CN108201529A - A kind of pharmaceutical composition containing urate transporter inhibitor and preparation method thereof - Google Patents
A kind of pharmaceutical composition containing urate transporter inhibitor and preparation method thereof Download PDFInfo
- Publication number
- CN108201529A CN108201529A CN201711354222.3A CN201711354222A CN108201529A CN 108201529 A CN108201529 A CN 108201529A CN 201711354222 A CN201711354222 A CN 201711354222A CN 108201529 A CN108201529 A CN 108201529A
- Authority
- CN
- China
- Prior art keywords
- pharmaceutical composition
- weight
- filler
- hydroxypropyl cellulose
- sulfenyl
- 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.)
- Granted
Links
Classifications
-
- 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
- A61K31/47—Quinolines; Isoquinolines
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The present invention relates to a kind of pharmaceutical compositions containing urate transporter inhibitor and preparation method thereof.Specifically, described pharmaceutical composition contains 1 ((6 bromoquinoline, 4 base) sulfenyl) cyclobutyl formate or its officinal salt and low-substituted hydroxypropyl cellulose, which has good dissolution rate and superior stability.
Description
Technical field
The invention belongs to pharmaceutical technology fields, are related to a kind of medicine group for containing urate transporter (URAT1) inhibitor
Close object.
Background technology
In recent years, with the improvement of economic life level, the illness rate of gout rises year by year, and age of onset presentation becomes younger
Trend.Male, menopausal woman are apt to occur in, 40-50 Sui is onset peak.Its clinical manifestation is that hyperuricemia, gout are impatient
Property arthritis recurrent exerbation, tophaceous deposition, characteristic chornic arthritis and joint deformity, often involve kidney and cause chronic interstitial
Ephritis and kidney calculus urate etc..The prerequisite of gout morbidity is hyperuricemia, i.e., at 37 DEG C, the saturated concentration of serum uric acid
About 420umol/L (70mg/L), is hyperuricemia higher than this value.However hyperuricemia person's only a part is developed into and is faced
Bed gout, transition mechanisms are unknown, only Patients with Hyperuricemia occur urate crystal deposition, arthritis and (or) nephrosis,
Durings kidney stone etc., gout could be referred to as.Therefore, hyperuricemia is the important biochemical basis mark of gout and the generation of gout
It is closely related.Hyperuricemia and hypertension, hyperlipidemia, atherosclerosis, obesity, the close phase of generation of insulin resistance
It closes, it has also become threaten the serious metabolic disease of human health.
Uric acid is the dead end product of mankind's purine metabolism, leads to this enzyme due to the uricase gene mutation in human evolution
Lack, it is impossible to excrete uric acid metabolism, therefore the serum of hyperuricemia for soluble allantoin (allantoin)
Uric acid concentration is excessively high.During the morbidity of hyperuricemia due to：(1) generation of uric acid increases, the ratio for causing gout morbidity shared
Example is 15%~20%.The high purine diet of Excess free enthalpy increases and nucleic acid including vivo acid, nucleotide synthesis uric acid
Catabolism produces excessive uric acid；(2) uric acid excretion reduction and reabsorption increase be hyperuricemia and gout morbidity
Main mechanism, account for about 80%~85%.The reabsorption of uric acid about 95% is the urine by being located at epithelial cell in Renal proximal tubular
Acid transporter albumen 1 (Uric Acid Transporter 1, URAT1) is come what is completed.URAT1 is one and is located at the complete of kidney
Memebrane protein, belong to solute transporter 22 (SLC22) family, perform lithate-anion exchange, be responsible for adjusting in blood
The level of lithate.Therefore URAT1 inhibitor can promote the excretion of uric acid by inhibiting this reabsorption.
