CN103908454B - A kind of pharmaceutical composition and its preparation method and application - Google Patents
A kind of pharmaceutical composition and its preparation method and application Download PDFInfo
- Publication number
- CN103908454B CN103908454B CN201410155681.9A CN201410155681A CN103908454B CN 103908454 B CN103908454 B CN 103908454B CN 201410155681 A CN201410155681 A CN 201410155681A CN 103908454 B CN103908454 B CN 103908454B
- Authority
- CN
- China
- Prior art keywords
- pharmaceutical composition
- aspirin
- nonaqueous carrier
- preparation
- present
- 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
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention relates to field of medicaments, disclose a kind of pharmaceutical composition and its preparation method and application.Pharmaceutical composition of the present invention includes the bisulfate clopidogrel treating effective dose and aspirin and the nonaqueous carrier comprising phospholipid.Aspirin and bisulfate clopidogrel are prepared the pharmaceutical composition becoming brand-new together with phospholipid by the present invention, it considerably lowers the gastrointestinal damage risk produced because of bisulfate clopidogrel and aspirin combination medication, do not change the pharmacokinetics level of two kinds of active component simultaneously, can be applicable in the various drug forms of preparation prevention and treatment cardiovascular and cerebrovascular disease.
Description
Technical field
The present invention relates to field of medicaments, be specifically related to a kind of pharmaceutical composition and its preparation method and application.
Background technology
Aspirin is the first-selection of cardiovascular patient prophylactic treatment medication, present stage clinical general increase
The second suppression platelet aggregation drugs-bisulfate clopidogrel so that it is improve with aspirin combination medication
Therapeutic effect, but this drug combination also brings some stomach damage (such as symptoms such as gastrorrhagias) simultaneously
Hidden danger.Result of study shows, relative to aspirin+placebo group, bisulfate clopidogrel+Ah Si
Woods group has lower cardiovascular event risk (p < 0.01), but has higher major bleeding events simultaneously
Risk (p < 0.01).
Although some researcher or mechanism's suggestion use PPI(proton pump inhibitor) reduce gastrorrhagia and send out
Raw probability, but bisulfate clopidogrel and PPI are all by CYP450 enzyme (especially in liver
CY2C19 enzyme) metabolism, when the two uses simultaneously, PPI may pass through competitive inhibition CYP2C19
(important member in CYP450 enzyme the second subfamily is the drug metabolism enzyme wanted of body weight for humans) and affect chlorine
The bioconversion of pyrrole Gray, affects its suppression platelet aggregation, and then causes the effect of drug combination
Have a greatly reduced quality, easily cause the generation of cardiovascular disease.Damage additionally, PPI is only capable of reducing upper digestive tract-stomach
Wound, there is no minimizing effect for lower digestive tract-intestinal injury.
For present case, PPI is restricted with the drug combination of bisulfate clopidogrel, only by
(mainly upper gastrointestinal hemorrhage, advanced age use China simultaneously to recommend to be used for the patient with High risk of bleeding
Method woods, aspirin, and with helicobacter pylori infections), and avoid use and CYP2C19 to have high parent
With the PPI of power, such as omeprazole and esomeprazole.
In a word, bisulfate clopidogrel aspirin combination medication adds the risk of injury of gastrointestinal tract, should
This is reduced, but the use of PPI is restricted and may weaken bisulfate clopidogrel drug effect and
To intestinal injury without minimizing effect, therefore, it is badly in need of developing a kind of new pharmaceutical composition, stomach can be reduced
The generation of intestinal injury, can not affect again the pharmacokinetics level of two kinds of principal agents.
Summary of the invention
In view of this, it is an object of the invention to provide a kind of pharmaceutical composition and preparation method thereof, make institute
State pharmaceutical composition and can reduce the gastrointestinal produced because of bisulfate clopidogrel and aspirin combination medication
Road damages, and does not affect the pharmacokinetics level of two kinds of principal agents simultaneously；
It is a further object to provide described pharmaceutical composition in preparation prevention and treatment cardiovascular disease
Application in medicine.
For achieving the above object, the present invention provides following technical scheme:
A kind of pharmaceutical composition, including the bisulfate clopidogrel for the treatment of effective dose and aspirin with
And nonaqueous carrier, described nonaqueous carrier comprises phospholipid.
