AU2019100729A4 - Compound Composition of Sunflower Head and Coix Seed and Use Thereof in Treatment of Liver Injury - Google Patents
Compound Composition of Sunflower Head and Coix Seed and Use Thereof in Treatment of Liver Injury Download PDFInfo
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/899—Poaceae or Gramineae (Grass family), e.g. bamboo, corn or sugar cane
- A61K36/8994—Coix (Job's tears)
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/10—Preparation or pretreatment of starting material
- A61K2236/19—Preparation or pretreatment of starting material involving fermentation using yeast, bacteria or both; enzymatic treatment
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/333—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using mixed solvents, e.g. 70% EtOH
Abstract
Abstract The present invention provides a compound composition of sunflower head and coix seed and use thereof in the treatment of liver injury, wherein medicinal and edible sunflower head and coix seed are used to make up a compound preparation for treating liver injury. This solves the problem that currently available drugs have side effects and can not be used in a long-term medication. The synergistic action of the two components not only strengthens liver repair, but also promotes the discharge of liver metabolites. * e I *IV4# *4 & o Tw9 Ao * s9, e F Fig.56 , Fig.6
Description
Compound Composition of Sunflower Head and Coix Seed and Use Thereof in
Treatment of Liver Injury
Technical Field [0001] The present invention discloses a compound composition of sunflower head and coix seed, wherein sunflower head and coix seed are used to make up of a compound preparation. The compound composition has an obvious effect in the treatment of a liver injury disease and belongs to the field of traditional Chinese medicine pharmaceutical technology.
Background Art [0002] Drug-induced liver injury has gradually become a problem that can not be ignored in the medical and pharmaceutical fields. Drug-induced liver injury refers to liver function damage caused by the drug itself and its metabolites, or immune system damage due to hypersensitivity caused by its metabolites. Common drugs that are prone to cause drug-induced liver injury comprise antibiotics, anti-tuberculosis drugs, Chinese herbal medicines, antipyretic analgesics, halothane anesthetics, anti-tumour drugs and the like.
[0003] The development of existing drugs used for liver injury repair such as interferon and bicyclol has become a concern in the medical field. However, for the reasons such as price and adverse reactions, the popularization of such drugs have been limited to some extent. The research and development of the compound composition of medicinal and edible sunflower head and coix seed provides a good natural drug with no toxic or side effects.
[0004] The prior art closest to the present invention application, an earlier application CN 108354956 A by the present inventors, discloses “use of sunflower head extract and its active ingredients in preparation of a medicament for repairing damaged hepatocytes”, and states that “sunflower head extract and its active ingredients have good anti-inflammatory and repair effects on damaged hepatocytes caused by hyperuricemia”. However, during the actual use, patients experienced side effects such as joint pain, diarrhea, and low fever, affecting the therapeutic effect of
2019100729 03 Jul 2019 “sunflower head extract”.
Summary of the Invention [0005] The present invention provides a compound composition of sunflower head and coix seed, wherein medicinal and edible sunflower head and coix seed are used to make up a compound preparation for treating a liver injury disease. This solves the problem that currently available drugs used for treating liver injury have side effects and can not be used in a long-term medication. The present invention proves that coix seed can assist to enhance the ability of sunflower head extract to repair damaged liver cells, promote the discharge of liver toxins, and can also reduce the side effects caused by taking sunflower head extract alone. The two components have a good synergistic effect.
[0006] The present invention provides a compound composition of sunflower head and coix seed, wherein it is made of the following raw materials in parts by mass: sunflower head: 25-35 parts; and coix seed: 15-20 parts.
The present invention relates to a compound composition of sunflower head and coix seed, preferably in the following ratio:
sunflower head: 30 parts; and coix seed: 15 parts.
[0007] The present invention relates to a method for preparing the compound composition of sunflower head and coix seed, comprising the following steps:
step 1), taking 25-35 parts of sunflower head, and adding 20-fold by mass of deionized water; after soaking sufficiently, adding neutral protease with a mass fraction of 0.2% to perform enzymolysis under a pH of 6.0-7.0 at a temperature of 40-50°C for 2 hours, and then adjusting the pH to 8; and performing full reaction in a reactor at 45-50°C for 60 min to obtain a sunflower head extract;
step 2), taking 10-20 parts of coix seed, and adding 20-fold by mass of ethanol; soaking sufficiently for 2 h; and performing full reaction in a reactor at 45-50°C for 2 h to obtain a coix seed extract;
step 3), filtering an aqueous extract obtained in step 1) and performing rotary evaporation at 80-90°C to dryness to obtain a solid powder;
step 4), filtering an alcohol extract obtained in step 2) and performing rotary
2019100729 03 Jul 2019 evaporation at 55-60°C to dryness to obtain a solid powder; and step 5) mixing the solid powders from step 3) and step 4) uniformly at a mass ratio of 2 : 1, and dissolving in 2-fold distilled water to prepare a compound preparation.
