CN104771363A - Chidamide solid dispersion and preparing method and application thereof - Google Patents
Chidamide solid dispersion and preparing method and application thereof Download PDFInfo
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- CN104771363A CN104771363A CN201410016221.8A CN201410016221A CN104771363A CN 104771363 A CN104771363 A CN 104771363A CN 201410016221 A CN201410016221 A CN 201410016221A CN 104771363 A CN104771363 A CN 104771363A
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Abstract
The invention relates to the chemical pharmaceutical field, and discloses a chidamide solid dispersion and a preparing method and an application thereof. The invention also discloses an oral preparation containing the chidamide solid dispersion. The chidamide solid dispersion is composed of chidamide and a water soluble carrier material, and the weight ratio of chidamide to the water soluble carrier material is 1:1 to 1:20. Chidamide of the chidamide solid dispersion can be highly dispersed in the water soluble carrier material in a molecular form or an amorphous state, and thus the water solubility of chidamide is greatly improved, and the dissolution rate and bioavailability of chidamide are improved.
Description
Technical field
The present invention relates to chemical pharmacy field, relate to a kind of chidamide solid dispersion and preparation method thereof and application specifically.Particularly relate to a kind of N-(2-amino-4-fluorophenyl)-4-[N-[(E)-3-(3-pyridine) acryloyl group] aminomethyl] Benzoylamide solid dispersion and preparation method thereof and application.
Background technology
Chidamide (English name: Chidamide) is a kind of new type anticancer medicine with brand-new chemical constitution and Global Knowledge property right by Shenzhen Weixin Biological Science and Technology Co., Ltd's autonomous Design and synthesis.Chidamide has histon deacetylase (HDAC) inhibit activities, may be used for treating the disease relevant to Differentiation and proliferation, as cancer and psoriasis, especially has excellent curative effect to leukemia and solid tumor.The I phase clinical study results completed shows: chidamide has definite curative effect to the various lymphoma comprising lymphoma cutis, simultaneously also to some other entity tumors as pulmonary carcinoma, renal carcinoma, colorectal cancer, carcinoma of endometrium etc. have the effect of stable disease, its aggregative indicator (safety, preliminary efficacy, Pharmacokinetic Characteristics) is obviously better than the result of study same period of international similar mechanism of action medicine.
Oral solid formulation enters after in body, all needs through process in leaching, could be absorbed through biomembrane by body.Insoluble drug, because its dissolution rate is by the restriction of dissolubility, have impact on drug absorption, and therefore slowly, bioavailability is lower in effect.
The dissolubility of chidamide in water is minimum, dissolves hardly, and bioavailability is lower.Therefore, the dissolution rate and the bioavailability that improve chidamide are significant.
Summary of the invention
In view of this, the present invention seeks to the shortcoming for prior art, provide a kind of can improve chidamide water solublity, improve the dissolution rate of chidamide and the chidamide solid dispersion of bioavailability.
For realizing object of the present invention, the present invention adopts following technical scheme:
A kind of chidamide solid dispersion, be made up of chidamide and water soluble carrier material, the weight ratio of described chidamide and water soluble carrier material is 1:1 ~ 1:20.
By research, applicant finds that chidamide and water soluble carrier material are by weight the combination being 1:1 ~ 1:20, chidamide can be highly dispersed in water soluble carrier material with molecular forms or amorphous state, thus greatly improve the water solublity of chidamide, improve dissolution rate and the bioavailability of chidamide.
In some embodiments, the weight ratio of described chidamide and water soluble carrier material is 1:1; In some embodiments, the weight ratio of described chidamide and water soluble carrier material is 1:5; In other embodiments, the weight ratio of described chidamide and water soluble carrier material is 1:20.
Chidamide of the present invention has structure shown in formula (I); its chemical name is N-(2-amino-4-fluorophenyl)-4-[N-[(E)-3-(3-pyridine) acryloyl group] aminomethyl] Benzoylamide; in its structural formula, 3-pyridine acryloyl group be configured as E type.
As preferably, described in chidamide solid dispersion of the present invention, water soluble carrier material is polyvidone, Polyethylene Glycol or poloxamer.Be more preferably PVP K30.
Present invention also offers the preparation method of described chidamide solid dispersion, for taking chidamide and water soluble carrier material respectively, adding organic solvent, in 60 DEG C ~ 90 DEG C heating in water bath, dissolve completely to chidamide and water soluble carrier material; Then boil off organic solvent, collect solid, drying and crushing and get final product; The weight ratio of wherein said chidamide and water soluble carrier material is 1:1 ~ 1:20.