Gout suppressant kind on China's medical market is seldom, and market does not have new better anti-gout drugs to develop
Come.Still based on allopurinol and Benzbromarone.The Febuxostat of FDA approvals in 2009 belongs to xanthine oxidase XO inhibition
Agent treats gout by reducing the generation of uric acid.The RDEA-594 for entering clinical three phases (US) in December, 2011 is to pass through suppression
Urate transporter URAT1 processed promotes uric acid excretion, and then achievees the purpose that reduce serum uric acid concentration.It is controlled with RDEA-594
After treating 4 weeks, blood uric acid (sUA) is horizontal to reduce by 16%, 22%, and 30% (allopurinol 3%), last observation backtracking (LOCF) divides
Analysis：Response rate (sUA<6mg/dl) it is respectively 71%, 76% and 89% (allopurinol 29%).Curative effect is not by renal function and not fast
Purine alcohol Dose Effect.For treating hyperuricemia and gout RDEA-594 developed by Ardea Biosciences companies,
The transhipment effect of OAT1/OAT3 (Organic Anion Transporter 1/3) can't be influenced in clinical measures range, and
And it interacts less to target spot specificity higher, with other drugs than other uricosuric agents.But RDEA-594 is to grind
Study carefully what is be found in treatment HIV infection clinical drug trial, not high to the activity of urate transporter URAT1, IC50 is big
It is approximately 7uM.And it is higher in Clinical practice middle dosage, daily dosage is about 400mg.
Disclose a large amount of substituted heterocycles for being used as NPY5 receptor antagonists in US5939462, some of them be with it is following
The similar S- triazolyl mercapto-acetanils of Formulas I；CN101817793A is disclosed as hiv inhibitor S- triazolyls-alpha-mercapto second
Anilide.
WO2014183555 disclose a new generation high-efficiency low-toxicity for URAT1 target spots inhibitor 1- ((6- bromoquinolines-
4- yls) sulfenyl) cyclobutyl formate and its pharmaceutical salt, there is good activity, and it is dense to show excellent drop serum uric acid
Degree treats hyperuricemia and pain wind action.
Researcher has found that 1- ((6- bromoquinoline -4- bases) sulfenyl) cyclobutyl formates or its officinal salt are prepared into solid medicine
After compositions, pharmaceutical composition dissolution rate reduces after long-term placement, meanwhile, composition has degradable characteristic, even if will
Pharmaceutical composition is made to place under very harsh storage requirement, still unavoidably.For this purpose, the present invention provides one kind containing urine
The pharmaceutical composition of acid transporter albumen (URAT1) inhibitor solves to contain urate transporter inhibitor 1- ((6- bromoquinolines -4-
Base) sulfenyl) dissolution and stability problem are placed for a long time after cyclobutyl formate or its officinal salt patent medicine.
Invention content
The present invention provides a kind of pharmaceutical composition, contains active constituent 1- ((6- bromoquinoline -4- bases) sulfenyl) cyclobutylmethyl
Acid or its officinal salt and low-substituted hydroxypropyl cellulose.The pharmaceutical composition is fitted into aluminium foil bag, be positioned over 40 DEG C/
Under the conditions of RH75%, the content of 1 month rear impurity A, which increases, is no more than 0.25%, preferably more than 0.1%, more preferably no more than
0.05%；After 3 months, pharmaceutical composition dissolution rate remains unchanged, which there is long-term preserve to remain good molten
Out-degree and preferable stability, convenient for storage.
Further, the dosage of low-substituted hydroxypropyl cellulose of the present invention account for pharmaceutical composition weight 0.5~
20%, preferably 1~10%, can be 1.0,1.2,1.5,1.8,2,2.3,2.5,2.7,3,3.5,4,4.5,5,5.5,6,
6.5th, 7,7.5,8,8.5,9,9.5,10%, in terms of pharmaceutical composition weight.
Active constituent 1- ((6- bromoquinoline -4- bases) sulfenyl) cyclobutyl formates of the present invention or its officinal salt content are
0.1~10%, can be 0.1,0.2,0.4,0.6,0.8,1.0,1.2,1.4,1.6,1.8,2.0,2.2,2.4,2.6,2.8,
3.0、3.2、3.4、3.6、3.8、4.0、4.2、4.4、4.6、4.8、5.0、5.2、5.4、5.6、5.8、6.0、6.2、6.4、6.6、
6.8th, 7.0,7.2,7.6,8.0,8.4,8.8,9.0,9.4,9.6,10.0%, in terms of pharmaceutical composition weight；Of the invention real
In proved recipe case, the active constituent weight be 1~20mg, can be 1,2,5,6,8,10,12,14,16,18,20mg.
