CN105769876B - The medical usage of Bile acid and bear gall - Google Patents
The medical usage of Bile acid and bear gall Download PDFInfo
- Publication number
- CN105769876B CN105769876B CN201610131100.7A CN201610131100A CN105769876B CN 105769876 B CN105769876 B CN 105769876B CN 201610131100 A CN201610131100 A CN 201610131100A CN 105769876 B CN105769876 B CN 105769876B
- Authority
- CN
- China
- Prior art keywords
- bear gall
- model
- group
- acid
- bile acid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/575—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/37—Digestive system
- A61K35/413—Gall bladder; Bile
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Biomedical Technology (AREA)
- Zoology (AREA)
- Virology (AREA)
- Immunology (AREA)
- Developmental Biology & Embryology (AREA)
- Cell Biology (AREA)
- Biotechnology (AREA)
- Engineering & Computer Science (AREA)
- Physiology (AREA)
- Nutrition Science (AREA)
- Steroid Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention relates to medicines, more particularly to a kind of Bile acid and the medical usage of bear gall.Bile acid and bear gall of the invention can be used for preventing and treating depression.
Description
Technical field
The present invention relates to Medicines and Health Product fields, more particularly to a kind of Bile acid and the medical usage of bear gall.
Background technique
Depression is a kind of common mental disease, is mainly shown as depressed, and interest lowers, pessimistic, retardation of thinking,
Lack initiative, serious person may occur in which suicidal thought and behavior.In the research of modern popular disease, depression has become the mankind
Focus of attention, it is contemplated that it will develop as the second largest disease after coronary heart disease in the coming years, seriously endanger the mankind
Health and Living.
Current clinically common antidepressant includes Iricyclic antidepressants, monoamine oxidase inhibitors, selection
Property serotonin reuptake inhibitor etc., often side effect is big or price costly, limit its clinical extensive use.It is logical
Drug therapy is crossed, wherein most patient can get different degrees of curative effect.In addition, clinically there are also a considerable amount of depressions
Neurosis patient although novel antidepressant comes into being, but still can not meet the demand of clinical various people.With clinic
The appearance of medication bottleneck and depression mechanism is understood in depth, the research and development of natural antidepressant become
New hot spot and development trend.Currently used depression model have chronic mild unpredictable stress stimulus depression model (CUMS),
Drug-induced depression model (glucocorticoid inducible, olfactory bulb removal depression model, transgenic animal model etc..Although all multimodes
Type cannot all simulate the symptom of Clinical depression patient completely, but what is certain is that pressure can result in depression.Therefore, pressure
Caused depression animal model application is more universal.Chronic mild unpredictable stress stimulus depression model be evaluation depressive symptom and
Screen antidepressant more effectively and a kind of reliable model, by the detection of a series of Animal Behavior Science (FST, TST,
OFT, EPMT and SIT), whether testing model succeeds.CUMS model has the validity of height, and sustainable some months, substantially
The requirement for meeting depression model is widely used model in antidepressant research both at home and abroad at present.
Bear gall is one of four big rare animal drugs, is the drying gall-bladder of ursidae animal.Bear gall is as medicinal first recorded in the Tang Dynasty
" Tang materia medica ", away from the present have more than 1,300 years history;The Compendium of Material Medica of Li Shizhen of the Ming Dynasty is also loaded with: bear gall, smell
It is bitter cold, nontoxic, enter liver and gallbladder the heart channel of Hang-Shaoyin.Modern medicine and pharmacology research confirms that bear gall has clearing heat and detoxicating, soothing liver-gallbladder, goes screen improving eyesight, solves
Convulsion analgesic activity.In the treatment of many illnesss such as the liver and gall, cardio-cerebrovascular, neuropsychiatric of the mankind, have
Wide application value.Substitute of the dry product of drain-out bear gall as natural bear gall is used as medicine and examines listing, name
For " bear gall powder ", it is widely used on tcm clinical practice.The chemical component of bear gall powder mainly contains mating type ursodesoxycholic acid, goose deoxidation
Cholic acid, cholic acid, deoxycholic aicd, Tauro ursodesoxy cholic acid, Taurochenodeoxycholic Acid etc..
