CN105837533A - Pharmaceutical composition of alarelin acetate and medical application of pharmaceutical composition - Google Patents
Pharmaceutical composition of alarelin acetate and medical application of pharmaceutical composition Download PDFInfo
- Publication number
- CN105837533A CN105837533A CN201610262113.8A CN201610262113A CN105837533A CN 105837533 A CN105837533 A CN 105837533A CN 201610262113 A CN201610262113 A CN 201610262113A CN 105837533 A CN105837533 A CN 105837533A
- Authority
- CN
- China
- Prior art keywords
- compound
- pharmaceutical composition
- acetate
- alarelin
- alarelin acetate
- 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.)
- Pending
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
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/336—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having three-membered rings, e.g. oxirane, fumagillin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/08—Peptides having 5 to 11 amino acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D301/00—Preparation of oxiranes
- C07D301/32—Separation; Purification
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D303/00—Compounds containing three-membered rings having one oxygen atom as the only ring hetero atom
- C07D303/02—Compounds containing oxirane rings
- C07D303/36—Compounds containing oxirane rings with hydrocarbon radicals, substituted by nitrogen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Immunology (AREA)
- Gastroenterology & Hepatology (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The invention discloses a pharmaceutical composition of alarelin acetate and medical application of the pharmaceutical composition. The pharmaceutical composition of the alarelin acetate contains alarelin acetate and a novel-structure natural product compound (I) separated from dried rhizomes of blackberry lily. By virtue of independent action of the alarelin acetate and the compound (I), the content of serum transaminase, bilirubin and urea nitrogen of liver injured animals can be decreased, the jaundice and the renal dysfunction can be relieved, and the content of toxin in plasma can be decreased; and by virtue of combined action of alarelin acetate and the compound (I), the pharmaceutical effect is more obvious, so that the alarelin acetate and the compound (I) can be developed into drugs for treating acute hepatic failure. Compared with the prior art, the pharmaceutical composition has the outstanding substantive characteristics and remarkable progress.
Description
Technical field
The invention belongs to biomedicine field, relate to the new application of alarelin acetate, be specifically related to the medicine of alarelin acetate
Compositions and the application in acute hepatic failure thereof.
Background technology
Alarelin acetate is the nonapeptide analog of the gonadotropin releasing hormone (GnRH) of synthetic, and the medication initial stage can sting
Swash hypophysis release interstitialcellstimulating hormone (ICSH) (LH) and follicle stimulating hormone (FSH), cause the of short duration rising of steroid hormone of ovary source；Weight
Multiplexing medicine can suppress hypophysis to discharge LH and FSH, makes the estradiol level in blood decline, reaches the effect of medicine removal ovary, this
Plant inhibitory action to can be used for treating the hormone-dependent diseases such as endometriosis.
Hepatitis protective agents is the most various in style, but the most weary effective protective agents to acute hepatic failure.
Up to now, there is not yet the dependency report of alarelin acetate and pharmaceutical composition thereof and acute hepatic failure.
Summary of the invention
It is an object of the invention to provide the pharmaceutical composition of a kind of alarelin acetate, containing acetic acid the third ammonia in this pharmaceutical composition
Rayleigh and the natural product of a kind of novel structure, alarelin acetate and this natural product can be with Synergistic treatment acute hepatic failure.
The above-mentioned purpose of the present invention is achieved by techniques below scheme:
A kind of compound (I) with following structural formula,
The pharmaceutical composition of a kind of alarelin acetate, including alarelin acetate, compound as claimed in claim 1 (I)
Pharmaceutically acceptable carrier, is prepared as the dosage form needed.
Further, pharmaceutically acceptable carrier includes diluent, excipient, filler, binding agent, wetting agent, collapses
Solve agent, absorption enhancer, surfactant, absorption carrier or lubricant.
Further, described dosage form include tablet, capsule, oral liquid, suck agent, granule, electuary, pill, powder,
Unguentum, sublimed preparation, suspensoid, powder, solution, injection, suppository, spray, drop or patch.
