CN105777684A - Pharmaceutical composition of fenofibrate and pharmaceutical application of pharmaceutical composition - Google Patents
Pharmaceutical composition of fenofibrate and pharmaceutical application of pharmaceutical composition Download PDFInfo
- Publication number
- CN105777684A CN105777684A CN201610277991.7A CN201610277991A CN105777684A CN 105777684 A CN105777684 A CN 105777684A CN 201610277991 A CN201610277991 A CN 201610277991A CN 105777684 A CN105777684 A CN 105777684A
- Authority
- CN
- China
- Prior art keywords
- fenofibrate
- compound
- pharmaceutical composition
- extract
- preparation
- 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.)
- Withdrawn
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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/216—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acids having aromatic rings, e.g. benactizyne, clofibrate
-
- 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
- A61K31/365—Lactones
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/92—Naphthofurans; Hydrogenated naphthofurans
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Emergency Medicine (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses a pharmaceutical composition of fenofibrate and pharmaceutical application of the pharmaceutical composition. The pharmaceutical composition comprises the fenofibrate and a natural product compound (I) of a novel structure; when in single action, the fenofibrate and the compound (I) have therapeutical effect in mice kidney yang deficiency; when the fenofibrate and the compound (I) are in combined action, the therapeutical effect in mice kidney yang deficiency is further improved; the pharmaceutical composition can be developed into drugs for treating kidney yang deficiency; compared with the prior art, the pharmaceutical composition has outstanding substantial characteristics and significant improvement.
Description
Technical field
The invention belongs to biomedicine field, relate to the new application of fenofibrate, be specifically related to the pharmaceutical composition of fenofibrate and the application in insufficiency of kidney-YANG thereof.
Background technology
Fenofibrate becomes fenofibrate to play effect for reducing blood fat through the effect rapid metabolization of esterase in vivo, has and significantly reduces serum cholesterol, the effect of triglyceride and high density lipoprotein increasing.
Up to now, there is not yet the dependency of fenofibrate and pharmaceutical composition thereof and insufficiency of kidney-YANG report.
Summary of the invention
It is an object of the invention to provide the pharmaceutical composition of a kind of fenofibrate, containing fenofibrate and a kind of natural product in this pharmaceutical composition, fenofibrate and this natural product can Synergistic treatment insufficiency of kidney-YANG.
The above-mentioned purpose of the present invention is achieved by the techniques below scheme:
A kind of compound (I) with following structural formula,
The pharmaceutical composition of a kind of fenofibrate, including fenofibrate, compound as claimed in claim 1 (I) and pharmaceutically acceptable carrier, prepares into the dosage form of needs.
Further, pharmaceutically acceptable carrier includes diluent, excipient, filler, binding agent, wetting agent, disintegrating agent, absorption enhancer, surfactant, absorption carrier or lubricant.
Further, described dosage form includes tablet, capsule, oral liquid, sucks 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), comprise following operating procedure: Herba Ecliptae is pulverized by (a), extract with 70～80% alcohol heat reflux, united extraction liquid, it is concentrated into without alcohol taste, successively with petroleum 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 n-butyl alcohol extract macroporous resin remove impurity in () step (a), first with 6 column volumes of 15% ethanol elution, then with 10 column volumes of 70% ethanol elution, collects 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 80:1,30:1,15:1 and 5:1 methylene chloride-methanol gradient elution obtain 4 components；D in () step (c), component 3 separates further by purification on normal-phase silica gel, successively with volume ratio be 25:1,15:1 and 2:1 methylene chloride-methanol gradient elution obtain 3 components；E reverse phase silica gel that in () step (d), component 2 is bonded by octadecylsilane separates, with the methanol aqueous solution isocratic elution that concentration expressed in percentage by volume is 72%, collecting 8～14 column volume eluents, eluent concentrating under reduced pressure obtains pure compound (I).
