CN103263385A - Celecoxib long-acting nano injection and preparation method thereof - Google Patents
Celecoxib long-acting nano injection and preparation method thereof Download PDFInfo
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- CN103263385A CN103263385A CN2013101830876A CN201310183087A CN103263385A CN 103263385 A CN103263385 A CN 103263385A CN 2013101830876 A CN2013101830876 A CN 2013101830876A CN 201310183087 A CN201310183087 A CN 201310183087A CN 103263385 A CN103263385 A CN 103263385A
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Abstract
The invention relates to long-acting nano injection containing celecoxib serving as a main component and being used for treating rheumatoid arthritis and a preparation method of the long-acting nano injection. The celecoxib is slowly released in a human body through an intramuscular or subcutaneous injection method to reach a long-acting effect, and the effect can be kept for 3 days or longer. According to the preparation method, the long-acting nano injection of the celecoxib is prepared by combining airflow crushing and high pressure homogenization, the release degree and the bioavailability of the celecoxib are improved, and the effect of the celecoxib is prolonged at the same time. The celecoxib long-acting nano injection can be preserved in a prefilled syringe in a suspension form or preserved in a sealed container in a dry powder form. The injection in the prefilled syringe can be directly used for injecting, and the injection in the sealed container can be blended with a matched injection solution to form a suspension for injecting.
Description
The present invention relates to a kind of main constituent and be the long-acting nano injection agent and preparation method thereof of the treatment rheumatoid arthritis of celecoxib.
Background technology
Celecoxib be a kind of treat acute stage or chronic phase osteoarthritis and the medicine of rheumatoid arthritis, its English Celecoxib by name is the inhibitor of a species specificity Cycloxygenase-2(COX-2), structure is as follows:
The generation of Cycloxygenase-2 can cause generation and the accumulation of inflammatory prostaglandins material (as PGE2 etc.), thereby causes inflammation.Celecoxib can suppress the generation of Cycloxygenase-2 effectively as a kind of Cycloxygenase-inhibitor 2, reaches the effect of anti-inflammatory analgesic.
Celecoxib belongs to biopharmacy categorizing system (BCS) 2 class medicines, is characterized in that dissolubility and bioavailability are all very low in water.Thereby bioavailability refers to medicine and can be utilized the degree that produces drug effect by human body after entering human body.Bioavailability is determined by multiple factor, comprising the dosage form of medicine and the physicochemical property of active substance etc.The bioavailability of chemicals depends on the dissolubility of active substance to a great extent, and therefore, the low solubility of celecoxib is the main cause that causes its low bioavailability.
At present, celecoxib has only oral formulations listing (for example celecoxib capsule of commodity celecoxib by name), and the shortcoming of celecoxib oral formulations is very outstanding.At first, the low solubility of celecoxib causes the bioavailability of its oral formulations very low, so oral absorption is very slow.Secondly, the celecoxib oral formulations, must be taken medicine once at least so medicine is stored in the body for a long time owing to utilize the gastrointestinal metabolism to absorb every day.Cause celecoxib blood drug level to produce fluctuation at period in a medicine and take medicine every day, can't keep mild blood drug level.
Therefore, a kind of shortcoming that can overcome the celecoxib oral formulations, the preparation that prolongs the celecoxib drug effect in the bioavailability that increases celecoxib better treats selection will for the patient.
Summary of the invention
Summary of the invention
The present invention is prepared into celecoxib can pass through muscle or hypodermic nano suspension.Said preparation has overcome oral formulations can't make medicine retain in vivo shortcoming for a long time, is reaching long-acting purpose thereby celecoxib is stored in after by injection slowly discharges in the body.Effective drug duration is 3 days or longer, and the length of concrete effective drug duration is controlled by regulating celecoxib granular size and dosage.The present invention provides a kind of simultaneously and prepares the method for the long-acting nano injection agent of above-mentioned celecoxib in conjunction with comminution by gas stream and high pressure homogenization technique.