As preferably, described bisulfate clopidogrel and the gross weight of aspirin and the weight of nonaqueous carrier
Amount is than being 1:20-20:1, it is highly preferred that bisulfate clopidogrel and the gross weight of aspirin and non-aqueous
The weight ratio of carrier is 1:4-4:1, it is further preferred that bisulfate clopidogrel and aspirin is total
The weight ratio of weight and nonaqueous carrier is 1:1-2:1.
As preferably, in described nonaqueous carrier, the concentration of phospholipid is 10%-40%, more preferably 37%.
Treatment effective dose of the present invention refers to the aspirin of 30mg-300mg every day, and
Every day 50mg-160mg bisulfate clopidogrel, it is conventional that the proportioning of two kinds of principal agents can refer to this area
Aspirin-bisulfate clopidogrel drug combination proportioning, as preferably, hydrogen sulfate chlorine in the present invention
The weight ratio of pyrrole Gray and aspirin is 3:4.
Phospholipid of the present invention includes multiple zwitterionic phospholipid, includes but not limited to, phosphatidyl gallbladder
Alkali, Phosphatidylserine, PHOSPHATIDYL ETHANOLAMINE, sphingomyelins and other ceramide, and multiple
Other zwitterionic phospholipid.As preferably, nonaqueous carrier of the present invention also comprises bio-compatible
Property oil.Biocompatibility oil of the present invention refers to that the people of any CFDA approval uses or animal is used
Oil.
As preferably, described nonaqueous carrier is lecithin oil, it is highly preferred that described lecithin oil is big
Bean lecithin.
Pharmaceutical composition of the present invention significantly reduces stomach/damage of intestines scoring in rat stomach/damage of intestines test,
Relative to not adding the aspirin-bisulfate clopidogrel drug combination group of phospholipid, medicine group of the present invention
Compound shows splendid reduction stomach/damage of intestines effect.
Meanwhile, the pharmaceutical composition pharmacokinetics level of the present invention experiment carried out in New Zealand white rabbit
Result shows, compared with aspirin and bisulfate clopidogrel, the present composition does not change two
Person's active metabolite serum levels.
Based on this, the present invention provides described pharmaceutical composition at preparation prevention and treatment cardiovascular and cerebrovascular disease
Application in medicine.When preparing related drugs, its dosage form be non-aqueous solution, paste, suspensoid,
Dispersant, colloid suspensions, capsule, aqueous emulsion or microemulsion, can be used for vivo medicine-feeding, be administered orally
Or topical.
Additionally, present invention also offers the preparation method of described pharmaceutical composition, with solvent with comprise phosphorus
The nonaqueous carrier mix homogeneously of fat, is subsequently adding bisulfate clopidogrel and the A Si for the treatment of effective dose
The mixing of woods, then cooling, filtration sterilization, lyophilizing removing solvent, it is thus achieved that described pharmaceutical composition.
As preferably, described bisulfate clopidogrel and the gross weight of aspirin and the weight of nonaqueous carrier
Amount is than being 1:20-20:1, it is highly preferred that bisulfate clopidogrel and the gross weight of aspirin and non-aqueous
The weight ratio of carrier is 1:4-4:1, it is further preferred that bisulfate clopidogrel and aspirin is total
The weight ratio of weight and nonaqueous carrier fat is 1:1-2:1.
As preferably, in described nonaqueous carrier, the concentration of phospholipid is 10%-40%, more preferably 37%.
Treat effective dose described in preparation method of the present invention and refer to the Ah Si of 30mg-300mg every day
Woods, and the bisulfate clopidogrel of 50mg-160mg every day, the proportioning of two kinds of principal agents can refer to
Aspirin-bisulfate clopidogrel drug combination proportioning that this area is conventional, as preferably, the present invention
The weight ratio of middle bisulfate clopidogrel and aspirin is 3:4.
Phospholipid described in preparation method of the present invention includes multiple zwitterionic phospholipid, includes but not limited to,
Phosphatidylcholine, Phosphatidylserine, PHOSPHATIDYL ETHANOLAMINE, sphingomyelins and other ceramide,
And multiple other zwitterionic phospholipid.As preferably, nonaqueous carrier of the present invention also comprises
Biocompatibility oil.Biocompatibility oil of the present invention refers to that the people of any CFDA approval uses
Or the oil of animal.
