CN111565714A - Pharmaceutical preparation comprising everolimus and capable of achieving stabilization - Google Patents
Pharmaceutical preparation comprising everolimus and capable of achieving stabilization Download PDFInfo
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- CN111565714A CN111565714A CN201980007209.1A CN201980007209A CN111565714A CN 111565714 A CN111565714 A CN 111565714A CN 201980007209 A CN201980007209 A CN 201980007209A CN 111565714 A CN111565714 A CN 111565714A
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- everolimus
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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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1617—Organic compounds, e.g. phospholipids, fats
-
- F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
- F41—WEAPONS
- F41A—FUNCTIONAL FEATURES OR DETAILS COMMON TO BOTH SMALLARMS AND ORDNANCE, e.g. CANNONS; MOUNTINGS FOR SMALLARMS OR ORDNANCE
- F41A17/00—Safety arrangements, e.g. safeties
- F41A17/42—Safeties for locking the breech-block or bolt in a safety position
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1635—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
-
- 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
- A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
- A61K9/2077—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
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- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- General Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Transplantation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Nutrition Science (AREA)
- Physiology (AREA)
Abstract
The present invention relates to a pharmaceutical preparation comprising everolimus for achieving stabilization. In particular, the present invention relates to a pharmaceutical preparation comprising particles containing everolimus as an active ingredient and butylated hydroxytoluene as an antioxidant. Also, the present invention relates to a method for preparing a pharmaceutical preparation comprising everolimus as an active ingredient and butylhydroxytoluene as an antioxidant, comprising the steps of preparing a mixture by dissolving everolimus, butylhydroxytoluene and a binder; a step of preparing particles from the above mixture; and a step of preparing a particle mixture by putting a lubricant into the above particles.
Description
Technical Field
The present invention relates to a pharmaceutical preparation comprising everolimus for achieving stabilization. In particular, the present invention relates to a pharmaceutical preparation comprising particles containing everolimus as an active ingredient and butylated hydroxytoluene as an antioxidant.
Background
Immunosuppressants are pharmaceutical compounds that reduce the activity of the immune system. Immunosuppressants are commonly used in the treatment of autoimmune diseases. Autoimmune diseases include several forms of allergic reactions of the immune system, such as Crohn's disease, multiple sclerosis, rheumatoid arthritis, ulcerative colitis, Addison's disease, and various diseases in addition to these. In addition, immunosuppressive agents are also used for the prevention and treatment of organ transplant rejection after organ transplantation due to differences in the haplotype of human leukocyte antigens between donors and recipients.
Immunosuppressive agents developed for therapeutic use can be classified according to their chemical structure and mechanism of action. Immunosuppressive compounds include pimecrolimus, sirolimus, rapamycin, temsirolimus, and zotarolimus.
Everolimus (everolimus) is a sirolimus derivative in which hydroxyethyl is added to 40-O of sirolimus for the purpose of preventing organ transplant rejection, and pharmaceutical preparations for Nowa include
Is sold in the United states under the trade name of
Is sold in korea and europe. And, in addition to the use of an immunosuppressant, the drug exhibits anticancer activity by inhibiting the expression of Vascular Endothelial Growth Factor (VEGF) through inhibition of the mTOR pathway, and recently, has been used for the treatment of progressive renal cell carcinoma that fails in the course of Vascular Endothelial Growth Factor target therapy using sunitinib or sorafenib
Is sold under the trade name of (1). In addition, many clinical tests have been conducted on breast cancer, gastric cancer, liver cancer, pancreatic cancer, and the like.
Everolimus is defined as dihydroxy-12- { (2R) -1- [ (1S,3R,4R) -4- (2-hydroxyethoxy) -3-methoxycyclohexyl ] propan-2-yl } -19, 30-dimethoxy-15, 17,21,23,29, 35-hexamethyl-11, 36-dioxin-4-azatricyclo [30.3.1.0(4,9) ] triacontahexa-16, 24,26, 28-tetraene-2, 3,10,14, 20-pentanone represented by the following chemical formula 1.
