JP2015524813A - Application of Takasago Sanchisou to the manufacture of drugs for treating hepatitis or foods for health - Google Patents

Abstract

The present invention discloses the application of Takasago Sanchichiso to the manufacture of drugs for treating hepatitis or foods for health use. The high-dose group of Takasago Sansitoshi ethanol extract and water extract can remarkably suppress mouse acute liver damage caused by carbon tetrachloride, reduce serum glutamate pyruvate transaminase and glutamate oxaloacetate transaminase, and Degeneration and necrosis can also be reduced.

Description

  The present invention relates to the field of traditional Chinese medicine, and in particular, to the use of Takasago Sanshichiso as a simple prescription for Chinese medicine in pharmaceutical and health foods.

  Takasago Sanshichiso, also called White-backed Chichiso, is the entire plant of the Asteraceae Takasago Sanshichiso Gynura divaricata (L) DC. [G.oualis DC.; G.pseudo-china (L) DC.]. Other names for Takasago Sanshichiso include Daiichi beef (“Guangzhou botanical magazine”), dough, white vegetarian medicine, sanguyan (“Guangxi medicinal plant magazine”), Tsuchida 7 (“Guangxi Chinese medicine magazine”), katana There are medicines, Seishin vegetables, white blood skin vegetables, seven peas, major manic medicines, Taiwan herbs, Masuju shinso, life tree, dragon senso, shinso. Takasago Sanshichiso is a perennial, 30 to 60 cm in height, its stems are upright, most of them are slanted from the base, are woody, have a streak-like ridge after drying, do not branch, or at the top May have inflorescence branches, hairless or covered with short fur, and a little pale purple. Leaf quality is thick, usually concentrated in the lower part, with a handle or almost no handle.

  The leaves are oval, elliptical or fallen needle-shaped, 2-15 cm long and 1.5-5 cm wide, with the apex being blunt or sharp, and the base Is wedge-shaped, thinned, or stretched downward into a petiole, almost cut or heart-shaped, with a rough serrated edge, and some that can be broken into violin-like shapes. The whole edge is rare, the upper surface is green and the lower surface is purple. There are 3-5 pairs of side veins, and the veins are generally connected to each other to form an almost parallel oval reticulum, and after drying, a black line is clearly present, and both sides are covered with short fur. The length of the petiole is 0.5-4 cm, with short soft hair, and the base is oval or ear-shaped with a half-moon-shaped saw tooth. The upper leaves gradually become smaller and are leafy, narrow, needle-like, linear, wing-like, cleaved, unpatterned, and slightly wrapped around the stem.

  A head-shaped inflorescence is a conical inflorescence with a diameter of 1.5 to 2 cm and usually (2) 3 to 5 arranged in an umbrella-like bunched shape at the end of a stem or a branch. There are many. The length of the floral pattern is 1 to 15 cm, covered with dense short soft hair, and has 1 to 3 linear ridges. The total kite is bell-shaped, has a length of 8 to 10 mm, a width of 6 to 8 mm, and has several linear or thread-like pieces on the base. There are 11-14 total collar pieces, a narrow needle-like shape with a length of 8-10 mm and a width of 1-2 mm. The apex gradually becomes pointed and becomes a long triangle, and the edges are dry. It is of quality and has 3 veins on the back and is sparsely covered with short hairs or almost hairless. The florets are orange-yellow and scented, slightly extended from the total buds, the corolla is 11-15 mm in length, the tube is thin, 9-11 mm in length, the upper part is enlarged, and the fragments are oval It has an oval shape with a red apex.

  The base of the chamber is dull, arrowhead-like, the style is narrow, the cone is attached, and it is covered with papillary hair. The fruits are cylindrical, have a length of about 5 mm, are brown, have 10 wrinkles, and are covered with fine hairs. The crown hair is white and silky and has a length of 10 to 12 mm.