As preferably, the described biocompatibility oil containing phospholipid is lecithin oil, it is highly preferred that institute
Stating lecithin oil is soybean lecithin.
As preferably, solvent described in preparation method of the present invention is alcohols solvent, it is highly preferred that described
Alcohols solvent is ethanol.
From above technical scheme, the present invention by aspirin and bisulfate clopidogrel together with phospholipid
Preparation becomes brand-new pharmaceutical composition, and it significantly reduces because of bisulfate clopidogrel and aspirin
Drug combination and the gastric injury risk that produces, do not change the pharmacokinetics level of two kinds of active component simultaneously,
Can be applicable in the various drug forms of preparation prevention and treatment cardiovascular disease.
Accompanying drawing explanation
Fig. 1 show aspirin active metabolite salicylic pharmacokinetics comparison diagram；Its
In, ASAPC(20mg/kg) represent that the broken line of embodiment 1 pharmaceutical composition and its aspirin are given
Dose；ASA(20mg/kg) represent aspirin and its individually dosed amount of broken line；
Fig. 2 show the pharmacokinetics comparison diagram of bisulfate clopidogrel active metabolite；Its
In, CLOPC(15mg/kg) represent the broken line of embodiment 1 pharmaceutical composition and its hydrogen sulfate chlorine pyrrole
Gray's dosage；CLO(15mg/kg) represent bisulfate clopidogrel and broken line it is individually dosed
Amount.
Detailed description of the invention
The invention discloses a kind of pharmaceutical composition and its preparation method and application, those skilled in the art can
To use for reference present disclosure, it is suitably modified technological parameter and realizes.Special needs to be pointed out is, all similar
Replacing and change apparent to those skilled in the art, they are considered as being included in this
Bright.Pharmaceutical composition of the present invention and its preparation method and application is carried out by preferred embodiment
Describing, related personnel substantially can be to side as herein described in without departing from present invention, spirit and scope
Method and application are modified or suitably change and combine, and realize and apply the technology of the present invention.
Hereinafter a kind of pharmaceutical composition provided by the present invention and its preparation method and application is done furtherly
Bright.
Embodiment 1: prepare pharmaceutical composition of the present invention
By straight alcohol (purity >=99.5%, 20ml) and soybean lecithin (use Phosal35SB,
The one of soybean lecithin, 1.75g, phospholipid concentration 37%) under the conditions of 75 DEG C, use homogenate in advance
Machine mixes；After 5 minutes, add 750mg bisulfate clopidogrel and 1.0g aspirin, continue
Continuous mixing 15 minutes；It is cooled to room temperature afterwards, and uses the filter of 0.2 micron pore size to filter；
Finally carry out lyophilizing and remove ethanol, it is thus achieved that described pharmaceutical composition.
Embodiment 2: prepare pharmaceutical composition of the present invention
By straight alcohol (purity >=99.5%, 20ml) and soybean lecithin (use Phosal35SB,
The one of soybean lecithin, 0.875g, phospholipid concentration 20%) under the conditions of 75 DEG C, use homogenate in advance
Machine mixes；After 5 minutes, add 375mg bisulfate clopidogrel and 0.5g aspirin, continue
Continuous mixing 15 minutes；It is cooled to room temperature afterwards, and uses the filter of 0.2 micron pore size to filter；
Finally carry out lyophilizing and remove ethanol, it is thus achieved that described pharmaceutical composition.
Embodiment 3: prepare pharmaceutical composition of the present invention
By straight alcohol (purity >=99.5%, 20ml) and soybean lecithin (use Phosal35SB,
The one of soybean lecithin, 17.5g, phospholipid concentration 10%) under the conditions of 75 DEG C, use homogenate in advance
Machine mixes；After 5 minutes, add 375mg bisulfate clopidogrel and 0.5g aspirin, continue
Continuous mixing 15 minutes；It is cooled to room temperature afterwards, and uses the filter of 0.2 micron pore size to filter；
Finally carry out lyophilizing and remove ethanol, it is thus achieved that described pharmaceutical composition.
