CN106880597A - A kind of everolimus piece - Google Patents
A kind of everolimus piece Download PDFInfo
- Publication number
- CN106880597A CN106880597A CN201510924102.7A CN201510924102A CN106880597A CN 106880597 A CN106880597 A CN 106880597A CN 201510924102 A CN201510924102 A CN 201510924102A CN 106880597 A CN106880597 A CN 106880597A
- Authority
- CN
- China
- Prior art keywords
- everolimus
- piece according
- cyclodextrin
- hydroxypropyl beta
- piece
- 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.)
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
-
- 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
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/436—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
A kind of everolimus piece, everolimus, HYDROXYPROPYL BETA-CYCLODEXTRIN, deoxycholic acid are dissolved in absolute ethyl alcohol, then will be pelletized on this solution pharmaceutically acceptable auxiliary material, are dried, and add mix lubricant compressing tablet to form.Compared with prior art, preparation process is simple of the present invention, dispersion of medicine, smoothly, drug-eluting is rapid for production process.
Description
Technical field
The invention belongs to pharmaceutical technology field, and in particular to a kind of everolimus piece.
Background technology
Everolimus is a kind of inhibitor of mTOR (rapamycin mammal target point), one kind of PI3K/AKT passage downstreams
Serine threonine kinases.Everolimus is developed at first by Novartis Co., Ltd of Switzerland (Novartis), trade name Certican,
Listed in Sweden first within 2003, European market was captured comprehensively in 2006.
FDA ratifies it and is used for the patient of Sutent or Sorafenib treatment advanced renal cell cancer failure, according to the research of Novartis, according to
Wei Mosi can slow down the growth of kidney cancer cell, reduce by 67% death rate.By suppressing growth and the propagation of tumour cell,
Directly act on tumour cell；By suppressing blood vessel generation, cause tumor vessel to be distributed and reduce and play indirectly-acting (by having
Effect suppresses the propagation of the endothelial cell of generation and the VEGF inductions of tumour cell VEGF).
2010, everolimus was approved for preventing the organ rejection of heart and renal transplant recipients.Additionally, except nephrocyte
Rejection after cancer and organ transplant, everolimus also carrying out to neuroendocrine tumor, lymthoma, other cancers and
The research of tuberous sclerosis, can share as unitary agent or with existing cancer treatment method.
Everolimus, molecular formula：C53H83NO14, molecular weight：958.22, structural formula is as follows：
Everolimus is white to micro-yellow powder, lipophilicity, and solubility is 10 μ g/mL or so in water at 25 DEG C, according to BCS
Genealogical classification judgment principle, everolimus belongs to the BCSII class compounds of low-solubility, high osmosis.Therefore how by system
Agent technology improves compound dissolubility to meet dissolution rate and stability requirement, so as to ensure that the product effectively plays its treatment
Effect, is finally reached the quality consistent with former triturate, and tool is of great significance and is worth.
Chinese patent CN102138903B discloses a kind of Everolimus solid oral medicinal composition, including everolimus or its
The composition of derivative and excipient composition, the pH value of the aqueous solution of the composition is 4~7, the everolimus or its spread out
The percentage by weight that biology accounts for the composition is 0.05~5%, main ingredient is carried out by fluid bed technique for packing dispersed.
Its shortcoming is complicated preparation technology, and production operation difficulty is big, high cost；Water or other solvents are used in preparation process and is needed
Heat, cause the impurity of the drug for preparing greatly, stability is poor.
Chinese patent CN103585122A is carrier material by using hydroxypropyl cellulose, Hydroxypropyl methylcellulose etc., will be according to dimension
Department is not prepared into solid dispersions.But it is easy to aging in solid dispersions storing process, causes dissolution rate to reduce；Meanwhile, should
Invention has used the toxic solvents such as dichloromethane, chloroform, methyl alcohol, there is potential safety hazard.
Chinese patent CN104721158A carries out micronization processes by by everolimus, then mixes with other auxiliary materials, passes through
Dry granulation compressing tablet or direct tablet compressing are prepared from.It is easy to after drug micronization in aggregation, influence mixing uniformity and medicine
Dissolution rate.