[ chemical formula 1]
The process for producing everolimus is described in U.S. Pat. No. 5665772. U.S. patent No. 5665772, which teaches a rapamycin and derivatives derived therefrom, discloses synthetic procedures and methods for everolimus.
Further details of the synthesis method and yield of everolimus in the above-mentioned U.S. Pat. No. 5665772 are disclosed in international patent publication No. WO 2012/066502.
When administered orally to humans, solid sirolimus derivatives such as everolimus hardly permeate gastrointestinal permeable membranes due to their low solubility in water and large molecular weight, and are hardly absorbed in an amount suitable for the bloodstream because they function as a matrix for efflux pumps (efflux pumps) such as P-glycoprotein (P-glycoprotein). Therefore, sirolimus derivatives such as everolimus have disadvantages such as unpredictable dissolution rate, uneven bioavailability, and instability.
A pharmaceutical composition for improving stability by preparing a mixture of sirolimus derivatives sensitive to oxidation and an antioxidant is disclosed in korean patent No. 0695834. In the above korean patent, the stability can be improved by preparing a mixed precipitate of an antioxidant and a sirolimus derivative, but has a disadvantage in that a very complicated procedure is required in an actual process.
Formulations containing everolimus as an active ingredient have a problem of reduced stability due to oxidation sensitivity of the main ingredient, and therefore this point is considered in the study of formulations.
Thus, the present inventors have developed a pharmaceutical preparation comprising everolimus as an active ingredient and having excellent pharmaceutical properties.
Disclosure of Invention
Technical problem
The purpose of the present invention is to provide a pharmaceutical preparation which contains everolimus as an active ingredient and has excellent pharmaceutical properties. Specifically, in a pharmaceutical preparation comprising everolimus as an active ingredient, it was surprisingly found that butylated hydroxytoluene exhibited an excellent antioxidant effect in the process of masking an antioxidant exhibiting an excellent antioxidant effect, thereby completing the present invention.
Also, the present inventors have found that when granules containing everolimus as an active ingredient and butylhydroxytoluene as an antioxidant are prepared and the above ingredients are contained on the granules at a specific weight ratio, a formulation having more excellent stability can be provided.
Technical scheme
The present invention provides particles comprising everolimus as an active ingredient and butylated hydroxytoluene as an antioxidant. The above particles may be prepared as wet particles, dry particles, etc., but preferably, should be prepared as wet particles.
When the preparation is prepared by wet granulation, any method known in the art may be used for the purpose of the present invention in order to achieve wet granulation.
Preferably, the above granules may comprise everolimus in an amount of 0.5 to 20 weight percent, more preferably 1 to 10 weight percent, with respect to the total content of the granules.
Also, preferably, the above particles may contain 0.05 to 10 weight percent of butylated hydroxytoluene as an antioxidant, more preferably, 0.1 to 5 weight percent of butylated hydroxytoluene, with respect to the total content of the particles.
Further, the above granules may further contain a binder, a disintegrant, an excipient, etc. Preferably, the above granules may further comprise hydroxypropylmethylcellulose as a binder.
Also, the pharmaceutical preparation of the present invention can be prepared by the following steps: a step (i) of preparing a mixture by dissolving everolimus, butylhydroxytoluene, and a binder; a step (ii) of preparing particles from the above mixture; and (iii) a step of preparing a mixture of particles by putting a lubricant into the above particles.
Also, the above final granules can be compressed by a tableting machine to provide a stable tablet containing everolimus as an active ingredient and butylhydroxytoluene as an antioxidant.
The pharmaceutical formulation of the present invention may further comprise a lubricant. The lubricant may be one or more selected from the group consisting of glyceryl behenate, magnesium stearate, sodium stearyl fumarate, and colloidal silicon dioxide, but is not limited thereto. Preferably, the lubricant of the present invention may be glyceryl behenate.