Further, in the preparation method of compound (I), step (a) is extracted with 75% 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) replaces ethyl acetate to extract with dichloromethane, obtains dichloromethane extract.
The above-claimed cpd (I) application in the medicine of preparation treatment insufficiency of kidney-YANG.
The application in the medicine of preparation treatment insufficiency of kidney-YANG of the pharmaceutical composition of above-mentioned fenofibrate.
Advantages of the present invention:
The pharmaceutical composition of fenofibrate provided by the invention contains the natural product of fenofibrate and a kind of novel structure, when fenofibrate and this natural product independent role, there is treatment insufficiency of kidney-YANG effect；During the two synergy, treat insufficiency of kidney-YANG better effects if, it is possible to develop into the medicine for the treatment of insufficiency of kidney-YANG.
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.Although the present invention being explained in detail with reference to preferred embodiment, it will be understood by those within the art that, it is possible to technical scheme is modified or equivalent replacement, without deviating from the spirit and scope of technical solution of the present invention.
Embodiment 1: compound (I) separates preparation and structural identification
Reagent source: ethanol, petroleum ether, ethyl acetate, n-butyl alcohol, dichloromethane are analytical pure, purchased from Shanghai Ling Feng chemical reagent company limited, methanol, analytical pure, purchased from Jiangsu Han Bang chemical reagent company limited.
Separation method: Herba Ecliptae (2kg) is pulverized by (a), (20L × 3 time) are extracted with 75% alcohol heat reflux, united extraction liquid, it is concentrated into without alcohol taste (4L), extract with petroleum ether (4L × 3 time), ethyl acetate (4L × 3 time) and water saturated n-butyl alcohol (4L × 3 time) successively, respectively obtain petroleum ether extract, acetic acid ethyl ester extract and n-butyl alcohol extract；B n-butyl alcohol extract D101 type macroporous resin remove impurity in () step (a), first with 6 column volumes of 15% ethanol elution, then with 10 column volumes of 70% ethanol elution, collects 70% eluent, concentrating under reduced pressure obtains 70% ethanol elution concentrate；C in () step (b), 70% ethanol elution concentrate purification on normal-phase silica gel separates, obtain 4 components with the methylene chloride-methanol gradient elution that volume ratio is 80:1 (8 column volumes), 30:1 (8 column volumes), 15:1 (8 column volumes) and 5:1 (10 column volumes) successively；D in () step (c), component 3 separates further by purification on normal-phase silica gel, obtain 3 components with the methylene chloride-methanol gradient elution that volume ratio is 25:1 (8 column volumes), 15:1 (10 column volumes) and 2:1 (5 column volumes) successively；E reverse phase silica gel that in () step (d), component 2 is bonded by octadecylsilane separates, with the methanol aqueous solution isocratic elution that concentration expressed in percentage by volume is 72%, collecting 8～14 column volume eluents, eluent concentrating under reduced pressure obtains compound (I) (purity is more than 98%).