Be dissolved in TC for everolimus, hydroxypropyl cellulose by Chinese patent CN104666261A, adds
Aerosil is adsorbed, then well mixed with pharmaceutically acceptable auxiliary material, is formed using the compacting of direct tablet compressing technique.
Due to there is organic solvent TC in preparation, a large amount of aerosil absorption are needed to cause piece weight larger, and
There are problems that sticking.
The content of the invention
In view of the deficiencies in the prior art, inventor intend providing a kind of Fast Stripping, be uniformly dispersed, without surfactant
Everolimus tablet.
Inventor considers that the purpose for preparing solid dispersions is exactly become because everolimus raw material is crystalline structure first
For amorphous.Prior art sticks to prepare everolimus solid dispersions, and if passing through preparation technique by everolimus system
It is standby then to reach effect same into amorphous, and in the absence of the aging phenomenon of solid dispersions.
Inventor attempts everolimus dissolving in ethanol, this solution as adhesive being pelletized on auxiliary material, obtains
The everolimus piece of same Fast Stripping, but the ethanol solution of everolimus viscosity is smaller, and the mobility of particle of preparation is poor,
Content uniformity is big；On this basis, inventor adds various adhesives in above-mentioned solution, although can be prepared into preferably
Particle, but in storage process, drug-eluting is substantially slack-off, it may be possible to and the amorphous drug of high-energy is slowly transformed into crystalline state
Medicine causes.
Unexpectedly, whether inventor is considered to combine and uses cyclodextrin inclusion technique, and hydroxypropyl is added in above-mentioned solution
Betadex, unbodied everolimus inclusion compound is prepared by simple granulation, drying, and using hydroxypropyl again he
Cyclodextrin has certain viscosity in ethanol, is used as adhesive, and the mobility of particle for obtaining is good.But,
Inclusion compound also occurs the problem that everolimus crystallization is separated out in long-time is placed, and causes drug-eluting slack-off.
Further, if inventor is considered in inclusion compound preparation process, a kind of material is added, is separated out with suppressing crystallization,
Effect is might have, by many experiments, inventor, as carrier, not only suppresses drug crystallization from deoxycholic acid, and
Dissolution rate can be improved.
Specifically, the present invention is achieved through the following technical solutions：
A kind of everolimus tablet, everolimus, HYDROXYPROPYL BETA-CYCLODEXTRIN, deoxycholic acid are dissolved in absolute ethyl alcohol,
Then will be pelletized on this solution pharmaceutically acceptable auxiliary material, dried, compressing tablet is formed.
Described everolimus tablet, everolimus is 1 with the weight ratio of HYDROXYPROPYL BETA-CYCLODEXTRIN:5-15.
Preferably, everolimus and the weight ratio of HYDROXYPROPYL BETA-CYCLODEXTRIN are 1:10.
Described everolimus tablet, everolimus is 1 with the weight ratio of deoxycholic acid:3-5.
Preferably, everolimus and the weight ratio of deoxycholic acid are 1:4.
Described everolimus tablet, pharmaceutically acceptable auxiliary material is filler, disintegrant and lubricant.
Described filler be lactose and mannitol in one or two.
Described disintegrant is one or more in PVPP, Ac-Di-Sol and sodium carboxymethyl starch.
Described lubricant is one or more in magnesium stearate, sodium stearyl fumarate and talcum powder.
Compared with prior art, preparation process is simple of the present invention, dispersion of medicine, without exhibiting high surface activating agent, production
Smoothly, drug-eluting is rapid for process.
Specific embodiment
Following examples further describe beneficial effects of the present invention, and embodiment is only used for the purpose of illustration, does not limit the present invention
Scope, while those of ordinary skill in the art are also contained in this hair according to the obvious change made of the present invention and modification
Within the scope of bright.