Further, also containing at least one of filler, adhesive, lubricant in pharmaceutical composition of the present invention
Pharmaceutic adjuvant.
Filler provide volume, by tablet be made can working process actual size, it is also possible to contribute to working process, change
The hardness of the physical property such as mobility of kind pharmaceutical composition, compressibility and solid pharmaceutical preparation.By the institute in pharmaceutical composition
It is larger with the dosage of filler, it is in direct contact with active constituent (or reactive compound), therefore, filler and active constituent
Interaction is that those skilled in the art pay special attention to.Filler of the present invention is known to those skilled in the art or can be true
Fixed, it may be selected from but be not limited to dextrin, lactose, sucrose, starch, pregelatinized starch, mannitol, calcium monohydrogen phosphate, microcrystalline cellulose
At least one of；Preferably, the dosage of the filler accounts for the 75~95% of pharmaceutical composition weight, can be 75,76,
77th, 78,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93,94,95%, with pharmaceutical composition weight
Meter.
Adhesive of the present invention is known to those skilled in the art or confirmable, may be selected from but is not limited to polyethylene pyrrole
In pyrrolidone, starch, methylcellulose, carboxycellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, alginate
It is at least one；Preferably, the dosage of described adhesive accounts for the 0.5~10% of pharmaceutical composition weight, can be 0.5,0.6,
0.7、0.8、0.9、1.0、1.2、1.5、1.8、2、2.3、2.5、2.7、3、3.2、3.5、3.7、4、4.5、5、5.5、6、6.5、7、
7.5th, 8,8.5,9,9.5,10%, in terms of pharmaceutical composition weight.
" in terms of weight of pharmaceutical composition " of the present invention for not comprising coating agent label weight meter calculate activity into
Point or other type pharmaceutic adjuvants usage amount numberical range, for details, reference can be made to embodiment 1.
Lubricant is commonly used to facilitate processing, prevents formulation materials from adhering to production equipment, and less intergranular friction changes
It is apt to the flow rate of preparation and preparation is contributed to be discharged from production equipment.Lubricant of the present invention is ordinary skill people
Member is known or confirmable, may be selected from but is not limited to magnesium stearate, stearic acid, palmitic acid, calcium stearate, talcum powder, titanium dioxide
At least one of silicon, Brazil wax, sodium stearyl fumarate, the dosage of preferably described lubricant account for pharmaceutical composition weight
0.1~5%, can be 0.1,0.2,0.3,0.4,0.5,0.6,0.7,0.8,0.9,1,1.5,2,2.5,3,3.5,4,4.5,
5%, in terms of pharmaceutical composition weight.
Further, pharmaceutical composition of the present invention contains following ingredient：
A) 1- ((6- bromoquinoline -4- bases) sulfenyl) cyclobutyl formates or its officinal salt of 0.1~10% weight,
B) low-substituted hydroxypropyl cellulose of 1~10% weight,
C) filler of 75~95% weight, the preferably described filler in lactose or microcrystalline cellulose at least one
Kind,
D) lubricant of 0.1~5% weight.
It is particularly preferred that the officinal salt of 1- ((6- bromoquinoline -4- bases) sulfenyl) cyclobutyl formate is alkali metal salt,
Such as sodium salt, sylvite.
Further, coating agent can also be contained in pharmaceutical composition of the present invention, the coating agent can be selected from but not
It is limited to hydroxypropyl methylcellulose, methylcellulose, ethyl cellulose, methylcellulose or hydroxypropyl cellulose, polyvinyl alcohol, poly- dimension
Ketone, vinylite or Pioloform, polyvinyl acetal lignocaine acetic acid esters, EudragitRS PO
With EUDRAGIT NE 30 D dispersion, carbohydrate includes sugar alcohol sucrose, mannitol paste or trade name
Opadry II, preferably Opadry II.
The present invention also provides the method for preparing foregoing pharmaceutical composition, this method includes：1) by 1- ((6- bromoquinolines -4-
Base) sulfenyl) cyclobutyl formate or its officinal salt and low-substituted hydroxypropyl cellulose, filler and optional Autoadhesive, lubrication
At least one of agent pharmaceutic adjuvant mixes, 2) will from tabletting after the granulating mixture that step 1) obtains or filling capsule, directly
Tabletting or directly filling capsule.
Further, coating steps are further included after the granulation step, coating agent used is Opadry II, hypromellose
Element, ethyl cellulose or polyvinyl alcohol, preferably Opadry II.
Granulation mode of the present invention can be wet granulation and dry granulation, can when selecting wet granulation scheme
To be pelletized using fluidized bed granulation or bulk drug of pretreatment adds with interior.
In embodiments, using high-shearing granulation technique, step is as follows：
1) by 1- ((6- bromoquinoline -4- bases) sulfenyl) cyclobutyl formates or its officinal salt and filler, low substitution hydroxyl
Propyl cellulose mixes,
2) it will be made in the solution addition 1 containing adhesive after carrying out wet whole grain after softwood, dry, whole grain,
3) granular substance into step 2 adds in lubricant and mixes,
4) it is the mixture in step 3 is tabletted.
Or in embodiments, using fluidized bed granulation technique, step is as follows：
1) by 1- ((6- bromoquinoline -4- bases) sulfenyl) cyclobutyl formates or its officinal salt and filler, low-substituted hydroxypropyl
Base cellulose mixes,
2) mixture of powders in step 1 is fluidized, then the solution containing adhesive is sprayed to powder blending surface
Afterwards, it is dry, whole grain,
3) granular substance into step 2 adds in lubricant and mixes,
4) it is the mixture in step 3 is tabletted.
In a preferred embodiment, granulation mode of the present invention uses high-shearing granulation.
Pharmaceutical composition of the present invention be solid pharmaceutical preparation, preferred tablet, granula, pulvis (including fine granula),
Or capsule.Solid pharmaceutical preparation can be obtained by widely known preparation method, and the maximum of final dry particle is aqueous after granulation
Then control 3% is hereinafter, filling capsule or be bagged directly into granule.When dosage form be tablet, tabletting is controlled in tableting processes
Ambient humidity ensures that the water content of final plain piece is less than 3% (less than 3%), and by using vacuum drying to final composition
Method processing ensures that the water content of final composition is less than 3%.
It, can be by compressing the particle preparation obtained as described above when Pharmaceutical composition of the present invention uses tablet.
The pressure of compression can be determined in proper range.Moreover, figure of tablet is without specifically limited, preferably lablab shape, disc, circle
Shape, ellipse (such as caplet), tear drop shape or polygonal (such as triangle or diamond shape).Pan coater (pan coater) can be passed through
The tablet of preparation is coated by the mode for spraying the suspension/solution of coating agent.
When Pharmaceutical composition of the present invention uses granule, the particle obtained as described above can be used directly or can pass through
Proper technology is granulated into desired granular.In addition, the particle thus prepared can be used by spraying the suspension/solution of coating agent
Coating agent is coated.
The dissolution rate of pharmaceutical composition of the present invention is according to 2015 editions four general rules, 0931 method dissolution rates of Chinese Pharmacopoeia
The second method (paddle method) is measured to be measured, using 0.1M aqueous hydrochloric acid solutions as dissolution medium, the preferred aqueous hydrochloric acid solution of 1000ml,
And dissolution test is carried out to the present composition with the paddle speed of 50rpm at 37 ± 0.5 DEG C, dissolution rate is greater than or equal within 45 minutes
90%, it can be excellent more than or equal to 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 100%
Choosing is greater than or equal to 94%.
