CN102178675A - Application of quercetin and composition thereof to preparation of anti-hypoxia medicaments - Google Patents

Application of quercetin and composition thereof to preparation of anti-hypoxia medicaments Download PDF

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CN102178675A
CN102178675A CN 201110076784 CN201110076784A CN102178675A CN 102178675 A CN102178675 A CN 102178675A CN 201110076784 CN201110076784 CN 201110076784 CN 201110076784 A CN201110076784 A CN 201110076784A CN 102178675 A CN102178675 A CN 102178675A
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quercetin
compositions
hypoxia
group
application
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王晓炜
王平
刘尧
曹苹
毛羽
郑俊霞
李军
鲁艺
王乃利
姚新生
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Shenzhen Institute for Drug Control
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Abstract

The invention provides application of quercetin to preparation of anti-hypoxia medicaments. The invention also provides a composition. The composition comprises the quercetin with pharmaceutical effective dose, a pharmaceutically acceptable auxiliary material and chlorogenic acid and/or protocatechuic acid with pharmaceutical effective dose. The quercetin and the quercetin-containing composition can be widely applied to developing and preparing more effective and low-toxicity anti-hypoxia natural medicaments due to the activity in the anti-hypoxia aspect, and have a wide application prospect.

Description

The application in the preparation anti-anoxic medicine of Quercetin and compositions thereof
Technical field
The present invention relates to field of medicaments, relate in particular to Quercetin, contain the compositions of Quercetin and in the application of preparation in the anti-anoxic medicine.
Background technology
Oxygen is the first element of human life.The people does not have a meal and can survive several weeks, and do not drink water and can survive several days, but will be dead after a few minutes when not having oxygen.In all histoorgans of human body, the oxygen that organs such as brain, heart and lung need is maximum, and is the most responsive to the supply of oxygen.When oxygen content drops to 15-19% in the air, can not feel like oneself, it is unable to have a headache, and work efficiency descends; If continue 6-12 month, chronic fatigue syndrome, sexual dysfunction or subhealth state can occur; If continue 10-20, may suffer from cancer.When oxygen content drops to 12-15% in the air, can cause accelerated breathing, to palpitate quickly, judgment descends, and pulmonary edema or cerebral edema may occur; If continue 6-12 month, what is called " altitude sickness " that the high aborigines of part plateau visitor and minority suffer from that Here it is erythrocytosis, hypertension and heart disease may appear.About 1000 meters of the every rising of height above sea level, the air oxygen content will reduce 10%, and more than height above sea level 3000-4000 rice, the air oxygen content can drop to below 15%, as the Qinghai-Tibet Platean.When oxygen content drops to 10-12% in the air, can be dazzled, lip is blue, moves malfunctioning.When oxygen content dropped to 8-10% in the air, the meeting green around the gills was lost consciousness.When oxygen content dropped to 4-8% in the air, the mankind will be dead in 5 minutes.This shows that oxygen is very important to the mankind's importance.
The area of China 1/2 is positioned at western part, and natural environment is abominable relatively, and natural causes such as plateau hypoxia have had a strong impact on this place crowd's inhabitation, existence, but west area aboundresources, exploitation and having a high potential of developing.For promoting the overall, concerted and sustainable development of economic society, the Party Central Committee, State Council have proposed the strategic task of " development of the West Regions ".The induced effect of highlands economic construction will cause these regional unprecedented flows of personnel, more needs effective medical protection.In addition, strategic point, China border area major part is positioned at the extreme natural environment area, and mostly is ethnic groups gathering ground.Therefore, can effectively manage and develop the extreme natural environment area, except economy, social meaning, the profound politics and the meaning of national defense safety be arranged also.In order to reach the purpose of " expand life space, develop western resource, safeguard national security, promote overall development ", certainly will need a large amount of personnel to enter this type of area life, work, the research of therefore carrying out hypoxic plateau environment factor injury protection becomes more and more important.
At present, the anti-anoxic medicine that uses clinically comprises: (1) biological preparation: multiple plain, the cytochrome third gradegrade C of brain; (2) chemicals: piracetam, nimodipine and fiunarizine etc.; (3) Chinese medicine preparation: Radix Rhodiolae, Radix Et Caulis Acanthopanacis Senticosi and puerarin etc.In recent years, along with the further investigation of people's centering pharmaceutically active ingredient and pharmacological action, the oxygen lack resistant function of finding Chinese medicine and extract thereof has characteristics such as effect lasting stability and toxic and side effects are little.And, because treatment by Chinese herbs has globality and comprehensive advantage, thought widely that at present it is having broad application prospects aspect raising body hypoxia-bearing.
PC12 anoxia-induced apoptosis model can be used for the power of detection of drugs anti-anoxia ability, its screening principle is as follows, PC12 is the pheochromocytoma cell clone, transplants out a kind of tumor cell in 1975 in radiation rat pheochromocytoma, and the cell strain that obtains through continuous monolayer culture.Discover that anoxia is cultivated the PC12 cell strain can cause the cell mortality, mainly shows as apoptosis.According to apoptotic number can the detection of drugs anti-anoxia ability power.