Embodiment 4: prepare pharmaceutical composition of the present invention
By straight alcohol (purity >=99.5%, 20ml) and soybean lecithin (use Phosal35SB,
The one of soybean lecithin, 43.75mg, phospholipid concentration 40%) use under the conditions of 75 DEG C in advance even
Pulp grinder mixes；After 5 minutes, add 375mg bisulfate clopidogrel and 0.5g aspirin,
Continue mixing 15 minutes；It is cooled to room temperature afterwards, and uses the filter of 0.2 micron pore size to carry out
Filter；Finally carry out lyophilizing and remove ethanol, it is thus achieved that described pharmaceutical composition.
Embodiment 5: prepare pharmaceutical composition of the present invention
By straight alcohol (purity >=99.5%, 20ml) and soybean lecithin (use Phosal35SB,
The one of soybean lecithin, 3.5g, phospholipid concentration 15%) under the conditions of 75 DEG C, use refiner in advance
Mixing；After 5 minutes, add 375mg bisulfate clopidogrel and 0.5g aspirin, continue
Mix 15 minutes；It is cooled to room temperature afterwards, and uses the filter of 0.2 micron pore size to filter；
Finally carry out lyophilizing and remove ethanol, it is thus achieved that described pharmaceutical composition.
Embodiment 6: prepare pharmaceutical composition of the present invention
By straight alcohol (purity >=99.5%, 20ml) and soybean lecithin (use Phosal35SB,
The one of soybean lecithin, 218.75mg, phospholipid concentration 25%) use under the conditions of 75 DEG C in advance even
Pulp grinder mixes；After 5 minutes, add 375mg bisulfate clopidogrel and 0.5g aspirin,
Continue mixing 15 minutes；It is cooled to room temperature afterwards, and uses the filter of 0.2 micron pore size to carry out
Filter；Finally carry out lyophilizing and remove ethanol, it is thus achieved that described pharmaceutical composition.
Embodiment 7: prepare pharmaceutical composition of the present invention
By straight alcohol (purity >=99.5%, 20ml) and soybean lecithin (use Phosal35SB,
The one of soybean lecithin, 437.5mg, phospholipid concentration 30%) use under the conditions of 75 DEG C in advance even
Pulp grinder mixes；After 5 minutes, add 375mg bisulfate clopidogrel and 0.5g aspirin,
Continue mixing 15 minutes；It is cooled to room temperature afterwards, and uses the filter of 0.2 micron pore size to carry out
Filter；Finally carry out lyophilizing and remove ethanol, it is thus achieved that described pharmaceutical composition.
Embodiment 8: gastric injury is tested
In SD rat (often group 22-25 is only, 150-200g), use embodiment of the present invention 1-7
Pharmaceutical composition gastric infusion 63mg/kg, after 10 minutes, rat oral gavage gives 1ml0.6mol/L
Hydrochloric acid, dissects after 1h, carries out stomach lesion assessment.Normal saline group is set simultaneously and uses merely
The matched group of aspirin+bisulfate clopidogrel.Result of the test is shown in Table 1.
Stomach method for estimating damage: stomach is immersed 4mL2% formalin 30min, then along stomach
Big curved incision stomach, uses slide calliper rule to measure the length and width (unit is mm) of each petechia,
(unit is mm to stomach damage=length x width2).
Gastric injury testing result respectively organized by table 1
As shown in Table 1, relative to normal saline group, the stomach damaged area of matched group dramatically increases
(p < 0.01)；And relative to matched group, the stomach damage surface of various embodiments of the present invention pharmaceutical composition
Amassing and substantially reduce (p < 0.01), minimizing amplitude reaches 60%.
Embodiment 9: injury of small intestine is tested
In the empty stomach SD rat using isoflurane anesthesia (often group 20～22,150～200g),
Use embodiment of the present invention 1-7 pharmaceutical composition through duodenum near-end be administered 100mg/kg, 90 points
Testing index after clock.Wherein, cut whole section of small intestinal (n=9～12) after partial rat euthanasia to be used for rushing
Intestinal lavage chamber also measures the hemoglobin concentration of flushing liquor；Another part rat (n=9～12) is being administered
60 minutes posterior veins injection Evans Blue dye liquid (10mg/ml), and when 90 minutes by small intestinal
Near-end 30cm cuts off, and observes staining conditions, then hatched with formamide solution under anatomic microscope
At night, measure the concentration (concentration height means that vascular permeability is big) of Azo-Blue；Physiology is set simultaneously
Saline group and use merely the matched group of aspirin+bisulfate clopidogrel.Result of the test is shown in Table
2。
Injury of small intestine testing result respectively organized by table 2
As shown in Table 2, relative to normal saline group, the enteric hemorrhage (hemoglobin concentration of matched group
And Azo-Blue concentration) dramatically increase (p < 0.01)；And relative to matched group, each reality of the present invention
The enteric hemorrhage executing example pharmaceutical composition substantially reduces (p < 0.01), and minimizing amplitude reaches 60%.
