CN103479972B - A kind of for antioxidative composition and method of making the same and purposes - Google Patents
A kind of for antioxidative composition and method of making the same and purposes Download PDFInfo
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Abstract
The invention discloses a kind of for antioxidative compositions, it is the preparation be prepared from by following raw material: Rhizoma Polygoni Cuspidati extract, Rhizoma Curcumae Longae extract, green tea extract, alpha-lipoic acid and coenzyme Q10.The invention also discloses preparation method and the purposes of foregoing.Rhizoma Polygoni Cuspidati extract, Rhizoma Curcumae Longae extract, green tea extract, alpha-lipoic acid, coenzyme Q10 combinationally use by the present invention, have obvious antioxidation, effectively can suppress the generation of oxygen-derived free radicals, can be used for treating and/or preventing ischemical reperfusion injury.
Description
Technical field
The present invention relates to a kind of for antioxidative compositions.
Background technology
The material that oxygen produces chemical property active by one-electron reduction is in vivo called active oxygen, comprises Superoxide radical anion, hydrogen peroxide and hydroxyl radical free radical etc.Oxygen-derived free radicals can with DNA, protein and polybasic unsaturated fatty acid effect, cause DNA chain interruption and oxidative damage, albumen and albumen and crosslinked and lipid peroxidation occur between albumen and DNA.Lipid peroxidation is the main cause causing organism oxidative damage.Lipid peroxidation causes the destruction of biofilm structure and function, thus causes a series of chronic diseases such as cancer, aging, cardiovascular disease.Therefore, antioxidation has extremely important effect to health, day by day causes the concern of people.
Rhizoma Polygoni Cuspidati is rhizome and the root of polygonaceae plant Rhizoma Polygoni Cuspidati.The main chemical compositions of Rhizoma Polygoni Cuspidati has: dissociated anthraquinone and anthraquinone glycoside, is mainly emodin, physcione, chrysophanol, anthra-glucoside, fallacinol etc.; Stilbene compound, as resveratrol, polydatin; Protocatechuic acid etc.Resveratrol is a kind of active skull cap components, and it can with free state (cis, trans) and glucosides combined state (cis, trans) 2 kinds of form distributions in vegetable drug (Rhizoma Polygoni Cuspidati), and wherein the biological activity of transisomer is better than cis.Great many of experiments shows; resveratrol has stronger antioxidation; obviously can reduce the mda content in tissue; improve superoxide dismutase, catalase, activity of glutathione peroxidase; protective effect (Xue Lan is had to body ischemia and tissue injury; pharmacological research progress [J] of Polygonum cuspidatum Sieb. et Zucc. CHINA JOURNAL OF CHINESE MATERIA MEDICA, 2000,25 (11): 651-653.).
Rhizoma Curcumae Longae is the dry rhizome of zingiberaceous plant Rhizoma Curcumae Longae.The active component of isolated Rhizoma Curcumae Longae has kind more than 40, is mainly volatile oil and curcumin.Wherein curcumin is the main active composition of Turmeric.Curcumin energy scavenging activated oxygen and play antioxidant activity.Curcumin can improve rat heart muscle hypoxia-bearing capability; to the ischemia injury of rat heart muscle, there is certain protective effect; and infer that this effect may be main relevant with the activity of free radical resisting; in addition; its stabilizing cell membrane, raising superoxide dismutase activity etc. may also play a role (Han Ting etc., the chemical composition of Rhizoma Curcumae Longae and pharmacology activity research progress [J]. PLA's Acta Pharmaceutica Sinica; 2001,17 (2): 95-97).
Green tea is without the tea made that ferments, the more natural materials remaining fresh leaf.Tea polyphenols (teatolyphenols) is the main active of green tea drug effect, accounts for the 15%-20% of dry weight of tea leaves, and its key component is catechin (catechins).Tea polyphenols has eliminates the biological activity such as free radical, antioxidation, antibacterial, antiviral, prevention and cure of cardiovascular disease, to protect the liver etc. in have good effect.Experimentation proves, tea polyphenols can obviously alleviate hepatic injury that CCl4 and ethanol etc. causes (Rao Guangyu etc., the protective effect [J] of Tea Polyphenol on experimental liver injury in mice. CHINA JOURNAL OF CHINESE MATERIA MEDICA, 2001,26 (3): 191-193; Zhou Xiaorong etc., green tea polyphenol is to the therapeutical effect [J] of experimental alcoholic liver injury in rats. and world Chinese digests magazine, and 2006,14 (1): 51-56.).