Summary of the invention
The purpose of the present invention is intended to provide the new medical usage of Bile acid and bear gall.
Specifically, there is provided a kind of formula (I) compounds in the medicine for preparing prevention and treatment depression for the first aspect of the present invention
Application in object or food
Wherein, R1、R2、R3It is each independently selected from H or OH, R4Selected from NH (CH2)2SO3H、NH(CH2)2SO3Na or
OH。
In a preferred example, the compound is Tauro ursodesoxy cholic acid, Taurochenodeoxycholic Acid, ursodesoxycholic acid, goose
Deoxycholic aicd, taurocholate or cholic acid.
In another preferred example, the compound as unique active constituent be used to prepare prevention and treatment depression drug or
Food.
Application of the second aspect of the present invention there is provided bear gall in the drug or food of preparation prevention and treatment depression, it is described
Bear gall is using formula (I) compound as active constituent:
Wherein, R1、R2、R3It is each independently selected from H or OH, R4Selected from NH (CH2)2SO3H、NH(CH2)2SO3Na or
OH。
In a preferred example, the compound is Tauro ursodesoxy cholic acid, Taurochenodeoxycholic Acid, ursodesoxycholic acid, goose
Deoxycholic aicd, taurocholate or cholic acid.
In another preferred example, the bear gall is used to prepare the drug or food of prevention and treatment depression as unique active constituent
Product.
The details of various aspects of the present invention will be able to detailed description in subsequent chapters.By hereafter and claim
Description, the features of the present invention, purpose and advantage will become apparent from.
Detailed description of the invention
Fig. 1 chronic unpredictable stress mouse gives the behaviouristics performance after bear gall powder
A. the dead time of forced swimming test;B. the dead time of tail test is hanged.(mean ± S.E.M, n=12;With mould
Type group compares *, P < 0.05;**,P<0.01;***,P<0.001)
Fig. 2 bile acid standard items total ion current figure
1.TUDCA, 2.THDCA, 3.GUDCA, 4.TCA, 5.GCA, 6.TCDCA, 7.UDCA, 8.TDCA, 9.HDCA,
10.GCDCA, 11.CA, 12.GDCA, 13.TLCA, 14.CDCA, 15.DCA, 16.LCA
Bile acid total ion current figure in Fig. 3 bear gall powder
1.TUDCA, 2.TCA, 3.Unknow, 4.TCDCA, 5.UDCA, 6.CA, 7.Unknow, 8.CDCA, 9.Unknow
After Fig. 4 chronic unpredictable stress mouse gives TUDCA, TCDCA, UDCA, TCA, CDCA, CA
Behaviouristics performance
A. the dead time of forced swimming test;B. the dead time of tail test is hanged.(mean ± S.E.M, n=12;With mould
Type group compares *, P < 0.05;**,P<0.01;***,P<0.001)
Specific embodiment
Appearance part of the invention is had been surprisingly found that based on such a: Bile acid and bear gall can reduce it is chronic not
The dead time in forced swimming and tail-suspention test of predictable stress depression mouse, so it can be used as depression
Prevent and treat drug.
As used in the present invention, Bile acid compound of the invention has the following structure formula:
Wherein, R1、R2、R3It is each independently selected from H or OH, R4Selected from NH (CH2)2SO3H、NH(CH2)2SO3Na or
OH。
As well known to those skilled in the art, above compound is respectively provided with following structural formula:
Bile acid and bear gall of the invention can be by commercial sources from Heilungkiang Hei Bao medicine company limited liability company etc.
Place's purchase obtains.Its purity meets medicinal standard.
Bile acid and bear gall of the invention can be used alone or be used in the form of pharmaceutical composition.Pharmaceutical composition
Object includes the Bile acid and bear gall and pharmaceutical acceptable carrier of the invention as active constituent.Preferably, drug of the invention
Composition contains the Bile acid and bear gall of the invention as active constituent of 0.1-99.9% weight percent.It " can medicine
With carrier " pharmaceutical active of Bile acid and bear gall of the invention, while its effective dose will not be destroyed, drug can be played
Dosage when carrier function is nontoxic to the human body.