The preparation method of above-claimed cpd (I), comprises following operating procedure: the dry rhizome of Rhizoma Belamcandae is pulverized by (a), uses
75～85% alcohol heat reflux extract, united extraction liquid, be concentrated into without alcohol taste, use petroleum ether, ethyl acetate and water saturated successively
N-butanol extraction, respectively obtains petroleum ether extract, acetic acid ethyl ester extract and n-butyl alcohol extract；In (b) step (a)
N-butyl alcohol takes thing macroporous resin remove impurity, first with 8 column volumes of 25% ethanol elution, then with 12 cylinders of 70% ethanol elution
Long-pending, collect 70% eluent, concentrating under reduced pressure obtains 70% ethanol elution concentrate；C in () step (b), 70% ethanol elution is dense
Contracting thing purification on normal-phase silica gel separates, and obtains with the methylene chloride-methanol gradient elution that volume ratio is 85:1,45:1,25:1 and 15:1 successively
To 4 components；D in () step (c), component 4 separates further by purification on normal-phase silica gel, be 20:1,15:1 by volume ratio successively
3 components are obtained with the methylene chloride-methanol gradient elution of 1:1；Component 2 octadecylsilane key in (e) step (d)
The reverse phase silica gel closed separates, and with the methanol aqueous solution isocratic elution that concentration expressed in percentage by volume is 72%, collects 10～16 column volumes and washes
De-liquid, eluent is concentrated under reduced pressure to give compound (I).
Further, in the preparation method of compound (I), step (a) is extracted with 80% alcohol heat reflux, united extraction liquid.
Further, in the preparation method of compound (I), described macroporous resin is D101 type macroporous adsorbent resin.
Further, in the preparation method of compound (I), step (a) replace ethyl acetate to extract with dichloromethane,
Obtain dichloromethane extract.
The above-claimed cpd (I) application in the medicine of preparation treatment acute hepatic failure.
The application in the medicine of preparation treatment acute hepatic failure of the pharmaceutical composition of above-mentioned alarelin acetate.
Advantages of the present invention:
Containing alarelin acetate and a kind of dry rhizome from Rhizoma Belamcandae in the pharmaceutical composition of the alarelin acetate that the present invention provides
When the natural product of the novel structure of middle isolated, alarelin acetate and this natural product independent role, to acute hepatic
Exhaustion has therapeutical effect；During the two synergy, the therapeutic effect of acute hepatic failure is improved further, can develop
Become the medicine for the treatment of acute hepatic failure.The present invention compared with prior art has prominent substantive distinguishing features and significantly progress.
Detailed description of the invention
Further illustrate the essentiality content of the present invention below in conjunction with embodiment, but do not limit scope with this.To the greatest extent
The present invention is explained in detail by pipe with reference to preferred embodiment, it will be understood by those within the art that, can be to the present invention
Technical scheme modify or equivalent, without deviating from the spirit and scope of technical solution of the present invention.
Embodiment 1: compound (I) separates preparation and structural identification
Separation method: the dry rhizome (2kg) of Rhizoma Belamcandae is pulverized by (a), extracts (15L × 3 time) with 80% alcohol heat reflux,
United extraction liquid, is concentrated into without alcohol taste (3L), successively with petroleum ether (3L × 3 time), ethyl acetate (3L × 3 time) and
Water saturated n-butyl alcohol (3L × 3 time) extracts, and respectively obtains petroleum ether extract, acetic acid ethyl ester extract and n-butanol extraction
Thing；B acetic acid ethyl ester extract D101 type macroporous resin remove impurity in () step (a), first with 8 posts of 25% ethanol elution
Volume, then with 12 column volumes of 70% ethanol elution, collect 70% eluent, concentrating under reduced pressure obtains 70% ethanol elution concentrate；
In (c) step (b) 70% ethanol elution concentrate with purification on normal-phase silica gel separate, successively with volume ratio be 85:1 (10 column volumes),
45:1 (8 column volumes), 25:1 (10 column volumes) and the methylene chloride-methanol gradient elution of 15:1 (8 column volumes)
Obtain 4 components；D in () step (c), component 4 separates further by purification on normal-phase silica gel, be 20:1 (10 by volume ratio successively
Individual column volume), the methylene chloride-methanol gradient elution of 15:1 (8 column volumes) and 1:1 (6 column volumes) obtain 3 groups
Point；E reverse phase silica gel that in () step (d), component 2 is bonded by octadecylsilane separates, and is 72% by concentration expressed in percentage by volume
Methanol aqueous solution isocratic elution, collect 10～16 column volume eluents, eluent is concentrated under reduced pressure to give compound (I)
(320mg, HPLC normalization purity is more than 98%).