Alpha-lipoic acid (Alpha Lipoic Acid) is a kind of material of not only having had water solublity but also a fat-soluble vitamins of tool.Alpha-lipoic acid contains two sulfur five-membered ring structure, and electron density is very high, has significant electrophilicity and the ability with radical reaction; therefore it has non-oxidizability; in addition, the sulfydryl of thioctic acid is easy to carry out redox reaction, therefore sulfydryl enzyme can be protected from the murder by poisoning of heavy metal ion.Have experimentation to confirm, alpha-lipoic acid is to hepatic ischemia-reperfusion injury and CCl
4caused acute liver have obvious protective effect (the neat Song rising sun etc., the experimentation of alpha-lipoic acid Preconditioning On Liver Ischemia Reperfusion In Jury In Rat. China and foreign countries' medical research, 29 phases in 2011; Yang Guoyu etc., alpha-lipoic acid causes the protective effect of acute liver to CCl4. veterinary drug and feed additive, 6 phases in 2002).
Coenzyme Q10 has another name called coenzyme, ubiquinone, is a kind of fat-soluble quinones, extensively exists in animals and plants, microbial cell.Coenzyme Q10, as the important hydrogen carrier in respiratory chain, is the important factor of the generation of biological cell energy and cellular metabolism.Coenzyme Q10 is one of most important antioxidant in organism; energy scavenging free radicals; prevent the macromolecular substances such as protein, lipid, DNA oxidized; the antioxidant capacity of tocopherol can also be made to strengthen (Sang Yanshuan etc.; the biochemical action mechanism of coenzyme Q10 and clinical drug application progress [J]. Chinese Medicine guide; 2005,7 (5): 371-373; Siemieniuk E, et al.CoenzymeQ10:its biosynthesis and biological significance in animal organisms and inhumans.Postepy Hig Med Dosw, 2005,18 (59): 150-159).
Now have no and the cooperation of Rhizoma Polygoni Cuspidati extract, Rhizoma Curcumae Longae extract, green tea extract, alpha-lipoic acid and coenzyme Q10 is used for antioxidative report.
Summary of the invention
The object of this invention is to provide one for antioxidative compositions.Another object of the present invention there is provided preparation method and the purposes of said composition.
Antioxidative compositions of the present invention is the preparation be prepared from containing following raw material: Rhizoma Polygoni Cuspidati extract, Rhizoma Curcumae Longae extract, green tea extract, alpha-lipoic acid and coenzyme Q10.
Preferably, described compositions is the preparation that the raw material containing following weight proportioning is prepared from:
Rhizoma Polygoni Cuspidati extract 2 ~ 12 parts, Rhizoma Curcumae Longae extract 1 ~ 8 part, green tea extract 1 ~ 5 part, alpha-lipoic acid 1 part, coenzyme Q10 1 part.
More a step is preferably, and it is the preparation be prepared from by the raw material of following weight proportioning:
Rhizoma Polygoni Cuspidati extract 5 parts, Rhizoma Curcumae Longae extract 4 parts, green tea extract 4 parts, alpha-lipoic acid 1 part, coenzyme Q10 1 part.
In described Rhizoma Polygoni Cuspidati extract, Resveratrol content is 15 ~ 68%w/w; In described Rhizoma Curcumae Longae extract, curcumin content is 4 ~ 35%w/w; Green tea extract medium green polyphenol content is 10 ~ 40%w/w.
Wherein, in described Rhizoma Polygoni Cuspidati extract, Resveratrol content is 50%(w/w); In described Rhizoma Curcumae Longae extract, curcumin content is 20%(w/w); Green tea extract medium green polyphenol content is 40%(w/w); Alpha-lipoic acid purity >=98%, described coenzyme Q10 purity >=98%.
The present composition is active component by Rhizoma Polygoni Cuspidati extract, Rhizoma Curcumae Longae extract, green tea extract, alpha-lipoic acid, coenzyme Q10, adds the preparation that in pharmacy or food, acceptable adjuvant or complementary composition are prepared from.