  The flower and fruit period is from August to October. The properties of the medicinal material and the decoction are bulky rhizomes and have long and thin roots. The stem is cylindrical, brown-purple, covered with short hair, the leaves are alternating, the pods are a little bit thick, and the complete leaf piece is from a long oval to an oval fallen oval shape, 5-15 cm in length The tip is blunt or short with a width of 2.5-8 cm. There may be two ears at the base and irregular cuts and saw teeth on the leaf edges. The upper and lower surfaces have fur. May have a head-shaped inflorescence or a total wing. The fruits are deep brown and the crown hair is white. Slightly pungent and light taste.

  Takasago Sanshichisou is distributed in Guangdong (Guangzhou, Nanhai), Hainan (Sumien, Cliff Prefecture, Wanning, Baoting, Zhongchun, Ulsan, etc.), Hong Kong, Yunnan (Jingdong, Red River, Green Spring) . It is also distributed in the northern part of Vietnam. Takasago Sanshichiso has the effects of refreshing cool blood, active pain, hemostasis, cough, bronchitis, pulmonary tuberculosis, pressure ulcer, pain, burn (burn), bruise, joint pain, collapsing, trauma bleeding, pertussis Treat fractures, bleeding from wounds, and sores. Takasago Sanshichiso includes n-Eicosane, Tetracosanol, Octacosanoic acid, Octacosyl alcohol, Palmitic acid, Stigmasterol-3-O- Components such as β-D-glucopyranoside (Stigmasterol-3-O-β-D-glucopyranoside), stigmasterol (Stigmasterol), s-sitosterol (β-Sitosterol), daucosterol (Daucosterol), and Friedelin (Friedelin) Contained. Modern research has shown that scorpionfish has the effect of lowering blood glucose levels.

  An object of the present invention is to provide a new use capable of effectively protecting the liver in scorpionfish.

In order to solve the above technical problem, the technical solution according to the present invention is as follows.
It is an application to the manufacture of a medicine or health food for treating hepatitis of Takasago Sanchichi, which is mixed with a normal dose of a medically recognized excipient (auxiliary material). And is clinically recognized.

The above-mentioned Takasago Sanshichisou extract is a water extract or an ethanol extract.
The method for producing the water extract comprises adding 8 to 12 times the amount of water to Takasago Sanshichiso, decocting for 1.5 to 2 hours, adding 5 to 8 times the amount of water to the obtained residue, It includes a step of decocting for 1.5 hours, combining the obtained extracts, filtering, and concentrating.

  The ethanol extract was prepared by adding 8 to 12 times the amount of 75-90% ethanol to Takasago Sanshichiso, performing reflux extraction for 1.5-2 hours, and further adding 75-90% to the resulting residue. It includes a step of adding an amount of water, decocting for 1 to 1.5 hours, combining the obtained extracts, filtering, collecting ethanol, and concentrating.

  The preparation is a clinically recognized granule, capsule, tablet or oral solution.

As a result of the research, the following was found. According to the present invention, the high-dose group of Takasago Sanshichisou ethanol extract and water extract showed a remarkable inhibitory action against acute liver damage caused by administration of carbon tetrachloride (CCl ₄ ). The inhibitory action decreased serum glutamate pyruvate transaminase and serum glutamate oxaloacetate transaminase, and also reduced the degree of hepatocyte degeneration and necrosis.

  The contents described below are some examples of the present invention, and are used to further describe the present invention, but the present invention is not limited to these examples.

Example 1 (water extraction)
Eight times the amount of water was added to Takasago Sanshichiso, and the first extraction was performed for 2 hours. The residue was further added eight times the amount of water, and the second extraction was performed for 1.5 hours. The obtained extracts were combined, filtered, concentrated, and dried to a dark brown powder. The yield of the extract (final powder yield / weight of administered drug) was 6-10%.

Example 2 (water extraction)
Ten times the amount of water was added to Takasago Sanshichiso, and the first extraction was performed for 1.5 hours. The residue was further extracted for the second time by adding six times the amount of water and 1.2 hours. The obtained extracts were combined, filtered, concentrated, and dried until a dark brown powder was obtained. The extract yield was 6-10%.

