CN106543137A - Stable glug row purification compound - Google Patents
Stable glug row purification compound Download PDFInfo
- Publication number
- CN106543137A CN106543137A CN201510604133.4A CN201510604133A CN106543137A CN 106543137 A CN106543137 A CN 106543137A CN 201510604133 A CN201510604133 A CN 201510604133A CN 106543137 A CN106543137 A CN 106543137A
- Authority
- CN
- China
- Prior art keywords
- glug
- water purification
- compound
- row water
- composition
- 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.)
- Pending
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D335/00—Heterocyclic compounds containing six-membered rings having one sulfur atom as the only ring hetero atom
- C07D335/02—Heterocyclic compounds containing six-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention belongs to pharmaceutical technology field, and in particular to glug arranges a net hydrated compound, the glug row water purification compound that the present invention is obtained, containing a crystallization water, has the advantage that：Purity is high, good stability, even if moisture absorption weightening is not also obvious under high humidity conditions.
Description
Technical field
The invention belongs to pharmaceutical technology field, and in particular to glug row water purification compound and preparation method thereof.
Background technology
Glug row are net（Luseogliflozin）It is a kind of new SGLT-2 inhibitor medicaments, ratified for treating diabetes B in 2014.
Its structural formula is as follows：
Glug arranges net structural formula
The present inventor studied through net to glug row, a kind of new glug row water purification solvate crystal of the present invention, is had the advantage that：Purity is high, and maximum contaminant is less than 1 ‰；Good stability, even if moisture absorption weightening is not also obvious under high humidity conditions.
The content of the invention
One object of the present invention, discloses a kind of glug and arranges net monohydrate.
Another object of the present invention, discloses the preparation method that glug arranges net monohydrate.
A further object of the present invention, discloses the pharmaceutical composition that net monohydrate is arranged comprising glug.
Present invention is specifically described in conjunction with the purpose of the present invention.
The invention provides a kind of glug arranges net monohydrate（Shown in formula I）,
（Ⅰ）
Karl_Fischer method（Karl Fischer methods）In being a kind of all kinds of chemical methodes for determining moisture in material, method the most single-minded to water, the most accurate has been listed in the standard method of determination of moisture in many materials, especially organic compound, reliable results.6 batches of Jing are determined, and the moisture that described invention compound contains is between 3.12% -4.89% (percentage by weight).It is 3.98% that glug arranges the theoretical content of water in net times of semihydrate, it can be assumed that invention compound contains a crystallization water.
The glug arranges net monohydrate crystal, is determined using D/Max-2500.9161 types x-ray diffractometer, condition determination：Cu Ka targets, tube voltage 40KV, tube current 100mA.X-ray powder diffraction characteristic absorption peak（2θ）It is as follows with D values.
In the present invention, the measure of 2 θ values uses light source, and precision is ± 0.2 °, therefore represents above-mentioned taken value and allowed certain rational error range, and its error range is ± 0.2 °.
Fusing point test：According to Pharmacopoeia of People's Republic of China（2010 editions, two）VI the first methods of C of annex determine fusing point, and the fusing point for measuring is 159.4 DEG C -160.5 DEG C.
Another object of the present invention, discloses the preparation method of glug row water purification solvate crystal, by glug is arranged only in the dissolving of acetone-heated in water solution, naturally cools to room temperature, then is incubated a period of time and obtains.
Specifically include the following steps：Glug row are net to add 4-5 times（Weight or measurement (WM) ratio）Acetone-water=7-5：In the mixed liquor of 2-1,70 DEG C -75 DEG C are heated to, are filtered while hot, filtrate naturally cools to room temperature, then is incubated 5-10 hours, separate out crystallization, filtered, drying is obtained.
Glug row used can be readily obtained by commercial sources only.
A further object of the present invention, there is provided the composition comprising glug row water purification solvate crystal and the glug row water purification compound of one or more pharmaceutically acceptable carrier composition.