Wherein, described preparation is oral formulations, comprises microemulsion oral agent, capsule, soft capsule, tablet or pill.
Present invention also offers a kind of method preparing described compositions, it comprises the steps:
A, according to aforementioned weight proportioning, take each raw material;
B, add that in pharmacy or food, acceptable adjuvant or complementary composition are prepared into conventional preparation.
Present invention also offers described compositions and prepare the purposes in anti-oxidation medicine or health food.
Wherein, described medicine or health food are the medicine or the health food that treat and/or prevent ischemical reperfusion injury.Preferably, described medicine or health food treat and/or prevent medicine or the health food of myocardial ischemia reperfusion injury.
Ischemical reperfusion injury: recover blood flow on the basis of ischemia after, the histoorgan damaged that excessive free radicals causes.
Rhizoma Polygoni Cuspidati extract, Rhizoma Curcumae Longae extract, green tea extract, alpha-lipoic acid, coenzyme Q10 are that active ingredient combinations uses by the present invention, and have obvious antioxidation, can be used for the oxidative damage for the treatment of and prevention ischemia-reperfusion causes, potential applicability in clinical practice is good.
Obviously, according to foregoing of the present invention, according to ordinary technical knowledge and the customary means of this area, not departing under the present invention's above-mentioned basic fundamental thought prerequisite, the amendment of other various ways, replacement or change can also be made.
The detailed description of the invention of form by the following examples, is described in further detail foregoing of the present invention again.But this should be interpreted as that the scope of the above-mentioned theme of the present invention is only limitted to following example.All technology realized based on foregoing of the present invention all belong to scope of the present invention.
Accompanying drawing explanation
Fig. 1 embodiment 1 prepares the grain size distribution of microemulsion
HUVECs cell dihydro second ingot coloration result after Fig. 2 compositions and each one-component process
HUVECs cell dihydro second ingot coloration result after each example composition process of Fig. 3
Fig. 4 left ventricular systolic pressure recovery rate
Creatine kinase mb emission levels in Fig. 5 venous plasma
Detailed description of the invention
Experiment material:
Rhizoma Polygoni Cuspidati extract, purchased from Rayleigh, Xi'an bio tech ltd, wherein Resveratrol content is 50%(w/w);
Rhizoma Curcumae Longae extract, purchased from Rayleigh, Xi'an bio tech ltd, wherein curcumin content is 20%(w/w);
Green tea extract, according to Jiang Li, Different Extraction Method is on the impact of tea polyphenols physicochemical property, Food Science, 2010, the ultrasonic extraction described in 31 (14): 136-139 extracts, and concrete grammar is: take a certain amount of Folium Camelliae sinensis, pulverize, add distilled water by solid-to-liquid ratio 20:1ml/g, adjust pH to 5.0, adding cellulase to final concentration is 200U/g, reaction temperature is 40 DEG C, carry out supersound extraction 20 ~ 30min with 600W ultrasonic power, concentrated extracting solution, obtain green tea extract, wherein, green tea polyphenol content is 40%(w/w);
Alpha-lipoic acid purchased from Xi'an Jin Lv biotechnology company limited, purity >=98%;
Coenzyme Q10 purchased from Xi'an Jin Lv biotechnology company limited, purity >=98%.
Embodiment 1: the preparation of microemulsion of the present invention
Compositions proportioning: (content in every 100mL microemulsion)
By aforementioned proportion mixture 24g, first add the PEG400 of 100ml, mixing, add 200ml soybean oil, in 70 DEG C of constant temperature stirring and evenly mixings, then add 60ml polyoxyethylene sorbitan monoleate, 50ml glycerol with the water of, 1500ml, oil phase is stirred to obtain again in 70 DEG C of constant temperature, then stir and at the uniform velocity instilled in suitable quantity of water by oil phase, obtain microemulsion formulation by emulsion dispersion, the adjustment final volume that adds water is to 2L.The diameter characterization of microemulsion formulation as shown in Figure 1.
Embodiment 2: the preparation of microemulsion of the present invention
Compositions proportioning: (content in every 100mL microemulsion)
Preparation method is with embodiment 1.
Embodiment 3: the preparation of microemulsion of the present invention
Compositions proportioning: (content in every 100mL microemulsion)
Preparation method is with embodiment 1.