Structural identification: yellow powder；HR-ESI-MS shows [M+Na]+For m/z 264.1014, molecule can be obtained in conjunction with nuclear-magnetism feature
Formula is C15H15NO2, degree of unsaturation is 9.Hydrogen nuclear magnetic resonance modal data δH(ppm, DMSO-d6, 600MHz): H-3 (3.31,
M), H-4 (5.65, d, J=0.96), H-7 (1.26, s), H-8 (2.14, d, J=0.96), H-9 (8.15, d,
J=12.8), H-10 (12.02, d, J=12.8), H-2 ', 6 ' (7.31, d, J=8.7), H-3 ', 5 ' (7.38, dd, J=8.7,
7.4), H-4 ' (7.08, t, J=7.4)；Carbon-13 nmr spectra data δC(ppm, DMSO-d6, 150MHz): 192.7
(C, 1-C), 76.3 (C, 2-C), 60.6 (CH, 3-C), 122.8 (CH, 4-C), 133.7 (C, 5-C),
121.3 (C, 6-C), 16.8 (CH3, 7-C), 21.7 (CH3, 8-C), 145.1 (CH, 9-C), 138.6 (C,
1 '-C), 117.2 (CH, 2 ', 6 '-C), 129.1 (CH, 3 ', 5 '-C), 124.3 (CH, 4 '-C).IR spectrum shows this
Compound contains carbonyl (1687cm-1) and amido (3254cm-1) functional group.1H-NMR spectrum two methyl of display (δ H1.26,
S, H3-7) and (δ H2.14, d, J=0.96Hz, H3-8), an oxygen-containing methine (δ H3.31, m, H-3), two
Olefinic methine [(δ H5.65, d, J=0.96Hz, H-4) and (δ H8.15, d, J=12.8Hz, H-9)], and five virtues
Race's proton (δ H7.31, d, J=8.7Hz, H-2 ', 6 '；7.38, dd, J=8.7,7.4Hz, H-3 ', 5 '；7.08, t, J=7.4Hz,
H-4’).The low field chemical shift of aromatic and coupling constant thereof show this compound contain secondary enamine (δ H12.02, d,
J=12.8Hz, H-10).13C-NMR spectrum 15 carbon signals of display, including two methyl, (one oxygen-containing secondary for eight methines
Methyl, seven olefinic methines), five quaternary carbons (an oxygen-containing quaternary carbon, a ketone carbonyl, three alkene quaternary carbons).Above-mentioned
Nuclear magnetic data, in conjunction with insatiable hunger sum, shows that this compound is two ring structures.1H-1H COSY spectrum shows three main knots
Tile section: mono-substituted benzyl ring, enamine system (=CH-NH-) and substructure [C (CH3)=CH].In HMBC spectrum,
Oxygen-containing methine proton signal (δ H3.31, m, 1H) shows with two oxygen-containing carbon signals (δ C76.3 and 60.6) chemical shift
This compound contains an epoxy construction, and (δ H1.26,3H, s) with oxygen-containing quaternary carbon C-2 and oxygen-containing time for methyl proton signal in addition
The intersection peak of methyl carbon C-3 shows that C-2 position is also connected with a methyl.HMBC spectrum in, olefinic proton H-4 (δ H5.65) with
C-2, CH3This part-structure of the relevance verification of-8 and C-6.In HMBC spectrum, NH-10 and aromatic carbon C-1 ' (δ C138.6),
C-2 ', 6 ' (δ C117.2) and quaternary carbon C-6 (δ C121.3) intersect peak and show that monosubstituted phenyl ring and another annulus are by enamine function
Group couples together.H-9 and C-1, C-5, C-6 and C-1 in HMBC spectrum ' the above-mentioned inference of relevance verification.NOESY
In spectrum, the dependency of H-9 and methyl Me-8 shows that enamine is Z configuration.Comprehensive hydrogen spectrum, carbon spectrum, HMBC spectrum and NOESY
Spectrum, and document is about correlation type nuclear magnetic data, can substantially determine that this compound is as follows, spatial configuration passes through further
ECD test determines, theoretical value is basically identical with experiment value.
This compound chemical formula and carbon atoms numbered are as follows:
Embodiment 2: pharmacological action
1, materials and methods
1.1 animal
Wistar rat, body weight 170～200g, male and female dual-purpose.