Described pharmaceutical acceptable carrier includes but is not limited to: soft phosphatide, aluminum stearate, aluminium oxide, ion exchange material, self-emulsifying
Drug delivery system, tween or other surfaces activator, haemocyanin, buffer substance for example phosphate, amion acetic acid, sorbic acid,
Water, salt, electrolyte such as sulfate protamine, disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salt, magnesium silicate, saturated fatty acid
Partial glyceride mixtures etc..
Other common excipient substance such as adhesives (such as microcrystalline cellulose), filler (such as starch, glucose, anhydrous lactitol
Sugar and lactose bead), disintegrating agent (such as cross-linked pvp, crosslinked carboxymethyl fecula sodium, croscarmellose sodium, low-substituted hydroxypropyl
Base cellulose), lubricant (such as magnesium stearate) and sorbefacient, absorption carrier, flavouring agent, sweetener, excipient, dilution
Agent, wetting agent etc..
Bile acid and bear gall and its pharmaceutical composition of the invention can be prepared by conventional method in that art and can be with
Pass through enteron aisle or non-bowel or topical routes.Oral preparation includes capsule, tablet, oral solution, granule, pill, dissipates
Agent, sublimed preparation, paste etc.;Non-intestinal drug delivery agent includes injection etc.;Local administration preparation includes creme, patch, ointment, spray
Mist agent etc..Preferably oral preparation.
The administration route of Bile acid and bear gall and its pharmaceutical composition of the invention can be oral, sublingual, warp
Skin, through muscle or subcutaneous, mucocutaneous, vein, urethra, vagina etc..
Other than medicament is made, antioxidant, pigment, enzyme can also be added in Bile acid and bear gall of the invention
Health food is made by the conventional method of this field in the various food additives such as preparation.
Present invention will be further explained below with reference to specific examples.It should be understood that these embodiments are merely to illustrate the present invention
Rather than it limits the scope of the invention.In the following examples, the experimental methods for specific conditions are not specified, usually according to conventional strip
Part or according to the normal condition proposed by manufacturer.Unless otherwise stated, otherwise all percentage, ratio, ratio or number is pressed
Poidometer.
Unless otherwise defined, it anticipates known to all professional and scientific terms as used herein and one skilled in the art
Justice is identical.In addition, any method similar to or equal to what is recorded and material can be applied to the method for the present invention.Wen Zhong
The preferred implement methods and materials are for illustrative purposes only.
The feature that the features described above or embodiment that the present invention mentions are mentioned can be in any combination.Patent specification is taken off
All features shown can be used in combination with any composition form, and each feature disclosed in specification any can provide phase
The alternative characteristics of same, impartial or similar purpose replace.Therefore except there is special instruction, revealed feature is only impartial or similar
The general example of feature.
1 bear gall antidepression pharmacodynamic study of embodiment
Material:
Bear gall powder sample source: Heilungkiang Hei Bao medicine company limited liability company, lot number: 150516+20141112.
Method:
1. the foundation and administration of Chronic unpredictable stress depression mouse model
Four week old male C57BL/6 mouse adaptive feeding two weeks, are randomly divided into blank control group, model from after buying
Group, positive drug group (Venlafaxine 12.5mg/kg), bear gall powder low dose group (low 0.05g/kg), bear gall powder middle dose group
(middle0.1g/kg), bear gall powder high dose group (high 0.2g/kg), every group 12~16.The every cage 4 of naive mice is only just
Often raising, other group of mouse single cage orphan supports, and following stimulation is given in not timing daily: 1. fettering 3h, 2. overturns 48h round the clock, 3.
Fasting for 24 hours, 4. prohibits water 12h, 5. cold bath 5min, and 6. moist padding 12h, 7. presss from both sides tail 1min, and 8. empty cage is for 24 hours (without pad in cage
Material), 9. tilt 45 ° of processing for 24 hours, 10. rat padding interferes for 24 hours.Every kind of stimulation discontinuously repeats, and total stimulation time is 5
Week.Give mouse stimulation start gastric infusion third week, successive administration two weeks, wherein blank control group and model group were given
Isometric solvent.