Embodiment 4: the preparation of microemulsion of the present invention
Compositions proportioning: (content in every 100mL microemulsion)
Preparation method is with embodiment 1.
Embodiment 5: the preparation of microemulsion of the present invention
Compositions proportioning: (content in every 100mL microemulsion)
Preparation method is with embodiment 1.
Embodiment 6: the preparation of capsule of the present invention
Compositions proportioning: (content in every seed lac wafer)
Take the mixture of aforementioned proportion, add starch, cellulose, stearic acid granulate, then add gelatin and silicon dioxide is encapsulated, obtain capsule.
Embodiment 7: the preparation of soft capsule of the present invention
Compositions proportioning: (content in every soft capsule)
The mixture taking aforementioned proportion mixes by 1:1.2 with the mixed-matrix such as soybean oil, soybean lecithin, adds hot melt molten, namely obtains soft capsule content after mixing; The preparation of rubber: in gelatin: water: the ratio of glycerol 1:0.8:0.4, first puts into container by gelatin and water, is heated to 80 DEG C, continuous stirring makes it to dissolve, then add glycerol to continue to stir, stop heating until completely dissolved, after naturally cooling to room temperature, make soft capsule material; The content of above-mentioned gained and soft capsule material are suppressed on soft capsule press, namely obtains soft capsule through cleaning, drying, sterilizing, packaging.
Embodiment 8: the preparation of Tablets
Compositions proportioning: (content in every tablet)
Take the mixture of aforementioned proportion, add appropriate amount of starch slurry and to sieve obtained wet grain after mixing, wet grain dry after after sieve, then add the magnesium stearate tabletting of 0.6 ~ 3%, obtain tablet.
Embodiment 9: the preparation of pill of the present invention
Compositions proportioning: (content in every pill)
Take the mixture of aforementioned proportion, cross six to No. seven sieves after fully pulverizing, mixing, then adds distillation water pill, dry, obtains pill.
Beneficial effect of the present invention is proved below by way of concrete pharmacodynamics test.
Test example 1 present composition is to the effect (compositions and each one-component comparative experiments) of the oxygen-derived free radicals produced during Human umbilical vein endothelial cells (HUVECs) hypoxia-reoxygenation
1, experimental technique
Human umbilical vein endothelial cells (HUVECs) is purchased from Huaxi Hospital Attached to Sichuan Univ scientific base cell bank.Fluorescent dye dihydro second ingot (DHE) is purchased from sigma company, is first dissolved in a small amount of DMSO reagent before use, is then diluted to 10 μm of ol/L with cell culture fluid.Get HUVECs cell (3 × 10
3) be inoculated in 96 orifice plates, after cultivating 24 hours with 100 μ L DMEM, be divided into following 7 groups:
After completing process, each group of cell distinguishes anoxic treatment 1 hour, and then reoxygenation 2 hours, then adds 100 μ L fluorescent dye DHE reagent to final concentration 5 μm of ol/L, after hatching 20 minutes, under excitation wavelength/emission wavelength=480/580nm, measure each group of fluorescence intensity with spectrofluorophotometer.
All data all represent with mean ± standard deviation, and parallel one factor analysis of variance (SPSS16.0 software), P < 0.05 represents that difference has statistical significance.* P<0.01, * * P<0.001vs. matched group;
compositions group.
2, experimental result
Experimental result as shown in Figure 2, with Rhizoma Polygoni Cuspidati extract, Rhizoma Curcumae Longae extract, green tea extract, a-thioctic acid or coenzyme Q10 individual processing HUVECs cell, after the dyeing of dihydro second ingot, fluorescence intensity ratio matched group has and reduces in various degree, and after using institute of the present invention compositions-treated, after the dyeing of dihydro second ingot, fluorescence intensity is significantly lower than any one (p<0.01) of being used alone wherein component.
Experimental result explanation, the present composition can reduce the generation of free radical, there is antioxidation, and, compared with being used alone with each component, under same dose, the antioxidation of pharmaceutical composition of the present invention is more excellent (p<0.01), and the effect of Synergistic of each ingredient exerts is described in the present composition.