The present invention can't realize the shortcoming of long-acting release medicine except overcoming oral formulations, also improved after its injection in vivo drug release rate and bioavailability by celecoxib being prepared into the nano-particle suspensoid.This is because the dissolubility of medicine follows the size of drug particles to be inversely proportional to, so the granule of medicine is more little, dissolubility is also just more high, and its drug release rate and bioavailability are also just more high.World patent WO0032189 and WO141760 mention that all celecoxib crude drug particle diameter is to the influence of its blood drug level.It shows as after the celecoxib grain diameter is decreased to micron order even nanoscale, and the highest blood drug level significantly increased after it was taken, and reaching, the time of high blood drug level then significantly shortens.
Yet conventional medicine breaking method is difficult to the granule of celecoxib is decreased to below 5 microns, more can't effectively control the size of particle diameter.And certain methods such as solvent evaporates rule need with an organic solvent be dissolved crude drug, may cause organic solvent residue, and can not accurately control the particle diameter of crude drug.And the celecoxib crude drug becomes needle-like, has very high adsorptivity and relatively poor flowability, is not suitable for directly being prepared into nanometer formulation by technology such as high pressure homogenize.
In order to address the above problem, the present invention utilizes comminution by gas stream that celecoxib is carried out preprocessing, makes the crude drug of celecoxib become the graininess micropowder from needle-like, reduces the adsorptivity of celecoxib, improves its flowability.Subsequently, be deployed into the suspension that can be used for high pressure homogenize by adding the celecoxib of surface stabilizer after comminution by gas stream, and then utilize high pressure homogenize that celecoxib is prepared into nanometer suspension liquid.
Two kinds of methods of comminution by gas stream and high pressure homogenize all do not need to add abrasive media or with an organic solvent, avoid medium and organic solvent residue.The particle diameter of celecoxib nanometer suspension liquid can be controlled by the intensity of high pressure homogenize.
Nanometer suspension liquid drying behind the high pressure homogenize can be mixed with into the high concentration suspension that is stored in precharging type syringe with other adjuvants and water after handling.But the nanometer suspension liquid behind the high pressure homogenize also drying is deposited in the sealed container with the form of dried sprills after handling, and mixes the back with the injection solution that contains other adjuvants before using and forms suspension for injection.
In sum, the present invention is by being prepared into long-acting nano injection agent in conjunction with comminution by gas stream and two kinds of methods of high pressure homogenize with celecoxib.This injection has following advantage:
1. traditional oral formulations every day is changed into long-acting injection, this injection does not need frequent injection, only need be in injection in 3 days or longer time once.
2. significantly improve dissolubility and the bioavailability of celecoxib.
In the preparation process not with an organic solvent, can not cause organic solvent residue, improve the safety of preparation.
4. because the granule of nano injection agent is very little, can make the faster generation drug effect of medicine.
5. can utilize the mode administration of injection.
6. do not need to add non-existent other materials or medium (as abrasive media etc.) in the final form formula in the preparation process, can not produce the residual of medium.
The mean diameter that the present invention mentions is D50 as not indicating in addition.D50 refers to the by volume calculation, and 50% granule is lower than this numerical value.The concentration of mentioning among the present invention is indicated the weight ratio that is based on suspension as not adding in addition.If said preparation is preserved with the form of dried sprills, concentration then is the weight ratio that powder and injection solution mix the formed suspension in back.
Detailed Description Of The Invention
It is a kind of for muscle or the long-acting nano injection agent of hypodermic celecoxib that one aspect of the present invention provides, and a kind of method for preparing this injection is provided on the other hand.
The long-acting nano injection agent of celecoxib of the present invention can allow the celecoxib granule be stored in the body after by muscle or subcutaneous injection, and these granules are enough to discharge the medicine that concentration reaches effective treatment level in 3 days or longer time.
The long-acting nano injection agent of celecoxib of the present invention comprises celecoxib and at least a surface stabilizer.The hydrophobicity on celecoxib surface causes the celecoxib granule to be difficult to be configured to suspension with water, surface stabilizer be adsorbed in the celecoxib nano-particle the surface but not can with celecoxib generation chemical reaction, be used for to improve the hydrophilic of celecoxib granule.Injection of the present invention can comprise two kinds and two or more surface stabilizers, comprising but be not limited to organic or inorganic pharmaceutic adjuvant.These adjuvants comprise various polymer, low-molecular-weight oligomer and surfactant.Surfactant comprises nonionic, ion, anion, cation and zwitterionic surfactant.
Surface stabilizer can be selected from but be not limited to: hydroxypropyl cellulose, hydroxypropyl emthylcellulose, hydroxy methocel, ethyl cellulose, polyvidone, NaTDC, polyvinylpyrrolidone, polysorbate, poloxamer etc.Surface stabilizer can be selected a kind of, also can be two kinds or two or more.The concentration of surface stabilizer is preferably 0.01% to 99.5%, and more preferably 0.01% to 40%, most preferably be 0.1% to 10%.
The preparation method of the long-acting nano injection agent of celecoxib of the present invention is characterized in that utilizing earlier comminution by gas stream that celecoxib crude drug powder particles is crushed to mean diameter below 200 microns.Celecoxib powder after the pulverizing and surface stabilizer and water are mixed and made into suspension, further reduce the celecoxib particle grain size by high pressure homogenize then.Size is controlled by the number of times of regulating the circulation of homogenization pressure and homogenizing.
In the above-mentioned preparation method, the mean diameter of celecoxib granule should be less than 200 microns behind the comminution by gas stream, and more excellent is less than 100 microns, and optimum is less than 50 microns.Celecoxib and surface stabilizer after the pulverizing are mixed into suspension, and the proportion of celecoxib in suspension is preferred 0.01% to 50%, and more preferably 0.1% to 40%, optimum 1% to 30%.
Pressure is unsuitable too high during high pressure homogenize, preferred 50 to 2000 bar, more excellent 300 to 1800 bar, optimum 400 to 1500 bar.The celecoxib particle diameter of the cycle-index of high pressure homogenize after according to comminution by gas stream determines.Preferred 50 nanometer to 5000 nanometers of celecoxib mean diameter behind the high pressure homogenize, more excellent is 100 nanometer to 4000 nanometers, optimum is 200 nanometer to 3000 nanometers.
The concentration of celecoxib suspension is unsuitable too high during high pressure homogenize, otherwise the too high reduction homogenizing of the viscosity of suspension efficient.During preparation earlier the suspension with low concentration carry out high pressure homogenize, by modes such as vacuum lyophilization or spray drying drying suspension, as required concentration was deployed into suspension for injection after the drying after homogenizing was finished.
The packing forms that utilizes the prepared injection of the present invention can be pre-filled suspending agent or the sterile injection powder agent that is directly used in injection.The sterile injection powder agent is deposited with the form of solid state powder, and the first and supporting injection solution of needs is deployed into suspension for injection during injection.
The long-acting nano injection agent of celecoxib of the present invention can be added a kind of or two kinds, even two or more antiseptic, also can not add antiseptic.Selective antiseptic is including, but not limited to methyl parahydroxybenzoate, and preferred concentration is about 0.18%; Phenol, preferred concentration is about 0.5%; Benzyl alcohol, preferred concentration is about 2%.
Can contain a kind of in the long-acting nano injection agent of the present invention or more than one suspending agent.Suspending agent is including, but not limited to Polyethylene Glycol (PEG), carbomer, hydroxypropyl emthylcellulose (HPMC), hyaluronate sodium etc.Preferred Polyethylene Glycol wherein, molecular weight polyethylene glycol is preferably between 400 to 12000, and wherein more preferably 1000 to 8000, most preferably be 3000 to 5000.
Long-acting nano injection agent of the present invention can be added a kind of or two kinds, even two or more pH regulator agent, also can not add.The pH regulator agent of selecting is including, but not limited to sodium hydroxide, citric acid, sodium dihydrogen phosphate, sodium hydrogen phosphate etc.Preferred pH regulator value is 5-10, and more excellent is 6-8.
