JP5577129B2 - Liver function improving agent in patients with viral hepatitis - Google Patents

Description

The present invention relates to a pharmaceutical product having a liver function-improving action in patients with viral hepatitis.

  Currently, interferon is widely used for the treatment of viral hepatitis such as hepatitis C. However, as shown in Non-Patent Document 1, the treatment with interferon has a problem that the effective rate is about 50% and the effect is insufficient, and side effects often occur, and the burden on the patient is large.

  Accordingly, there is a need for a method that can effectively improve viral hepatitis without burdening the patient. In particular, in patients with chronic hepatitis C, it is desirable to maintain liver function without burden on patients because it is necessary to maintain liver function within the normal range in patients who have been treated with interferon. Is also required.

And Drug you contain also plum extract with the present invention are disclosed in Patent Document 1. Patent Document 1 discloses an autophagy inducer containing a hydrophobic organic solvent extract of ume meat extract or a neutralized product of ume meat extract as an active ingredient. Autophagy is a cellular phenomenon in which self-cellular components taken up by autophagosomes are degraded by lysosomal enzymes. Patent Document 1 does not disclose any relationship between plum meat extract and viral hepatitis.

Japanese Patent Application Laid-Open Publication No. 2007-143452

Clinical Training Practice 2009, Vol.6, No.11

  An object of this invention is to provide the liver function improving agent in a patient with viral hepatitis.

  According to the present invention, there is provided a liver function improving agent in a patient with viral hepatitis characterized by containing a plum extract or a neutralized product of plum extract.

  ADVANTAGE OF THE INVENTION According to this invention, the liver function improving agent in viral hepatitis patient can be provided.

FIG. 1 is a diagram showing changes in the ALT value in Test Example 1. FIG. 2 is a diagram showing changes in the AST value in Test Example 1. FIG. 3 is a diagram showing a change in γGTP value in Test Example 1. FIG. 4 is a diagram showing changes in LDH values in Test Example 1. FIG. 5 is a diagram showing changes in ALP values in Test Example 1. FIG. 6 is a diagram showing a change in the ALT value in Test Example 2. FIG. 7 is a diagram showing changes in the AST value in Test Example 2.

  Hereinafter, embodiments of the present invention will be described in detail.

  The liver function improving agent in patients with viral hepatitis of the present invention is characterized by containing a plum extract or a neutralized product of a plum extract. The present inventors have found that the components contained in the ume meat extract have an effect of improving the liver function of patients with viral hepatitis, and have reached the present invention. Viral hepatitis is hepatitis A, hepatitis B, hepatitis C, etc., for example.

  In one embodiment, the liver function improving agent in viral hepatitis patients of the present invention is characterized by containing a plum extract. The manufacturing method will be described below.

  First, the collected plums are crushed. Specifically, the ume is crushed with a mixer, separated into seeds and pulp (plum meat), and crushed to a size that is easy to squeeze. Squeeze from the crushed plums to obtain a plum juice. Squeezing is performed by squeezing pulverized plum meat using a squeezer using centrifugal force and collecting the separated juice. According to this method, about 8 kg of plum juice can be collected from 20 kg of plum. Subsequently, the obtained plum juice is concentrated to obtain a plum extract. Specifically, a plum extract is obtained by heating and boiling a plum juice for about 90 hours to make a concentrated solution, and further heat-treating at 100 ° C. for 24 hours. According to this method, about 2 kg of concentrated liquid is obtained from 8 kg of plum juice, and finally about 0.4 kg of plum extract is obtained. Since the plum extract can be stored for a long period of time, it can be prepared and used when needed.

  As another embodiment of the present invention, the liver function improving agent in patients with viral hepatitis of the present invention contains a neutralized product of plum extract.

  The ume meat extract obtained by the above production method is neutralized to obtain a neutralized product. You may neutralize the squeeze juice before heat concentration. The neutralization treatment is preferably performed using sodium hydroxide, sodium carbonate, potassium hydroxide or the like, and neutralized so that the pH is 6-8. The neutralization treatment is performed for the purpose of facilitating formulation processing and alleviating the strong acidity of plums. More specifically, the plum extract is diluted with an equal amount of water to form a suspension, and an appropriate amount of a neutralizing solution is added to the suspension to adjust the pH of the suspension to 6-8. Adjust to neutralize. After neutralization, if necessary, insoluble matter may be removed by centrifugation. Moreover, you may sterilize through a commercially available sterilization filter. Furthermore, saccharides may be added to adjust the taste to be more suitable for eating and drinking.

  In the case of plum extract, the effective intake is 1 to 5 g / day for adults. In the case of a neutralized product of plum extract, the effective intake is 6.5 to 32.5 g / day for an adult.

A carrier is added to the ume meat extract or ume meat extract neutralized product obtained as described above to prepare the liver function improving agent for viral hepatitis patients of the present invention. The carrier to be added is not particularly limited as long as it is pharmaceutically acceptable. Liver function improving agent of the present invention can be provided as pharmaceutical products. When provided as pharmaceuticals, excipients, lubricants, diluents, binders, disintegrants, emulsifiers, stabilizers, flavoring agents, etc. are used as carriers, tablets, capsules, granules, powders, syrups it has preferred to oral preparations such agents.

  As indicators of liver function, AST: aspartate aminotransferase (GOT: glutamate oxaloacetate transaminase) and ALT: alanine aminotransferase (GPT: glutamate pyruvate transaminase) are frequently used clinically. As shown in the following Examples, the improvement of numerical values of ALT and AST was observed by giving the liver function improving agent in patients with viral hepatitis of the present invention to chronic hepatitis C patients. Furthermore, other indices related to liver function such as γGTP and LDH were also improved.

  In addition, when antiviral therapy with interferon or the like is ineffective (that is, a state in which the virus cannot be negative), the liver function improving agent in the patient with viral hepatitis of the present invention is given to the patient with chronic hepatitis C of the present invention. Further improvement in liver function was seen.

  The agent for improving liver function in patients with viral hepatitis of the present invention is an ingredient whose active ingredient is contained in plum. Therefore, it is possible to effectively improve viral hepatitis without causing side effects such as those seen in drugs such as interferon. Furthermore, even when a patient who has insufficient improvement in liver function after treatment is ingested, further improvement in liver function is observed, and this case is also useful in that it can be taken without worrying about side effects.

<Example 1>
Preparation of ume meat extract 20 kg of ume just after collection was crushed with a mixer, separated into seeds and pulp (plum meat), and ume meat was crushed to a size easy to squeeze. The pulverized plum meat was squeezed with a squeezer using centrifugal force, and the separated juice was collected to obtain 8 kg of plum juice. This plum juice was heated to boiling and concentrated for about 90 hours, and further heat-treated at 100 ° C. for 24 hours to obtain 0.4 kg of plum extract.

<Example 2>
Preparation of Plum Meat Extract Neutralized Product Plum meat extract obtained by the same method as in Example 1 was diluted with an equal amount of water to form a suspension, 8N NaOH aqueous solution was added to this suspension, pH 7. Neutralized to zero. Next, the neutralized solution was centrifuged (3000 rpm) to precipitate insoluble matter. Further, the solution was sterilized by passing through a sterilizing filter (0.2 μm pore size, manufactured by Sartorius), and insolubles were removed to obtain a neutralized product.

<Test Example 1>
A mixture of 1 g of the neutralized ume meat extract prepared in Example 2 and 5.5 g of saccharide was used as a single dose, and was administered twice daily in the morning and evening to the patient to be tested. While continuing administration for 12 weeks, each evaluation item was evaluated. The test subject was a patient with chronic hepatitis C and a patient with a disease state in which inflammation in the liver persisted for 6 months or more. Patients under 20 years of age, patients over 76 years of age, patients with cirrhosis, liver cancer, other malignant tumors, patients receiving strong minophagen C, and patients receiving interferon are excluded from the study subjects. Excluded.

The background of the test subject patients (27 cases) is summarized in Table 1 below.

  The result of having measured the value of each evaluation item over time about the test subject patient is shown in FIGS. In the figure, the administration period is from week 0 to week 12. Each graph shows an average value ± standard deviation. Statistical processing was performed by the Wilcoxon signed rank test, and * was displayed when p <0.05, and # was displayed when p <0.01.

  FIG. 1 is a diagram showing a change in the ALT value of a test subject patient. It can be seen from FIG. 1 that the ALT value of the test subject patient decreased.

  FIG. 2 is a diagram showing a change in the AST value of the test subject patient. From FIG. 2, it can be seen that the AST value of the test subject patient decreased.