Test example 2 present composition is to the effect (compositions optimum proportioning screening experiment) of the oxygen-derived free radicals produced during Human umbilical vein endothelial cells (HUVECs) hypoxia-reoxygenation
1, experimental technique
Human umbilical vein endothelial cells (HUVECs) is purchased from Huaxi Hospital Attached to Sichuan Univ scientific base cell bank.Fluorescent dye dihydro second ingot (DHE) is purchased from sigma company, is first dissolved in a small amount of DMSO reagent before use, is then diluted to 10 μm of ol/L with cell culture fluid.Get HUVECs cell (3 × 10
3) be inoculated in 96 orifice plates, after cultivating 24 hours with 100 μ L DMEM, be divided into following 6 groups:
After completing process, each group of cell distinguishes anoxic treatment 1 hour, and then reoxygenation 2 hours, then adds 100 μ L fluorescent dye DHE reagent to final concentration 5 μm of ol/L, after hatching 20 minutes, under excitation wavelength/emission wavelength=480/580nm, measure each group of fluorescence intensity with spectrofluorophotometer.
All data all represent with mean ± standard deviation, and parallel one factor analysis of variance (SPSS16.0 software), P < 0.05 represents that difference has statistical significance.* P<0.001vs. matched group.
2, experimental result
As shown in Figure 3, after compositions-treated HUVECs cell prepared by embodiment 1 ~ 5, dihydro second ingot fluorescent staining strength ratio matched group all has obvious reduction (p<0.001) to experimental result; Wherein, compositions 1 group, compositions 3 groups and compositions 4 groups, dihydro second ingot fluorescent staining intensity is a little less than compositions 2 groups and compositions 5 groups, and the dihydro second ingot fluorescent staining intensity of compositions 1 group is minimum.
Experimental result illustrates, compositions prepared by the embodiment of the present invention 1 ~ 5 all has good antioxidation, and wherein, composition effect prepared by embodiment 1,3,4 is relatively excellent, and composition effect prepared by embodiment 1 is optimum.
Test example 3 present composition is to the effect of the damage caused by the oxidative stress during Ischemia and Reperfusion in vivo in Rats
1, experimental technique
Adult male SD rats 20 (being purchased from Da Shuo bio tech ltd, Chengdu), 250 ~ 350 grams, be divided into matched group and experimental group at random, often organize 10, perform the operation first three day every day respectively gavage give 2.5 ml physiological salines and the microemulsion prepared by embodiment 1.
During experiment, animal lumbar injection pentobarbital sodium (30mg/kg) is anaesthetized, and then faces upward position and is fixed on operating-table, open BL2410 biological functional system, and electrocardiogram led in record II continuously.Insert tracheal intubation, and be connected with animal respirator (respiratory quotient is 1: 2, respiratory pressure 110 ~ 210kPa for respiratory frequency 60 ~ 70 beats/min, tidal volume 8 ~ 12 milliliters).Carotid artery intubate, and explore downward to left ventricle, record left systolic pressure continuously.Femoral venous catheter, for injecting sample and venous blood samples.After completing, thoracic cavity is opened in left border of sternum 4th ~ 5 intercostal, expose heart, cut off pericardium, gently press rat abdomen, extrude heart, left anterior descending branch (LAD) trunk is found between pulmonary trunk and left auricle, flat left auricle lower edge 1cm place penetrates the looper of band 5/0 suture, hook around LAD, in pulmonary conus branch pin.After stablizing 30 minutes, ligation LAD30 minute.Ligation Success Flag: visible electrocardiogram J point or ST section is raised or QRS ripple increases, broadeningly merge with T ripple in 5 minutes after (1) ligation, the upwards monophasic curve in the back of a bow; (2) perusal left ventricle antetheca cardiac muscle color is first pale transfers cyanosis to again.
After ischemia completes, opening fills with 2 hours again.Collect the creatine kinase mb emission levels in left ventricular systolic pressure and venous plasma.The one factor analysis of variance adopting repeated measure is compared between the group of left ventricular systolic pressure recovery rate; Creatine kinase mb emission levels data acquisition t inspection difference more between two, P<0.05 is considered to there is significant difference.
Data represent with mean ± standard deviation.* P<0.05vs. matched group.
2, experimental result
Experimental result as shown in Figures 4 and 5, test group of animals is during heart ischemia reperfusion, the recovery rate of left ventricular systolic pressure is significantly higher than matched group (p<0.05) (as Fig. 4), and experimental group creatine kinase mb emission levels is significantly lower than matched group (as Fig. 5).