Description of drawings: Fig. 1 is the particle size distribution figure of celecoxib granule after 180 circulations of high pressure homogenize under the pressure of 800 bar.
Fig. 2 is the graph of a relation of celecoxib granule its average diameter and homogenizing period when carrying out high pressure homogenize under the pressure of 800 bar.
Fig. 3 is through the celecoxib nanometer suspension liquid of high pressure homogenize with only through comminution by gas stream but without the dissolution comparison diagram of the celecoxib suspension of crossing high pressure homogenize.
Fig. 4 is the bioavailability comparison diagram of celecoxib nanometer long-acting injection and oral celecoxib capsule preparations.
The specific embodiment
Below by embodiment technical scheme of the present invention is further specified.Following embodiment is used for explanation the present invention but the present invention is not construed as limiting.
Embodiment 1: the preparation of celecoxib suspension.
With jet mill the celecoxib crude drug is carried out the high pressure pulverizing and make micropowder, celecoxib bulk density behind comminution by gas stream improves, and adsorptivity also significantly reduces.Subsequently, the celecoxib micropowder is mixed with 0.5% polysorbas20 solution, this mixture is made 5% celecoxib suspension after 2 minutes at mixing under the rotating speed of 2000 rpm through high-speed shearing machine.
Embodiment 2: the preparation of celecoxib nano powder.
The celecoxib suspension is slowly added high pressure homogenizer, after 180 circulations of homogenizing under the pressure of 800 bar, form nanometer suspension liquid.Celecoxib nanometer suspension liquid behind the high pressure homogenize is made nanometer powder after vacuum lyophilization.
The grain diameter of the nanometer suspension liquid that is prepared from behind high pressure homogenize with the light diffraction measurement, gauge is Malvern Mastersizer 2000 laser particle analyzers.Pump speed is 1250 rev/mins during measurement, and obscurity is measured after stablizing 1 minute between 10%, and Measuring Time is 30 seconds.Recording mean diameter is 1080 nanometers.Particle size distribution is seen Fig. 1.
Embodiment 3: the preparation of pre-filled celecoxib injection nano suspension.
Celecoxib nano powder among the embodiment 2 and other adjuvant are mixed and made into the injection suspensoid of component such as following table.
| Material | Weight ratio (%) |
| The | 40 |
| | 1% |
| Sodium dihydrogen phosphate-water | 0.25 |
| Disodium hydrogen phosphate,anhydrous | 0.5 |
| PEG 4000 | 7 |
Embodiment 4: the preparation of celecoxib nano powder injection.
Be equipped with the supporting solution of injection according to following table, this supporting liquid separates the sealing preservation with the celecoxib nano powder of embodiment 2.Inject the above two according to the 4(nano powder): mixed 6(solution) is mixed with injection nanometer suspension liquid.
| Material | Weight ratio (%) |
| | 1% |
| Sodium dihydrogen phosphate-water | 0.4 |
| Disodium hydrogen phosphate,anhydrous | 0.84 |
| PEG 4000 | 11.5 |
The control of embodiment 5. size.
This embodiment is by the size of the grain diameter of the period control celecoxib nanometer suspension liquid of control high pressure homogenize.Celecoxib micropowder behind the comminution by gas stream is mixed with 0.5% polysorbas20 solution, and this mixture is made 5% celecoxib suspension after 2 minutes at mixing under the rotating speed of 2000 rpm through high-speed shearing machine.The celecoxib suspension is slowly added high pressure homogenizer, under the pressure of 800 bar, carry out high pressure homogenize, respectively through 10,20,30,60,90,120, sampling and measuring particle diameter after 150,180 and 210 circulations.The result as shown in Figure 2.As can be seen from Figure 2, the grain diameter of celecoxib can be under the high pressure homogenize pressure of 800 bar be controlled until less than 1 micron effectively by regulating the homogenizing period.