Structural identification: HR-ESI-MS shows [M+H]+For m/z261.1087, can obtain molecular formula in conjunction with nuclear-magnetism feature is C15H16O4, degree of unsaturation is 8.Hydrogen nuclear magnetic resonance modal data δH(ppm, CDCl3null，500MHz): H-3 (5.69，s)，H-5(2.61，d，J=11.7Hz)，H-6(3.93，dd，J=11.7，10.6Hz)，H-7(2.54，dt，J=3.2，10.6Hz)，H-8α(2.05，m)，H-8β(1.65，ddt，J=12.3，3.6，13.2Hz)，H-9α(2.21，dt，J=4.1，13.2Hz)，H-9β(1.94，dt，J=13.2，3.6Hz)，H-13(5.46，d，J=3.1Hz)，H-13(6.08，d，J=3.1Hz)，H-14(1.11，s)，H-15(1.93，d，J=1.3Hz)；Carbon-13 nmr spectra data δC(ppm, CDCl3, 125MHz): 183.5 (C, 1-C), (187.1 C, 2-C), 125.4 (CH, 3-C), 175.1 (C, 4-C), (44.8 CH, 5-C), 80.3 (CH, 6-C), (49.4 CH, 7-C), 20.9 (CH2, 8-C), 38.2 (CH2, 9-C), 46.2 (C, 10-C), 138.3 (C, 11-C), 170.3 (C, 12-C), 117.9 (CH2, 13-C), 18.2 (CH3, 14-C), 23.6 (CH3, 15-C).1716cm in infrared spectrum-1236nm absorption band in absorption band and UV spectrum shows that this compound contains α, β-unsaturated gamma lactone structure, further and by analysis13δ in C-NMR spectrumC80.3, the carbon signal of 49.4,138.3,170.3,117.9 is known exists the outer methylene gamma lactone structure of ring.13C-NMR, DEPT and hsqc spectrum show 15 carbon signals, including two methyl, three methylene (an alkene carbon), four methines (company's oxygen carbon and an alkene carbon), and six quaternary carbons (two alkene carbon and three carbonyl carbon).In conjunction with insatiable hunger sum, function above structure shows that this compound is tricyclic structure.1H-NMR spectrum shows two methyl proton signal δ in conjunction with hsqc spectrumH1.11 (3H, s), 1.93 (3H, d, J=1.3Hz), pair of end olefinic proton signals δH6.08 (1H, d, J=3.1Hz) and 5.46 (1H, d, J=3.1Hz), a company oxygen methine proton signal δH3.93 (1H, dd, J=11.7,10.6Hz), an olefinic methine proton signal δH5.69 (1H, s).Pass through1H-1H-5/H-6/H-7/H in HCOSY spectrum2-8/H2-9 coherent signals, and H-3 and the C-1 shown in HMBC spectrum, C-2, C-4 and C-5, H-5 and C-6 and C-10, H-6 and C-7, C-8, C-11 and C-12, H-7 and C-6, C-11, C-12 and C-13, H2-13 with C-7 and C-12, H3-14 with C-10 coherent signal, the connected mode of this compound can be built, and above-mentioned spectral data shows that this compound is eudesmane, and there is the outer methylene gamma lactone structure of ring, C-5 in this compound, C-6, C-7 and C-10 are chiral carbon, confirm relative configuration by NOESY test with H-H coupling constant.In NOESY spectrum, H-6/H-8 β, H-6/H-14 and H-8 β/H-14 coherent signal shows that these hydrogen are in the same side, another H-5/H-7, H-5/H-9 α and H-7/H-9 α coherent signal shows that these hydrogen are in the same side, these coherent signals are consistent to the result of relevant coupling constant, and also indicating that the trans connection of A/B and B/C ring, therefore above coherent signal may indicate that the C-5 of this compound, C-6, C-7 and C-10 are configured as 5S, 6S, 7S and 10R.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 is determined by ECD test further, and theoretical value is basically identical with experiment value.
This compound chemistry formula and carbon atoms numbered are as follows:
Embodiment 2: pharmacological action
The present embodiment uses hydrocortisone injection to prepare Mouse Kidney model of yang asthenia, observe medicine and each group of mice is detected Serum testosterone (T), lutropin (LH), follotropin (FSH) level, the impact that sperm concentration, motility of sperm change.
1, materials and methods
1.1 animals
Regular grade health male mice in kunming 50, age in days 50d, weight 17～22g, room temperature 16～20 DEG C, humidity 65%～70%, feed of freely drinking water (provides by Hunan University of Traditional Chinese Medicine's Experimental Animal Center) above.
1.2 reagent and sample
Fenofibrate is purchased from Nat'l Pharmaceutical & Biological Products Control Institute.Compound (I) is made by oneself, and preparation method is shown in embodiment 1.Hydrocortisone injection (specification: 10mg/2mL；Tianjin Pharmaceutical Group Xinzheng Co., Ltd. produces).Human Serum Testosterone (T) radioimmunoassay kits (Beimian-Dongya Inst. of Biotechnology, Beijing's production).Human luteinizing hormone (LH) radioimmunoassay kits (Beimian-Dongya Inst. of Biotechnology, Beijing's production).Human follicle-stimulating generates hormone (FSH) radioimmunoassay kits.