Embodiment 10: pharmacokinetics hydraulic test
In New Zealand white rabbit (often group 3, totally 3 groups), the 1st group uses the embodiment of the present invention 1
Gastric infusion 70mg/kg, the aspirin of the 2nd group of gastric infusion 20mg/kg, the 3rd group of gavage is given
The bisulfate clopidogrel of medicine 15mg/kg；And successively 0,0.5,1,2,4,8,12,24h
Totally 8 time points gather blood sample, analyze aspirin active metabolite salicylic acid, sulfur respectively
The serum levels of acid hydrogen clopidogrel hydrogen active metabolite.Result of the test as depicted in figs. 1 and 2,
As seen from the experiment, pharmaceutical composition of the present invention does not only change aspirin and hydrogen sulfate hydrogen chlorine pyrrole
Gray's pharmacokinetics level, and from whole result of the test figure, the medicine of pharmaceutical composition of the present invention
Obtain some for kinetics level to improve, be better than simple aspirin and hydrogen sulfate clopidogrel hydrogen.
The above is only the preferred embodiment of the present invention, it is noted that general for the art
For logical technical staff, under the premise without departing from the principles of the invention, it is also possible to make some improvement and profit
Decorations, these improvements and modifications also should be regarded as protection scope of the present invention.
Claims (9)
1. a pharmaceutical composition, it is characterised in that include the hydrogen sulfate chlorine pyrrole lattice treating effective dose
Thunder and aspirin and nonaqueous carrier, described nonaqueous carrier comprises phospholipid；
The weight ratio of described bisulfate clopidogrel and the gross weight of aspirin and nonaqueous carrier is
1:20-20:1。
Pharmaceutical composition the most according to claim 1, it is characterised in that described nonaqueous carrier is also
Comprise biocompatibility oil.
Pharmaceutical composition the most according to claim 2, it is characterised in that described nonaqueous carrier is
Lecithin oil.
Pharmaceutical composition the most according to claim 1, it is characterised in that in described nonaqueous carrier
The concentration of phospholipid is 10%-40%.
5. pharmaceutical composition described in claim 1 is in preparation prevention and treatment cardiovascular disease medicine
Application.
6. the preparation method of pharmaceutical composition described in claim 1, it is characterised in that with solvent with
Comprise the nonaqueous carrier mix homogeneously of phospholipid, be subsequently adding the hydrogen sulfate chlorine pyrrole lattice for the treatment of effective dose
Thunder and aspirin mixing, then filtration sterilization, it is thus achieved that described pharmaceutical composition.
Preparation method the most according to claim 6, it is characterised in that described nonaqueous carrier also wraps
Containing biocompatibility oil.
Preparation method the most according to claim 7, it is characterised in that described nonaqueous carrier is ovum
Phosphatide oil.