1.2 reagent and sample
Alarelin acetate is purchased from Nat'l Pharmaceutical & Biological Products Control Institute.Compound (I) is made by oneself, and preparation method is shown in embodiment 1.
Galactosamine (GalN) is purchased from Medical University Of Chongqing, and hall reagent is produced by reward chemical reagent work of Xiamen City.
1.3 instrument
Automatic amino acid analyser (Beckman company)
Prepared by 1.4 rat packets and model
Rat is randomly divided into 5 groups, often group 12, respectively Normal group, model control group, alarelin acetate group
(64mg·kg-1), compound (I) group (64mg kg-1), alarelin acetate and compound (I) compositions group [32mg kg-1
Alarelin acetate+32mg kg-1Compound (I)].Experiment starts to be administered treated animal subcutaneous injection medicine.q12h×3.Secondary
Afternoon day, in addition to Normal group, laboratory animal lumbar injection GalN 1800mg/kg, after 40 hours under etherization, abdomen master
Arterial blood extracting, makees Analysis of Plasma Concentrations of Free Amino.
1.5 measure part blood biochemistry index
After etherization, abdominal aortic blood, measure ALT, plasma bilirubin (T) B and blood urea nitrogen (Bun) content.
1.6 endotoxin assay
After etherization, abdominal aortic blood, measured endotoxin content with improveing chloric acid method.
1.7 statistical method
Experimental data mean ± standard deviation (x ± s) represents, application SPSS18.0 version statistical software carry out one factor analysis of variance and
T checks, statistically significant for difference with P ＜ 0.05.
2, experimental result
2.1 pairs of acute hepatic failure animal blood Biochemical Effects
Comparing with Normal group, model control group animal blood slurry ALT, TB, Bun content is significantly raised, and animal there occurs urgency
, there is hyperbilirubinemia and renal dysfunction in property hepatic insufficiency.Medicine treated animal, ALT, TB and Bun are less than model pair
According to group；Compare with model control group, alarelin acetate and compound (I) compositions treated animal plasma A LT, TB, Bun
Content substantially reduces (P ＜ 0.01)；Compare with model control group, alarelin acetate group, compound (I) treated animal blood plasma
ALT, TB, Bun content reduces (P ＜ 0.05), shows that medicine can alleviate yellow cellulitis and prevent hepatorenal syndrome from occurring.It is shown in Table 1.
2.2 impacts on acute hepatic failure animal blood slurry endotoxin content
Comparing with Normal group, model control group animal blood slurry endotoxin content is significantly raised, it is meant that occur in that serious interior
Endotoxemia, and through the animal of Drug therapy, plasma endotoxin content declines.Compare with model control group, alarelin acetate
It is decreased obviously (P ＜ 0.01) with compound (I) compositions group plasma endotoxin content；Compare with model control group, acetic acid third
Ammonia Rayleigh group, compound (I) group plasma endotoxin content declines (P ＜ 0.05).The results are shown in Table 2.
2.3 impacts on Plasma Amino Acid
Comparing with Normal group, in model control group animal blood slurry, aromatic amino acid is significantly raised；Compare with model control group,
Alarelin acetate is decreased obviously (P ＜ 0.01) with aromatic amino acid in compound (I) compositions group blood plasma；With model pair
Comparing according to group, in alarelin acetate group, compound (I) group blood plasma, aromatic amino acid declines (P ＜ 0.05).Show medicine
When thing can improve liver failure, Amino Acid is unbalance, prevents the generation of hepatic encephalopathy.The results are shown in Table 2.