[0008] The present invention relates to a compound composition of sunflower head and coix seed, which can be formulated into any pharmaceutical preparation in pharmacology.
[0009] The basis of the formulating prescription of the present invention is as follows:
the formulating prescription described in the present invention is based on the recordings about traditional Chinese medicines for treating liver injury and the modern Chinese medicine theory and is summarized by a large number of animal experiments and clinical cases.
[0010] The sources and efficacy of raw materials used in the present invention are as follows:
1. Sunflower head, a sweet medicinal material that is non-toxic and cold in property, targets the liver meridian; and according to “Chinese Materia Medica”, it has the functions of clearing away heat, freeing lung, relieving pain, and stopping bleeding, and is mainly used for headache and dizziness treatment, anti-inflammation, diuresis, liver protection and the like.
[0011] 2. Coix seed, with sweet and weak taste, slightly cold in property, has rich pharmacological functions such as invigorating spleen to remove dampness, clearing away heat and toxic materials, alleviating pain and diminishing inflammation, and tonifying spleen and supplementing qi.
[0012] Traditional Chinese medicine theory states that most liver diseases are related to pathogenic dampness invading the body. The present invention uses sunflower head to repair liver injury, and at the same time, utilizes the good dampness removing effect of coix seed to promote the excretion of liver metabolites by facilitating urination, thereby improving metabolic capacity, enhancing oxidation resistance, and prevents the imbalance and oxidation of purine to generate of uric acid. Sunflower head and coix seed work collaboratively to achieve the effects of
2019100729 03 Jul 2019 “expulsing pathogen and removing dampness, tonifying spleen and benefiting liver, invigorating spleen and facilitating urination, clearing away heat and toxins, alleviating pain and diminishing inflammation”, enhance the repair of liver injury, and promotes the excretion of liver metabolites through urine.
[0013] The positive effects and advantages of the present invention are as follows:
a compound preparation is made from sunflower head and coix seed, in which the coix seed can help to enhance the ability of sunflower head extract to repair damaged liver cells. The synergistic effect of the two not only strengthens liver repair ability, but also promotes the discharge of liver metabolites, thereby providing an overall comprehensive solution to the side effects existed such as joint pain, diarrhea, and fever when taking single sunflower head. Through animal experiments and clinical medical treatments, it is proved that the composition of sunflower head and coix seed can relieve liver injury, and can be used continuously in a long-term medication, so that the repair effect is improved and the previous concern about the side effects of single sunflower head is alleviated simultaneously.
Brief Description of the Drawings [0014] Figure 1 shows a liver tissue section of the blank control group;
Figure 2 shows a liver tissue section of the model group;
Figure 3 shows a liver tissue section of the positive control group;
Figure 4 shows a liver tissue section of the coix seed extract group;
Figure 5 shows a liver tissue section of the sunflower head extract group;
Figure 6 shows a liver tissue section of the sunflower head and coix seed composition group 1 of the present invention;
Figure 7 shows a liver tissue section of the sunflower head and coix seed composition group 2 of the present invention; and
Figure 8 shows a liver tissue section of the sunflower head and coix seed composition group 3 of the present invention.
Detailed Description of Embodiments [0015] In order to make a person skilled in the art better understand and implement
2019100729 03 Jul 2019 the technical solutions of the present invention, the present invention will be further described below in conjunction with specific experimental examples. However, the experimental examples are not intended to limit the present invention.