Working sample is the celecoxib nanometer suspension liquid of the same concentration of 5% celecoxib suspension (being embodiment 1) and process high pressure homogenize (pressure is 800 bar, and cycle-index is 180 times) for the concentration through comminution by gas stream.Second appendix XC measures second method according to Chinese Pharmacopoeia version in 2010, adds working sample 1ml in digestion instrument, and rotating speed is that per minute 100 changes, and temperature is 37C, uses 900 milliliter 0.5% SDS phosphate (pH=6.8) to be dissolution medium.The sampling capacity is 4 ml during measurement, and the dissolution medium of additional same capability.Sampling is measured trap by centrifugal reaching by 0.22 micron filter paper filtering dilution back with spectrophotography (measuring wavelength is 253 nanometers), calculates stripping quantity.Stripping the results are shown in Figure 3.Fig. 3 shows that the dissolution of the celecoxib nanometer suspension liquid of process high pressure homogenize is apparently higher than the suspension that does not have nanorize.
The test of embodiment 7. bioavailability.
12 male beagle Canis familiaris L.s are divided into two groups, wherein one group every the celecoxib suspension by intramuscular injection 10 mg/kg embodiment 3 preparations.0.5,1,2,4,8,24,48 and 72 hours vein haemospasias before administration and after the administration.Another the group every oral 10 mg/kg of Canis familiaris L. celecoxib capsule (Pfizer), before administration and administration after 0.5,1,2,4,8,24 hours vein haemospasias.Sample goes out blood plasma through centrifugalize, detects blood drug level with high performance liquid chromatography.Average blood drug level testing result is seen Fig. 4.
The zoopery result shows that the celecoxib nanometer suspension liquid of embodiment 3 can keep higher blood drug level to 72 hour (3 days) after injection, and its highest blood drug level and bioavailability (AUC) all are significantly higher than traditional oral formulations.
Claims (10)
1. long-acting nano injection agent of celecoxib, its characteristics are: (a) be made of at least a drug particles, wherein active substance is celecoxib; (b) contain a kind of surfactant at least; (c) drug effect of this injection is 3 days or longer.
2. the long-acting nano injection agent of celecoxib according to claim 1 is characterized in that: (a) to calculate by weight be 0.01% to 99.5% to its active drug concentration; (b) have a kind of surface stabilizer at least, it is 0.01% to 99.5% that its concentration is calculated by weight; (c) active drug granule mean diameter is 200 to 3000 nanometers.
3. the long-acting nano injection agent of celecoxib according to claim 1, its preparation method is characterised in that: (a) utilize the method for comminution by gas stream to pulverize the celecoxib granule, tentatively reduce grain diameter; (b) utilize high pressure homogenize that the celecoxib granule behind the comminution by gas stream is further reduced.
4. the preparation method of the long-acting nano injection agent of celecoxib according to claim 3 is characterized in that the homogenization pressure in the high pressure homogenize process is 50 to 2000 bar, and more excellent is 300 to 1800 bar, and optimum is 400 to 1500 bar.
5. the preparation method of the long-acting nano injection agent of celecoxib according to claim 3 is characterized in that the homogenizing circulation in the high pressure homogenize process is 1 to 2000 circulation, and more excellent is 5 to 1000 circulations, and optimum is 50 to 600 circulations.
6. one kind is passed through the treatment osteoarthritis of injection celecoxib suspension and the method for rheumatoid arthritis, its suspension is characterized as: (a) be made of at least a drug particles, wherein active drug is celecoxib, and effective mean diameter of its granule is 200 to 3000 nanometers; (b) this suspension contains a kind of surface stabilizer at least; (c) drug effect of this suspension is 3 days or longer.
7. the long-acting nano injection agent of celecoxib according to claim 1 can have two kinds of packing forms: (a) this injection leaves in the syringe of the bottle of sealing or sealing with the form of suspension, and this suspension can be directly used in injection; (b) granule of this injection is deposited in the container with the state of dried powder, and the solution of allotment suspension is then deposited in the other container, and both are mixed into suspension for injection before injection.
8. the long-acting nano injection agent of celecoxib according to claim 7 if effective ingredient is deposited with the form of dried powder, is characterized in that so: (a) dried powder at least also comprises more than one surface stabilizer except active drug; (2) the suspension drying that contain active drug composition of powder after by high pressure homogenize obtains, and drying means comprises vacuum lyophilization and spray drying, perhaps other similar drying meanss.
9. the long-acting nano injection agent of celecoxib according to claim 7, its component characteristics are to contain the material of the raising resuspension degree that comprises more than one, such as HPMC and PEG, and preferred PEG wherein; Wherein the molecular weight of PEG is 400 to 12000, and more excellent is 1000 to 8000, and optimum is 3000 to 5000; It is 10 to 150 mg/ml that PEG concentration is calculated by weight, is preferably 50 to 100 mg/ml; For the injection of depositing with dried powder, this PEG concentration is particle powder and the mixed concentration of injection solution.
10. the long-acting nano injection agent of celecoxib according to claim 7, its component characteristics are that it can comprise the pH regulator agent, and as sodium hydroxide, citric acid, sodium dihydrogen phosphate, sodium hydrogen phosphate etc., preferred pH value is 5-10, and more excellent is 6-8.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103585164A (en) * | 2013-11-08 | 2014-02-19 | 海南合瑞制药股份有限公司 | Celecoxib solid composition with increased dissolution rate, and preparation method and application thereof |
| CN105147607A (en) * | 2015-10-14 | 2015-12-16 | 中国药科大学 | Celecoxib nanosuspension and preparation method thereof |
| CN114917188A (en) * | 2022-05-06 | 2022-08-19 | 沈阳药科大学 | Celecoxib long-acting nano suspension |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1512822A (en) * | 2002-12-27 | 2004-07-14 | ������������ʽ���� | Piezoelectric diaphragm and piezoelectric electroacoustic converter using piezoelectric diaphragm |
| CN101217939A (en) * | 2005-05-27 | 2008-07-09 | 灵药生物技术有限公司 | Injectable compositions and process of preparation thereof |
| CN102000018A (en) * | 2010-02-09 | 2011-04-06 | 浙江大学宁波理工学院 | Solid dispersion containing celecoxib as well as preparation method and application thereof |
| WO2012101242A1 (en) * | 2011-01-27 | 2012-08-02 | Capsulution Pharma Ag | Novel pharmaceutical suspension for parenteral application |
-
2013
- 2013-05-17 CN CN201310183087.6A patent/CN103263385B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1512822A (en) * | 2002-12-27 | 2004-07-14 | ������������ʽ���� | Piezoelectric diaphragm and piezoelectric electroacoustic converter using piezoelectric diaphragm |
| CN101217939A (en) * | 2005-05-27 | 2008-07-09 | 灵药生物技术有限公司 | Injectable compositions and process of preparation thereof |
| CN102000018A (en) * | 2010-02-09 | 2011-04-06 | 浙江大学宁波理工学院 | Solid dispersion containing celecoxib as well as preparation method and application thereof |
| WO2012101242A1 (en) * | 2011-01-27 | 2012-08-02 | Capsulution Pharma Ag | Novel pharmaceutical suspension for parenteral application |
Non-Patent Citations (2)
| Title |
|---|
| 李祥等: "塞来昔布微球的制备及体外释放考察", 《中国医院药学杂志》 * |
| 束雯等: "药品气流粉碎中的工艺参数研究", 《中成药》 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103585164A (en) * | 2013-11-08 | 2014-02-19 | 海南合瑞制药股份有限公司 | Celecoxib solid composition with increased dissolution rate, and preparation method and application thereof |
| CN103585164B (en) * | 2013-11-08 | 2015-12-02 | 海南合瑞制药股份有限公司 | Celecoxib solid composition that a kind of dissolution increases and its preparation method and application |
| CN105147607A (en) * | 2015-10-14 | 2015-12-16 | 中国药科大学 | Celecoxib nanosuspension and preparation method thereof |
| CN114917188A (en) * | 2022-05-06 | 2022-08-19 | 沈阳药科大学 | Celecoxib long-acting nano suspension |
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