Embodiment 1
Preparation technology：
Everolimus, HYDROXYPROPYL BETA-CYCLODEXTRIN, deoxycholic acid are dissolved in absolute ethyl alcohol, then by this solution in lactose
Pelletized with sodium carboxymethyl starch, 40 DEG C of dryings, 20 mesh sieve whole grains add magnesium stearate in dry particl, be well mixed, pressure
Piece is formed.
Embodiment 2
Preparation technology：
Everolimus, HYDROXYPROPYL BETA-CYCLODEXTRIN, deoxycholic acid are dissolved in absolute ethyl alcohol, then by this solution in lactose
Pelletized with Ac-Di-Sol, 40 DEG C of dryings, 20 mesh sieve whole grains add magnesium stearate in dry particl, mixing is equal
Even, compressing tablet is formed.
Embodiment 3
Preparation technology：
Everolimus, HYDROXYPROPYL BETA-CYCLODEXTRIN, deoxycholic acid are dissolved in absolute ethyl alcohol, then by this solution in sweet dew
Pelletized on alcohol and PVPP, 40 DEG C of dryings, 20 mesh sieve whole grains add magnesium stearate in dry particl, be well mixed, pressure
Piece is formed.
Embodiment 4
Preparation technology：
Everolimus, HYDROXYPROPYL BETA-CYCLODEXTRIN, deoxycholic acid are dissolved in absolute ethyl alcohol, then by this solution in lactose
Pelletized with PVPP, 35 DEG C of dryings, 18 mesh sieve whole grains add magnesium stearate in dry particl, be well mixed, compressing tablet
Form.
Comparative example 1
Preparation technology：
Everolimus is dissolved in absolute ethyl alcohol, then this solution is pelletized in lactose, 35 DEG C of dryings, 18 mesh sieve whole grains,
Magnesium stearate is added in dry particl, is well mixed, compressing tablet is formed.
Comparative example 2
Preparation technology：
Recipe quantity everolimus is taken, is processed through air-flow crushing, make median particle diameter D50 no more than 100 μm, by everolimus
It is well mixed with BHT, lactose, HPMC, PVPP, magnesium stearate, compressing tablet is obtained final product.
Comparative example 3
(1) preparation of everolimus solid dispersions
1 part of everolimus
4 parts of absolute ethyl alcohol
0.3 part of hydroxypropyl cellulose
Preparation technology：After everolimus is dissolved in into absolute ethyl alcohol, hydroxypropyl cellulose is added, then stirring and dissolving utilizes
Prepared by supercritical fluid technique, by supercritical fluid quick expansion method, solution is passed through nozzle, capillary and depressurize, super to face
Boundary's fluid rapid expanding, generates the extremely tiny solid dispersions containing everolimus.
(2) preparation of everolimus piece
Preparation technology：Everolimus solid dispersions and lactose, sodium carboxymethyl starch, magnesium stearate are mixed, compressing tablet is obtained final product.
Comparative example 4
Preparation technology：
Everolimus, HYDROXYPROPYL BETA-CYCLODEXTRIN are dissolved in absolute ethyl alcohol, then by this solution in lactose and the poly- dimension of crosslinking
Pelletized on ketone, 35 DEG C of dryings, 18 mesh sieve whole grains add magnesium stearate in dry particl, be well mixed, compressing tablet is formed.
Comparative example 5
Preparation technology：
Everolimus, HYDROXYPROPYL BETA-CYCLODEXTRIN, PVP are dissolved in absolute ethyl alcohol, then by this solution in lactose and
Pelletized on PVPP, 35 DEG C of dryings, 18 mesh sieve whole grains add magnesium stearate in dry particl, be well mixed, compressing tablet and
Into.
Comparative example 6
Preparation technology：
Everolimus, HYDROXYPROPYL BETA-CYCLODEXTRIN, poloxamer are dissolved in absolute ethyl alcohol, then by this solution in lactose
Pelletized with Ac-Di-Sol, 35 DEG C of dryings, 18 mesh sieve whole grains add magnesium stearate in dry particl, mixing is equal
Even, compressing tablet is formed.