[0016] Example 1
Step 1) comprises: taking 25 kg of sunflower head, and pulverizing it to 30 mesh; adding 20-fold by mass of deionized water; after soaking sufficiently, adding neutral protease with a mass fraction of 0.2% to perform enzymolysis under a pH of 6.0-7.0 at a temperature of 40-50°C for 2 hours; fully stirring evenly and adjusting the pH to 8 with sodium hydroxide; and performing full reaction in a reactor at 45-50°C for 60 min to obtain a sunflower head extract;
step 2) comprises: taking 25 kg of coix seed, and pulverizing it to 30 mesh; adding 20-fold by mass of ethanol; soaking sufficiently for 2 h; and performing full reaction in a reactor at 45-50°C for 2 h to obtain a coix seed extract;
step 3) comprises: filtering an aqueous extract obtained in step 1) and performing rotary evaporation at 80-90°C to dryness to obtain a solid powder;
step 4) comprises: filtering an alcohol extract obtained in step 2) and performing rotary evaporation at 55-60°C to dryness to obtain a solid powder; and step 5) comprises mixing the solid powders from step 3) and step 4) uniformly at a mass ratio of 2 : 1, and dissolving in 2-fold distilled water to prepare a compound preparation.
[0017] Example 2
Step 1) comprises: taking 30 kg of sunflower head, and pulverizing it to 30 mesh; adding 20-fold by mass of deionized water; after soaking sufficiently, adding neutral protease with a mass fraction of 0.2% to perform enzymolysis under a pH of 6.0-7.0 at a temperature of 40-50°C for 2 hours; fully stirring evenly and adjusting the pH to 8 with sodium hydroxide; and performing full reaction in a reactor at 45-50°C for 60 min to obtain a sunflower head extract;
step 2) comprises: taking 20 kg of coix seed, and pulverizing it to 30 mesh; adding 20-fold by mass of ethanol; soaking sufficiently for 2 h; and performing full reaction in a reactor at 45-50°C for 2 h to obtain a coix seed extract;
step 3) comprises: filtering an aqueous extract obtained in step 1) and performing
2019100729 03 Jul 2019 rotary evaporation at 80-90°C to dryness to obtain a solid powder;
step 4) comprises: filtering an alcohol extract obtained in step 2) and performing rotary evaporation at 55-60°C to dryness to obtain a solid powder; and step 5) comprises mixing the solid powders from step 3) and step 4) uniformly at a mass ratio of 2 : 1, and dissolving in 2-fold distilled water to prepare a compound preparation.
[0018] Example 3
Step 1) comprises: taking 35 kg of sunflower head, and pulverizing it to 30 mesh; adding 20-fold by mass of deionized water; after soaking sufficiently, adding neutral protease with a mass fraction of 0.2% to perform enzymolysis under a pH of 6.0-7.0 at a temperature of 40-50°C for 2 hours; fully stirring evenly and adjusting the pH to 8 with sodium hydroxide; and performing full reaction in a reactor at 45-50°C for 60 min to obtain a sunflower head extract;
step 2) comprises: taking 15 kg of coix seed, and pulverizing it to 30 mesh; adding 20-fold by mass of ethanol; soaking sufficiently for 2 h; and performing full reaction in a reactor at 45-50°C for 2 h to obtain a coix seed extract;
step 3) comprises: filtering an aqueous extract obtained in step 1) and performing rotary evaporation at 80-90°C to dryness to obtain a solid powder;
step 4) comprises: filtering an alcohol extract obtained in step 2) and performing rotary evaporation at 55-60°C to dryness to obtain a solid powder; and step 5) comprises: mixing the solid powders from step 3) and step 4) uniformly at a mass ratio of 2 : 1, and dissolving in 2-fold distilled water to prepare a compound preparation.