Example 3 (water extraction)
A 12-fold amount of water was added to Takasago Sanshichiso for the first extraction for 1.5 hours, and a 5-fold amount of water was added to the residue for a second extraction for 1 hour. The obtained extracts were combined, filtered, concentrated, and dried to a dark brown powder. The extract yield was 6-10%.

Example 4 (Ethanol extraction)
Ten times the amount of 80% ethanol was added to Takasago Sanshichiso, and reflux extraction was performed for 2 hours. The residue was further added with 80% amount of water and decocted for 1.5 hours. The obtained extracts were combined, filtered, ethanol was collected, concentrated, and dried to a dark brown powder. The extract yield was 6-8%.

Example 5 (ethanol extraction)
90 times ethanol of 8 times amount was added to Takasago Sanshichiso, reflux extraction was performed for 1.5 hours, and 90% times amount of water was further added to the residue and decocted for 1 hour. The obtained extracts were combined, filtered, ethanol was collected, concentrated, and dried to a dark brown powder. The extract yield was 6-8%.

Example 6 (ethanol extraction)
12 times the amount of 75% ethanol was added to Takasago Sanshichiso, reflux extraction was performed for 2 hours, and the residue was further decocted for 1.5 hours with an additional 75% amount of water. The obtained extracts were combined, filtered, ethanol was collected, concentrated, and dried to a dark brown powder. The extract yield was 6-8%.

Example 7 (granule)
Formulation: 1 part by weight of the water extract obtained by Example 1, 2.5 parts by weight of sucrose, and 1.5 parts by weight of dextrin, calculated in parts by weight.
Production method: Sucrose and dextrin were added to the extract powder and mixed uniformly to prepare granules, then dried and individually packaged.
Properties: This product is yellowish brown granule with a slightly sweet taste and bitterness.
Dosage and administration: Take 7.5g at a time, 2-3 times a day with hot water.

Example 8 (granule)
Formulation: 1 part by weight of water extract obtained from Example 3, 2.5 parts by weight of sucrose, and 1.5 parts by weight of dextrin, calculated in parts by weight.
Production method: Sucrose and dextrin were added to the extract powder and mixed uniformly to prepare granules, then dried and individually packaged.
Properties: This product is yellowish brown granule with a slightly sweet taste and bitterness.
Dosage and administration: Take 2.5 g at a time, 2-3 times a day with hot water.

Example 9 (capsule)
Formulation: 1 part by weight of ethanol extract obtained from Example 4 and 2 parts by weight of starch, calculated in parts by weight.
Production method: Starch was added to the extract powder and uniformly mixed to prepare granules, then dried and put into capsules.
Properties: This product is a capsule, the contents are dark brown granules or powder, and the taste is slightly bitter.
Dosage and administration: Orally administer 3 tablets at a time, 2-3 times a day.

Example 10 (tablets)
Formulation: Calculated in parts by weight, 1 part by weight of ethanol extract obtained from Example 5, 2 parts by weight of starch, and appropriate amount of magnesium stearate.
Production method: Starch was added to the extract powder, and the mixture was uniformly mixed to prepare granules. After drying, magnesium stearate was added and tableted.
Properties: This product is a dark brown tablet with a slightly bitter taste.
Dosage and administration: Orally administer 3 tablets at a time, 2-3 times a day.

  In the contents described below, the action mechanism and advantageous effects of the drug in the present invention will be further described based on experiments.

one. Experimental materials and methods Experimental drugs: Takasago Sanshichiso water extract (1.3 g herbal medicine / ml), ethanol extract (2.6 g herbal medicine / ml), bifendate pills (Bifendate Pills, Guangzhou Star Cluster (Pharmaceuticals) Co., Ltd., lot Number JF40021).