ADVANTAGEOUS EFFECTS OF INVENTION
The present invention relates to a pharmaceutical preparation comprising everolimus as an active ingredient, which has excellent stability, and has advantages of simple preparation process and mass production.
Detailed Description
The present invention provides a pharmaceutical preparation comprising particles containing everolimus as an active ingredient and butylated hydroxytoluene as an antioxidant.
Specifically, the particles comprise everolimus in an amount of 0.5 to 20 weight percent and butylated hydroxytoluene in an amount of 0.05 to 10 weight percent, relative to the total content of the particles, and thus have more excellent stability.
More specifically, the particles comprise 1 to 10 weight percent of everolimus and 0.1 to 5 weight percent of butylated hydroxytoluene relative to the total content of the particles, and have the best stability.
The above particles can be prepared by a general particle preparation method including a dry particle method, a wet particle method, etc., and preferably, can be prepared by a wet particle method.
The above-mentioned particles of the present invention may further comprise a binder. In the present invention, the "binder" means a substance capable of imparting elasticity and cohesiveness to the formulation in order to improve the strength of the formulation, particularly to improve the strength of the formed tablet. The binder of the present invention may use a commonly used binder, and preferably, may be hydroxypropylmethyl cellulose.
The pharmaceutical formulation of the present invention may further comprise a lubricant. In the present invention, "lubricant" means a substance that provides improved flow characteristics to the formulation. The lubricant may be one or more selected from the group consisting of glyceryl behenate, magnesium stearate, sodium stearyl fumarate, and colloidal silicon dioxide, but is not limited thereto. Preferably, glyceryl behenate may be used as a lubricant.
The pharmaceutical formulation of the present invention may further comprise a diluent. In the present invention, "diluent" means an inactive substance used as a filter in order to achieve appropriate volume (bulk), flowability and compression characteristics in the preparation of a solid dosage form for administration. For example, lactose hydrate, lactose anhydrous, white sugar, corn starch, or calcium hydrogen phosphate may be mentioned, but the invention is not limited thereto.
The pharmaceutical formulation of the present invention may also comprise a disintegrant. In the present invention, "disintegrant" means a substance used in order to release a pharmaceutically effective active ingredient in a formulation in a short time by accelerating disintegration (disintegration) of a solid formulation. For example, the disintegrant may be carboxymethylcellulose calcium (CMC-Ca), crospovidone, sodium carboxymethyl starch, croscarmellose sodium, or low-substituted hydroxypropylcellulose, but is not limited thereto.
The pharmaceutical preparation of the present invention may be prepared in the form of oral administration, and the oral administration may be in the form of tablets, but is not limited thereto.
The pharmaceutical formulation of the present invention can be used for preventing or treating organ transplant rejection.
The present invention provides a method for preparing a pharmaceutical preparation comprising everolimus as an active ingredient and butylhydroxytoluene as an antioxidant, comprising: a step of preparing a mixture by dissolving everolimus, butylhydroxytoluene, and a binder; a step of preparing particles from the above mixture; and a step of preparing a particle mixture by putting a lubricant into the above particles.
The present invention will be described more specifically with reference to examples. However, these examples are merely illustrative for better understanding of the present invention, and the scope of the present invention is not limited to the following examples.
Method for preparing tablets containing everolimus
To an organic solvent, hydroxypropylmethylcellulose, butylhydroxytoluene, and everolimus were added to prepare a conjugate solution. The mixture of lactose hydrate, crospovidone and hydroxypropylmethylcellulose is put into the binder solution and polymerized, and then dried and granulated by a granulator. After mixing the granules, lactose hydrate, anhydrous lactose, and crospovidone, glyceryl behenate was added for final mixing, thereby preparing an everolimus granule mixture. The final mixture was compressed by a tablet press, thereby preparing tablets. The tablets prepared contained 1.0mg of everolimus.