[0019] I. The following anti-inflammation experiment at cell level was conducted to prove that sunflower head and coix seed extracts have a certain anti-inflammatory effect, and the composition of the two components has a synergistic effect in term of anti-inflammation:
1. Experiment reagents Medium 1640 | Hyclone Company, US; |
Fetal bovine serum | Kangyuan Biotechnology Company; |
Cell culture plate | NEB Company, UK; |
2019100729 03 Jul 2019
RAW264. 7 cells (mouse macrophages) Nanjing KeyGEN BioTECH Co.,
Ltd.;
NO Elisa kit Bestgene Biotechnology Co., Ltd.;
LPS Sigma Company, US;
2. Applying the drug to RAW264.7 cells and detecting the anti-inflammatory effect by the NO level:
(1) RAW264.7 cells were cultured in RPMI medium 1640 containing 10% serum, subcultured after the cells grew to a certain amount, and then cryopreserved;
(2) RAW264.7 cells in logarithmic growth phase were transferred into a 24-well plate, 30,000 cells per well, and cultured in RPMI medium 1640 containing 10% serum (500 μΐ volume per well) for 1 hour;
(3) as required by the experiment, 200 μΐ of each of 30 mg/ml Ganshuang granules, 60 mg/ml sunflower head extract granules, and each solution formulated by the compositions prepared in Example 1, Example 2 and Example 3, respectively, were added into the corresponding wells, and culture was continued for 3 hours;
(4) LPS at a final concentration of 1 pg/ml was added to each well of the LPS control group and the reaction time was 18 hours; and (5) the NO kit was taken out of the 4°C refrigerator and left at room temperature for 15-30 minutes, and subsequent operations were performed in accordance with the kit instruction;
3. Detection of NO secretion amount:
(1) Sample preparation: 50 μΐ of the culture medium supernatant of the cells stimulated by the addition of the drug was pipetted;
(2) Sample loading: blank wells (there were no sample or enzyme immunoassay reagent added to the blank control wells), standard wells, and test wells were provided respectively. 50 μΐ of standard sample was added to a standard well accurately, and 50 μΐ of test sample was added to a test well. The samples were added to the bottom of the ELISA plate without touching the wall of the wells as far as possible, and were gently shaken well;
(3) Incubation: the plate was sealed with a sealing membrane, and then incubated at 37°C for 30 min;
2019100729 03 Jul 2019 (4) Fluid preparation: a 30-fold concentrated washing liquid was 30x diluted with distilled water for subsequent use;
(5) Washing: the sealing membrane was peeled off carefully, the liquid was discarded, and the plate was spin-dried; each well was filled with a washing liquid; after standing for 30s, the liquid was discarded, and this process was repeated 5 times; and the plate was patted dry;
(6) Enzyme loading: 50 μΐ of enzyme immunoassay reagent was added to each well, except for blank wells;
(7) Incubation: the plate was sealed with a sealing membrane, and then incubated at 37°C for 30 min;
(8) Washing: the sealing membrane was peeled off carefully, the liquid was discarded, and the plate was spin-dried; each well was filled with a washing liquid; after standing for 30s, the liquid was discarded, and this process was repeated 5 times; and the plate was patted dry;
(9) Colour development: 50 μΐ of colour developing agent A was added to each well, then 50 μΐ of colour developing agent B was added; and the plate was gently shaken well and protected from light to perform colour development at 37°C for 15 min;
(10) Stopping: 50 μΐ of a stop solution was added to each well to stop the reaction (the colour turns from blue to yellow immediately at the moment); and (11) Detection: the blank well was used for zeroing, and the absorbance (OD value) of each well was measured at a wavelength of 450 nm; and the detection should be carried out within 15 min after adding the stop solution;
4. Experiment results
Table 1. Comparison of NO inhibition rate of each drug group on RAW264.7 cells:
Drugs (1 mg/ml) | NO concentration (pg/ml) | Inhibition rate (%) |
Negative control | 397.42 | |
Coix seed extract | 350.12 | 11.9 |
Sunflower head extract | 307.14 | 22.7 |
Example 1 | 264.28 | 33.5 |
Example 2 | 257.43 | 35.2 |
2019100729 03 Jul 2019
Example 3 | 236.55 | 40.5 |
Conclusion: The in vitro cell experiment showed that when RAW264.7 cells were used and NO concentration was detected to calculate the anti-inflammatory effect of the drugs, and when the concentration of the drug solution in each group is 1.0 mg/ml, the anti-inflammatory effect were as follows: Example 3 > Example 2 > Example 1 > sunflower head extract > coix seed extract. The data showed that among all the drugs, Example 3 has the best anti-inflammatory effect. Meanwhile, the experiment also showed that the single use of coix seed extract or sunflower head extract also had a certain anti-inflammatory effect, but the combination of the two had a significantly increased anti-inflammatory effect, indicating that the two components had a good synergistic effect when being used together at a certain ratio.
[0020] II. An animal experiment was used below to further verify the repair effect of the present invention on liver injury due to various causes:
(I) Repair of liver injury caused by a disease (hyperuricemia)
1. Experiment animals
Kunming mice of SPF grade, with a body mass of 20 ± 2 g, purchased from Liaoning Changsheng Biotechnology Co., Ltd.
[0021] 2. Experiment reagents
Yeast extract (Oxiod Company, UK);
Ganshuang Granules, lot number: Z20027671, Baoding Tianhao Pharmaceuticals Co., Ltd.;
coix seed extract;
sunflower head extract;
the sunflower head and coix seed composition obtained in Example 1; the sunflower head and coix seed composition obtained in Example 2; the sunflower head and coix seed composition obtained in Example 3;
3. Modelling and administration method
The mice were weighed before the study, 10 of which were used as the blank control group, and the remaining mice were used as the hyperuricemia model group. The mice were weighed every morning during the experiment. The model was established by intragastric administration of yeast extract, which increased UA value
2019100729 03 Jul 2019 and disturbed purine metabolism by administration of a large amount of purine substances, so that the blood UA value was temporarily increased in a short time. 80 mice were randomly divided into 8 groups (10 mice per group), i.e., blank control group, model group, positive control (Ganshuang granules) group, coix seed extract group, sunflower head extract group, and Example 1 group, Example 2 group, and Example 3 group, respectively. During the process of modelling, except for the blank control group (intragastric administration of an equal volume of water), mice in each of other groups received intragastric administration of 20 g’kg ' yeast extract every day, once a day, and the intragastric administration was continued for 20 d. Since day 9, intragastric administration of 200 μΙ/d drug was performed at the same time until the end of the experiment. Liver tissues were taken from the mice, made into liver tissue sections, and stained with HE. The changes of the tissue sections were observed under a microscope. (Figures 1-7)
4. Experiment results
The results of the liver tissue sections were shown in Figures 1-8. In the blank control group (Figure 1), the hepatocytes and hepatocyte cords in the hepatic lobule were clear, and hepatocyte cytoplasm was full. In the model group (Figure 2), hepatocytes and hepatocyte cords in partial hepatic lobules were not clear; and hepatocyte atrophy was commonly seen with scattered inflammatory cell infiltration lesions and punctate necrosis lesions, occasionally cavitated and lightly dyed hepatocytes around the central vein were seen, and great damage to hepatocytes was caused, indicating that modelling was successful. In the positive drug control group (Figure 3), the hepatocytes and hepatocyte cords in the hepatic lobules were clear, and scattered necrosis lesions and inflammatory cell infiltration were occasionally seen. In the coix seed extract group (Figure 4), scattered punctate necrosis lesions and eosinophilic changes were occasionally seen. In the sunflower head extract group (Figure 5), eosinophilic changes were occasionally seen, showing a certain repair effect on hepatocytes. In the Example 1 group, the Example 2 group, and the Example 3 group (Figures 6-8), hepatocytes and hepatocyte cords in the hepatic lobules were clear, and hepatocyte cytoplasm was full. The microscopic structure suggested that the sunflower head and coix seed composition has a better effect than the single
2019100729 03 Jul 2019 preparation of sunflower head and has a better repair effect on damaged hepatocytes, among which the Example 3 group has the best effect.
[0022] (II) Repair of drug-induced liver injury
1. Experiment animals
Kunming mice of SPF grade, with a body mass of 20 ± 2 g, purchased from the Animal Experiment Centre of the First Hospital of Jilin University;
2. Experiment reagents
Carbon tetrachloride, lot number: 10006428, Sinopharm Chemical Reagent Co., Ltd.;
Ganshuang Granules, lot number: Z20027671, Baoding Tianhao Pharmaceuticals Co., Ltd.;
3. Experimental modelling and administration method mice were randomly divided into 8 groups, i.e., blank control group, model group, positive control group, coix seed extract group, sunflower head extract group, sunflower head and coix seed composition group 1, sunflower head and coix seed compound group 2, and sunflower head and coix seed composition group 3, respectively. Each group had 10 mice. The blank control group received normal daily diet and water, while the remaining groups received an intraperitoneal injection of 0.5% CCL4 injection every three days at an injection dose of 10 μΐ/g. Except for the blank control group, each experimental group received intragastrical administration of drugs at a dose of 200 μΐ/mouse every day, and the experiment was performed for six weeks. At the end of the experiment, blood was taken from the orbit of the mice, and aspartate aminotransferase (AST) content and alanine aminotransferase (ALT) content in the serum were determined.