Wherein, described water soluble carrier material is preferably polyvidone, Polyethylene Glycol or poloxamer, is more preferably PVP K30.
As preferably, described organic solvent is dehydrated alcohol, 95% ethanol, methanol, acetonitrile or acetone.
Further, the weight ratio of described chidamide and organic solvent is preferably 1:100 ~ 1:1000, is more preferably 1:200 ~ 1:1000.In some embodiments, the weight ratio of described chidamide and organic solvent is 1:200; In some embodiments, the weight ratio of described chidamide and organic solvent is 1:250; In other embodiments, described chidamide and organic solvent weight ratio be 1:1000.
Further, in the preparation method of chidamide solid dispersion of the present invention, described in boil off organic solvent for Rotary Evaporators pressure reducing and steaming organic solvent.
Further, described drying is preferably in 60 DEG C ~ 80 DEG C dry 2h ~ 8h.
Further, 60 ~ 100 mesh sieves were preferably pulverized in described pulverizing.
First the present invention detects the dissolubility of described chidamide solid dispersion in water, and the dissolubility of result display chidamide crude drug in water is 4.64 μ g/mL; And the dissolubility of solid dispersion in water be made up for 1:5 by weight of chidamide and PVP K30 is 66.7 μ g/mL, improve 14.4 times than crude drug.Show that chidamide solid dispersal physical ability of the present invention increases the dissolubility of medicine, accelerate the dissolution rate of medicine.
The present invention also adopts dissolution in vitro to test and measures chidamide crude drug respectively, embodiment 1 reaches the stripping situation of this drug amine by chidamide and PVP K30 by weight the solid dispersion Chinese and Western of making for 1:20 by weight the solid dispersion made for 1:5, embodiment 3 by chidamide and PVP K30 by weight the solid dispersion made for 1:1, embodiment 2 by chidamide and PVP K30.Dissolution determination adopts Chinese Pharmacopoeia version in 2010 two annex XC second methods, and dissolution medium is 1000mL water, and dissolution time is 45min, and rotating speed is 50rpm, and temperature is 37 ± 0.5 DEG C.The sampling amount of solid dispersion prepared by the solid dispersion of working sample chidamide crude drug, embodiment 1 preparation, embodiment 2 and solid dispersion prepared by embodiment 3 is respectively 100mg, 200mg, 600mg and 2100mg.Measurement result shows, the dissolution of chidamide crude drug is 4.71%, and the dissolution of solid dispersion prepared by solid dispersion prepared by embodiment 1, embodiment 2 and solid dispersion prepared by embodiment 3 is respectively 60.3%, 79.1% and 82.2%, all comparatively crude drug has clear improvement.
Further, the present invention adopts X-ray powder diffraction to investigate prepared chidamide solid dispersion.X-ray powder diffraction shows, the X-ray powder diffraction pattern of chidamide crude drug has strong diffraction maximum (Fig. 1) between 3 ~ 50o, and embodiment 1 prepare solid dispersion, embodiment 2 prepare solid dispersion and embodiment 3 prepare solid dispersion X-ray powder diffraction pattern in, the peak crystallization of medicine disappears (Fig. 2, Fig. 3 and Fig. 4), show that the chidamide in chidamide solid dispersion of the present invention is highly dispersed in carrier material, be dispersed in wherein with molecular forms or amorphous state.
The present invention utilizes chidamide solid dispersion of the present invention to carry out clinical tests, result display is of the present invention by chidamide and the PVP K30 tablet by weight the solid dispersion made for 1:5, is 32.9% to the Overall response rate of the clinical trial of Relapsed and refractory lymphoma peripheral T cell (PTCL) after repeatedly chemotherapy etc. is treated.Show there is good curative effect to cancer patient clinically by the oral formulations that chidamide solid dispersion of the present invention is made.
Therefore, present invention also offers the application of described chidamide solid dispersion in the medicine preparing Therapeutic cancer.
Wherein, described cancer is lymphoma, entity tumor or hematological system tumor.
Further, the preferred lymphoma peripheral T cell of described cancer.