  2. Animals: Animals are NIH mice, SPF grade, male, weighing 18-22 g. The test animal quality pass certificate number is 2006A051, the SPF class test animal environmental condition pass certificate number is 2006B023, and the SPF class test animal production pass certificate number is SCXK 粤 2011-0015. Animals were provided by the Southern Medical University Animal Experiment Center.

  3. Main chemical reagents and detection equipment: alanine aminotransferase (ALT) measurement reagent kit (Nakasei Kitaen Biological Technology Co., Ltd., lot number: 121881), aspartate aminotransferase (AST) measurement reagent kit (Nakasei Kitaenshi) Science Co., Ltd., lot number: 120921), carbon tetrachloride solution (analysis pure, Tianjin Fengning Precision Chemicals Co., Ltd., lot number: 11110), formaldehyde solution (analysis pure, lot number: 20111007, Guangdong Guanghua Technology Co., Ltd.) , Anhydrous ethanol (analysis pure, lot number: 2011416, Tianjin Shinfeng Chemical Co., Ltd.), xylene (analysis pure, lot number: 20101224, Guangdong Guanghua Chemical Co., Ltd.), hematoxylin (biological dye, lot number: 060408, Beijing Yasukuni Biological Technology Co., Ltd. imported by FLUKA and individually packaged Ones), Eosin Y (biological dye, lot number 20050912, China East China Normal University of Plant), ECHO LCD biochemical analyzer (Italy, AiYasushisha production). OLYMPUS AU5421 fully automated biochemical analyzer (manufactured by OLYMPUS, Japan), Japan OLYMPUS BH-2 fluorescence microscope (manufactured by OLYMPUS, Japan), BECKMAN ™ 30 cryogenic centrifuge (manufactured by BACKMAN, USA), LEICA RM2135 section Machine (manufactured by LEICA, Germany), SARTORIUS electronic balance (manufactured by SARTORIUS, Germany).

  4). Experimental methods and doses: Animals were normal control group, model group, bifendate group (0.2 g / kg), high water extract group (1.12 g / kg), medium extract group (0.56 g) / kg), water extract low dose group (0.28 g / kg), ethanol extract high dose group (1.12 g / kg), ethanol extract medium dose group (0.56 g / kg), ethanol extract low dose Divided into dose groups (0.28 g / kg), each group had 12 animals. Intragastric administration was performed once a day for 7 consecutive days. The normal control group and model group were administered the same volume of tap water intragastrically. The volume of intragastric administration was 0.25 ml / 10 g mouse, and the mice were allowed to eat food freely. One hour after the last intragastric administration, 0.12% (volume ratio) carbon tetrachloride (prepared with pure peanut oil) was injected intraperitoneally in an amount of 0.2 ml / animal. Sixteen hours after the fasting, the eyeballs were removed, collected, centrifuged, and serum was collected to measure glutamate pyruvate transaminase and glutamate oxaloacetate transaminase.

  5. Pathological examination: The left lobe of the liver was collected and fixed with neutral formalin, and then usually dehydrated, 4 μm sections were embedded in paraffin, HE stained, and pathology of liver tissue under an optical microscope. Changes were observed. The degree of liver tissue damage was divided from grade 0 to grade 4. Among them, grade 0 (−) has normal liver tissue structure, and there is no obvious degeneration, necrosis and infiltration of inflammatory cells. In the first grade (+), the structure of the hepatic lobule is still normal, and turbid swelling of some hepatocytes, air balloon degeneration or steatosis, and scattered punctate necrosis are observed. In the second grade (++), the structure of the hepatic lobule is unclear, clear necrotic necrosis is observed, and infiltration of inflammatory cells is accompanied. Class 3 (++++): The structure of the liver lobule is unclear, clear flaky necrosis is observed, and inflammatory cell infiltration is accompanied.