2. determining the antidepressant effect of bear gall powder with behaviouristics detection means
The detection of 2.2 behaviouristics: mouse forced swimming test (forced swimming test, FST): is placed in preparatory note
There is 20cm depth clear water to record every mouse respectively in 25 ± 1 DEG C of temperature of cylindrical type transparent utensil (high 30cm, diameter 20cm)
Accumulative dead time in 6min, the accumulative dead time after comparing in 4min;Outstanding tail tests (tail suspension
Test, TST): will be fixed on a horizontal waddy at mouse tail 2cm with adhesive tape, animal made to be in projecting state, head from
Horizontal plane about 5~6cm, the accumulative dead time of 4min after recording every animal respectively in 6min.
As a result:
Result of study shows: chronic unpredictable stress mouse finds after giving bear gall powder, the suppression of mouse
Strongly fragrant symptom is significantly improved (Fig. 1).
From Figure 1A as it can be seen that the non-swimming time of model group increases (P < 0.01) compared to significant compared with Normal group, prompt
Model group mouse is easier despair, modeling success, and swims not after giving positive drug and bear gall powder middle dose group and high dose group
The dynamic time compared with model group compared to substantially reduce (P < 0.01 middle vs model P < 0.001, high vs model,
P < 0.05 positive vs model), close to normal group.From Figure 1B as it can be seen that the outstanding tail dead time of model group is relatively normal right
According to group compared to (P < 0.05) is significantly increased, hints model group mouse is easier despair, modeling success, and gives positive drug and bear gall
Powder middle dose group and high dose group rear overhang tail dead time compared with model group compare significant shortening (middle vs model P <
0.05, high P < 0.05 vs model P < 0.001, positive vs model), even more than normal group close to normal group
It is short.
The detection of Bile acid and antidepression pharmacodynamic study in 2 bear gall of embodiment
1. utilizing the Bile acid in UPLC-MS detection bear gall
1.1. standard items total ion current figure
Mode is swept using UPLC-MS entirely, standard items are swept entirely, obtains finger-print result such as Fig. 2.
The preparation of reference substance solution: taking 16 kinds of bile acid reference substance (table 1) each 2mg, accurately weighed, respectively plus 1mL methanol
Make to dissolve, each reference substance solution of 2mg/mL is made.It takes each reference substance solution appropriate, methanol is added to mix, be made 100 μ g/mL's
Mixed reference substance solution.
Table 1
Bear gall powder sample source: Heilungkiang Hei Bao medicine company limited liability company, lot number: 150516+20141112.
Chromatographic condition: chromatographic column is ACQUITY UPLC BEH column (1.7 μm, 1.0mm × 100mm);To contain 0.1% formic acid
5mM ammonium acetate solution be mobile phase A, methanol is Mobile phase B, by table 2 progress gradient elution;Flow velocity: 0.3mL/min;Column temperature:
45℃;Autosampler temperature: 4 DEG C;Sampling volume: 5 μ L.
2 bear gall powder UPLC-MS bile acid determination eluent gradient elution requirement of table
The preparation of test solution: taking bear gall powder sample 100mg, accurately weighed, adds 10mL methanol, is ultrasonically treated 5min,
It is cooling, the weight of less loss is supplied with methanol, is centrifuged, takes supernatant appropriate, crosses 0.22 μm of film, then plus 30 times of methanol dilution, shake up,
Centrifugation, takes supernatant as test solution.
Mode is swept using UPLC-MS entirely, bear gall powder sample is swept entirely, obtains finger-print result such as Fig. 3.Such as Fig. 3 institute
Show: taurine-conjugated bile acids content highest in bear gall powder, sequestered bile acid is less, does not contain glycine binding type bile
Acid.Wherein taurine-conjugated bile acids content is 49.91%-52.80%;Sequestered Determination of Bile Acids is 2.06%-
2.51%;Total bile acid content is 51.92%-54.87%.The highest TUDCA of content and TCDCA is respectively 25.54%-
28.02% and 22% or so, the ratio range of quality proportioning (TUDCA/TCDCA) is 1.1-1.3.The lower bile of remaining content
Acid content is respectively TCA (1.56%-1.89%), CDCA (0.74%-1.67%), UDCA (0.62%-1.14%), CA
(0.12%-0.19%).