Further, which is fitted into aluminium foil bag, be positioned under the conditions of 40 DEG C/RH75%, after 3 months,
Described pharmaceutical composition dissolution rate still maintain be greater than or equal to 90%, can be greater than or equal to 90%, 91%, 92%, 93%,
94%th, 95%, 96%, 97%, 98%, 99%, 100%, preferably greater than or equal to 94%.
" content " of the present invention is detected by HPLC and obtained；Testing conditions are：Chromatographic column Waters Xbridge
Shield RP18 columns (150 × 4.6mm, 3.5 μm)；Detection wavelength 230nm；Using ammonium dibasic phosphate solution or acetonitrile as flowing
Phase.
Impurity A relative retention time 0.27min of the present invention.
1- ((6- bromoquinoline -4- bases) sulfenyl) cyclobutyl formates of the present invention or its officinal salt can be according to
Method described in WO2014183555 obtains.Pharmaceutic adjuvant used in the present invention can be bought by commercial sources, for example low substitution
Hydroxypropyl cellulose etc..
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 the skill of the present invention
Art scheme, and non-limiting the spirit and scope of the invention.
Embodiment 1
Active pharmaceutical ingredient 1- ((6- bromoquinoline -4- bases) sulfenyl) cyclobutyl formate sodium is mixed with lactose, microcrystalline cellulose
Close, then respectively with low-substituted hydroxypropyl cellulose, crosslinked polyvinylpyrrolidone, sodium carboxymethyl starch and cross-linked carboxymethyl fiber
Plain sodium mixing, adhesive is PVP K30 aqueous solution, and particle is prepared using high-shearing granulation technique, then will
The particle drying, sieving, then be uniformly mixed with magnesium stearate tabletted.Specific data are shown in Table 1.
Table 1
The tablet that will be prepared in experimental example 1~4 is packed into aluminium foil bag, is positioned under the conditions of 40 DEG C/RH75%, in 0,
1st, 2, the 45 minutes dissolution rates and Impurity A content of tablet are measured by sampling in March, investigate the stability of tablet.It the results are shown in Table 2.
Table 2
The above results show during stability test, when low-substituted hydroxypropyl cellulose is selected in pharmaceutical composition, tool
There is the related substance data that stable dissolution rate is become reconciled；And when selecting crosslinked polyvinylpyrrolidone, although with stable molten
Out-degree, but Impurity A content dramatically increases at any time；When selecting sodium carboxymethyl starch and croscarmellose sodium, impurity A contains
Amount nothing rises appreciably, but the dissolution rate of pharmaceutical composition decreased significantly at any time.
Embodiment 2
By active pharmaceutical ingredient 1- ((6- bromoquinoline -4- bases) sulfenyl) cyclobutyl formate sodium and mannitol, microcrystalline cellulose
Mixing, adhesive are PVP K30 aqueous solution, prepare particle using fluid-bed marumerization technique, then should
Particle drying, sieving.Particle obtained mixes respectively with low-substituted hydroxypropyl cellulose, crosslinked polyvinylpyrrolidone, then with
Magnesium stearate is uniformly mixed tabletted.The tablet composition of experimental example 5 to 6 is shown in Table 3.
Table 3
The tablet that will be prepared in experimental example 5,6 is packed into aluminium foil bag, is positioned under the conditions of 40 DEG C/RH75%, in 0,1
45 minutes dissolution rates of tablet and related substance is measured by sampling in the moon, investigates the stability of tablet.It the results are shown in Table 4.
Table 4
The above results show during stability test, when low-substituted hydroxypropyl cellulose is selected in pharmaceutical composition, tool
There are stable dissolution rate and good related substance data；And when selecting crosslinked polyvinylpyrrolidone, although with stable
Dissolution rate, but Impurity A content dramatically increases at any time.
Embodiment 3
Active pharmaceutical ingredient 1- ((6- bromoquinoline -4- bases) sulfenyl) cyclobutyl formate sodium is mixed with lactose, microcrystalline cellulose
It closes, is mixed respectively with low-substituted hydroxypropyl cellulose, crosslinked polyvinylpyrrolidone, then mixed with talcum powder, magnesium stearate
It is even tabletted.The tablet composition of experimental example 7 to 8 is shown in Table 5.