Prepared by 1.3 mice group and model
First from 50 mices, extract 10 with random digits table and be only used as normal group, remaining 40 are only used as modeling group: all intragluteal injection hydrocortisone injection 25mg/ every days (kg d), continuous 12d, the objective indicator according to insufficiency of kidney-YANG symptom: be afraid of cold, aversion to cold and preference for warmth, extremity are not warm, the atrophy fat, spiritual of clear urine in large amounts, thready pulse, light red tongue, become thin etc. and to determine model success or not.After modeling success, then adopt random digits table that modeling mice is divided into model control group, fenofibrate group (80mg kg-1), compound (I) group (80mg kg-1), fenofibrate and compound (I) compositions group [40mg kg-1Fenofibrate+40mg kg-1Compound (I)].Except normal group, all the other each group started continuous gavage 28d in the 13rd day, 2 times/d, the morning 8:30～9:30, afternoon 3:00～each 1 time of 4:00.Model group and normal group all give normal saline every time.
1.4 serum T, LH, FSH horizontal detection
Mouse stomach 4 weeks, water 12h, etherization are can't help in fasting, and glass capillary is taken a blood sample from eyeground vein clump, separate serum, 4 DEG C of preservations.According to the method in test kit description, T, LH, FSH level in mice serum is measured.
1.5 semen quality situation detections
Mouse stomach 4 weeks, water 12h is can't help in fasting, carries out sperm count, sperm motility rate under microscope, and motility of sperm measures.
1.6 statistical methods
Experimental data mean ± standard deviation (x ± s) represents, application SPSS18.0 version statistical software carries out one factor analysis of variance and t inspection, statistically significant for difference with P < 0.05.
2, experimental result
2.1 impacts on kidney-yang deficiency model mice serum T, LH, FSH level
Compare with Normal group, androgenic testosterone (T) level of model control group mice is decreased obviously, and lutropin (LH), follotropin (FSH) level relevant with male mice Reproductive Performance are also decreased obviously (P < 0.01).Compared with model group, fenofibrate group and compound (I) group T, LH, FSH level raise (P < 0.05), and fenofibrate and compound (I) compositions group T, LH, FSH significantly raise (P < 0.01).Result is in Table 1.
Table 1 mice with kidney-yang deficiency T, LH, FSH situation of change compares (mIU/mL)
| Group | T | LH | FSH |
| Normal group | 246.84±14.80 | 3.06±0.13 | 1.79±0.19 |
| Model control group | 152.23±35.30 | 1.66±0.23 | 0.80±0.22 |
| Fenofibrate group | 240.97±9.36 | 2.92±0.16 | 1.62±0.23 |
| Compound (I) group | 246.79±14.58 | 3.03±0.15 | 1.68±0.24 |
| Fenofibrate and compound (I) compositions group | 270.22±7.51 | 3.55±0.94 | 1.83±0.78 |
2.2 impacts on kidney-yang deficiency model mice semen quality situation
Comparing with Normal group, the semen quality of model control group mice is decreased obviously (P < 0.01).Compared with model group, fenofibrate group and compound (I) group sperm concentration raise (P < 0.05) with motility of sperm, and fenofibrate and compound (I) compositions group sperm quality significantly raise (P < 0.01).Result is in Table 2.