Chidamide solid dispersion of the present invention can make the pharmaceutical preparation with Therapeutic cancer function with the pharmaceutic adjuvant combination of routine, comprises oral solid formulation, as tablet, capsule or granule etc.Pharmaceutical preparation of the present invention can contain the chidamide solid dispersion of 5 ~ 50% and the pharmaceutic adjuvant of 50 ~ 95%.Wherein said pharmaceutic adjuvant, comprises fluidizer as Pulvis Talci, magnesium stearate, micropowder silica gel etc., comprises disintegrating agent as carboxymethyl starch sodium, polyvinylpolypyrrolidone, low-substituted hydroxypropyl cellulose etc., comprises filler as lactose, microcrystalline Cellulose, starch etc.
Chidamide solid dispersion of the present invention is made up of chidamide and water soluble carrier material, and the weight ratio of described chidamide and water soluble carrier material is 1:1 ~ 1:20.Chidamide solid dispersion chidamide of the present invention can be highly dispersed in water soluble carrier material with molecular forms or amorphous state, thus greatly improves the water solublity of chidamide, improves dissolution rate and the bioavailability of chidamide.
Accompanying drawing explanation
Fig. 1 shows the X-ray powder diffraction pattern of chidamide crude drug;
Fig. 2 shows the X-ray powder diffraction pattern of chidamide-PVP K30 solid dispersion (weight ratio is 1:1) prepared by embodiment 1;
Fig. 3 shows the X-ray powder diffraction pattern of chidamide-PVP K30 solid dispersion (weight ratio is 1:5) prepared by embodiment 2;
Fig. 4 shows the X-ray powder diffraction pattern of chidamide-PVP K30 solid dispersion (weight ratio is 1:20) prepared by embodiment 3.
Detailed description of the invention
The embodiment of the invention discloses a kind of chidamide solid dispersion and preparation method thereof and application.Those skilled in the art can use for reference present disclosure, and suitable improving technique parameter realizes.Special needs to be pointed out is, all similar replacements and change apparent to those skilled in the art, they are all deemed to be included in the present invention.Product of the present invention, method and application are described by preferred embodiment, related personnel obviously can not depart from content of the present invention, spirit and scope product as herein described, method and application are changed or suitably change with combination, realize and apply the technology of the present invention.
In order to understand the present invention further, below in conjunction with embodiment, the present invention is described in detail.Percentage ratio of the present invention, except indicating especially, is all weight percentage.Chidamide described in the embodiment of the present invention is except indicating especially; be N-(2-amino-4-fluorophenyl)-4-[N-[(E)-3-(3-pyridine) acryloyl group] aminomethyl] Benzoylamide; the solid dispersion of chidamide described in the embodiment of the present invention, except indicating especially, is N-(2-amino-4-fluorophenyl)-4-[N-[(E)-3-(3-pyridine) acryloyl group] aminomethyl] Benzoylamide solid dispersion.Numerical range described in description, as measurement unit or percentage ratio, is all to provide undoubted desk reference.Those skilled in the art, when putting into practice this patent, are used in outside this scope or are different from the temperature, concentration, quantity etc. of single numerical value, still can obtain expected result.Wherein, described X-ray powder diffraction and dissolution determination test method as follows:
X-ray powder diffraction test condition: Rigaku company of instrument: D/MAX-1200(Japan); Radiation source: Cu-K α (40kV, 40mA).
Dissolution determination condition: instrument: RC806 type drug dissolution analyzer; Dissolution medium: water 1000mL; Rotating speed: 50rpm, temperature: 37 ± 0.5 DEG C.
Embodiment 1: the preparation of chidamide-PVP K30 solid dispersion (weight ratio is 1:1)
Get 4g chidamide and 4g PVP K30, add 800g dehydrated alcohol, in 60 DEG C of heating in water bath, chidamide and PVP K30 are dissolved completely, with Rotary Evaporators pressure reducing and steaming dehydrated alcohol, collects solid, put in heated-air circulation oven in 60 DEG C of dry 8h, pulverize, cross 60 mesh sieves, obtain chidamide solid dispersion.The dissolution of the 45min of this solid dispersion is 60.3%, and its X-ray powder diffraction pattern is shown in Fig. 2.
Embodiment 2: the preparation of chidamide-PVP K30 solid dispersion (weight ratio is 1:5)
Get 4g chidamide and 20g PVP K30, add 1000g dehydrated alcohol, in 90 DEG C of heating in water bath, chidamide and PVP K30 are dissolved completely, with Rotary Evaporators pressure reducing and steaming dehydrated alcohol, collects solid, put in heated-air circulation oven in 80 DEG C of dry 2h, pulverize, cross 100 mesh sieves, obtain chidamide solid dispersion.The dissolution of the 45min of this solid dispersion is 79.1%, and its X-ray powder diffraction pattern is shown in Fig. 3.
Embodiment 3: the preparation of chidamide-PVP K30 solid dispersion (weight ratio is 1:20)
Get 4g chidamide and 80g PVP K30, add 4000g dehydrated alcohol, in 90 DEG C of heating in water bath, chidamide and PVP K30 are dissolved completely, with Rotary Evaporators pressure reducing and steaming dehydrated alcohol, collects solid, put in heated-air circulation oven in 80 DEG C of dry 4h, pulverize, cross 100 mesh sieves, obtain chidamide solid dispersion.The dissolution of the 45min of this solid dispersion is 82.2%, and its X-ray powder diffraction pattern is shown in Fig. 4.
Embodiment 4: containing the preparation of the tablet of chidamide solid dispersion
Prescription (1000):
Preparation technology: take the solid dispersion of recipe quantity, lactose, microcrystalline Cellulose and carboxymethyl starch sodium, mix homogeneously, take suitable quantity of water as wetting agent soft material, with 20 mesh sieve wet granulars, be dried to pellet moisture lower than 4% in 60 DEG C, with 18 mesh sieve granulate, add the Pulvis Talci of recipe quantity, mix homogeneously, tabletting and get final product.
Embodiment 5: containing the preparation of the tablet of chidamide solid dispersion
Prescription (1000):
Preparation technology: take the solid dispersion of recipe quantity, lactose, microcrystalline Cellulose and carboxymethyl starch sodium, mix homogeneously, take suitable quantity of water as wetting agent soft material, with 20 mesh sieve wet granulars, be dried to pellet moisture lower than 4% in 60 DEG C, with 18 mesh sieve granulate, add Pulvis Talci and the magnesium stearate of recipe quantity, mix homogeneously, tabletting and get final product.
Embodiment 6: containing the preparation of the capsule of chidamide solid dispersion
Prescription (1000):
Preparation technology: take the solid dispersion of recipe quantity, microcrystalline Cellulose, lactose and carboxymethyl starch sodium, mix homogeneously, take suitable quantity of water as wetting agent soft material, with 20 mesh sieve wet granulars, be dried to pellet moisture lower than 4% in 60 DEG C, with 18 mesh sieve granulate, add recipe quantity magnesium stearate, mix homogeneously, fill capsule and get final product.
Embodiment 7: containing the preparation of the granule of chidamide solid dispersion
Prescription (1000 bag):
Preparation technology: take the solid dispersion of recipe quantity, lactose, soluble starch, microcrystalline Cellulose and carboxymethyl starch sodium, mix homogeneously take suitable quantity of water as wetting agent soft material, with 20 mesh sieve wet granulars, pellet moisture is dried to lower than 4% in 60 DEG C, with 18 mesh sieve granulate, subpackage and get final product.
Embodiment 8: chidamide solid dispersion tablet in treatment relapsed or stubborn peripheral t of the present invention is thin
The lymphadenomatous key II clinical trial phase of born of the same parents
1, the preparation of test medicine
20081020 batches of chidamide solid dispersion tablets of the present invention: get 180g chidamide and 900g PVP K30, add 36000g dehydrated alcohol, in 90 DEG C of heating in water bath, solid is dissolved completely, with Rotary Evaporators pressure reducing and steaming dehydrated alcohol, collects solid, put in heated-air circulation oven in 80 DEG C of dry 2h, pulverize, cross 100 mesh sieves, obtain solid dispersion; By gained solid dispersion and 1080g microcrystalline Cellulose, 1800g lactose and 360g carboxymethyl starch sodium, mix homogeneously, take suitable quantity of water as wetting agent soft material, with 20 mesh sieve wet granulars, be dried to pellet moisture lower than 4% in 60 DEG C, with 18 mesh sieve granulate, add 180g Pulvis Talci, mixing, by 5mg specification tabletting, to obtain final product.
20100322 batches of chidamide solid dispersion tablets of the present invention: get 160g chidamide and 800g PVP K30, add 32000g dehydrated alcohol, in 90 DEG C of heating in water bath, solid is dissolved completely, with Rotary Evaporators pressure reducing and steaming dehydrated alcohol, collects solid, put in heated-air circulation oven in 80 DEG C of dry 2h, pulverize, cross 100 mesh sieves, obtain solid dispersion; By gained solid dispersion and 960g microcrystalline Cellulose, 1600g lactose and 320g carboxymethyl starch sodium, mix homogeneously, take suitable quantity of water as wetting agent soft material, with 20 mesh sieve wet granulars, be dried to pellet moisture lower than 4% in 60 DEG C, with 18 mesh sieve granulate, add 160g Pulvis Talci, mixing, by 5mg specification tabletting, to obtain final product.
20120509 batches of chidamide solid dispersion tablets of the present invention: get 158g chidamide and 790g PVP K30, add 31200g dehydrated alcohol, in 90 DEG C of heating in water bath, solid is dissolved completely, with Rotary Evaporators pressure reducing and steaming dehydrated alcohol, collects solid, put in heated-air circulation oven in 80 DEG C of dry 2h, pulverize, cross 100 mesh sieves, obtain solid dispersion; By gained solid dispersion and 948g microcrystalline Cellulose, 1580g lactose and 316g carboxymethyl starch sodium, mix homogeneously, take suitable quantity of water as wetting agent soft material, with 20 mesh sieve wet granulars, be dried to pellet moisture lower than 4% in 60 DEG C, with 18 mesh sieve granulate, add 158g Pulvis Talci, mixing, by 5mg specification tabletting, to obtain final product.
2, testing program
This test is the II clinical trial phase of described chidamide solid dispersion tablet in treatment relapsed or stubborn lymphoma peripheral T cell of the present invention.Adopt the design of single armed, nonrandom, open, polycentric II clinical trial phase.Observe the efficacy and saferry of PTCL patient under fixing administering mode and dosage.Treatment is until progression of disease or safety reasons exit.Whole test cut-off enters to organize patient's completed 6 weeks and treat to all and follow up a case by regular visits to 1 month or stopped treatment or because of any reason death.
3, title, specification, lot number, the usage and dosage of test medicine
Title: chidamide solid dispersion tablet of the present invention
Specification: 5mg/ sheet
Lot number: 20081020,20100322,20120509
Usage and dosage: patient is in early taking medicine with warm water 200ml in 30 minutes after meal.Take medicine weekly twice (administration Monday four or two or five administrations, the rest may be inferred), without the drug withdrawal rest period, each medication dose is 30mg.
4, result of the test
In the II clinical trial phase of chidamide solid dispersion tablet in treatment relapsed or refractory PTCL of the present invention, enter the routine patient of group 83 altogether, in carry out therapeutic evaluation 79 routine patients, Overall response rate is: 32.9%(26/79), wherein 8 routine patient's complete incidence graph (10.1%), the uncertain complete incidence graph of 4 routine patient (5.1%), 14 routine patient's partial rcsponses (17.7%).
The explanation of above embodiment just understands the present invention and core concept thereof for helping.It should be pointed out that for those skilled in the art, under the premise without departing from the principles of the invention, can also carry out some improvement and modification to the present invention, these improve and modify and also fall in the protection domain of the claims in the present invention.
Claims (10)
1. a chidamide solid dispersion, is characterized in that, is made up of chidamide and water soluble carrier material, and the weight ratio of described chidamide and water soluble carrier material is 1:1 ~ 1:20.
2. chidamide solid dispersion according to claim 1, is characterized in that, described chidamide has structure shown in formula (I),
3. chidamide solid dispersion according to claim 1, it is characterized in that, described water soluble carrier material is polyvidone, Polyethylene Glycol or poloxamer.
4. chidamide solid dispersion according to claim 1, it is characterized in that, described water soluble carrier material is PVP K30.
5. a preparation method for chidamide solid dispersion, is characterized in that, takes chidamide and water soluble carrier material respectively, adds organic solvent, in 60 DEG C ~ 90 DEG C heating in water bath, dissolves completely to chidamide and water soluble carrier material; Then boil off organic solvent, collect solid, drying and crushing and get final product; The weight ratio of wherein said chidamide and water soluble carrier material is 1:1 ~ 1:20.
6. the preparation method of chidamide solid dispersion according to claim 4, it is characterized in that, described organic solvent is dehydrated alcohol, 95% ethanol, methanol, acetonitrile or acetone.
7. the preparation method of chidamide solid dispersion according to claim 4, it is characterized in that, the weight ratio of described chidamide and organic solvent is 1:100 ~ 1:1000.
8. the application of chidamide solid dispersion in the medicine preparing Therapeutic cancer described in claim 1.