The pharmaceutical composition of the present invention prepares as follows：Using standard and conventional technique, the compounds of this invention is combined with acceptable solid or liquid-carrier on galenic pharmacy, and be allowed to arbitrarily be combined with acceptable adjuvant and excipient on galenic pharmacy and be prepared into particulate or microballoon.Said composition is used to prepare oral formulations, injection.
The active ingredient contained in pharmaceutical composition and unit dosage form（The compounds of this invention）Amount can be specifically applied according to the situation of the state of an illness of patient, diagnosis, the amount or concentration of compound used are adjusted in a wider scope, and the amount scope of reactive compound is the 1%～40% of composition（Weight）.
Present invention also offers application of the glug row water purification compound in the medicine of manufacture treatment diabetes.
Stability test
Inventor is studied to the chemical stability of the crystal formation of the present invention, and investigation condition is high temperature（60℃±2℃）, strong illumination（4500Lx±500lx）, high humidity（92.5%,RH）Inspection target is outward appearance, content and relevant material.
As a result：From 0-10 days under high light, high temperature, super-humid conditions, outward appearance, relevant material, content do not change, and illustrate that chemical stability is good, are adapted to the manufacture and long term storage of pharmaceutical preparation.
At 40 DEG C, different relative humidity（RH）Condition（75%, 92.5%）Under, the measure of moisture in hydrate crystal of the present invention：
As a result：At 40 DEG C, different relative humidity（RH）Condition（75%, 92.5%）Under, water tariff collection is constant, and explanation has good stability, and is adapted to the manufacture and long term storage of pharmaceutical preparation.
At 40 DEG C, different relative humidity（RH）Condition（75%, 92.5%）Under, the measure of moisture during glug row are net：
As a result：At 40 DEG C, different relative humidity（RH）Condition（75%, 92.5%）Under, glug row have moisture absorption to increase weight only, to moist lability.
Specific embodiment：
With reference to embodiment, the present invention is described further, makes professional and technical personnel in the field be better understood from the present invention.Embodiment is only explanatory, is in no way intended to it and limits the scope of the present invention by any way.
In the present invention, glug used row are obtained only from commercial channels, purity 99.1% (HPLC normalization methods), its chemical constitution Jing proton nmr spectra, elementary analysis confirmation, it was demonstrated that chemical constitution is correct.
It is 0.22% with the moisture that Karl_Fischer method is measured.
Embodiment
1
In equipped with stirring, thermometer, the 2000ml reaction bulbs of condenser, 200 Kruegers are added to arrange the acetone-water of net and 1000ml（5：2）Mixed liquor, starts stirring, is heated to 70 DEG C -75 DEG C, treats all molten clear, filters while hot.Filtrate naturally cools to room temperature, then is incubated 8 hours, separates out crystallization, filters, Jing indoor seasonings, obtains glug and arranges 181.6 grams of net white crystals, and fusing point is 183.1 DEG C -184.6 DEG C, content 99.86%.Jing Karl_Fischer methods are determined, the moisture containing 3.98% (percentage by weight).
INSTRUMENT MODEL and condition determination：2500 type diffractometers of Rigaku D/max； CuKa 40Kv 100mA;2 θ sweep limits：0-50°。
Using standard and conventional technique, the compounds of this invention is combined with acceptable solid or liquid-carrier on galenic pharmacy, and be allowed to arbitrarily be combined with acceptable adjuvant and excipient on galenic pharmacy and be prepared into particulate or microballoon.Said composition is used to prepare oral formulations, injection.Only citing is illustrated, and is in no way intended to it and limits the scope of the present invention by any way.
Embodiment
2
The tablet of net monohydrate is arranged containing glug
Prescription：Glug arranges 80 grams of net monohydrate, and 210 grams of lactose, 25 grams of PEG-4000,6 grams of magnesium stearate, 30 grams of PVP K30s, 33 grams of Ac-Di-Sol distill appropriate amount of water, make 1000.
Technique：PEG-4000 arranges net monohydrate with glug and crushes jointly, crosses 80 mesh sieves, and with distilled water softwood after mixing with other materials, the pelleting of 16 mesh sieves is mixed in adding dry particl in 40-45 DEG C of drying, 16 mesh sieve whole grains, magnesium stearate in putting drying box, compressing tablet.
Claims (6)
1. the row of glug shown in formula I purify compound,
（Ⅰ）
Determined with Karl_Fischer method, the hydrate contains the moisture of 3.12% -4.89% (percentage by weight)；
The crystal of the glug row water purification compound, in being determined as characteristic X-ray powder with CuKa rays, its collection of illustrative plates has the following 2 θ angles of diffraction and D values,
The error of the 2 θ angles of diffraction is ± 0.2.
2. the preparation method of glug row water purification solvate crystal described in claim 1, by glug is arranged only in acetone-heated in water solution dissolving, naturally cools to room temperature, then is incubated a period of time and obtains.
3. according to the method for claim 2, it is characterised in that comprise the following steps：Glug row add 4-5 times of weight/volume acetone-water=7-5 only：In the mixed liquor of 2-1,70 DEG C -75 DEG C are heated to, are filtered while hot, filtrate naturally cools to room temperature, then is incubated 5-10 hours, separate out crystallization, filtered, drying is obtained.
4. the composition of the glug row water purification compound of a kind of glug row water purification solvate crystal containing described in claim 1 and one or more pharmaceutically acceptable carrier composition.
5. 4 required by right described in glug row water purification compound composition, it is characterised in that said composition be used for prepare oral formulations.
6. application of the glug row water purification compound described in claim 1 in the medicine of manufacture treatment diabetes.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510604133.4A CN106543137A (en) | 2015-09-22 | 2015-09-22 | Stable glug row purification compound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510604133.4A CN106543137A (en) | 2015-09-22 | 2015-09-22 | Stable glug row purification compound |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN106543137A true CN106543137A (en) | 2017-03-29 |
Family
ID=58364605
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510604133.4A Pending CN106543137A (en) | 2015-09-22 | 2015-09-22 | Stable glug row purification compound |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106543137A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107857753A (en) * | 2017-12-04 | 2018-03-30 | 威海贯标信息科技有限公司 | A kind of glug arranges net novel crystal forms |
-
2015
- 2015-09-22 CN CN201510604133.4A patent/CN106543137A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107857753A (en) * | 2017-12-04 | 2018-03-30 | 威海贯标信息科技有限公司 | A kind of glug arranges net novel crystal forms |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN106543072A (en) | Mo Fanselin compounds | |
| CN104447771A (en) | Stable asenapine maleate sublingual compound | |
| CN106554315A (en) | Stable olaparib compound | |
| CN106543124A (en) | dapagliflozin compound | |
| CN106543256A (en) | Stable shellfish cholic acid compound difficult to understand | |
| CN106543137A (en) | Stable glug row purification compound | |
| CN105646520A (en) | Stable Halaven compound | |
| CN107778295A (en) | Mai Rui replaces Buddhist nun's compound | |
| CN107663166A (en) | Lome Tapai and its production and use | |
| CN106543250A (en) | A kind of stable tofogliflozin hydrate compound | |
| CN106699630A (en) | Brivaracetam sesquihydrate compound | |
| CN104447683A (en) | Stable Bilastine compound | |
| CN105669673A (en) | Stable Ticagrelor compound | |
| CN106146498A (en) | A kind of new Li Gelieting compound | |
| CN107344955A (en) | A kind of dexamethasone hydrate compound | |
| CN106543164A (en) | Stable Su Wolei raw compounds | |
| CN106543020A (en) | Stable agomelatine compound | |
| CN106543161A (en) | Stable iloperidone compound | |
| CN105646320A (en) | Stable Vernakalant compound | |
| CN106543225A (en) | Stable minodronic acid compound | |
| CN105646654A (en) | Carfilzomib compound | |
| CN106543160A (en) | Difficult to understand card friend's compound | |
| CN105646583A (en) | Stable ceftaroline compound | |
| CN106543258A (en) | A kind of stable Abiraterone acetate hydrate compound | |
| CN107663198A (en) | Olmesartan medoxomil and its production and use |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| WD01 | Invention patent application deemed withdrawn after publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20170329 |