Mice with kidney-yang deficiency sperm quality is compared by table 2
| Group | Sperm concentration (106) | Motility of sperm (%) |
| Normal group | 22.36±1.19 | 14.50±1.35 |
| Model control group | 16.90±0.75 | 10.60±1.26 |
| Fenofibrate group | 21.34±1.44 | 13.41±1.17 |
| Compound (I) group | 21.45±1.41 | 13.60±1.51 |
| Fenofibrate and compound (I) compositions group | 24.78±0.46 | 16.24±0.41 |
This experiment adopts hydrocortisone to carry out the making of Mouse Kidney model of yang asthenia, and this is the insufficiency of kidney-YANG modeling method of classics, is characterized in that model is identical with the performance of insufficiency of kidney-YANG, it is possible to embody the pathological changes mechanism of insufficiency of kidney-YANG, and modeling method is fixed, success rate height.After this experiment modeling, the symptom that Animal performance goes out is more consistent with insufficiency of kidney-YANG symptom.
The above results shows, when fenofibrate, compound (I) independent role, Mouse Kidney yang deficiency is had therapeutical effect；When fenofibrate and compound (I) synergy, the therapeutic effect of Mouse Kidney yang deficiency is improved further, it is possible to develop into the medicine for the treatment of insufficiency of kidney-YANG.
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, it is possible to technical scheme is modified or equivalent replacement, without deviating from essence and the protection domain of technical solution of the present invention.
Claims (10)
1. a compound (I) with following structural formula,
2. the pharmaceutical composition of a fenofibrate, it is characterised in that: include fenofibrate, compound as claimed in claim 1 (I) and pharmaceutically acceptable carrier, prepare into the dosage form of needs.
3. the pharmaceutical composition of fenofibrate according to claim 2, it is characterised in that: pharmaceutically acceptable carrier includes diluent, excipient, filler, binding agent, wetting agent, disintegrating agent, absorption enhancer, surfactant, absorption carrier or lubricant.
4. the pharmaceutical composition of fenofibrate according to claim 2, it is characterised in that: described dosage form includes tablet, capsule, oral liquid, sucks agent, granule, electuary, pill, powder, unguentum, sublimed preparation, suspensoid, powder, solution, injection, suppository, spray, drop or patch.
5. the preparation method of the compound (I) described in claim 1, it is characterized in that, comprise following operating procedure: Herba Ecliptae is pulverized by (a), extract with 70～80% alcohol heat reflux, united extraction liquid, it is concentrated into without alcohol taste, successively with petroleum ether, ethyl acetate and water saturated n-butanol extraction, respectively obtains petroleum ether extract, acetic acid ethyl ester extract and n-butyl alcohol extract；B n-butyl alcohol extract macroporous resin remove impurity in () step (a), first with 6 column volumes of 15% ethanol elution, then with 10 column volumes of 70% ethanol elution, collects 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 80:1,30:1,15:1 and 5:1 methylene chloride-methanol gradient elution obtain 4 components；D in () step (c), component 3 separates further by purification on normal-phase silica gel, successively with volume ratio be 25:1,15:1 and 2:1 methylene chloride-methanol gradient elution obtain 3 components；E reverse phase silica gel that in () step (d), component 2 is bonded by octadecylsilane separates, with the methanol aqueous solution isocratic elution that concentration expressed in percentage by volume is 72%, collecting 8～14 column volume eluents, eluent concentrating under reduced pressure obtains pure compound (I).
6. the preparation method of compound according to claim 5 (I), it is characterised in that: step (a) is extracted with 75% alcohol heat reflux, united extraction liquid.
7. the preparation method of compound according to claim 5 (I), it is characterised in that: described macroporous resin is D101 type macroporous adsorbent resin.
8. the preparation method of compound according to claim 5 (I), it is characterised in that: step (a) replaces ethyl acetate to extract with dichloromethane, obtains dichloromethane extract.
9. the application in the medicine of preparation treatment insufficiency of kidney-YANG of the compound (I) described in claim 1.
10. the pharmaceutical composition of the arbitrary described fenofibrate of claim 2～4 application in the medicine of preparation treatment insufficiency of kidney-YANG.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610277991.7A CN105777684A (en) | 2016-04-28 | 2016-04-28 | Pharmaceutical composition of fenofibrate and pharmaceutical application of pharmaceutical composition |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610277991.7A CN105777684A (en) | 2016-04-28 | 2016-04-28 | Pharmaceutical composition of fenofibrate and pharmaceutical application of pharmaceutical composition |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN105777684A true CN105777684A (en) | 2016-07-20 |
Family
ID=56399020
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610277991.7A Withdrawn CN105777684A (en) | 2016-04-28 | 2016-04-28 | Pharmaceutical composition of fenofibrate and pharmaceutical application of pharmaceutical composition |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105777684A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105837422A (en) * | 2016-04-20 | 2016-08-10 | 宋晓梅 | Pharmaceutical composition of buprenorphine hydrochloride and application thereof in biomedicine |
-
2016
- 2016-04-28 CN CN201610277991.7A patent/CN105777684A/en not_active Withdrawn
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105837422A (en) * | 2016-04-20 | 2016-08-10 | 宋晓梅 | Pharmaceutical composition of buprenorphine hydrochloride and application thereof in biomedicine |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN105943532A (en) | Application of diterpenoid compound to preparation of medicament for treating liver cancer | |
| CN105801526A (en) | Drug composition of cyproheptadine hydrochloride and application thereof in biomedicine | |
| CN106008543A (en) | Novel diterpenoid compound and preparation method thereof | |
| CN105777842A (en) | Halcinonide medicine composition and application of same to biological medicine | |
| CN105949159A (en) | Medicine composition with pramipexole dihydrochloride and application of medicine composition to treating migraine | |
| CN105859739A (en) | Boc-L-valine pharmaceutical composition and application in biological pharmacy | |
| CN105524063A (en) | Novel terpene indole alkaloid compound, and preparation method and medical application thereof | |
| CN105669621A (en) | Pharmaceutical composition of chlortetracycline hydrochloride and medical application of pharmaceutical composition | |
| CN105669690A (en) | Clopidogrel hydrogen sulfate medicinal composition and medicinal application thereof | |
| CN105777684A (en) | Pharmaceutical composition of fenofibrate and pharmaceutical application of pharmaceutical composition | |
| CN105820144A (en) | Pharmaceutical composition of cefdinir and medical application thereof | |
| CN105198897A (en) | New kaurane diterpenoid compound, preparation method and medical application of compound in treating liver cancer | |
| CN106109459A (en) | The pharmaceutical composition of dipivefrine hydrochloride and the application in biological medicine thereof | |
| CN105753830A (en) | Estazolam medicine composition and application thereof in biological medicine | |
| CN105753681A (en) | Drug composition of citicoline sodium and medical application of drug composition | |
| CN105801541A (en) | Pharmaceutical composition of amoxicillin and medical application of pharmaceutical composition | |
| CN106188087A (en) | The pharmaceutical composition of a kind of naloxone hydrochloride and medical usage thereof | |
| CN105777670A (en) | Clemastine fumarate pharmaceutical composition and application thereof in biological medicine | |
| CN105884716A (en) | Pharmaceutical composition of glibenclamide and medical application thereof | |
| CN105906645A (en) | Novel indole alkaloid compounds as well as preparation method and medical application thereof | |
| CN105693493A (en) | Clobetasol propionate drug composition and medical application thereof | |
| CN105801590A (en) | Alprazolam pharmaceutical composition and anti-inflammatory and analgesic effects thereof | |
| CN105820143A (en) | Medicine composition of cholinophylline and application thereof to biological medicines | |
| CN105949150A (en) | Ifosfamide medicinal composition and application of ifosfamide medicinal composition in biological medicine | |
| CN105777695A (en) | Pharmaceutical composition of emetine hydrochloride and application of pharmaceutical composition in biomedicine |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C04 | Withdrawal of patent application after publication (patent law 2001) | ||
| WW01 | Invention patent application withdrawn after publication |
Application publication date: 20160720 |