9. the application of solid dispersion as claimed in claim 1 in the medicine for the preparation for the treatment of lymphoma peripheral T cell.
10. a pharmaceutical formulation, is characterized in that, comprises chidamide solid dispersion according to claim 1 and pharmaceutic adjuvant.
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| US10287353B2 (en) | 2016-05-11 | 2019-05-14 | Huya Bioscience International, Llc | Combination therapies of HDAC inhibitors and PD-1 inhibitors |
| US10385131B2 (en) | 2016-05-11 | 2019-08-20 | Huya Bioscience International, Llc | Combination therapies of HDAC inhibitors and PD-L1 inhibitors |
| US10385130B2 (en) | 2016-05-11 | 2019-08-20 | Huya Bioscience International, Llc | Combination therapies of HDAC inhibitors and PD-1 inhibitors |
| US12122833B2 (en) | 2016-05-11 | 2024-10-22 | Huyabio International, Llc | Combination therapies of HDAC inhibitors and PD-1 inhibitors |
| US11535670B2 (en) | 2016-05-11 | 2022-12-27 | Huyabio International, Llc | Combination therapies of HDAC inhibitors and PD-L1 inhibitors |
| CN109276543B (en) * | 2017-07-19 | 2021-01-08 | 深圳微芯生物科技股份有限公司 | Sitaglipta solid dispersion and preparation method and application thereof |
| CN109276543A (en) * | 2017-07-19 | 2019-01-29 | 深圳微芯生物科技股份有限公司 | A kind of Xi Gelieta solid dispersions and its preparation method and application |
| CN114681455A (en) * | 2018-08-17 | 2022-07-01 | 深圳微芯生物科技股份有限公司 | Combination of histone deacetylase inhibitor and protein kinase inhibitor and pharmaceutical application thereof |
| CN110833544B (en) * | 2018-08-17 | 2022-08-09 | 深圳微芯生物科技股份有限公司 | Combination of histone deacetylase inhibitor and protein kinase inhibitor and pharmaceutical application thereof |
| CN110833544A (en) * | 2018-08-17 | 2020-02-25 | 深圳微芯生物科技股份有限公司 | Combination of histone deacetylase inhibitor and protein kinase inhibitor and pharmaceutical application thereof |
| WO2020034916A1 (en) * | 2018-08-17 | 2020-02-20 | 深圳微芯生物科技股份有限公司 | Combination of histone deacetylase inhibitor and protein kinase inhibitor and pharmaceutical use thereof |
| CN111195251A (en) * | 2018-11-20 | 2020-05-26 | 深圳微芯生物科技股份有限公司 | Application of Sidapamide |
| CN112294810A (en) * | 2019-07-29 | 2021-02-02 | 深圳微芯生物科技股份有限公司 | Pharmaceutical composition containing cideramide and surfactant |
| WO2021018318A1 (en) * | 2019-07-29 | 2021-02-04 | 深圳微芯生物科技股份有限公司 | Pharmaceutical composition containing chidamide and surfactant |
| CN112294810B (en) * | 2019-07-29 | 2024-03-01 | 深圳微芯生物科技股份有限公司 | Pharmaceutical composition containing cetadalimamine and surfactant |
| WO2021037091A1 (en) * | 2019-08-28 | 2021-03-04 | 深圳微芯生物科技股份有限公司 | Chidamide pharmaceutical composition, preparation method therefor and application thereof |
| CN112438978A (en) * | 2019-08-28 | 2021-03-05 | 深圳微芯生物科技股份有限公司 | Sidapamide pharmaceutical composition and preparation method and application thereof |
| EP4023212A4 (en) * | 2019-08-28 | 2023-08-30 | Shenzhen Chipscreen Biosciences Co., Ltd. | Chidamide pharmaceutical composition, preparation method therefor and application thereof |
| CN112438978B (en) * | 2019-08-28 | 2024-03-01 | 深圳微芯生物科技股份有限公司 | Sidamide pharmaceutical composition and preparation method and application thereof |
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Address after: 518057 room 601-606, building 2, Shenzhen biological incubator, ten Nanshan District high tech Middle Road, Shenzhen, Guangdong, China Applicant after: Shenzhen microbiology Polytron Technologies Inc Address before: 518057 room 601-606, building 2, Shenzhen biological incubator, ten Nanshan District high tech Middle Road, Shenzhen, Guangdong, China Applicant before: Shenzhen Weixin Biological Science and Technology Co., Ltd. |
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Application publication date: 20150715 |