The impact that blood biochemistry is changed by table 1
| Group | ALT(U) | TB(μmol/)L | Bun(mmol/L) |
| Normal group | 131.9±5.9 | 6.67±0.77 | 2.08±0.30 |
| Model control group | 449.1±20.2 | 44.67±8.69 | 5.28±0.22 |
| Alarelin acetate group | 236.0±39.4 | 21.21±0.53 | 3.75±0.14 |
| Compound (I) group | 223.6±13.1 | 23.11±0.25 | 3.61±0.59 |
| Alarelin acetate and compound (I) compositions group | 136.0±21.1 | 8.57±0.53 | 2.75±0.31 |
Table 2 is on plasma endotoxin content and on the impact of aromatic amino acid content in blood plasma
| Group | Endotoxin (ng/L) | Tyrosine | Tryptophan |
| Normal group | 0.144±0.14 | 64.1±12.1 | 14.78±2.89 |
| Model control group | 0.327±0.62 | 408.5±12.8 | 27.89±2.17 |
| Alarelin acetate group | 0.211±0.33 | 203.2±17.2 | 20.43±2.12 |
| Compound (I) group | 0.226±0.14 | 212.1±12.6 | 21.19±1.17 |
| Alarelin acetate and compound (I) compositions group | 0.165±0.20 | 60.1±15.8 | 15.78±1.03 |
The above results shows, when alarelin acetate, compound (I) independent role, can reduce Liver damaged animal serum and turn
Ammonia enzyme, bilirubin and urea nitrogen content, alleviate yellow cellulitis and renal dysfunction, and can reduce plasma endotoxin content；Acetic acid the third ammonia
When Rayleigh and compound (I) synergy, pharmacological action becomes apparent from, and can develop into the medicine for the treatment of acute hepatic failure.
The effect of above-described embodiment indicates that the essentiality content of the present invention, but does not limit protection scope of the present invention with this.
It will be understood by those within the art that, technical scheme can be modified or equivalent, and not take off
Essence and protection domain from technical solution of the present invention.
Claims (10)
1. a compound (I) with following structural formula,
2. the pharmaceutical composition of an alarelin acetate, it is characterised in that: include alarelin acetate, such as claim 1 institute
The compound (I) stated and pharmaceutically acceptable carrier, be prepared as the dosage form needed.
The pharmaceutical composition of alarelin acetate the most according to claim 2, it is characterised in that: pharmaceutically acceptable
Carrier include diluent, excipient, filler, binding agent, wetting agent, disintegrating agent, absorption enhancer, surfactant,
Absorption carrier or lubricant.
The pharmaceutical composition of alarelin acetate the most according to claim 2, it is characterised in that: described dosage form include tablet,
Capsule, oral liquid, suck agent, granule, electuary, pill, powder, unguentum, sublimed preparation, suspensoid, powder, solution
Agent, injection, suppository, spray, drop or patch.
5. the preparation method of the compound (I) described in claim 1, it is characterised in that comprise following operating procedure: (a)
The dry rhizome of Rhizoma Belamcandae is pulverized, with 75～85% alcohol heat reflux extraction, united extraction liquid, is concentrated into without alcohol taste, uses stone successively
Oil ether, ethyl acetate and water saturated n-butanol extraction, respectively obtain petroleum ether extract, acetic acid ethyl ester extract and n-butyl alcohol
Extract；B in () step (a), n-butyl alcohol takes thing macroporous resin remove impurity, first with 8 column volumes of 25% ethanol elution, then
With 12 column volumes of 70% ethanol elution, collecting 70% eluent, concentrating under reduced pressure obtains 70% ethanol elution concentrate；(c) step
Suddenly in (b), 70% ethanol elution concentrate purification on normal-phase silica gel separates, and is 85:1,45:1,25:1 and 15:1 by volume ratio successively
Methylene chloride-methanol gradient elution obtain 4 components；D in () step (c), component 4 separates further by purification on normal-phase silica gel,
3 components are obtained successively with the methylene chloride-methanol gradient elution that volume ratio is 20:1,15:1 and 1:1；(e) step (d)
The reverse phase silica gel that middle component 2 is bonded by octadecylsilane separates, and washes with the methanol aqueous solution that concentration expressed in percentage by volume is 72% is isocratic
De-, collect 10～16 column volume eluents, eluent is concentrated under reduced pressure to give compound (I).
The preparation method of compound the most according to claim 5 (I), it is characterised in that: step (a) 80% second
Alcohol circumfluence distillation, united extraction liquid.
The preparation method of compound the most according to claim 5 (I), it is characterised in that: described macroporous resin is D101
Type macroporous adsorbent resin.
The preparation method of compound the most according to claim 5 (I), it is characterised in that: step (a) is used dichloromethane
Alkane replaces ethyl acetate to extract, and obtains dichloromethane extract.
9. the application in the medicine of preparation treatment acute hepatic failure of the compound (I) described in claim 1.