2. the pharmacodynamic study of Bile acid in bear gall
Four week old male C57BL/6 mouse adaptive feeding two weeks, are randomly divided into blank control group, model from after buying
Group, positive drug group (Venlafaxine 12.5mg/kg), TUDCA group (0.02g/kg), TCDCA group (0.02g/kg), UDCA group
(0.01g/kg), TCA group (0.01g/kg), CDCA group (0.01g/kg) and CA group (0.01g/kg) every group 12~16.Modeling
Method and behaviouristics detection method are the same as embodiment 1.
Result of study shows: TUDCA, TCDCA, UDCA, TCA, CDCA and CA have antidepressant effect (Fig. 4).From figure
4A is as it can be seen that the non-swimming time of model group increases (P < 0.001) compared to significant compared with Normal group, and hints model group mouse is more
It is easy despair, modeling success, and gives non-swimming time after positive drug and TUDCA, TCDCA, UDCA, TCA, CDCA, CA group
It is compared compared with model group and substantially reduces (TUDCA vs model P < 0.05, TCDCA vs model P < 0.05, UDCA vs
model P<0.05,TCA vs model P<0.001,CDCA vs model P<0.05,CA vs model P<0.001,
P < 0.001 positive vs model), close to normal group.From Fig. 4 B as it can be seen that the outstanding tail dead time of model group is relatively normal right
According to group compared to significantly increasing (P < 0.05), hints model group mouse is easier despair, and modeling is successful, and give positive drug and
TUDCA, TCDCA, UDCA, TCA, CDCA, CA group rear overhang tail dead time shorten (TUDCA vs compared to significant compared with model group
model P<0.01,TCDCA vs model P<0.05,UDCA vs model P<0.001,TCA vs model P<0.05,
P < 0.01 CDCA vs model P < 0.05, CA vs model P < 0.05, positive vs model), close to normal group
It is even more shorter than normally organizing.
Research conclusion:
The above result of study shows: bear gall powder and its Bile acid can reduce Chronic unpredictable stress depression
The dead time in forced swimming and tail-suspention test of mouse, so its drug that can be used as prevention and treatment depression.
Various aspects of the present invention have been described above.However, it should be understood that without departing from spirit of that invention
Under the premise of, those skilled in the art can carry out equivalent change and modification to it, and the change and modification equally fall into the application
The coverage area of appended claims.
Claims (4)
1. application of formula (I) compound as unique active constituent in the drug or food of preparation prevention and treatment depression
Wherein, R1、R2、R3It is each independently selected from H or OH, R4Selected from NH (CH2)2SO3H、NH(CH2)2SO3Na or OH.
2. application as described in claim 1, which is characterized in that the compound is Tauro ursodesoxy cholic acid, the deoxidation of ox sulphur goose
Cholic acid, ursodesoxycholic acid, chenodeoxycholic acid, taurocholate or cholic acid.
3. application of the bear gall as unique active constituent in the drug or food of preparation prevention and treatment depression, the bear gall is with formula
(I) compound is active constituent:
Wherein, R1、R2、R3It is each independently selected from H or OH, R4Selected from NH (CH2)2SO3H、NH(CH2)2SO3Na or OH.