[0023] Table 2. Changes in the serum aspartate aminotransferase level in each experimental group: (U/L)
Group | Administration dosage | AST (U/L) |
Blank control | Distilled water 200 μΐ/mouse | 30.71 ±5.16** |
Model group | Distilled water 200 μΐ/mouse | 80.16 ±6.74 |
Positive drug group | Ganshuang Granules 200 μΐ/mouse | 45.62 ±3.87* |
2019100729 03 Jul 2019
Coix seed extract | Drug obtained in step 2 of Example 3 200 μΐ/mouse | 47.94 ± 2.34* |
Sunflower head extract group | Sunflower head extract granules 200 μΐ/mouse | 42.15± 1.34* |
Example 1 group | Composition 1 drug 200 μΐ/mouse | 38.36 + 3.31* |
Example 2 group | Composition 2 drug 200 μΐ/mouse | 35.64 + 2.97** |
Example 3 group | Composition 3 drug 200 μΐ/mouse | 33.20 + 2.12** |
Note: compared with the model group, *P < 0.05, **P < 0.01.
[0024] Conclusion: as can be seen from Table 2, compared with the blank control group, the serum AST level of the model group was increased significantly (**P < 0.01), indicating that the drug caused a serious damage to liver, resulting in abnormal elevation of AST level; compared with the model group, all the example groups of the present invention had decreased serum AST level (*P < 0.05, **P < 0.01), in which the AST level decreasing effect was as follows: Example 3 > Example 2 > Example 1 > sunflower head extract > positive drug > coix seed extract, indicating that both of the sunflower head and coix seed used in the invention had a certain repair effect on drug-induced liver injury, and the effect of the combination of the two components was more obvious, and the AST level of Example 3 group was already close to a normal value, indicating that the combined action of sunflower head and coix seed had a synergistic effect and had a better repair effect on liver.
[0025] Table 3. Changes in the serum alanine aminotransferase level in each experimental group: (U/L)
Group | Administration dosage | ALT (U/L) |
Blank control | Distilled water 200 μΐ/mouse | 15.71+2.12** |
Model group | Distilled water 200 μΐ/mouse | 98.16+1.98 |
Positive drug group | Ganshuang Granules 200 μΐ/mouse | 42.67 + 4.16* |
Coix seed extract | Drug obtained in step 2 of Example 3 200 μΐ/mouse | 47.23 ± 2.28* |
Sunflower head extract group | Sunflower head extract granules 200 μΐ/mouse | 35.73 + 4.46* |
Example 1 group | Composition 1 drug 200 μΐ/mouse | 25.19+ 1.92* |
Example 2 group | Composition 2 drug 200 μΐ/mouse | 22.96 + 3.62** |
Example 3 group | Composition 3 drug 200 μΐ/mouse | 19.85 + 3.17** |
2019100729 03 Jul 2019
Note: compared with the model group, *P < 0.05, **P < 0.01.
[0026] Conclusion: as can be seen from Table 3, compared with the blank control group, the serum ALT level of the model group was increased significantly (**P < 0.01), indicating that the drug caused a serious damage to liver, resulting in abnormal elevation of ALT level; compared with the model group, all the administration groups of the present invention had decreased serum ALT level (*P < 0.05, **P < 0.01), in which the AST level decreasing effect was as follows: Example 3 > Example 2 > Example 1 > sunflower head extract > positive drug> coix seed extract, indicating that both of the sunflower head and coix seed used in the invention had a certain repair effect on drug-induced liver injury, and the effect of the combination of the two components was more obvious, and the ALT level of Example 3 group was already close to a normal value, indicating that the combined action of sunflower head and coix seed had a synergistic effect and had a better repair effect on liver.
[0027] (III) The repair effect on acute alcoholic liver injury in mice
1. Experiment animals
Kunming male mice of SPF grade, with a body mass of 20 ± 2 g, purchased from the Animal Experiment Centre of the First Hospital of Jilin University.