Comparative example 7
Preparation technology：
Everolimus is dissolved in TC, adds hydroxypropyl cellulose, is stirred to dissolve, and adds prescription
The aerosil absorption of amount, is then well mixed, using direct with microcrystalline cellulose, PVPP, magnesium stearate
Tablet forming technique compacting is formed.
Checking embodiment
1st, dissolution rate
Chromatographic condition：It is filler with octadecylsilane chemically bonded silica；With acetonitrile -5mmol/L potassium dihydrogen phosphates (70：
30) it is mobile phase, 50 DEG C of column temperature, Detection wavelength is 277nm.
Test specimen mentioned above is taken, according to dissolution method (two methods of annex XC second of Chinese Pharmacopoeia 2010 edition), with
Water 500ml is dissolution medium, and rotating speed is 50 turns per minute, is operated in accordance with the law, during through 3 minutes, takes solution in right amount, filtration,
Subsequent filtrate is taken as need testing solution.Another precision weighs everolimus reference substance about 12.5mg, is placed in 50ml measuring bottles, first
Plus acetonitrile 5ml dissolves it, then solubilization goes out medium to scale, shakes up, and precision measures 1ml and is placed in 100ml measuring bottles,
Solubilization goes out medium to scale, shakes up, used as reference substance solution.Precision measures each 100 μ l of above two solution, injects liquid
Chromatography, records chromatogram, calculates the stripping quantity of every with main peak and isomers peak area sum by external standard method.Limit is
The 80% of labelled amount, should meet regulation.
2nd, relevant material
Take this product fine powder appropriate (being approximately equivalent to everolimus 2.5mg), accurately weighed, in putting 10ml measuring bottles, plus acetonitrile is molten
Scale is solved and be diluted to, is shaken up, be centrifuged, take supernatant liquid filtering, take subsequent filtrate as need testing solution；Precision is measured for examination
Product solution 1ml, in putting 100ml measuring bottles, plus dilution in acetonitrile is to scale, shakes up, used as contrast solution.According to high-efficient liquid phase color
Spectrometry (two D of annex V of Chinese Pharmacopoeia version in 2010) is determined, with octadecylsilane chemically bonded silica as filler；Flowing
Phase A is 5mmol/L potassium dihydrogen phosphates, and Mobile phase B is acetonitrile；Flow velocity is 1.0ml per minute, linear gradient elution；
55 DEG C of column temperature；Detection wavelength is 277nm.Everolimus peak and isomers peak (relative retention time with main peak is about 1.05)
Separating degree should meet regulation, number of theoretical plate is calculated by everolimus peak and is not less than 5000.Precision measures the μ l of contrast solution 20
Injection liquid chromatograph, adjusts detection sensitivity, makes the 20%~25% of the peak height about full scale at principal component peak；It is accurate again
Need testing solution and each 20 μ l of contrast solution are measured, liquid chromatograph is injected separately into, chromatogram is recorded.Need testing solution chromatogram
If any impurity peaks in figure, in addition to solvent peak and isomers peak (relative retention time with main peak is about 1.05), single impurity
Peak area cannot be greater than the 1/5 (0.2%) of contrast solution main peak area, each impurity peak area and cannot be greater than contrast solution master
2 times (2.0%) of peak area.(any peak less than 0.05 times of contrast solution main peak area is negligible in need testing solution)
3rd, uniformity of dosage units
Chromatographic condition：It is filler with octadecylsilane chemically bonded silica；With acetonitrile -5mmol/L potassium dihydrogen phosphates (70：
30) it is mobile phase, 50 DEG C of column temperature, Detection wavelength is 277nm.
Take this product a piece of, in putting 5ml measuring bottles, plus flow phased soln and be diluted to scale, shake up, filter, take subsequent filtrate work
It is need testing solution, is determined according to the lower method of assay, calculate content, regulation (Chinese Pharmacopoeia version two in 2010 should be met
The E of portion's annex Ⅹ).