4. application as claimed in claim 3, which is characterized in that the compound is Tauro ursodesoxy cholic acid, the deoxidation of ox sulphur goose
Cholic acid, ursodesoxycholic acid, chenodeoxycholic acid, taurocholate or cholic acid.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201610131100.7A CN105769876B (en) | 2016-03-08 | 2016-03-08 | The medical usage of Bile acid and bear gall |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201610131100.7A CN105769876B (en) | 2016-03-08 | 2016-03-08 | The medical usage of Bile acid and bear gall |
Publications (2)
Publication Number | Publication Date |
---|---|
CN105769876A CN105769876A (en) | 2016-07-20 |
CN105769876B true CN105769876B (en) | 2019-01-29 |
Family
ID=56387174
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201610131100.7A Active CN105769876B (en) | 2016-03-08 | 2016-03-08 | The medical usage of Bile acid and bear gall |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN105769876B (en) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN114288325A (en) * | 2022-01-14 | 2022-04-08 | 上海凯宝药业股份有限公司 | Application of artificially cultured bear gall powder in preparation of medicine for treating depression |
CN115624555A (en) * | 2022-02-24 | 2023-01-20 | 中国药科大学 | Application of hyodeoxycholic acid in preparation of antidepressant drug |
CN115337312A (en) * | 2022-08-19 | 2022-11-15 | 金熊药业(珠海横琴)有限公司 | Cholic acid complex and preparation method and application thereof |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2005281278A (en) * | 2004-03-31 | 2005-10-13 | Daicho Kikaku:Kk | Nutrient, digestive organ agent, antidepressant, climacteric disorder agent, anti-senile dementia agent, anti-alzheimer agent, muscle reinforcing agent and anti-inflammatory agent |
CN103340841A (en) * | 2013-07-02 | 2013-10-09 | 康美药业股份有限公司 | Chinese medicine film as well as preparation method and application thereof |
CN103417906A (en) * | 2012-05-22 | 2013-12-04 | 贵州益佰制药股份有限公司 | Applications of compound mylabris traditional Chinese medicine composition and preparations thereof in preparing drugs for curing depression |
-
2016
- 2016-03-08 CN CN201610131100.7A patent/CN105769876B/en active Active
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2005281278A (en) * | 2004-03-31 | 2005-10-13 | Daicho Kikaku:Kk | Nutrient, digestive organ agent, antidepressant, climacteric disorder agent, anti-senile dementia agent, anti-alzheimer agent, muscle reinforcing agent and anti-inflammatory agent |
CN103417906A (en) * | 2012-05-22 | 2013-12-04 | 贵州益佰制药股份有限公司 | Applications of compound mylabris traditional Chinese medicine composition and preparations thereof in preparing drugs for curing depression |
CN103340841A (en) * | 2013-07-02 | 2013-10-09 | 康美药业股份有限公司 | Chinese medicine film as well as preparation method and application thereof |
Also Published As
Publication number | Publication date |
---|---|
CN105769876A (en) | 2016-07-20 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Bonetti et al. | Side effects of anabolic androgenic steroids abuse | |
Daubert et al. | Acute clenbuterol overdose resulting in supraventricular tachycardia and atrial fibrillation | |
Llewellyn | Anabolics | |
CN105769876B (en) | The medical usage of Bile acid and bear gall | |
JP2008502711A (en) | Carrot composition for preventing or improving deterioration of concentration and memory | |
McMillan | Leukotrienes in respiratory disease | |
JP2020530831A (en) | Corticotropin-releasing factor receptor antagonist | |
JP2013529654A (en) | Pharmaceutical composition comprising levocarnitine and dobesylate | |
CA2737335C (en) | 1-amino-alkylcyclohexane derivatives for the treatment of mast cell mediated diseases | |
Fuchs et al. | Hot-water immersion does not increase postprandial muscle protein synthesis rates during recovery from resistance-type exercise in healthy, young males | |
CN102014931A (en) | Use and preparation of paeoniflorin and the composition thereof | |
JP2018500297A (en) | Use of a composition comprising a ferrous amino acid chelate for the manufacture of a medicament for the regulation of fat metabolism | |
Almdal et al. | Increased amino acid clearance and urea synthesis in a patient with glucagonoma. | |
WO2010090546A1 (en) | Composition of amino acids for sublingual applying for enhanced skin integument repigmentation in vitiligo and method of its administration | |
US4150111A (en) | Enteric coated magnesium chloride | |
US11278509B2 (en) | Lithium salts of N-substituted glycine compounds and uses thereof | |
US11020439B2 (en) | Honey fraction | |
CN106924277A (en) | Ginsenoside Rg5Application in antidepressant is prepared | |
Pisani et al. | Increased dipropylacetic acid bioavailability from dipropylacetamide by food | |
CN111643486A (en) | Huperzine A acupoint sustained-release gel patch for treating senile dementia and preparation method thereof | |
CN110151725A (en) | A kind of stable rosuvastain calcium capsule and preparation method thereof | |
CN104510752A (en) | Medical application of astrapterocarpan | |
CN109260217A (en) | 3`- deoxyinosine nucleosides is in preparation for the application in a variety of disease drugs, food or health care product | |
CN109663123A (en) | Capsule for improving liver injury and body fatigue and preparation method thereof | |
CN104586835B (en) | The medical usage of andrographolide |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant |