CN109381436A - A Pa is for Buddhist nun's pharmaceutical composition and preparation method thereof - Google Patents
A Pa is for Buddhist nun's pharmaceutical composition and preparation method thereof Download PDFInfo
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- CN109381436A CN109381436A CN201810914090.3A CN201810914090A CN109381436A CN 109381436 A CN109381436 A CN 109381436A CN 201810914090 A CN201810914090 A CN 201810914090A CN 109381436 A CN109381436 A CN 109381436A
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- Prior art keywords
- buddhist nun
- pharmaceutical composition
- pharmaceutically acceptable
- acceptable salt
- tablet
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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
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- 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
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4866—Organic macromolecular compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicinal Preparation (AREA)
Abstract
The present invention relates to Ah pas for Buddhist nun's pharmaceutical composition and preparation method thereof.Specifically, the present invention relates to a kind of comprising Ah pa for Buddhist nun or the combination of oral medication of its pharmaceutically acceptable salt and pharmaceutically acceptable excipient.Wherein, excipient includes croscarmellose sodium.The pharmaceutical composition has the characteristics that good dissolution, prescription favorable reproducibility, related content of material are low.
Description
Technical field
The present invention relates to field of pharmaceutical preparations, in particular to the pharmaceutical composition and preparation method thereof of Buddhist nun is replaced containing Ah pa.
Background technique
In the growth and transfer of malignant tumour, the new vessels formation of tumour plays very important effect.Work as tumour
Volume growth when being more than 1mm3, need to generate new blood vessel or from existing blood vessel budding generate vessel branch, to mention
The survival of tumour cell is supported for enough blood supplies.The speed of growth and metastasis tendency and angiogenesis promoting factor level of tumour
And newborn microvessel quantity is related.From the beginning of the seventies in last century, Folkman propose " antiangiogenesis therapy " hypothesis it
Afterwards, people have considerable progress to the understanding in this field, inhibit tumor angiogenesis to be acknowledged as a kind of brand-new
Anticancer strategy.
Tyrosine kinase vascular endothelial growth factor (VEGF) and its receptor (VEGFR) are in the new vessels of tumour generate
It is the important target spot blocked in tumor angiogenesis with extremely important effect.Vascular endothelial growth factor (VEGF)
It is the factor of most important promotion angiogenesis in vivo.VEGF and the vascular endothelial growth factor receptor for being located at endothelial cell
(VEGFR) reaction for leading to a variety of angiogenesis after combining, as cell Proliferation, migration, vasopermeability increase, before endothelial cell
Body is removed from marrow.
VEGFR tyrosine kinase inhibitor can be by the letter after inhibiting VEGFR tyrosine kinase activity, blocking VEGF to combine
Number conduction, cause Tumor Angiongesis to inhibit, to treat tumour.Compared with the conventional cell cytotoxic drug for inhibiting tumour growth,
Targeting the therapeutic agent that new vessels generate has higher specificity, lower toxicity, and is conducive to overcome the resistance to of tumour
Pharmacological property, and can be used for the treatment of kinds of tumors.
Compound N-[4- (1- cyan cyclopentyl) phenyl] -2- (4- picolyl) amino-Niacinamide is a kind of
VEGFR inhibitor, the compound and its salt are disclosed in CN1502608A and CN101676267A for information about.
CN106243031A discloses the preparation method that Ah pa replaces Buddhist nun.CN105712929A,CN104961676A,CN104072413A,
CN105017142A, CN104072412A etc. disclose the crystal form that methanesulfonic acid Ah pa replaces Buddhist nun.The compound is VEGFR tyrosine-kinase
The new type antineoplastic medicine of enzyme inhibitor class selectively inhibits the tyrosine of vascular endothelial cell growth factor R-2 (KDR)
Kinase activity, effect are 13.7 times of another VEGFR inhibitor PTK787 of Novartis research and development, external anti-angiogenic life
It is better than or is equivalent to control compound PTK787 at effect.2014, methanesulfonic acid Ah pa was approved for late gastric cancer for Buddhist nun
Treatment, in Discussion on Chinese Listed.
Zhiwang Song etc. discloses cyclic annular arginyl glycyl aspartic acid (cRGD) and polyethylene glycol (PEG) is modified
Liposome (cRGD-Lipo-PEG) as Ah pa to be delivered to the targeted delivery of human colon cancer cell line HCT116 for Buddhist nun
System (Cyclic RGD peptide-modified liposomal drug delivery system for targeted
oral apatinib administration:enhanced cellular uptake and improved
therapeutic effects.International Journal of Nanomedicine.2017,12:1941-1958)；
Ji Hoon Jeong etc. discloses to deliver water-insoluble Ah pa for Buddhist nun, by drug encapsulation by human serum albumins
(HSA)-conjugation polyethylene glycol (PEG) composition nano particle (Therapeutic effect of apatinib-loaded
nanoparticles on diabetes-induced retinal vascular leakage.International
Journal of Nanomedicine.2016,11:3101-3109)。
CN102048737A, which is disclosed, replaces Buddhist nun or the combination of oral medication of its salt comprising Tarceva or its salt and A Pa,
Described pharmaceutical composition is tablet, capsule etc., and preparation method is wet granulation process or dry granulation method, pharmaceutical composition it is non-
Active constituent includes the excipient selected from lubricant, adhesive, diluent, disintegrating agent, wetting agent, preservative etc..In embodiment
Buddhist nun's maleate, erlotinib Hydrochloride, microcrystalline cellulose, starch slurry, magnesium stearate are replaced comprising Ah pa for Buddhist nun's mesylate/Ah pa
For the pharmaceutical composition of component.
Methanesulfonic acid Ah pa replaces Buddhist nun's slightly soluble in the phosphate buffer of pH2.0, in the phosphate buffer of pH4.0,6.0,8.0
In it is almost insoluble.This limited solubility limit methanesulfonic acid Ah pa for the preparation of Buddhist nun selection, it is also possible to lead to low life
Object availability.Therefore, it is necessary to study a kind of dosage form, makes methanesulfonic acid Ah pa for Buddhist nun from dosage form and possibly exposed in vivo
Solubility in journey reaches maximum, improves bioavilability of the compound in vivo in process-exposed.
Summary of the invention
The present invention provides a kind of good dissolution characteristic, formulation and technology favorable reproducibility, replaces Buddhist nun in relation to the low Ah pa of content of material
Combination of oral medication.
Product of the invention, stable processing technique, reproducibility are strong.The preparation process that the present invention uses is easy to operate, is easy to
Production amplification.A Pa obtained is good for nylon 6 combination In Vitro Dissolution, and related content of material is low, carries out to the quality in relation to substance
Effective control, reduces the probability of adverse reaction, improves Drug safety.
The present invention provides a kind of medication compositions, comprising Ah pa for Buddhist nun or its pharmaceutically acceptable salt and crosslinking carboxylic first
Base sodium cellulosate.
Combination of oral medication provided by the invention, Ah pa for Buddhist nun or its pharmaceutically acceptable salt be sole active at
Point.
Combination of oral medication provided by the invention, croscarmellose sodium mass percentage are selected from 5-15%,
It preferably is selected from 7-15%, most preferably from 7-13%.
Medication compositions provided by the invention, can also include filler, filler be selected from microcrystalline cellulose, lactose,
Mannitol, pregelatinized starch, dextrin, sorbierite, mass percentage are selected from 5-20%, 7-15% preferably are selected from, most preferably from 11-
13%.
Combination of oral medication provided by the invention, can also include adhesive, and adhesive is selected from pregelatinized starch, poly- dimension
Ketone, hydroxypropyl cellulose, hypromellose, sodium carboxymethylcellulose, polyethylene glycol, mass percentage are selected from 1-
10%, it preferably is selected from 3-8%, most preferably from 5-7%.
Combination of oral medication provided by the invention, can also include lubricant, and lubricant is selected from stearic acid, stearic acid
Magnesium, superfine silica gel powder, talcum powder, Macrogol 4000, Macrogol 6000, mass percentage are selected from 0.5-5%, preferably are selected from
0.5-3.5%, most preferably from 1.0-3.5%.
Combination of oral medication provided by the invention, group are selected from: Ah pa is for Buddhist nun or its pharmaceutically acceptable salt, crosslinking
Sodium carboxymethylcellulose, microcrystalline cellulose, pregelatinized starch, magnesium stearate, superfine silica gel powder, preferred mass percentage composition are Ah pa
For Buddhist nun or its pharmaceutically acceptable salt 50-80%, croscarmellose sodium 7-15%, microcrystalline cellulose 7-15%, pre-
Gelling starch 3-8%, magnesium stearate 0.5-1.5%, superfine silica gel powder 0-3%, more preferable mass percentage are that Ah pa replaces Buddhist nun 65-
75%, croscarmellose sodium 7-13%, microcrystalline cellulose 11-13%, pregelatinized starch 5-7%, magnesium stearate 0.7-
1.3%, superfine silica gel powder 0-2.5%.
Ah pa provided by the invention replaces Buddhist nun's combination of oral medication, the mass percent of each component are as follows:
| Component | Mass percent (%) |
| A Pa replaces Buddhist nun or its pharmaceutically acceptable salt | 68.22 |
| Croscarmellose sodium | 12.09 |
| Microcrystalline cellulose | 12.00 |
| Pregelatinized starch | 6.59 |
| Magnesium stearate | 1.10 |
Ah pa provided by the invention replaces Buddhist nun's combination of oral medication, the mass percent of each component are as follows:
| Component | Mass percent (%) |
| A Pa replaces Buddhist nun or its pharmaceutically acceptable salt | 68.98 |
| Croscarmellose sodium | 8.89 |
| Microcrystalline cellulose | 12.13 |
| Pregelatinized starch | 6.67 |
| Magnesium stearate | 1.11 |
| Superfine silica gel powder | 2.22 |
Ah pa provided by the invention replaces Buddhist nun's combination of oral medication, the mass percent of each component are as follows:
| Component | Mass percent (%) |
| A Pa replaces Buddhist nun or its pharmaceutically acceptable salt | 70.54 |
| Croscarmellose sodium | 9.09 |
| Microcrystalline cellulose | 12.41 |
| Pregelatinized starch | 6.82 |
| Magnesium stearate | 1.14 |
Ah pa provided by the invention replaces Buddhist nun's combination of oral medication, the mass percent of each component are as follows:
Combination of oral medication provided by the invention, composition are in the agent selected from tablet, capsule, micro tablet or granule
Type, preferred tablet.
Tablet provided by the invention, plain piece have thin coating outside, and coating agent filmogen is selected from polyvinyl alcohol, hydroxy propyl cellulose
Element, hypromellose, polyacrylic resin, preferably polyvinyl alcohol.
The method for preparing composition provided by the invention:
(1) weigh following component: Ah pa replaces Buddhist nun or its pharmaceutically acceptable salt, filler, cross-linked carboxymethyl cellulose
Sodium, adhesive, lubricant；
(2) Ah pa is crossed into 80 meshes for Buddhist nun or its pharmaceutically acceptable salt, it is spare；
(3) adhesive and wetting agent are configured to solution, it is spare；
(4) recipe quantity Ah pa is mixed for Buddhist nun or its pharmaceutically acceptable salt and other auxiliary materials for being used to pelletize, it is spare；
(5) above-mentioned (3) are taken, material in (4), using fluid-bed marumerization or wet granulation, through drying, whole grain, system
It is spare at single-size；
(6) material in above-mentioned (5) is taken to mix with remaining auxiliary material, tabletting replaces Buddhist nun's tablet to get Ah pa；Or take above-mentioned (5)
Middle material is mixed with remaining auxiliary material, records capsule to get Ah pa for Buddhist nun's capsule.
When solid composite provided by the invention is tablet, mixed after granulation with suitable excipient such as lubricant etc.,
Mixture is pressed into the tablet of expectation strength, it is selectable to be coated.
When solid composite provided by the invention is capsule, mixed after granulation with suitable excipient such as lubricant etc.,
Mixture is directly filled into capsule.
Ah pa of the present invention can be selected from mesylate or hydrochloride for Buddhist nun's pharmaceutically acceptable salt.
Solid composite provided by the invention, it is characterised in that there is good stripping property, prescription favorable reproducibility, related substance
The low feature of content.
Specific embodiment
The present invention is explained in greater detail below with reference to embodiment, the embodiment of the present invention is merely to illustrate skill of the invention
Art scheme, the spirit and scope of the invention are not limited thereto.
Embodiment 1:
Methanesulfonic acid Ah pa is prepared for Buddhist nun's piece according to prescription shown in the following table 1, and measures dissolution rate.
Preparation method: purified water and pregelatinized starch being mixed, stirring, are configured to uniform pregelatinized starch slurry；By first
Sulfonic acid Ah pa mixes for Buddhist nun, microcrystalline cellulose, sodium carboxymethyl starch (or croscarmellose sodium, crospovidone)
It closes, starch slurry wet granular is then added；Wet granular is dried, whole grain；By dried dry particl and remaining auxiliary material
It is mixed, tabletting.
1 prescription screening table of table
Experimental result is shown, includes cross-linked carboxymethyl fiber in prescription compared with sodium carboxymethyl starch and crospovidone
When plain sodium, dissolution rate is good.
Embodiment 2
Primary stability is investigated.Tablet is prepared using prescription 6, and is wrapped to the Opadry II that polyvinyl alcohol is filmogen
Clothing, coating weight gain 3.0%.High temperature, high humidity, exposure experiments to light are carried out with the sample, according to research drug standard, examination refers to
Mark includes appearance, dissolution rate, related substance, content.Dissolution rate is measured according to 2010 editions two the second methods of annex XD of Chinese Pharmacopoeia,
HPLC measures related content of material.
2 sample effects factorial experiments result of table
Table 2 the result shows that, sample is after high temperature, high humidity are placed, and appearance, related substance, content, dissolution rate are without obvious
Variation, after illumination is placed, related substance is increased slightly, and is illustrated that the sample is basicly stable under various conditions, should be kept in dark place.
Embodiment 3
Investigate the stability between batch.Tablet is prepared using prescription 6, and is the Opadry of filmogen to polyvinyl alcohol
II coating, coating weight gain 3.0%.Stability test between carrying out batch with the sample.
The mass parameter of 3 different batches sample of table
| Sample lot number | Weight differential | Content (%) | Total miscellaneous (%) | Dissolution rate (%) | Face shaping |
| 1 | Meet regulation | 101.4 | 0.56 | 98.4-99.7 | Class white film |
| 2 | Meet regulation | 101.5 | 0.41 | 97.9-100.7 | Class white film |
| 3 | Meet regulation | 100.6 | 0.38 | 98.8-101.4 | Class white film |
| 4 | Meet regulation | 99.4 | 0.33 | 96.8-100.4 | Class white film |
| 5 | Meet regulation | 101.6 | 0.34 | 98.4-100.1 | Class white film |
| 6 | Meet regulation | 102.8 | 0.45 | 96.9-98.8 | Class white film |
| 7 | Meet regulation | 100.9 | 0.18 | 100.5-101.8 | Class white film |
Quality examination is carried out with sample of the quality standard to different batches according to clinic, as a result meets regulation, shows this
The stable processing technique of prescription.
Claims (15)
1. a kind of combination of oral medication, which is characterized in that comprising Ah pa for Buddhist nun or its pharmaceutically acceptable salt and crosslinking carboxylic
Sodium carboxymethylcellulose pyce.
2. pharmaceutical composition according to claim 1, which is characterized in that the Ah pa is for Buddhist nun or its is pharmaceutically acceptable
Salt as sole active agent.
3. pharmaceutical composition according to claim 1, which is characterized in that the croscarmellose sodium quality hundred
Divide content to be selected from 5-15%, 7-15% preferably is selected from, most preferably from 7-13%.
4. pharmaceutical composition according to claim 1, which is characterized in that the composition also includes selected from microcrystalline cellulose
Element, lactose, mannitol, pregelatinized starch, dextrin and sorbierite filler, the mass percentage of filler is selected from 5-
20%, it preferably is selected from 7-15%, most preferably from 11-13%.
5. pharmaceutical composition according to claim 1, which is characterized in that the composition also includes to form sediment selected from pregelatinated
Powder, povidone, hydroxypropyl cellulose, hypromellose, sodium carboxymethylcellulose and polyethylene glycol adhesive, adhesive
Mass percentage is selected from 1-10%, 3-8% preferably is selected from, most preferably from 5-7%.
6. pharmaceutical composition according to claim 1, which is characterized in that the composition also include selected from stearic acid,
Magnesium stearate, superfine silica gel powder, talcum powder, Macrogol 4000 and Macrogol 6000 lubricant, the quality percentage of lubricant
Content is selected from 0.5-5%, 0.5-3.5% preferably is selected from, most preferably from 1.0-3.5%.
7. pharmaceutical composition according to claim 1-6, which is characterized in that the pharmaceutical composition component packet
Contain: Ah pa replaces Buddhist nun or its pharmaceutically acceptable salt, croscarmellose sodium, microcrystalline cellulose, pregelatinized starch, tristearin
Sour magnesium, superfine silica gel powder, preferably Ah pa replace Buddhist nun or its pharmaceutically acceptable salt 50-80%, croscarmellose sodium 7-
15%, microcrystalline cellulose 7-15%, pregelatinized starch 3-8%, magnesium stearate 0.5-1.5%, superfine silica gel powder 0-3%, more preferably
A Pa replaces Buddhist nun or its pharmaceutically acceptable salt 65-75%, croscarmellose sodium 7-13%, microcrystalline cellulose for Ni Apa
Plain 11-13%, pregelatinized starch 5-7%, magnesium stearate 0.7-1.3%, superfine silica gel powder 0-2.5%.
8. a kind of pharmaceutical composition described in claim 1, the mass percent of each component are as follows:
9. a kind of pharmaceutical composition described in claim 1, the mass percent of each component are as follows:
10. a kind of pharmaceutical composition described in claim 1, the mass percent of each component are as follows:
11. a kind of pharmaceutical composition described in claim 1, the mass percent of each component are as follows:
12. according to claim 1 to 11 described in any item pharmaceutical compositions, it is characterised in that composition be selected from tablet, capsule,
The dosage form of micro tablet or granule, preferred tablet.
13. according to claim 1 to 11 described in any item pharmaceutical compositions, it is characterised in that the A Pa pharmaceutically may be used for Buddhist nun
The salt of receiving is selected from mesylate or hydrochloride.
14. pharmaceutical composition according to claim 13, which is characterized in that have film coating, coating agent outside the tablet
Filmogen is selected from polyvinyl alcohol, hydroxypropyl cellulose, hypromellose, polyacrylic resin, preferably polyvinyl alcohol.
15. a kind of method for preparing the described in any item pharmaceutical compositions of claim 1 to 14, it is characterised in that:
(1) weigh following component: Ah pa replaces Buddhist nun or its pharmaceutically acceptable salt, filler, croscarmellose sodium, glues
Mixture, lubricant；
(2) Ah pa is crossed into 80 meshes for Buddhist nun or its pharmaceutically acceptable salt, it is spare；
(3) adhesive and wetting agent are configured to solution, it is spare；
(4) recipe quantity Ah pa is mixed for Buddhist nun or its pharmaceutically acceptable salt and other auxiliary materials for being used to pelletize, it is spare；
(5) above-mentioned (3) are taken, material in (4), using fluid-bed marumerization or wet granulation, through drying, whole grain is made
Even particle, it is spare；
(6) material in above-mentioned (5) is taken to mix with remaining auxiliary material, tabletting replaces Buddhist nun's tablet to get Ah pa；Or take object in above-mentioned (5)
Material is mixed with remaining auxiliary material, records capsule to get Ah pa for Buddhist nun's capsule.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710689933 | 2017-08-14 | ||
| CN201710689933X | 2017-08-14 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN109381436A true CN109381436A (en) | 2019-02-26 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810914090.3A Pending CN109381436A (en) | 2017-08-14 | 2018-08-13 | A Pa is for Buddhist nun's pharmaceutical composition and preparation method thereof |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110063946A (en) * | 2019-04-18 | 2019-07-30 | 西南交通大学 | A kind of chitosan sodium alginate micro ball preparation method and application for containing Ah pa and replacing Buddhist nun |
| CN112891349A (en) * | 2019-12-03 | 2021-06-04 | 江苏恒瑞医药股份有限公司 | Apatinib oral pharmaceutical composition containing sedimentation inhibitor |
| CN115715764A (en) * | 2021-08-24 | 2023-02-28 | 北京理工大学 | Apatinib oral patch and preparation method thereof |
| CN118370734A (en) * | 2024-06-26 | 2024-07-23 | 山东则正医药技术有限公司 | Martinib sustained release tablet and preparation method thereof |
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| CN102048737A (en) * | 2009-10-28 | 2011-05-11 | 江苏恒瑞医药股份有限公司 | Pharmaceutical composition for treating tumor diseases |
| CN101676267B (en) * | 2008-09-16 | 2012-12-26 | 江苏恒瑞医药股份有限公司 | N-4-(1-cyan cyclopentyl) phenyl-2-(4-picolyl) amidogen-3-pyridinecarboxamide salt |
| WO2015194769A1 (en) * | 2014-06-20 | 2015-12-23 | 보령제약 주식회사 | Preparation, and manufacturing method therefor |
| CN106511289A (en) * | 2015-09-10 | 2017-03-22 | 湖北生物医药产业技术研究院有限公司 | Benzenesulfonicacid lapatinib tablets and preparing method thereof |
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| CN101676267B (en) * | 2008-09-16 | 2012-12-26 | 江苏恒瑞医药股份有限公司 | N-4-(1-cyan cyclopentyl) phenyl-2-(4-picolyl) amidogen-3-pyridinecarboxamide salt |
| CN102048737A (en) * | 2009-10-28 | 2011-05-11 | 江苏恒瑞医药股份有限公司 | Pharmaceutical composition for treating tumor diseases |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110063946A (en) * | 2019-04-18 | 2019-07-30 | 西南交通大学 | A kind of chitosan sodium alginate micro ball preparation method and application for containing Ah pa and replacing Buddhist nun |
| CN112891349A (en) * | 2019-12-03 | 2021-06-04 | 江苏恒瑞医药股份有限公司 | Apatinib oral pharmaceutical composition containing sedimentation inhibitor |
| CN115715764A (en) * | 2021-08-24 | 2023-02-28 | 北京理工大学 | Apatinib oral patch and preparation method thereof |
| CN115715764B (en) * | 2021-08-24 | 2024-06-25 | 北京理工大学 | Apatinib oral patch and preparation method thereof |
| CN118370734A (en) * | 2024-06-26 | 2024-07-23 | 山东则正医药技术有限公司 | Martinib sustained release tablet and preparation method thereof |
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