Each embodiment measurement result is as follows：
As seen from the table, embodiment of the present invention dissolution is rapid, and uniformity of dosage units preferably, accelerates to investigate, and relevant material is substantially not
Become.Comparative example 1, without HYDROXYPROPYL BETA-CYCLODEXTRIN, after acceleration, because raw material is to crystal transfer, causes dissolution to become
Slowly；Comparative example 2, and using prior art, by raw material micronization processes, uniformity of dosage units is poor, and dissolution improves not clear
It is aobvious；Comparative example 3, and solid dispersions are prepared using supercritical technology, in study on the stability, there are solid dispersions
Aging, dissolution is slack-off；Comparative example 4, and without deoxycholic acid, after accelerating to investigate, dissolution rate declines；Contrast is implemented
Example 5 is using PVP effect not as the present invention；Comparative example 6 is using poloxamer effect not as the present invention；Contrast is implemented
The uniformity of dosage units of example 7 is bad.
Claims (9)
1. a kind of everolimus piece, is made up of everolimus, HYDROXYPROPYL BETA-CYCLODEXTRIN and deoxycholic acid.
2. everolimus piece according to claim 1, it is characterised in that it by everolimus, HYDROXYPROPYL BETA-CYCLODEXTRIN,
Deoxycholic acid is dissolved in absolute ethyl alcohol, then will be pelletized on this solution pharmaceutically acceptable auxiliary material, is dried, and adds profit
Lubrication prescription mixed pressuring plate is formed.
3. everolimus piece according to claim 1, it is characterised in that the weight of everolimus and HYDROXYPROPYL BETA-CYCLODEXTRIN
Than being 1:5-15.
4. everolimus piece according to claim 1, it is characterised in that the weight of everolimus and HYDROXYPROPYL BETA-CYCLODEXTRIN
Than being 1:10.
5. everolimus piece according to claim 1, it is characterised in that everolimus is 1 with the weight ratio of deoxycholic acid:3-
5, preferably 1:4.
6. everolimus piece according to claim 2, it is characterised in that pharmaceutically acceptable auxiliary material is filler, disintegration
Agent and lubricant.
7. everolimus piece according to claim 6, it is characterised in that described filler is in lactose and mannitol
Plant or various.
8. everolimus piece according to claim 6, it is characterised in that described disintegrant is PVPP, crosslinking carboxylic
One or more in sodium carboxymethylcellulose pyce and sodium carboxymethyl starch.
9. everolimus piece according to claim 6, it is characterised in that described lubricant is rich magnesium stearate, stearic acid
One or more in horse acid sodium and talcum powder.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510924102.7A CN106880597B (en) | 2015-12-14 | 2015-12-14 | Everolimus tablet |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510924102.7A CN106880597B (en) | 2015-12-14 | 2015-12-14 | Everolimus tablet |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN106880597A true CN106880597A (en) | 2017-06-23 |
| CN106880597B CN106880597B (en) | 2022-06-07 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510924102.7A Active CN106880597B (en) | 2015-12-14 | 2015-12-14 | Everolimus tablet |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106880597B (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108938584A (en) * | 2018-08-17 | 2018-12-07 | 湖北欣瑞康医药科技有限公司 | A kind of tablet and preparation method thereof of the Tivozanib of inhibitor containing vegf receptor salt |
| CN112630367A (en) * | 2020-12-18 | 2021-04-09 | 卓和药业集团有限公司 | High performance liquid chromatography analysis method of everolimus |
Citations (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101098875A (en) * | 2005-01-05 | 2008-01-02 | 特瓦药厂私人有限公司 | Amorphous tacrolimus and preparation thereof |
| CN101115758A (en) * | 2005-02-04 | 2008-01-30 | 韩美药品株式会社 | Amorphous taclolimus solid dispersion having an enhanced solubility and pharmaceutical composition comprising same |
| CN101361703A (en) * | 2008-09-24 | 2009-02-11 | 宋洪涛 | Sirolimos sustained and controlled release preparation and preparation method thereof |
| CN101433721A (en) * | 2007-11-16 | 2009-05-20 | 华中科技大学 | Nimesulide-hydroxypropyl-beta-cyclodextrin inclusion compound eye drops and preparation method thereof |
| CN101664394A (en) * | 2009-09-25 | 2010-03-10 | 宋洪涛 | Tacrolimus sustained-release preparation and preparation method thereof |
| CN102008429A (en) * | 2009-09-25 | 2011-04-13 | 宋洪涛 | Tacrolimus controlled release preparation and preparation method thereof |
| US20120041068A1 (en) * | 2010-08-11 | 2012-02-16 | Aptapharma, Inc. | Extended Release Pharmaceutical Preparations for Active Pharmaceutical Ingredients with pH Dependent Solubility |
| CN102688243A (en) * | 2012-06-18 | 2012-09-26 | 中国药科大学 | Clathrate compound of perphenazine cyclodextrin derivative, and preparation method thereof |
| CN102784150A (en) * | 2012-09-04 | 2012-11-21 | 中国药科大学 | Clozapine cyclodextrin inclusion compound and preparation method thereof |
| EP2537534B1 (en) * | 2011-06-22 | 2014-12-17 | Hexal AG | Esters of (1S,9S)-9-[[(1S)-1-carboxy-3-phenylpropyl]amino]octahydro-10-oxo-6H-pyridazino[1,2-a][1,2]diazepine-1-carboxylic acid and their therapeutic use. |
-
2015
- 2015-12-14 CN CN201510924102.7A patent/CN106880597B/en active Active
Patent Citations (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101098875A (en) * | 2005-01-05 | 2008-01-02 | 特瓦药厂私人有限公司 | Amorphous tacrolimus and preparation thereof |
| CN101115758A (en) * | 2005-02-04 | 2008-01-30 | 韩美药品株式会社 | Amorphous taclolimus solid dispersion having an enhanced solubility and pharmaceutical composition comprising same |
| CN101433721A (en) * | 2007-11-16 | 2009-05-20 | 华中科技大学 | Nimesulide-hydroxypropyl-beta-cyclodextrin inclusion compound eye drops and preparation method thereof |
| CN101361703A (en) * | 2008-09-24 | 2009-02-11 | 宋洪涛 | Sirolimos sustained and controlled release preparation and preparation method thereof |
| CN101664394A (en) * | 2009-09-25 | 2010-03-10 | 宋洪涛 | Tacrolimus sustained-release preparation and preparation method thereof |
| CN102008429A (en) * | 2009-09-25 | 2011-04-13 | 宋洪涛 | Tacrolimus controlled release preparation and preparation method thereof |
| US20120041068A1 (en) * | 2010-08-11 | 2012-02-16 | Aptapharma, Inc. | Extended Release Pharmaceutical Preparations for Active Pharmaceutical Ingredients with pH Dependent Solubility |
| EP2537534B1 (en) * | 2011-06-22 | 2014-12-17 | Hexal AG | Esters of (1S,9S)-9-[[(1S)-1-carboxy-3-phenylpropyl]amino]octahydro-10-oxo-6H-pyridazino[1,2-a][1,2]diazepine-1-carboxylic acid and their therapeutic use. |
| CN102688243A (en) * | 2012-06-18 | 2012-09-26 | 中国药科大学 | Clathrate compound of perphenazine cyclodextrin derivative, and preparation method thereof |
| CN102784150A (en) * | 2012-09-04 | 2012-11-21 | 中国药科大学 | Clozapine cyclodextrin inclusion compound and preparation method thereof |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108938584A (en) * | 2018-08-17 | 2018-12-07 | 湖北欣瑞康医药科技有限公司 | A kind of tablet and preparation method thereof of the Tivozanib of inhibitor containing vegf receptor salt |
| CN108938584B (en) * | 2018-08-17 | 2021-01-26 | 湖北欣瑞康医药科技有限公司 | Tablet containing VEGF receptor inhibitor Tivozanib salt and preparation method thereof |
| CN112630367A (en) * | 2020-12-18 | 2021-04-09 | 卓和药业集团有限公司 | High performance liquid chromatography analysis method of everolimus |
Also Published As
| Publication number | Publication date |
|---|---|
| CN106880597B (en) | 2022-06-07 |
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