[ examples 1 to 5]
Everolimus and butylhydroxytoluene were mixed in different weight percentages with respect to the total internal contents according to the contents in table 1, and tablets in examples 1 to 5 were prepared according to the above preparation method.
[ Table 1]
[ Experimental example 1]
Flexible Material test of examples 1 to 5
The tablets of examples 1 to 5 were evaluated for stability under the following conditions for a soft substance test and by a soft substance test, and the amount of the soft substance was evaluated by a liquid chromatography method after storing each preparation for 4 weeks under severe conditions (temperature 60 ℃).
< Experimental method >
1) A detector: ultraviolet absorption photometer (measuring wavelength: 276nm)
2) A chromatographic column: zorbax SB-C184.6x250 mm,5 μm
3) Injection amount: 50 μ L
4) Flow rate: 2.0mL/min
5) Temperature of the column: a predetermined temperature of about 55 DEG C
6) Sample temperature: a predetermined temperature of about 4 DEG C
7) Analysis time: 60 minutes
8) Mobile phase:
mobile phase a-mixture of water, acetonitrile, methanol (30:20:50)
Mobile phase B-acetonitrile
| Time (minutes) | Mobile phase A | Mobile phase B |
| 0 | 100 | 0 |
| 38 | 100 | 0 |
| 50 | 30 | 70 |
| 55 | 100 | 0 |
| 60 | 100 | 0 |
Table 2 shows the flexible substance test results in examples 1 to 5.
[ Table 2]
Results of the Flexible Material test of examples 1 to 5
| Total flexible matter (%) | Example 1 | Example 2 | Example 3 | Example 4 | Example 5 |
| Harsh conditions for 2 weeks | 2.05 | 0.56 | 0.45 | 1.76 | 2.20 |
| Harsh conditions 4 weeks | 2.16 | 0.87 | 0.93 | 2.48 | 2.71 |
As shown in table 2, the total amount of the flexible materials in examples 2 and 3 was 1% or less, and the stability was high. In example 1, example 4 and example 5, 2 to 3 times higher than in example 2 and example 3 was confirmed.
[ Experimental example 2]
Stability test based on lubricant type
The lubricant is a substance that imparts improved flow characteristics to the formulation, and in this experiment, stability of the formulation based on the type of lubricant was evaluated using glyceryl behenate, magnesium stearate, sodium stearyl fumarate, and colloidal silicon dioxide as lubricants.
Examples 6 to 8 were prepared according to the compositions shown in table 3 and in the same manner as in examples 1 to 5.
[ Table 3]
The formulations of example 3 and examples 6 to 8 were stored under severe conditions (temperature 60 ℃) for 4 weeks, and the amount of the flexible substance was evaluated by the following experimental method and liquid chromatography.
< Experimental method >
1) A detector: ultraviolet absorption photometer (measuring wavelength: 276nm)
2) A chromatographic column: zorbax SB-C184.6x 250mm,5 μm
3) Injection amount: 50 μ L
4) Flow rate: 2.0mL/min
5) Temperature of the column: a predetermined temperature of about 55 DEG C
6) Sample temperature: a predetermined temperature of about 4 DEG C
7) Analysis time: 60 minutes
8) Mobile phase:
mobile phase a-mixture of water, acetonitrile, methanol (30:20:50)
Mobile phase B-acetonitrile
| Time (minutes) | Mobile phase A | Mobile phase B |
| 0 | 100 | 0 |
| 38 | 100 | 0 |
| 50 | 30 | 70 |
| 55 | 100 | 0 |
| 60 | 100 | 0 |
Table 4 shows the flexible substance test results of example 3 and examples 6 to 8 based on the kind of lubricant.