  FIG. 3 is a diagram showing changes in γ-glutamyltranspeptidase (γGTP) values of patients to be tested. γGTP is an enzyme known to have a high blood concentration when the liver is damaged. From FIG. 3, it can be seen that γGTP of the test subject patient decreased.

  FIG. 4 is a diagram showing changes in serum lactate dehydrogenase (LDH) values of test subject patients. LDH is an enzyme that is known to be released into the blood when the lesion occurs in the liver, resulting in a high blood concentration. From FIG. 4, a downward trend was seen in the LDH value of the test subject patients.

  FIG. 5 is a diagram showing a change in alkaline phosphatase (ALP) value of a test subject patient. ALP is an enzyme that is known to be released into the blood when a lesion occurs in the liver, resulting in a high blood concentration. FIG. 5 shows that the ALP value of the test subject patient decreased.

At the end of the study (after the end of 12 weeks of administration), the improvement in ALT and AST values was calculated in each subject patient. The results are summarized in Table 2 below.

  From Table 2, it can be seen that in both ALT and AST, an improvement rate of 30% or more was observed in about half of the patients. Including the invariant (0-30% improvement rate), it can be said that almost all cases showed an improvement trend.

<Test Example 2>
The test subject was a patient (n = 23) whose viral load in Table 1 is 5 log IU / L or more. Fifteen of these target patients are those who have received treatment with interferon alone or a combination of interferon and ribavirin. The remaining 8 cases were patients who received ursodeoxycholic acid (Urso: registered trademark, manufactured by Mitsubishi Tanabe Pharma Corporation) after receiving treatment with interferon alone or combined use of interferon and ribavirin. In either case, treatment with interferon and ribavirin was completed by 48 weeks before the start of the study, but antiviral therapy did not make the virus negative, resulting in abnormal ALT and AST values. The condition was as shown. In the group taking urso, urso was continued from the end of treatment with interferon and ribavirin until the end of the study.

  For the test subject patient as described above, a mixture of 1 g of the neutralized ume meat extract prepared in Example 2 and 5.5 g of sugar was taken as a single dose, and this was administered twice daily in the morning and evening. . Administration was continued for 12 weeks. The results of measuring the ALT value and the AST value over time for each patient are shown in FIG. 6 and FIG.

  FIG. 6 is a diagram showing a change in the ALT value in Test Example 2. FIG. 6A shows the result of the group not using urso together, and FIG. 6B shows the result of the group using urso together. In both figures, the treatment with interferon and ribavirin has already been completed at -48 weeks. The administration period of 1 g of neutralized ume meat extract prepared in Example 2 and 5.5 g of saccharide is 0 to 12 weeks in the figure. In the case of the urso combination group, urso was further taken from the end of the treatment with interferon and ribavirin to the end of the test (ie, −48 to 12 weeks in the figure).

  6 (a) and 6 (b), it can be seen that the ALT value is greatly reduced between 0 and 12 weeks. Therefore, it can be said that the ALT value can be further lowered by ingesting the liver function improving agent in the viral hepatitis patient of the present invention by the patient who has been ineffective in the treatment with interferon.

  FIG. 7 is a diagram showing changes in the AST value in Test Example 2. FIG. 7A shows the result of the group not using urso together, and FIG. 7B shows the result of the group using urso together. The treatment period with interferon, the administration period of the neutralized product of ume meat extract, and the administration period of urso are the same as described in FIG.

  In both FIGS. 7 (a) and (b), a decrease in the AST value was observed at 0 to 12 weeks. Therefore, it can be said that the AST value can be further reduced by ingesting the liver function-improving agent in the viral hepatitis patient of the present invention by a patient whose treatment with interferon is ineffective.

  The above examples have been described for the purpose of illustrating the present invention and are not intended to limit the scope of the present invention. Embodiments of the present invention can be expanded or modified within the scope of the technical idea of the present invention, and these expanded and modified embodiments are also included in the technical scope of the present invention.

Claims (2)

Agents made for use in improving liver function in patients with chronic hepatitis C, characterized by containing a neutralizing product of plum extract or該梅meat extract was concentrated plum juice and enrichment. The C-type chronic hepatitis patients, agents made for use in improving liver function according to claim 1, wherein the antiviral therapy is chronic hepatitis C patients were ineffective.

Images