In addition, body will produce a large amount of free radicals when suffering anoxia-induced apoptosis, excessive free radical can cause the nucleic acid base disappearance, hydrogen bond destroys, protein cross, polypeptide chain fracture, lipid peroxidation takes place, generate malonaldehyde (MDA), can form macromolecular lipofuscin simultaneously and in lysosome, deposit, cause cell function to be badly damaged.Therefore, the removing of free radical also is the important channel that organism improves hypoxia-bearing capability.Most of free-radical chemistry character are very active, and the life-span is extremely short, but also have the chemical property of minority free radical very stable, as 1,1-diphenyl-2-bitterness acyl group free radical (1,1-diphenyl-2-picrylhydrazyl, DPPH).The DPPH free radical is a kind of metastable free radical, and its stability is mainly from spatial obstacle of resonance stabilized effect and three phenyl ring, makes unpaired electron on its nitrogen-atoms that is clipped in the middle can not bring into play its due electronics and acts in pairs.The alcoholic solution of DPPH has strong light absorption value at the 517nm place, is purple.When the DPPH free radical is reduced by antioxidant or during with another combined with radical, light absorption value can reduce or disappear, so can utilize this characteristic to come specimen to provide proton to remove the effect of free radical.Blos in 1958 are applied to the screening study of antioxidant.
Summary of the invention
One aspect of the present invention provides the application of Quercetin as the preparation anti-anoxic medicine.
The present invention provides a kind of compositions on the other hand, contains pharmacy effective dose Quercetin and acceptable adjuvant pharmaceutically.Described adjuvant can be excipient and the additive that pharmaceutically is suitable for, as avirulent compatible filler, binding agent, disintegrating agent, buffer agent, antiseptic, antioxidant, lubricant, correctives, thickening agent, coloring agent, emulsifying agent etc.Quercetin can be with general dosage form administration, and the preferred oral dosage form is as tablet or capsule.
The present invention also provides the above-mentioned application of compositions in the preparation anti-anoxic medicine that contains Quercetin.
Can also add chlorogenic acid and/or protocatechuic acid in the above-mentioned composition.Above-mentioned composition can be the combination of Quercetin and chlorogenic acid, and the combination of Quercetin and protocatechuic acid can also be the compositions of Quercetin and chlorogenic acid and three kinds of compositions of protocatechuic acid.In above-mentioned composition, the weight percentage of Quercetin is 40% ~ 90%, preferred 50% ~ 90%.Above-mentioned composition can mix with acceptable adjuvant pharmaceutically, described adjuvant can be excipient and the additive that pharmaceutically is suitable for, as avirulent compatible filler, binding agent, disintegrating agent, buffer agent, antiseptic, antioxidant, lubricant, correctives, thickening agent, coloring agent, emulsifying agent etc.Above-mentioned composition can be with general dosage form administration, and the preferred oral dosage form is as tablet or capsule.
The present invention also provides the above-mentioned application of compositions in the preparation anti-anoxic medicine that contains Quercetin, chlorogenic acid and/or protocatechuic acid.
The present invention adopts mice seal anoxia-induced apoptosis body inner model to carry out anti-hypoxia active testing in the body, and adopt the antioxidation activity in vitro evaluation methodology of PC12 cell (rat adrenal gland pheochromocytoma cloning cell strain) anoxia-induced apoptosis external model and DPPH free radical scavenging that the active component in the Quercetin and the present composition has been carried out the investigation of anti-hypoxia active testing and DPPH radical scavenging activity simultaneously, all shown active preferably.
In vivo in the anti-hypoxia active testing, it is 0.5g/kg body weight ~ 1g/kg body weight to the effective dosage ranges of mice that the present invention has further provided Quercetin.Convert according to the drug dose between mice in the pharmacological evaluation and the people, the dosage scope that has further provided Quercetin is 50mg/kg body weight ~ 100mg/kg.
Quercetin and the activity of compositions aspect anti-hypoxia that contain Quercetin can be widely used in exploitation and preparation is more effective, the anti-hypoxia natural drug of low toxicity among the present invention, have broad application prospects.
Description of drawings
Fig. 1 is the test result of compositions such as Quercetin to mice normal pressure anoxia enduring model.
The specific embodiment
The invention will be further described below in conjunction with embodiment, and following examples will help those of ordinary skill in the art further to understand the present invention, but not limit the present invention in any form.
One, measures in the active body of main chemical compositions anti-hypoxia
1, experiment material
Quercetin, Quercitroside, protocatechuic acid, chlorogenic acid, baicalin are provided by Nat'l Pharmaceutical ﹠ Biological Products Control Institute; Rhodiola rosea capsules is that S﹠P Pharmaceutical Co., Ltd. produces, the 0.5g/ grain, and every 100g is equivalent to the 0.4g rhodioloside; Sodium carboxymethyl cellulose, F20050429, Chemical Reagent Co., Ltd., Sinopharm Group; Sodica calx, 20050701-1, Guangzhou Chemical Reagent Factory.The NIH mice, 18-20g, male, provide by Guangdong Medical Lab Animal Center; Sealable 250mL ground wide mouthed bottle; Stopwatch; Roberval's balance.
2, experimental model
It is the healthy male white mouse of 18 ± 2g that body weight is selected in experiment for use, be divided into each group of contrast and medicine at random, animal is in preceding 3 hours difference of anoxia intragastric infusion medicine (20mg/0.5mL, be equivalent to the 1g/kg body weight), matched group intragastric infusion or lumbar injection equivalent normal saline or 20% dimethyl sulfoxide (DMSO) diluent, 0.5 mL, then each group mice is put into 150 mL conical flasks respectively, simultaneously that bottleneck is tight with rubber plug cover, the time-to-live of under this airtight anoxia condition, observing mice.
3, experimental technique
Get 72 of the healthy male white mouses of 18-20g, be divided into 8 groups at random, 9 every group.The 1st group is the normal control group, irritates stomach and gives 0.5% sodium carboxymethyl cellulose 20mL/kg; 2nd, 3 groups are respectively Quercetin low dosage (10mg/0.4mL is equivalent to the 0.5g/kg body weight), Quercetin high dose (20mg/0.4mL is equivalent to the 1g/kg body weight) administration group; The 4-7 group is respectively chlorogenic acid, Quercitroside, protocatechuic acid, baicalin administration group, and dosage 20mg/0.4mL is equivalent to the 1g/kg body weight; The 8th group is Rhodiola rosea capsules administration group, contains rhodioloside 0.4g among the every 100g of capsule 's content, is made into that rhodioloside concentration is 1mg/mL behind 25% the solution, and dosage 0.4mg/0.4mL is equivalent to the 20mg/kg body weight.The ground wide mouthed bottle of 250 mL is put into mice respectively in administration after 3 hours, sealing (is put sodica calx 5g in the bottle, in order to absorbing carbon dioxide and water, wide mouthed bottle is with the preceding correction capacity that all is filled with water, bottleneck is coated with vaseline oil, with anti-gas-leak), be index with last breathing, observe the time-to-live of mice, all data all with mean ± standard deviation ((
Figure 445062DEST_PATH_IMAGE001
SPSS 13.0 statistical softwares are adopted in ± s) expression, take statistics to learn with t check between analysis of many between group variable and group and handle, and p<0.05 has statistical significance for difference.
4, experimental result
Experimental result as shown in Figure 1, the group label is 1 to 8 group and is respectively matched group, Quercetin low dose group, Quercetin high dose group, chlorogenic acid group, protocatechuic acid group, Quercitroside group, baicalin group and Radix Rhodiolae group among Fig. 1.
As seen from Figure 1, the time-to-live (min) of the mice of two positive controls baicalin groups and Radix Rhodiolae group is respectively 63.70 ± 8.80,59.33 ± 8.67, with matched group (47.73 ± 6.27) relatively, there were significant differences (P<0.05).The time-to-live (min) of the mice of Quercetin low dosage, Quercetin high dose, chlorogenic acid, protocatechuic acid group is respectively 68.85 ± 8.07,68.55 ± 10.15,62.49 ± 6.38,56.68 ± 7.80, compare with matched group (47.73 ± 6.27), there were significant differences (P<0.05), compare with positive controls, difference is remarkable (P>0.05) not.And also there is prolongation Quercitroside group (53.98 ± 4.23) the mice time-to-live, but and matched group comparing difference not significantly (P>0.05).
Above-mentioned experimental result explanation, Quercetin, chlorogenic acid and protocatechuic acid all can improve the time-to-live of mice under the airtight anoxia condition, have anti-hypoxia activity in the stronger body.The activity of active effect and baicalin, Rhodiola rosea capsules positive controls quite.
Two, the protective effect that main chemical compositions is damaged the PC12 cell hypoxia in Quercetin and the compositions thereof
1, experimental technique
Get and pass above PC12 cell of 5 generations, after trypsinization disperses, make 2 * 10 5The cell suspension of individual cell/mL density is inoculated in the 35 mm plastic culture dish that scribble the calf hide glue, and every ware 2mL places 36 ℃, contains 10% CO 2Incubator in cultivate.Culture fluid is made up of 85% DMEM, 5% tire oxen and horses serum, 10% horse serum, glutamine 0.10 g/L.
Get cultivate 8 days respectively organize the PC12 cell, be divided into matched group (H by experiment 2O, MeOH, DMSO) and each group (drug level is respectively 100 μ g/mL, 50 μ g/mL and 25 μ g/mL) of medicine.24 h add different pharmaceutical respectively before anoxic treatment.With in cell dislocation constant temperature (36 ℃) the airtight anoxia container, fill continuously then to contain 90% N 2With 10% CO 2Oxygenless gas, take out after under anoxia condition, continuing to cultivate 12 h, and dye with 4% trypan blue, inverted phase contrast microscope (400 *) down every ware by the adjacent visual field of Z word sequential counting medium blue dye (dead neuron) and not indigo plant dye the cell number of (survived neuronal), calculating neuronal cell percentage survival.Experiment repeats 2 times.
Successively chemical compound is carried out active testing with the experiment B group of the experiment A group of 25 μ g/mL, 50 μ g/mL, 100 μ g/mL concentration and 50 μ g/mL, 100 μ g/mL, 200 μ g/mL concentration.In the A group, make negative control with the DMSO equal solvent.In B group, make positive control with baicalin, the cell survival rate of each chemical compound is deducted the cell survival rate of positive control, the cell survival rate with its result and positive control is divided by then, thereby obtains relative survival rate.
2, experimental result see Table 1 and table 2 shown in.
The anti-hypoxia activity of table 1, Quercetin, Quercitroside (A group) (X ± SD, n=20)
Chemical compound Solvent Survival rate 100 μ g/mL (%) Survival rate 50 μ g/mL (%) Survival rate 25 μ g/mL (%)
Negative control group Water 13.06±4.69 12.01±6.23 ?14.06±4.48
Negative control group Methanol 14.63±5.96 11.77±5.77 12.87±4.36
Negative control group DMSO 11.77±4.01 13.28±4.79 ?12.01±6.31
Quercetin Methanol ?27.2±5.79** ?41.9±5.82** ?40.7±7.51**
Quercitroside Methanol ?24.3±4.22** ?42.9±7.87** ?37.3±6.90*
* p<0.05 is compared variant with matched group;
Significant difference has been compared with matched group in * p<0.01;
Experimental result shows that Quercetin and Quercitroside all have stronger anti-hypoxia activity, and wherein the anti-hypoxia activity of Quercetin is stronger.
The anti-hypoxia activity of table 2, protocatechuic acid, chlorogenic acid (B group) (X ± SD, n=20)
Chemical compound Relative survival rate 50 μ g/mL Relative survival rate 100 μ g/mL Relative survival rate 200 μ g/mL
Protocatechuic acid 1.7497** 1.8043** 1.1524**
Chlorogenic acid 0.1762 0.2663 0.5385