[ Table 4]
Results of the flexible substance experiments of example 3 and examples 6 to 8
| Total Flexible Material (%) | Example 3 | Example 6 | Example 7 | Example 8 |
| Harsh conditions for 2 weeks | 0.45 | 3.91 | 1.15 | 1.24 |
| Harsh conditions 4 weeks | 0.93 | 7.12 | 3.01 | 3.12 |
As shown in table 4 above, it was confirmed that example 3 exhibited the most excellent stability. Examples 7 and 8 produced 2 times more flexible substances than example 3, and example 6 produced 7 times more flexible substances than example 3.
As described above, in the inner portion (granules), the weight ratio of everolimus and antioxidant and the type of lubricant have an important influence on the stability of the formulation containing everolimus.
Claims (13)
1. A pharmaceutical preparation comprising everolimus as an active ingredient and butylated hydroxytoluene as an antioxidant.
2. The pharmaceutical formulation of claim 1, wherein the granules comprise everolimus in an amount of 0.5 to 20 weight percent and butylated hydroxytoluene in an amount of 0.05 to 10 weight percent, relative to the total content of the granules.
3. The pharmaceutical formulation of claim 2, wherein the granules comprise 1 to 10 weight percent everolimus and 0.1 to 5 weight percent butylated hydroxytoluene, relative to the total content of the granules.
4. The pharmaceutical formulation of claim 1, wherein the particles are prepared by a wet granulation process.
5. The pharmaceutical formulation of claim 1, wherein said granules further comprise hydroxypropylmethylcellulose as a binder.
6. The pharmaceutical formulation of claim 1, wherein said formulation further comprises a lubricant.
7. The pharmaceutical preparation according to claim 6, wherein the lubricant is one or more selected from the group consisting of glyceryl behenate, magnesium stearate, sodium stearyl fumarate and colloidal silicon dioxide.
8. The pharmaceutical formulation of claim 7, wherein the lubricant is glyceryl behenate.
9. The pharmaceutical formulation of claim 1, wherein said formulation is formulated for oral administration.
10. The pharmaceutical preparation according to claim 9, wherein the form for oral administration is a tablet.
11. The pharmaceutical preparation according to claim 1, wherein the preparation is a pharmaceutical preparation for preventing or treating organ transplant rejection.
12. A method for preparing a pharmaceutical formulation comprising everolimus as an active ingredient and butylated hydroxytoluene as an antioxidant, comprising:
a step of preparing a mixture by dissolving everolimus, butylhydroxytoluene, and a binder;
a step of preparing particles from the above mixture; and
a step of preparing a granule mixture by putting a lubricant into the above granules.
13. The method of claim 12, wherein the binder is hydroxypropylmethylcellulose and the lubricant is glyceryl behenate.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020180004458A KR102051806B1 (en) | 2018-01-12 | 2018-01-12 | Stabilized pharmaceutical formulation comprising Everolimus |
| KR10-2018-0004458 | 2018-01-12 | ||
| PCT/KR2019/000204 WO2019139313A1 (en) | 2018-01-12 | 2019-01-07 | Stabilized pharmaceutical formulation comprising everolimus |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN111565714A true CN111565714A (en) | 2020-08-21 |
| CN111565714B CN111565714B (en) | 2022-05-17 |
Family
ID=67219083
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201980007209.1A Active CN111565714B (en) | 2018-01-12 | 2019-01-07 | Pharmaceutical preparation comprising everolimus and capable of achieving stabilization |