及び等級/頻度グラフの資料で示し、spss8.0統計ソフトウエアOne-Way ANOVA LSD又はDunnett T3法及びNonparametric Test ２ Independent Samples Test法を利用して、データ処理を行った。 6). Experimental data is

Data was processed using spss8.0 statistical software One-Way ANOVA LSD or Dunnett T3 method and Nonparametric Test 2 Independent Samples Test method.

two. Detection result Liver function detection results Table 1 shows the detection results of mouse serum glutamate pyruvate transaminase and glutamate oxaloacetate transaminase.

  From the results shown in Table 1, the serum glutamate pyruvate transaminase and glutamate oxaloacetate transaminase were significantly increased (P <0.01) in the model group as compared to the normal group. Serum glutamate pyruvate transaminase in the bifendate group was significantly reduced (P <0.01), and serum glutamate pyruvate transaminase and glutamate oxaloacetate transaminase in the high-dose group of Takasago Sanshichiso water extract and ethanol extract were Both were significantly reduced (P <0.05). It was found that glutamic acid oxaloacetic acid transaminase in the medium-dose group of Takasago Sansitoshi ethanol extract was significantly reduced (P <0.05).

2. Effects on acute histopathologic injury in liver-injured mice Based on the results of pathological sections, normal control mice showed normal liver tissue structure, and hepatocytes showed a radial array centered on the central vein. The arrangement of cell cords and hepatic sinusoids was regular. The structure of the hepatic lobule was complete, and some animals showed pathological changes such as mild swelling of the hepatocytes and punctate necrosis.
In the carbon tetrachloride model group of mice, the majority of hepatocytes are distributed around the central vein, showing turbid swelling, cytoplasmic looseness, and some cells exhibiting ballooning degeneration. It was. The hepatocytes distributed under the central vein of the liver lobule and under the liver capsule showed punctate, nest-like, and flaky necrosis, indicating pathological alterations such as inflammatory cell infiltration.
It was found that hepatocyte necrosis was clearly reduced (P <0.05) in the bifendate group and the high-dose group of Takasago Sansitoshi ethanol extract and water extract.
Takasago Sanshichisou ethanol extract The results, high dose group of the water extract is found that there is a protective effect against liver damage by CC1 ₄ intraperitoneal injection. The pathological examination results are shown in Table 2.

three. Results Summary this experiment experiments on mice acute liver damage CC1 _4, Takasago Sanshichisou ethanol extract, high dose group of water extract showed significant inhibitory effect. As an effect of the inhibitory action, it was observed that glutamate pyruvate transaminase and glutamate oxaloacetate transaminase were reduced and the degree of degeneration and necrosis of hepatocytes was also reduced.

Claims (5)

  The drug or health food treats hepatitis Takasago, which is a clinically accepted formulation manufactured by mixing Takasago Sitoshi extract with normal doses of medically acceptable excipients Application to drug or health food production.   The said Takasago Sanshichisou extract is a water extract or an ethanol extract, The application to the manufacturing of the food for medical treatment or health food of Takasago Sansitoshio of Claim 1 characterized by the above-mentioned.   In the method for producing the water extract, 8 to 12 times the amount of water is added to Takasago Sanshichiso, decocted for 1.5 to 2 hours, and 5 to 8 times the amount of water is further added to the resulting residue. 3. Application to the manufacture of a pharmaceutical for treating hepatitis of Takasago Sanshichiso according to claim 2, comprising decoction for 5 hours, combining the obtained extracts, filtering, and concentrating.   In the method for producing the ethanol extract, 8 to 12 times the amount of 75 to 90% ethanol is added to Takasago Sanshichiso, and reflux extraction is performed for 1.5 to 2 hours, and the obtained residue is further added to 75 to 90% times. The medicine for treating hepatitis of Takasago Sansitou according to claim 2, comprising adding an amount of water, decocting for 1 to 1.5 hours, combining the obtained extracts, filtering, recovering ethanol, and concentrating. Or application to health food production.   2. The pharmaceutical preparation for treating a hepatitis of Takasago Sanshichiso according to claim 1, wherein the preparation is a clinically recognized granule, capsule, tablet or oral solution.