Table 5
The tablet that will be prepared in experimental example 7,8 is packed into aluminium foil bag, is positioned under the conditions of 40 DEG C/RH75%, in 0,1
45 minutes dissolution rates of tablet and related substance is measured by sampling in the moon, investigates the stability of tablet.It the results are shown in Table 6.
Table 6
The above results show during stability test, when low-substituted hydroxypropyl cellulose is selected in pharmaceutical composition, tool
There are stable dissolution rate and good related substance data；And when selecting crosslinked polyvinylpyrrolidone, although with stable
Dissolution rate, but Impurity A content dramatically increases at any time.
Embodiment 4
Tablet prepared by 1 prescription of experimental example in embodiment 1 is placed 24 under the conditions of 25 DEG C of ± 2 DEG C/RH60% ± 10%
A month, stability result was shown in Table 7.
Table 7
The above results show during stability test, when low-substituted hydroxypropyl cellulose is selected in pharmaceutical composition, tool
There is the related substance data that stable dissolution rate is become reconciled.
In conclusion according to the experimental result of experimental example 1~8, when using low substituted hydroxy-propyl fiber in pharmaceutical composition
When plain, long-term place remains to keep preferable dissolution rate, and with preferably tablet stability.
Claims (10)
1. a kind of pharmaceutical composition, containing active constituent 1- ((6- bromoquinoline -4- bases) sulfenyl) cyclobutyl formates or its is pharmaceutically acceptable
Salt and low-substituted hydroxypropyl cellulose, the dosage of preferably described low-substituted hydroxypropyl cellulose account for the 0.5 of pharmaceutical composition weight
~20%, more preferably 1~10%.
2. pharmaceutical composition according to claim 1, it is characterised in that the content of the active constituent is 0.1~10%,
In terms of pharmaceutical composition weight.
3. pharmaceutical composition according to claim 1 or 2, it is characterised in that described pharmaceutical composition also containing filler,
At least one of adhesive, lubricant pharmaceutic adjuvant.
4. pharmaceutical composition according to claim 3, it is characterised in that the filler is selected from dextrin, lactose, sucrose, shallow lake
At least one of powder, pregelatinized starch, mannitol, calcium monohydrogen phosphate, microcrystalline cellulose, the dosage of preferably described filler account for medicine
The 75~95% of compositions weight.
5. pharmaceutical composition according to claim 3, it is characterised in that described adhesive is selected from polyvinylpyrrolidone, forms sediment
At least one of powder, methylcellulose, carboxycellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, alginate,
It is preferred that the dosage of described adhesive accounts for the 0.5~10% of pharmaceutical composition weight.
6. pharmaceutical composition according to claim 3, it is characterised in that the lubricant be selected from magnesium stearate, stearic acid,
At least one of palmitic acid, calcium stearate, talcum powder, Brazil wax, sodium stearyl fumarate, the use of preferably described lubricant
Amount accounts for the 0.1~5% of pharmaceutical composition weight.
7. according to claims 1 to 3 any one of them pharmaceutical composition, it is characterised in that described pharmaceutical composition contains：
A) 1- ((6- bromoquinoline -4- bases) sulfenyl) cyclobutyl formates or its officinal salt of 0.1~10% weight,
B) low-substituted hydroxypropyl cellulose of 1~10% weight,
C) filler of 75~95% weight, preferably described filler are selected from least one of lactose or microcrystalline cellulose,
D) lubricant of 0.1~5% weight.
8. according to claim 1~7 any one of them pharmaceutical composition, it is characterised in that the dissolution of the pharmaceutical composition
Degree is measured according to 2015 editions four general rules of Chinese Pharmacopoeia, 0931 the second method of method dissolution determination (paddle method), the active constituent
Dissolution rate 45 minutes be greater than or equal to 90%, preferably greater than or equal to 94%.
9. a kind of pharmaceutical composition, containing active constituent 1- ((6- bromoquinoline -4- bases) sulfenyl) cyclobutyl formates or its is pharmaceutically acceptable
Salt and low-substituted hydroxypropyl cellulose, the wherein pharmaceutical composition are fitted into aluminium foil bag, are positioned under the conditions of 40 DEG C/RH75%,
The content of 1 month rear impurity A increases no more than 0.25%, preferably more than 0.1%, more preferably no more than 0.05%, most preferably
No more than 0.02%.
10. the method for claim 1~9 any one of them pharmaceutical composition is prepared, including：By 1- ((6- bromoquinoline -4- bases)
Sulfenyl) cyclobutyl formate or its officinal salt and low-substituted hydroxypropyl cellulose, filler and optional Autoadhesive, lubricant
At least one of pharmaceutic adjuvant mix, 2) will be from tabletting or filling capsule, directly pressure after the granulating mixture that step 1) obtains
Piece or directly filling capsule.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201611166225 | 2016-12-16 | ||
| CN201611166225X | 2016-12-16 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN108201529A true CN108201529A (en) | 2018-06-26 |
| CN108201529B CN108201529B (en) | 2021-10-08 |
Family
ID=62604896
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201711354222.3A Active CN108201529B (en) | 2016-12-16 | 2017-12-15 | Pharmaceutical composition containing uric acid transporter inhibitor and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108201529B (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2020088641A1 (en) * | 2018-11-02 | 2020-05-07 | 江苏恒瑞医药股份有限公司 | Joint use of compound a and compound b in preparation of medications for treatment of gout or hyperuricemia |
| CN113368067A (en) * | 2020-07-23 | 2021-09-10 | 太阳升(亳州)生物医药科技有限公司 | Method for preparing oral medicine tablet for reducing blood uric acid level |
| CN113368032A (en) * | 2020-07-23 | 2021-09-10 | 太阳升(亳州)生物医药科技有限公司 | Pharmaceutical composition, oral solid preparation and preparation method and application thereof |
| CN113368073A (en) * | 2020-07-23 | 2021-09-10 | 太阳升(亳州)生物医药科技有限公司 | Method for producing a pharmaceutical preparation for reducing blood uric acid levels |
| RU2783862C1 (en) * | 2018-11-02 | 2022-11-21 | Цзянсу Хэнжуй Медицин Ко., Лтд. | Combined use of compound a and compound b for production of drugs for treatment of gout or hyperuricemia |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014183555A1 (en) * | 2013-05-13 | 2014-11-20 | 上海恒瑞医药有限公司 | Cycloalkyl acid derivative, preparation method thereof, and pharmaceutical application thereof |
| WO2016188444A1 (en) * | 2015-05-27 | 2016-12-01 | 江苏恒瑞医药股份有限公司 | Sodium salt of uric acid transporter inhibitor and crystalline form thereof |
-
2017
- 2017-12-15 CN CN201711354222.3A patent/CN108201529B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014183555A1 (en) * | 2013-05-13 | 2014-11-20 | 上海恒瑞医药有限公司 | Cycloalkyl acid derivative, preparation method thereof, and pharmaceutical application thereof |
| WO2016188444A1 (en) * | 2015-05-27 | 2016-12-01 | 江苏恒瑞医药股份有限公司 | Sodium salt of uric acid transporter inhibitor and crystalline form thereof |
Non-Patent Citations (3)
| Title |
|---|
| 危华玲等: "羟丙基纤维素在片剂方面的应用", 《中国药业》 * |
| 邱湘龙等: "药用辅料羟丙基纤维素在制剂中的应用", 《中国现代应用药学杂志》 * |
| 郭宗华等: "应用低取代经丙墓纤维素改善片剂的崩解时限及溶出度的研究", 《贵阳医药》 * |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2020088641A1 (en) * | 2018-11-02 | 2020-05-07 | 江苏恒瑞医药股份有限公司 | Joint use of compound a and compound b in preparation of medications for treatment of gout or hyperuricemia |