Experimental result illustrates, the present composition can suppress the oxidative stress of Ischemia-reperfusion Period, alleviates the oxidative damage that ischemia-reperfusion causes, treatment and prevention myocardial ischemia reperfusion injury.
To sum up, the present composition can reduce oxygen-derived free radicals and produce, and has good antioxidation, and can be used for treating ischemical reperfusion injury, potential applicability in clinical practice is good.
Claims (10)
1. for an antioxidative compositions, it is characterized in that: it is the preparation be prepared from by following raw material:
Rhizoma Polygoni Cuspidati extract 2 ~ 12 parts, Rhizoma Curcumae Longae extract 1 ~ 8 part, green tea extract 1 ~ 5 part, alpha-lipoic acid 1 part, coenzyme Q10 1 part;
In described Rhizoma Polygoni Cuspidati extract, Resveratrol content is 15 ~ 68% (w/w); In described Rhizoma Curcumae Longae extract, curcumin content is 4 ~ 35% (w/w); In green tea extract, polyphenol content is 10 ~ 40% (w/w); Purity >=98% of described alpha-lipoic acid; Described coenzyme Q10 purity >=98%.
2. compositions according to claim 1, is characterized in that: it is the preparation be prepared from by the raw material of following weight proportioning:
Rhizoma Polygoni Cuspidati extract 5 parts, Rhizoma Curcumae Longae extract 4 parts, green tea extract 4 parts, alpha-lipoic acid 1 part, coenzyme Q10 1 part.
3. compositions according to claim 1 and 2, it is characterized in that: it be with Rhizoma Polygoni Cuspidati extract, Rhizoma Curcumae Longae extract, green tea extract, alpha-lipoic acid, coenzyme Q10 for active component, add the preparation that in pharmacy or food, acceptable adjuvant or complementary composition are prepared from.
4. compositions according to claim 3, is characterized in that: described preparation is oral formulations.
5. compositions according to claim 4, is characterized in that: described oral formulations is microemulsion, capsule, tablet or pill.
6. compositions according to claim 5, is characterized in that: described capsule is soft capsule.
7. prepare a method for compositions described in claim 1-6 any one, it comprises the steps:
A, by weight proportion described in claim 1-6 any one, take each raw material;
B, add that in pharmacy or food, acceptable adjuvant or complementary composition are prepared into conventional preparation.
8. the compositions described in claim 1-6 any one is preparing the purposes in anti-oxidation medicine or health food.
9. purposes according to claim 8, is characterized in that: described medicine or health food are the medicine or the health food that treat and/or prevent ischemical reperfusion injury.
10. purposes according to claim 9, is characterized in that: described medicine or health food treat and/or prevent medicine or the health food of myocardial ischemia reperfusion injury.
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| CN103976901A (en) * | 2014-05-22 | 2014-08-13 | 东南大学 | Coenzyme Q10 and tea polyphenol loaded micro-nano carrier, as well as preparation and application methods thereof |
| CN104172432A (en) * | 2014-07-30 | 2014-12-03 | 谢松芬 | Passion fruit seed oil antioxidant |
| JP6446552B2 (en) * | 2014-08-28 | 2018-12-26 | カリウェイ バイオファーマシューティカルズ カンパニー リミテッド | Compositions used for weight and body fat reduction and their pharmaceuticals and uses |
| US10537548B2 (en) | 2014-08-28 | 2020-01-21 | Caliway Biopharmaceuticals Co., Ltd. | Composition and medical product for reducing body weight and body fat, and use of said product |
| CN108041600A (en) * | 2017-12-18 | 2018-05-18 | 苏州诺衡生命科技有限公司 | A kind of formula and preparation method of comprehensive antioxidant functional food |
| CN109511649B (en) * | 2018-11-21 | 2021-06-25 | 嘉兴莱普晟医疗科技有限公司 | Normal-temperature mechanical perfusion system capable of expanding liver supply source |
| CN109602820A (en) * | 2019-02-21 | 2019-04-12 | 翟金孟 | The compound lozenge of plant extracts |
| CN114190555B (en) * | 2021-12-18 | 2023-06-23 | 江苏艾兰得营养品有限公司 | A dripping pill with antioxidant effect and its preparation method |
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