Experimental result shows that the anti-hypoxia activity of protocatechuic acid is very strong, is better than positive reference substance.
Three, the antioxidant activity of main chemical compositions in Quercetin and the compositions thereof
DPPH method active testing adopts the U.S. Spectra Max 340PC of Molecular Devices company type microplate reader.
1, experimental technique
The DPPH free radical is made into 2 * 10 with dehydrated alcohol -4The solution of M places 4 ℃ to keep in Dark Place.Each monomeric compound and positive reference substance all are made into the stock solution of 1mg/mL with dehydrated alcohol, be diluted to desired concn with dehydrated alcohol before the test.
The reference literature experimental technique is also improved, with the need testing solution 100 μ L and 2 * 10 of variable concentrations -4M DPPH solution 100 μ L add in each hole of 96 orifice plates, simultaneously with each concentration of need testing solution of not adding DPPH (replacing DPPH) with 100 μ L dehydrated alcohol in contrast to eliminate of the interference of test sample intrinsic colour to test result, and establish DPPH negative control (replacing test sample) with 100 μ L dehydrated alcohol, every group parallel establishes 4 multiple holes.96 orifice plates are put into microplate reader, shake 1 min, and under room temperature, lucifuge condition, preserve, measure them behind 30 min, be calculated as follows the free radical scavenging activity of test sample in the absorbance OD at 517 nm places value.
Free radical scavenging activity={ [OD DPPHcontrol-(OD Sample-OD Sample control)]/OD DPPHcontrol} * 100%
Wherein: OD DPPHcontrolMeansigma methods for DPPH negative control group OD value;
OD SampleMeansigma methods for sample sets OD value;
OD Sample controlMeansigma methods for sample ethanol reference substance OD value;
OD is a light absorption value.
2, experimental result
Adopt the antioxidation activity in vitro evaluation methodology of DPPH free radical scavenging, as positive control, main chemical compositions in Quercetin and the compositions thereof has been carried out removing the test of free radical ability with present widely used antioxidant Vc (ascorbic acid).
The ability that adopts above-mentioned experimental technique that chemical constituents such as Quercetin are removed the DPPH free radical under 40 μ g/mL and 10 μ g/mL concentration is tested, simultaneously with present widely used antioxidant Vc (ascorbic acid, concentration is 10 μ g/mL) as positive controls, the regulation free radical scavenging activity be higher than 50% think to have activity.Experimental result sees Table 3.
The DPPH free radical scavenging activity of main chemical compositions in table 3, Quercetin and the compositions thereof
Chemical compound Remove active 40 μ g/mL Remove active 10 μ g/mL
Vc - 95.40%
Quercetin 96.73% 95.52%
Quercitroside 81.05% 24.30%
Protocatechuic acid 95.85% 81.27%
Chlorogenic acid 95.07% 93.25%
From table 3 data as can be known, Quercetin, protocatechuic acid and chlorogenic acid have anti-hypoxia activity preferably.
Following examples are the dosage form embodiment in concrete the application for Quercetin of the present invention and compositions thereof.
Embodiment 1: tablet
Every consists of: Quercetin 100mg, lactose 122mg, corn starch 10% paste 30mg, corn starch 45mg, magnesium stearate 3mg.Earlier Quercetin and lactose were mixed 10 ~ 15 minutes, mixture is made granule with corn starch 10% paste that configures.By scalping wet granular is pulverized, dry afterwards.Dried granules is sieved and mixed 10 ~ 15 minutes with corn starch.Adding magnesium stearate again mixed 1 ~ 3 minute.On tablet machine, mixture is pressed into the tablet of suitable size and weight.
Embodiment 2: capsule
Consisting of of every capsules: Quercetin 100mg, lactose 116mg, corn starch 40mg, magnesium stearate 4mg.Earlier Quercetin, lactose and corn starch were mixed 10 ~ 15 minutes, add magnesium stearate again and mixed 1 ~ 3 minute.Mixture is packed in the capsule of suitable size.
Embodiment 3: tablet
Every consists of: Quercetin 50mg, chlorogenic acid 25mg, protocatechuic acid 25mg, lactose 122mg, corn starch 10% paste 30mg, corn starch 45mg, magnesium stearate 3mg.Earlier Quercetin, chlorogenic acid, protocatechuic acid and lactose were mixed 10 ~ 15 minutes, mixture is made granule with corn starch 10% paste that configures.By scalping wet granular is pulverized, dry afterwards.Dried granules is sieved and mixed 10 ~ 15 minutes with corn starch.Adding magnesium stearate again mixed 1 ~ 3 minute.On tablet machine, mixture is pressed into the tablet of suitable size and weight.
Embodiment 4: tablet
Every consists of: Quercetin 90mg, chlorogenic acid 10mg, lactose 122mg, corn starch 10% paste 30mg, corn starch 45mg, magnesium stearate 3mg.Earlier Quercetin, chlorogenic acid, protocatechuic acid and lactose were mixed 10 ~ 15 minutes, mixture is made granule with corn starch 10% paste that configures.By scalping wet granular is pulverized, dry afterwards.Dried granules is sieved and mixed 10 ~ 15 minutes with corn starch.Adding magnesium stearate again mixed 1 ~ 3 minute.On tablet machine, mixture is pressed into the tablet of suitable size and weight.
Embodiment 5: tablet
Every consists of: Quercetin 40mg, chlorogenic acid 30mg, protocatechuic acid 30mg, lactose 122mg, corn starch 10% paste 30mg, corn starch 45mg, magnesium stearate 3mg.Earlier Quercetin, chlorogenic acid, protocatechuic acid and lactose were mixed 10 ~ 15 minutes, mixture is made granule with corn starch 10% paste that configures.By scalping wet granular is pulverized, dry afterwards.Dried granules is sieved and mixed 10 ~ 15 minutes with corn starch.Adding magnesium stearate again mixed 1 ~ 3 minute.On tablet machine, mixture is pressed into the tablet of suitable size and weight.
Embodiment 6: capsule
Consisting of of every capsules: Quercetin 50mg, chlorogenic acid 25mg, protocatechuic acid 25mg, lactose 116mg, corn starch 40mg, magnesium stearate 4mg.Earlier Quercetin, chlorogenic acid, protocatechuic acid, lactose and corn starch were mixed 10 ~ 15 minutes, add magnesium stearate again and mixed 1 ~ 3 minute.Mixture is packed in the capsule of suitable size.