Country Status (7)
| Country | Link |
|---|---|
| JP (1) | JP7218372B2 (en) |
| KR (1) | KR102051806B1 (en) |
| CN (1) | CN111565714B (en) |
| BR (1) | BR112020014292A2 (en) |
| EA (1) | EA202091455A1 (en) |
| MX (1) | MX2020007434A (en) |
| WO (1) | WO2019139313A1 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111388455B (en) * | 2020-04-09 | 2022-09-02 | 沈阳药科大学 | Everolimus oral film and preparation method thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105106145A (en) * | 2015-08-27 | 2015-12-02 | 济川药业集团有限公司 | Everolimus tablet and preparation method thereof |
| CN105307640A (en) * | 2013-03-19 | 2016-02-03 | 诺华股份有限公司 | Pharmaceutical compositions comprising everolimus |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9826882D0 (en) | 1998-12-07 | 1999-01-27 | Novartis Ag | Organic compounds |
| US20100266590A1 (en) * | 2006-08-02 | 2010-10-21 | Demetri George D | Combination therapy |
| EP1952807A1 (en) * | 2007-01-24 | 2008-08-06 | LEK Pharmaceuticals D.D. | Sirolimus formulation |
| CA2937492C (en) * | 2008-11-11 | 2019-08-13 | The Board Of Regents Of The University Of Texas System | Inhibition of mammalian target of rapamycin |
| SG11201400730VA (en) * | 2011-10-06 | 2014-06-27 | Novartis Ag | Pharmaceutical compositions comprising 40 - o - ( 2 - hydroxy) ethyl - rapamycin |
| KR20140032586A (en) * | 2012-09-06 | 2014-03-17 | 한국원자력의학원 | A pharmaceutical composition for radiation therapy of egfr-tki-resistant lung cancer caused by pten function deficiency |
| MX367121B (en) | 2013-08-02 | 2019-08-06 | Laboratorio Raam De Sahuayo S A De C V | Stable solid composition of immunosuppressants. |
| KR20150138104A (en) * | 2014-05-30 | 2015-12-09 | 동아에스티 주식회사 | Pharmaceutical preperation containing Bepotastine and Glyceryl Behenate |
| CN104398483B (en) * | 2014-11-05 | 2018-01-26 | 上海医药集团青岛国风药业股份有限公司 | A kind of olmesartan medoxomil tablet and its preparation technology |
| EP3345601A4 (en) * | 2015-09-03 | 2019-05-15 | Nippon Kayaku Kabushiki Kaisha | Pharmaceutical composition containing rapamycin or derivative thereof |
| JP2018111662A (en) * | 2017-01-12 | 2018-07-19 | ニプロ株式会社 | Everolimus pharmaceutical preparation |
-
2018
- 2018-01-12 KR KR1020180004458A patent/KR102051806B1/en active IP Right Grant
-
2019
- 2019-01-07 JP JP2020538112A patent/JP7218372B2/en active Active
- 2019-01-07 EA EA202091455A patent/EA202091455A1/en unknown
- 2019-01-07 MX MX2020007434A patent/MX2020007434A/en unknown
- 2019-01-07 BR BR112020014292-1A patent/BR112020014292A2/en unknown
- 2019-01-07 WO PCT/KR2019/000204 patent/WO2019139313A1/en active Application Filing
- 2019-01-07 CN CN201980007209.1A patent/CN111565714B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105307640A (en) * | 2013-03-19 | 2016-02-03 | 诺华股份有限公司 | Pharmaceutical compositions comprising everolimus |
| CN105106145A (en) * | 2015-08-27 | 2015-12-02 | 济川药业集团有限公司 | Everolimus tablet and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| SUN WOO JANG等: ""Improved oral absorption and chemical stability of everolimus via preparation of solid dispersion using solvent wetting technique"", 《INTERNATIONAL JOURNAL OF PHARMACEUTICS》 * |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2019139313A1 (en) | 2019-07-18 |
| BR112020014292A2 (en) | 2020-12-08 |
| EA202091455A1 (en) | 2020-10-05 |
| KR20190086212A (en) | 2019-07-22 |
| MX2020007434A (en) | 2022-04-27 |
| JP7218372B2 (en) | 2023-02-06 |
| KR102051806B1 (en) | 2019-12-04 |
| CN111565714B (en) | 2022-05-17 |
| JP2021510374A (en) | 2021-04-22 |
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