[0028] 2. Experiment reagents
Red Star Erguotou (56°);
Ganshuang Granules, lot number: Z20027671, Baoding Tianhao Pharmaceuticals Co., Ltd.;
coix seed extract;
sunflower head extract;
the sunflower head and coix seed composition obtained in Example 1; the sunflower head and coix seed composition obtained in Example 2; the sunflower head and coix seed composition obtained in Example 3;
3. Experimental modelling and administration method
After 5 d of normal feeding, the mice received routine irradiation of sunlight and were randomly divided into blank control group, model group, positive control group, coix seed extract group, sunflower head extract group, Example 1 group, Example 2 group, and Example 3 group, 10 mice per group. The mice in the blank control group
2019100729 03 Jul 2019 and the model group received intragastrical administration of normal saline every day, while the remaining experimental groups received intragastrical administration of drugs at the same dose (200 μΙ/L), and the intragastric administration was continued for 20 d. 2 h after the last administration, except for that the normal control groups received intragastrical administration of the same amount of normal saline, each of other groups received intragastrical administration of Red Star Erguotou (56°) at a dose of 15 ml/kg every day. Each group was fasted but was allowed to drink water after the last dose. After being fasted for 16 h, eyeballs were enucleated and blood was taken in each group, and serum was separated for testing;
Table 4. Detection of biochemical indicators, i.e., serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels in the mice:
Group | Administration dosage | AST (U/L) | ALT (U/L) |
Blank control | Distilled water 200 μΐ/mouse | 20.53 ± | 33.95 ±5.63** |
Model group | Distilled water 200 μΐ/mouse | 93.06 ±7.31 | 117.36 ±2.41 |
Positive drug group | Ganshuang Granules 200 μΐ/mouse | 60.63 ±2.65 | 84.10 ±3.67 |
Coix seed extract | Drug obtained in step 2 of Example 3 200 μΐ/mouse | 71.25 ± 1.46 | 93.29 ±4.51 |
Sunflower head extract group | Sunflower head extract granules 200 μΐ/mouse | 58.31 ±2.98 | 74.36 ± 1.20 |
Example 1 group | Composition 1 drug 200 ul/mouse | 46.19 ±3.17* | 63.15 ± 1.79* |
Example 2 group | Composition 2 drug 200 μΐ/mouse | 41.74 ± 1.96* | 57.16 ±3.25* |
Example 3 group | Composition 3 drug 200 μΐ/mouse | 33.23 ± 1.09** | 45.58 ±2.07** |
Note: compared with the model group, *P < 0.05, **P < 0.01.
[0029] As can be seen from Table 4, compared with the blank control group, the serum AST level and ALT level of the model group was increased significantly (**P < 0.01); compared with the model group, all the Example groups 1-3 of the present invention had significantly decreased serum ALT level (*P < 0.05, **P < 0.01), in which the AST and ALT level decreasing effect was as follows: Example 3 > Example
2019100729 03 Jul 2019 > Example 1 > sunflower head extract > positive drug > coix seed extract, and the Example 3 group has a more obvious decreasing trend than the coix seed extract group, indicating that both of the sunflower head and coix seed used in the invention had a certain repair effect on drug-induced liver injury, and the effect of the combination of the two components was more obvious, and the AST level and ALT level of Example 3 group were already close to a normal value, indicating that the combined action of sunflower head and coix seed had a synergistic effect and had a better repair effect on acute alcoholic liver injury.
[0030] Conclusion: the present invention provides the application of the compound extract of sunflower head and coix seed in the repair of liver injury due to various causes, and it is proved through experiment that the compound extract have a good anti-inflammatory effect and a good repair effect on damaged liver cells, as well as a good decreasing effect on abnormally increased AST level and ALT level. The combined use of sunflower head and coix seed was more effective than the use of either of the two alone, indicating that the two components have a certain synergistic effect and can enhance the repair of damaged liver. Moreover, sunflower head and coix seed are medicinal and edible raw materials which are natural materials with no toxic or side effects, and the combined use of the two components provides an effective method for long-term medication to repair damaged hepatocytes.
[0031] ΙΠ. The following typical cases further demonstrate the medical efficacy of the present invention
Case 1
Patient Li, male, 54 years old, suffered from gout one year ago, with the symptoms of pain, redness and swelling in the toe joints. His blood uric acid value was tested to be 685 μιηοΙ/L in the local hospital. After taking a single sunflower head extract for three months, his blood uric acid value was decreased to 400 gmol/L, and his joint swelling got relieved greatly. However, during medication, he continuously had the symptoms of low fever. It was considered that the patient had been sick for a long time and had become weak, had spleen and stomach disorders, and had dampness, heat, pathogen and toxins that could not be discharged. After a change to taking the compound composition of the present invention for two weeks, his blood uric acid
2019100729 03 Jul 2019 value was dropped to 382 μιηοΙ/ L, indicating that blood uric acid was decreased at a faster pace, and the swelling of the toe joint was relieved, the symptom of low fever was also resolved, and there was no relapse after termination of medication for half a year.
Case 2
Patient Zhou, male, 37 years old, had hyperuricemia with blood uric acid value of 871 μιηοΙ/L, and was complicated with joint calculus. After taking a single sunflower head extract for two months, his uric acid value was stabilized to be 420 μιηοΙ/L, complicated with manifestations of redness, swelling and pain of joints. It was considered that the patient had been sick for a long time and had reduced liver and kidney metabolic function, and had damp-heat and turbid-heat that could not be discharged. After dissolution of joint calculus, the metabolites which could not be quickly excreted through the kidney caused local inflammation accumulation. After a change to taking the compound composition of the present invention for 15 days, his blood uric acid value was decreased to 392 μιηοΙ/L, and joint swelling and pain disappeared. After continuing the medication for two weeks, the blood uric acid value was stabilized at 370 μιηοΙ/L, renal excretion was strengthened, urinary metabolism was increased while joint pain was alleviated, and there was no relapse after termination of the medication for three months.
Case 3
Patient Qin, male, 40 years old, had hyperuricemia with blood uric acid value of 769 μιηοΙ/L. During taking a single sunflower head extract for one month, he developed symptoms of diarrhea and low fever, and blood uric acid value was decreased to 405 μιηοΙ/L. It was considered that the patient had reduced liver and kidney functions caused by long term hyperuricemia, and had dampness and heat that could not be discharged. Traditional Chinese medicine for invigorating spleen and facilitating dampness and harmful waste removal was prescribed. After a change to taking the compound composition of the present invention, his blood uric acid value was decreased to about 350 μιηοΙ/L after one week of medication. After continuing for another two weeks, the medication was stopped, his blood uric acid value was stable with no relapse, and the symptoms of diarrhea and low fever was resolved.
Claims (5)
- Claims1. A compound composition of sunflower head and coix seed, wherein it is made of the following raw materials in parts by mass:sunflower head: 25-35 parts; and coix seed: 15-25 parts.
- 2. The compound composition of sunflower head and coix seed according to claim 1, preferably in the following ratio:sunflower head: 35 parts; and coix seed: 15 parts.
- 3. A method for preparing the compound composition of sunflower head and coix seed according to claim 1 or claim 2, comprising the following steps:step 1), taking 25-35 parts of sunflower head, and pulverizing it to 30 mesh; adding 20-fold by mass of deionized water; after soaking sufficiently, adding neutral protease with a mass fraction of 0.2% to perform enzymolysis under a pH of 6.0-7.0 at a temperature of 40-50°C for 2 hours; fully stirring evenly and adjusting the pH to 8.0 with sodium hydroxide; and performing full reaction in a reactor at 45-50°C for 60 min to obtain a sunflower head extract;step 2), taking 15-25 parts of coix seed, and pulverizing it to 30 mesh; adding 20-fold by mass of ethanol; soaking sufficiently for 2 h; and performing full reaction in a reactor at 45-50°C for 2 h to obtain a coix seed extract;step 3), filtering an aqueous extract obtained in step 1) and performing rotary evaporation at 80-90°C to obtain a solid powder;step 4), filtering an alcohol extract obtained in step 2) and performing rotary evaporation at 55-60°C to obtain a solid powder; and step 5) mixing the solid powders from step 3) and step 4) uniformly at a mass ratio of 2 : 1, and dissolving in 2-fold distilled water to prepare a compound preparation.
- 4. Use of the compound composition of sunflower head and coix seed according to claim 1 in the preparation of a drug used for liver injury.
- 5. The compound composition of sunflower head and coix seed according to claim 1 or claim 2, wherein the compound composition can be formulated into any pharmaceutical preparation in pharmacology.
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CN109833443B (en) * | 2019-04-12 | 2021-07-27 | 中国农业科学院特产研究所 | Composite sunflower disc composition for reducing uric acid and relieving gout as well as preparation method and application thereof |
CN110327434A (en) * | 2019-08-14 | 2019-10-15 | 吉林省特医食品生物科技有限公司 | A kind of Chinese medicine composition that treating gout, compound Chinese medicinal preparation and preparation method thereof |
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