Claims (10)

1. the application of Quercetin in the preparation anti-anoxic medicine.
2. the application of Quercetin as claimed in claim 1 in the preparation anti-anoxic medicine is characterized in that described Quercetin dosage is 50mg/kg body weight ~ 100mg/kg body weight.
3. a compositions is characterized in that, comprises the Quercetin of pharmacy effective dose and acceptable adjuvant pharmaceutically.
4. compositions as claimed in claim 3 is characterized in that described compositions can be made tablet or capsule.
5. the application of the described compositions of claim 3 in the preparation anti-anoxic medicine.
6. the application of compositions as claimed in claim 5 in the preparation anti-anoxic medicine is characterized in that described Quercetin dosage is 50mg/kg body weight ~ 100mg/kg body weight.
7. compositions as claimed in claim 3 is characterized in that, described compositions also comprises the chlorogenic acid and/or the protocatechuic acid of pharmacy effective dose.
8. compositions as claimed in claim 7 is characterized in that, the weight percentage of described Quercetin is 40% ~ 90%.
9. compositions as claimed in claim 7 is characterized in that described compositions can be made tablet or capsule.
10. the application of the described compositions of claim 7 in the preparation anti-anoxic medicine.
CN 201110076784 2011-03-29 2011-03-29 Application of quercetin and composition thereof to preparation of anti-hypoxia medicaments Pending CN102178675A (en)

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Cited By (6)

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CN102988348A (en) * 2012-11-19 2013-03-27 何晓涛 Application of Aphanamixoid A for preparing anti-hypoxic medicine
CN103445181A (en) * 2013-09-17 2013-12-18 王喜军 Application of physalis pubescens in preparing anti-fatigue and anti-hypoxia health-care food
CN106924240A (en) * 2017-04-14 2017-07-07 印晓星 Medical composition and its use comprising Quercetin
CN108042525A (en) * 2017-12-20 2018-05-18 宀崇孩 A kind of pharmaceutical composition for treating Pathogenesis of Post-infarction Ventricular Remodeling
CN111615384A (en) * 2017-11-23 2020-09-01 阿法比奥治疗公司 Method for treating sinusitis
WO2024032710A1 (en) * 2022-08-11 2024-02-15 Ubi Pharma Inc. Method against snake envenomation

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Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102988348A (en) * 2012-11-19 2013-03-27 何晓涛 Application of Aphanamixoid A for preparing anti-hypoxic medicine
CN103445181A (en) * 2013-09-17 2013-12-18 王喜军 Application of physalis pubescens in preparing anti-fatigue and anti-hypoxia health-care food
CN106924240A (en) * 2017-04-14 2017-07-07 印晓星 Medical composition and its use comprising Quercetin
CN106924240B (en) * 2017-04-14 2019-11-19 印晓星 Medical composition and its use comprising Quercetin
CN111615384A (en) * 2017-11-23 2020-09-01 阿法比奥治疗公司 Method for treating sinusitis
CN108042525A (en) * 2017-12-20 2018-05-18 宀崇孩 A kind of pharmaceutical composition for treating Pathogenesis of Post-infarction Ventricular Remodeling
WO2024032710A1 (en) * 2022-08-11 2024-02-15 Ubi Pharma Inc. Method against snake envenomation

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Application publication date: 20110914