KR101213600B1 - Compositions for the renal 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 renal function comprising decansin and / or decusinol angelate, or Angelica extract, which is used as an active ingredient.

When the composition containing the decancin and / or the decosinol angelate of the present invention, or the Angelica extract comprising the decansin and / or decosinol angelate as an active ingredient, has an excellent effect on renal dysfunction, There is a prevention and treatment effect of renal function degradation by the drug, such as, it is possible to provide a safe renal function treatment agent, adjuvant therapy and health supplements without side effects even during long-term use.

Angelica Extract, Decusin, Decusinol Angelate, Renal Function Protection

Description

COMPOSITIONS FOR THE RENAL 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 renal function comprising decansin and / or decusinol angelate, or Angelica extract, which is used as an active ingredient.

The kidneys, along with the surrounding ureters, bladder and urethra, are responsible for waste metabolism and fluid equilibrium, and balance acid groups. In addition to maintaining the amount of fluid and balance blood pressure by balancing water and electrolytes, it plays an important role in helping hematopoiesis and activating vitamin D to participate in calcium resorption. Therefore, if the kidneys do not function properly for various reasons, protein or blood may be released into the urine, and waste products accumulate in the blood, water and electrolyte imbalance, decrease in urine volume, swelling, and high blood pressure. Broadly referred to as nephrotic syndrome.                         

Nephrotic syndrome typically causes renal glomerular tissue damage, causing proteinuria to pass through the glomerular membrane, hematuria, and systemic edema resulting from decreased osmotic pressure. Red or brown urine, edema in the eyelids or hands and feet, pain in the lower ribs, and increased blood pressure can be reported.

The causes of nephrotic syndrome are very diverse, but they may be caused by kidney-related diseases such as nephritis and complications such as hypertension and diabetes mellitus, and may also be caused by the administration of drugs such as anticancer drugs. You may not be able to do so, depending on the cause and symptoms, the extent of renal function, medication, kidney transplants and other surgical treatments.

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 demand for a drug that can be used safely and widely in patients who may be damaged or may be injured 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, pharmacologically or clinically identified effects related to renal function protection with compositions using decancin and / or decusinol angelate, or Angelica extract, which are used as an active ingredient of decansin and / or decusinol angelate. There was no bar.

Therefore, the inventors of the present invention are safer if the renal function protection action is confirmed in the decancin 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 inventors have determined that it would be possible to provide a widely available alternative drug.

In accordance with the above object, the present invention provides a therapeutic agent composition for renal function comprising a Angelica extract containing a deckerin represented by the following formula (1) or a deckerin represented by the following formula (1) as an active ingredient.

(1)

(One)

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

(2)

(2)

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

(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.

Deucin and / or decusinol angelate, or Angelica extract containing decusin and / or decusinol angelate, have a particularly desirable effect on renal dysfunction by drug administration.

The decancin and / or the decosinol angelate, or the decancin extract containing decansin and / or the decosinol angelate, is administered before or after the administration of an anticancer agent to exhibit a desirable renal function protective effect.

In the case of using the synthesized decomin, decosinol angelate or decosinol as the renal therapeutic agent composition, it may further include all inorganic salts, organic salts, complexes and the like which are known to be involved in the synthesis of the raw materials. have.

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 comprising lysine, ethanolamine, N, N'-dibenzylethylenediamine, and the like. , Pharmaceutically acceptable salts.

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 Renal function medicines are provided.

In addition, the present invention includes a decancin and / or decosinol angelate, or a sugar extract which contains the decansin and / or decosinol angelate as an active ingredient, and further comprises a pharmaceutically acceptable carrier, protective action of renal function Adjuvant therapy with this is provided.

 In addition, the present invention includes a decancin and / or decosinol angelate, or a sugar extract extract containing the decosin and / or decosinol angelate as an active ingredient, and further comprises a pharmaceutically acceptable food additive Supplemental 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.

Urine test method

The subjects were tested for creatinine clearance, hematuria, proteinuria, and bilirubinuria according to clinically common methods.

Example 1

As shown in Table 1, 33 patients with renal dysfunction classified into four groups for each clinical hospital who performed clinical experiments were checked for changes in serum creatinine clearance before and after administration of the composition of the present invention, and the results are shown in Table 1. Indicated.

Table 1

Patient group Number of patients CrC Reduction Cases No change CrC Increase Case I
Ⅱ
Ⅲ
Ⅳ 5
4
2
22 4 (80.0%)
2 (50.0%)
1 (50.0%)
15 (68.2%) 0 (0%)
2 (50.0%)
1 (50.0%)
7 (31.8%) 1 (20.0%)
050%)
0 (0%)
0 (0%) Sum 33 22 (66.7%) 10 (30.3%) 1 (3.0%)

(%)

Example 2

Nine cancer patients were given the composition of the present invention for two weeks in advance, followed by administration of one or two (16 total) anticancer drugs, and the change in serum creatinine clearance before and after each anticancer agent was confirmed and averaged. One result is shown in Table 2.

Table 2

Number of doses % Of CrC increase CrC Reduction Frequency (%) result 1 to 2 times for a total of 9 people
(16 times in total) 13 times (81.3%) 3 times (18.7%) Good

(%)

Example 3

As shown in Table 3, 38 subjects classified into two groups for each hospital which performed the clinical experiment 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 3.

TABLE 3

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 (20.0%) 6 (27.1%) 18 (51.4%) 4 (11.4%)

(%)

Example 4

As shown in Table 4 below, the subjects were examined for the presence or absence of proteinuria and bilirubinuria before and after administration of the composition of the present invention, and the results are shown in Table 4 below.

Table 4

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 serum creatinine clearance was observed in 66.7% of the renal disease patients at various stages of administration of the composition of the present invention, with only 3% of cases increased.

In addition, the reduction of overall serum creatinine clearance has been confirmed in patients with other relatively severe diseases (chronic renal failure patients), such as various cancers, to prevent damage to renal function of cancer patients and renal function damage of other patients due to surgery and chemotherapy. Example 2 (Table 2) also showed a remarkable protective effect. More interestingly, the result of pretreatment of the composition of the present invention for cancer patients for 2 weeks showed a decrease in serum creatinine clearance of 81.3%, thereby not only restoring renal function impairment in cancer patients, but also having a prophylactic effect. It is also expected to be effective as an adjuvant treatment before and after chemotherapy for cancer patients.

As predicted from the recovery of renal function values, administration of the composition of the present invention has been shown to provide therapeutic benefits in the recovery of hematuria, proteinuria, bilirubinuria (Examples 3-4, Tables 3-4).

A total of 23 cases (11.7%) were reported in 21 out of 196 patients with various syndromes receiving the composition of the present invention. There were 5 gastrointestinal side effects including nausea, and cardiovascular side effects with minor dizziness. 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 (14)

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) Chronic kidney-only renal function therapeutic composition comprising Angelica extract.

(One)

(2) delete delete delete The method of claim 1, wherein the target disease of the chronic renal function drug composition for chronic renal function is chronic renal function drug composition for chronic renal failure, characterized in that the impaired renal function. The method of claim 1, wherein the renal function therapeutic composition is administered before or after the administration of an anticancer agent. delete delete delete delete delete New renal function for chronic renal failure, comprising decansin and decosinol angelate, or Angelica extract as the active ingredient decosin and decosinol angelate, and further comprising a pharmaceutically acceptable carrier or medicament additive Therapeutic composition. An adjuvant with chronic renal function for chronic renal function, comprising a decancin and a decosinol angelate, or a Angelica extract comprising the decansin and decosinol angelate as an active ingredient, and further comprising a pharmaceutically acceptable carrier. delete