10. the pharmaceutical composition of the arbitrary described alarelin acetate of claim 2～4 is at preparation treatment acute hepatic failure
Application in medicine.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610262113.8A CN105837533A (en) | 2016-04-23 | 2016-04-23 | Pharmaceutical composition of alarelin acetate and medical application of pharmaceutical composition |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610262113.8A CN105837533A (en) | 2016-04-23 | 2016-04-23 | Pharmaceutical composition of alarelin acetate and medical application of pharmaceutical composition |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN105837533A true CN105837533A (en) | 2016-08-10 |
Family
ID=56590295
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610262113.8A Pending CN105837533A (en) | 2016-04-23 | 2016-04-23 | Pharmaceutical composition of alarelin acetate and medical application of pharmaceutical composition |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105837533A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105713065A (en) * | 2016-04-23 | 2016-06-29 | 何淑琼 | Azathioprine pharmaceutical composition and medical application thereof |
| CN105777855A (en) * | 2016-05-16 | 2016-07-20 | 李同芬 | Novel Withania kansuensis lactone compound and medicinal use thereof |
| CN106279344A (en) * | 2016-08-14 | 2017-01-04 | 吴芊葭 | A kind of native compound separated from Radix Saposhnikoviae and preparation method thereof, medical applications |
-
2016
- 2016-04-23 CN CN201610262113.8A patent/CN105837533A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105713065A (en) * | 2016-04-23 | 2016-06-29 | 何淑琼 | Azathioprine pharmaceutical composition and medical application thereof |
| CN105777855A (en) * | 2016-05-16 | 2016-07-20 | 李同芬 | Novel Withania kansuensis lactone compound and medicinal use thereof |
| CN106279344A (en) * | 2016-08-14 | 2017-01-04 | 吴芊葭 | A kind of native compound separated from Radix Saposhnikoviae and preparation method thereof, medical applications |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN105837533A (en) | Pharmaceutical composition of alarelin acetate and medical application of pharmaceutical composition | |
| CN102940687A (en) | Szechwan Chinaberry fruit extract and application thereof | |
| CN105777856A (en) | Medicine composition with acetylcysteine and medical application of medicine composition | |
| CN105949156A (en) | Pharmaceutical composition of itraconazole and pharmaceutical application of pharmaceutical composition | |
| CN105801526A (en) | Drug composition of cyproheptadine hydrochloride and application thereof in biomedicine | |
| CN106008485A (en) | Medicinal composition of glimepiride, and application thereof in biomedicines | |
| CN105085534A (en) | Novel skeleton alkaloid compound and extraction separation method thereof | |
| CN106083876A (en) | The pharmaceutical composition of cytarabine hydrochloride and the application in biological medicine thereof | |
| CN105884796A (en) | Allopurinol pharmaceutical composition and application thereof in biopharmaceuticals | |
| CN105669690A (en) | Clopidogrel hydrogen sulfate medicinal composition and medicinal application thereof | |
| CN105669621A (en) | Pharmaceutical composition of chlortetracycline hydrochloride and medical application of pharmaceutical composition | |
| CN105949042A (en) | Gabapentin pharmaceutical composition and medical application thereof | |
| CN110467522B (en) | Toluylene compound with anti-enteritis activity in natural indigo, and preparation method and application thereof | |
| CN105884716A (en) | Pharmaceutical composition of glibenclamide and medical application thereof | |
| CN105924351A (en) | Pharmaceutical composition of diprophylline and medical application thereof | |
| CN105801590A (en) | Alprazolam pharmaceutical composition and anti-inflammatory and analgesic effects thereof | |
| CN106008651A (en) | Pharmaceutical composition containing isosorbide dinitrate and medical application of pharmaceutical composition containing isosorbide dinitrate | |
| CN105777683A (en) | Bicyclol medicine composition and medical application thereof | |
| CN105693493A (en) | Clobetasol propionate drug composition and medical application thereof | |
| CN105777850A (en) | Pharmaceutical composition of famciclovir and pharmaceutical application of pharmaceutical composition | |
| CN112300185B (en) | Alkaloid compound with reduced hepatotoxicity, and preparation method and application thereof | |
| CN105906648A (en) | Ketotifen fumarate pharmaceutical composition and application thereof in biological medicines | |
| CN105949216A (en) | Pharmaceutical composition of celecoxib and novel application of pharmaceutical composition | |
| CN105713065A (en) | Azathioprine pharmaceutical composition and medical application thereof | |
| CN114249783B (en) | Phenyl butanediamide glycoside compound and preparation method and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WD01 | Invention patent application deemed withdrawn after publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20160810 |