Preparation method the most according to claim 6, it is characterised in that phosphorus in described nonaqueous carrier
The concentration of fat is 10%-40%.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410155681.9A CN103908454B (en) | 2014-04-17 | 2014-04-17 | A kind of pharmaceutical composition and its preparation method and application |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410155681.9A CN103908454B (en) | 2014-04-17 | 2014-04-17 | A kind of pharmaceutical composition and its preparation method and application |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103908454A CN103908454A (en) | 2014-07-09 |
| CN103908454B true CN103908454B (en) | 2016-08-24 |
Family
ID=51034660
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410155681.9A Active CN103908454B (en) | 2014-04-17 | 2014-04-17 | A kind of pharmaceutical composition and its preparation method and application |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103908454B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111228217B (en) * | 2020-02-13 | 2022-02-11 | 广东药科大学 | Submicron emulsion containing clopidogrel or phospholipid complex of clopidogrel salt and preparation method thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1415284A (en) * | 2002-10-29 | 2003-05-07 | 上海医药工业研究院 | Non-steroid anti-inflammatory drug phospholipid capsule bubble and its preparation method |
| CN1543358A (en) * | 2000-12-19 | 2004-11-03 | �ÿ���˹ϵͳ��ѧ���»� | Nsaid formulations comprising lecithin oils for protecting the gastrointestinal tract and providing enhanced therapeutic activity |
| CN101065108A (en) * | 2004-10-12 | 2007-10-31 | 得克萨斯大学体系董事会 | Purified phospholipid-non-steroidal anti-inflammatory drug associated compositions and methods for preparing and using same |
| CN101703513A (en) * | 2009-11-10 | 2010-05-12 | 沈阳药科大学 | Compound sustained-release preparation of aspirin and clopidogrel or pharmaceutically acceptable salt thereof |
-
2014
- 2014-04-17 CN CN201410155681.9A patent/CN103908454B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1543358A (en) * | 2000-12-19 | 2004-11-03 | �ÿ���˹ϵͳ��ѧ���»� | Nsaid formulations comprising lecithin oils for protecting the gastrointestinal tract and providing enhanced therapeutic activity |
| CN1415284A (en) * | 2002-10-29 | 2003-05-07 | 上海医药工业研究院 | Non-steroid anti-inflammatory drug phospholipid capsule bubble and its preparation method |
| CN101065108A (en) * | 2004-10-12 | 2007-10-31 | 得克萨斯大学体系董事会 | Purified phospholipid-non-steroidal anti-inflammatory drug associated compositions and methods for preparing and using same |
| CN101703513A (en) * | 2009-11-10 | 2010-05-12 | 沈阳药科大学 | Compound sustained-release preparation of aspirin and clopidogrel or pharmaceutically acceptable salt thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN103908454A (en) | 2014-07-09 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| RU2664700C2 (en) | Depot formulations of local anesthetic and methods for preparation thereof | |
| KR102593667B1 (en) | Compositions comprising 5-cholesten-3, 25-diol, 3-sulfate (25hc3s) or pharmaceutically acceptable salt thereof and at least one cyclic oligosaccharide | |
| US20210267896A1 (en) | Formulations for treating bladder cancer | |
| CN104136008A (en) | Hormone containing emulsion | |
| CN107519159A (en) | Compound | |
| CN103908454B (en) | A kind of pharmaceutical composition and its preparation method and application | |
| CN108135895A (en) | For the oral medication taxol for the treatment of cancer and the therapeutic combination of P-gp inhibitor | |
| CN105939705A (en) | Composition comprising EPA and DHA triglycerides for parenteral administration | |
| CN104546722B (en) | Miriplatin lipidosome and preparation method thereof | |
| KR101353443B1 (en) | Injectable composition of phosphatidylcholine devoid of sodium deoxycholate and manufacturing method thereof | |
| CN103054799B (en) | Amiodarone hydrochloride injection emulsion and preparation method thereof | |
| CN105939706A (en) | Composition comprising EPA and DHA ethylester for parenteral administration | |
| CN103893125B (en) | Anidulafungin nanoparticle and preparation method thereof | |
| US20200138840A1 (en) | Pharmaceutical composition and tumor immunoactivity promoter | |
| BR112021016212A2 (en) | PHARMACEUTICAL COMPOSITION TO PREVENT THE RECURRENCE OF GASTROESOPHAGEAL REFLUX DISEASE AND USE OF SUCH COMPOSITION | |
| WO2017121383A1 (en) | Application of pirenzepine for treating sepsis | |
| CN110461325A (en) | Treatment including oral or stomach application Edaravone | |
| CN103040723B (en) | Xiyanping lipidosome injection | |
| CN102603865B (en) | Dipeptidase derivant and application thereof | |
| CN106619585B (en) | The application of cinnamic acid and its derivative in the drug of preparation prevention and treatment pulmonary fibrosis | |
| CN110115766B (en) | Compound preparation containing flurbiprofen axetil and preparation method thereof | |
| TWI787189B (en) | Formulations for treating bladder cancer | |
| Gong et al. | Efficacy and mechanism of energy metabolism dual-regulated nanoparticles (atovaquone-albendazole nanoparticles) against cystic echinococcosis | |
| US20210330588A1 (en) | Compositions and methods for administering anesthetics | |
| US20160324795A1 (en) | Silibinin nanoparticle and a method of treating hepatitis c 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 | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant |