2) An anticancer drug composition comprising Angelica extract, comprising bladder cancer as a target disease.

(One)

(2) delete delete delete delete delete delete delete delete delete The anticancer agent composition according to claim 1, wherein the target disease of the anticancer agent composition is metastatic cancer. The anticancer agent composition according to claim 1, wherein the anticancer agent composition is used alone or in combination with an anticancer agent. delete delete delete delete delete Deckerin and decosinol angelate, or the extract of Angelica extract as an active ingredient of decosin and decosinol angelate, characterized in that it further comprises a pharmaceutically acceptable carrier or medicament additive, Anticancer agent composition which uses bladder cancer as a target disease. delete