| EP3875087A4 (en) * | 2018-11-02 | 2022-08-10 | Jiangsu Hengrui Medicine Co., Ltd. | Joint use of compound a and compound b in preparation of medications for treatment of gout or hyperuricemia |
| RU2783862C1 (en) * | 2018-11-02 | 2022-11-21 | Цзянсу Хэнжуй Медицин Ко., Лтд. | Combined use of compound a and compound b for production of drugs for treatment of gout or hyperuricemia |
| CN113368067A (en) * | 2020-07-23 | 2021-09-10 | 太阳升(亳州)生物医药科技有限公司 | Method for preparing oral medicine tablet for reducing blood uric acid level |
| CN113368032A (en) * | 2020-07-23 | 2021-09-10 | 太阳升(亳州)生物医药科技有限公司 | Pharmaceutical composition, oral solid preparation and preparation method and application thereof |
| CN113368073A (en) * | 2020-07-23 | 2021-09-10 | 太阳升(亳州)生物医药科技有限公司 | Method for producing a pharmaceutical preparation for reducing blood uric acid levels |
Also Published As
| Publication number | Publication date |
|---|---|
| CN108201529B (en) | 2021-10-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR101380088B1 (en) | Pharmaceutical composition | |
| CN108201529A (en) | A kind of pharmaceutical composition containing urate transporter inhibitor and preparation method thereof | |
| RU2552951C2 (en) | Pharmaceutical composition, containing one or more fumaric acid ethers in degradable matrix | |
| JP4868695B2 (en) | Oral preparation with good disintegration | |
| TWI433679B (en) | Pharmaceutical solid preparation | |
| US20210113472A1 (en) | Pharmaceutical composition comprising a potent inhibitor of urat1 | |
| EP3437646A1 (en) | Oral preparation having exceptional elutability | |
| CN101420938A (en) | Low flush niacin formulation | |
| JP6804585B2 (en) | Pharmaceutical dosage form | |
| WO2004054574A1 (en) | Solid drug for oral use | |
| WO2014030656A1 (en) | Medicament-containing hollow particle | |
| KR20100059912A (en) | Pharmaceutical combination of aliskiren and valsartan | |
| CN107405311A (en) | Apremilast sustained release preparation | |
| JP2008044960A (en) | Solid drug for oral use | |
| CN105833283A (en) | A composition comprising S-[2-([[1-(2-ethylbutyl)-cyclohexyl]-carbonyl]amino)phenyl] 2-methylpropanethioate and croscarmellose sodium | |
| US10709699B2 (en) | Pyridone derivative pharmaceutical composition and preparation method thereof | |
| CN112516094A (en) | Topiroxostat tablet and preparation method thereof | |
| JP6367042B2 (en) | Pharmaceutical composition comprising voriconazole | |
| TWI414310B (en) | Elution-improved pharmaceutical preparation | |
| MX2011002988A (en) | Fixed dose combination in form of a bilayered or monolayered tablet of aliskiren and amlodipine. | |
| JP2019019112A (en) | Sustained release formulation comprising 4-[5-(pyridin-4-yl)-1h-1,2,4-triazole-3-yl]pyridine-2-carbonitrile or salt thereof | |
| CN100455288C (en) | Formula of Reynoldazine hydrochloride prepn. | |
| JP5563371B2 (en) | Oral tablets containing quetiapine fumarate | |
| KR20160079178A (en) | Solid Preparation Comprising Silodosin for Oral Administration | |
| CN109700778A (en) | A kind of cinacalcet hydrochloride quick releasing formulation and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20230928 Address after: 361026 room 53, floor 1, building A19, Xiamen biomedical industrial park, 2036 wengjiao West Road, Haicang District, Xiamen City, Fujian Province Patentee after: Fujian Shengdi Pharmaceutical Co.,Ltd. Patentee after: JIANGSU HENGRUI MEDICINE Co.,Ltd. Address before: 222047 No. 7 Kunlun Shan Road, Lianyungang economic and Technological Development Zone, Jiangsu Patentee before: JIANGSU HENGRUI MEDICINE Co.,Ltd. |