CN105646673A - Telavancin compound - Google Patents
Telavancin compound Download PDFInfo
- Publication number
- CN105646673A CN105646673A CN201410632228.2A CN201410632228A CN105646673A CN 105646673 A CN105646673 A CN 105646673A CN 201410632228 A CN201410632228 A CN 201410632228A CN 105646673 A CN105646673 A CN 105646673A
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- Prior art keywords
- lawan star
- lawan
- compound
- crystal
- compound crystal
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/14—Peptides containing saccharide radicals; Derivatives thereof, e.g. bleomycin, phleomycin, muramylpeptides or vancomycin
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Medicinal Chemistry (AREA)
- Gastroenterology & Hepatology (AREA)
- Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention belongs to the technical field of medicines, and specifically relates to a novel crystal form of a telavancin compound and a preparation method thereof. The novel telavancin crystal is prepared through the following steps: adding telavancin into a mixed solution of ethanol, acetic acid and water in a specific proportion, and carrying out cooling in stages. The crystal has the following advantages: high purity, wherein the maximum content of impurities is less than one in a thousand; and good stability.
Description
Technical field
The invention belongs to pharmaceutical technology field, be specifically related to Te Lawan star novel crystal forms and preparation method thereof.
Background technology
The Vibativ (telavancin) that Theravance company and Astellas drugmaker help each other is that one type LG of having an injection kills pathogenic bacteria antibiotic, it is adaptable to treat caused a disease by following drawn up gram positive bacteria the adult's complexity skin infection caused by separator and skin structure infection (cSSSI): staphylococcus aureus (includes methicillin acumen staphylococcus aureus [MSSA] and methicillin-resistant staphylococcus aureus separator); Micrococcus scarlatinae; Streptococcus agalactiae; Streptococcus anginosus belongs to (including streptococcus anginosus, intermediate chain coccus and Streptococcus constellatus); And enterococcus faecalis (only to vancomycin acumen separator).
The structural formula of Te Lawan star is:
In research process, the method repeating prior art, the Te Lawan star impurity number obtained is more, and total impurities is higher. The Te Lawan star that the present invention obtains, has the advantage that: purity is high, and maximum contaminant is less than 1 ��; Good stability.
Summary of the invention
One object of the present invention, discloses a kind of Te Lawan star compound crystal.
Another object of the present invention, the preparation method disclosing Te Lawan star compound crystal.
Another purpose of the present invention, discloses the pharmaceutical composition of Te Lawan star.
In conjunction with the purpose of the present invention, present invention is specifically described.
The invention provides a kind of Te Lawan star compound, this Te Lawan star compound crystal, adopt D/Max-2500.9161 type x-ray diffractometer to measure, condition determination: CuKa target, tube voltage 40KV, tube current 100mA. X-ray powder diffraction characteristic absorption peak (2 ��) and D value are as follows,
In the present invention, the mensuration of 2 �� values uses light source, and precision is �� 0.2 ��, therefore represents above-mentioned taken value and has allowed certain reasonably range of error, and its range of error is �� 0.2 ��.
Another object of the present invention, the preparation method disclosing Te Lawan star compound crystal,
Bibliographical information, Te Lawan star has multiple preparation method, and because its process for purification is different, fusing point has relatively big difference; Quantity and the total amount of impurity are bigger. The present inventor is by substantial amounts of experiment, explore the relationship between quality of refining solvent and the Te Lawan star crystal obtained, by Te Lawan star is dissolved in alcohol, acetic acid heated in water solution, it is subsequently adding and lowers the temperature stage by stage, the preparation method obtaining Te Lawan star compound crystal of the present invention. Astoundingly, this Te Lawan star compound crystal has the advantage that: purity is high, and maximum contaminant is less than 1 ��; Good stability.
This preparation method screens from substantial amounts of single or mixed solvent, it does not have method can be instructed and be drawn.The partial solvent tested has, water; Methanol, ethanol, propanol, isopropanol, butanol, isobutanol, propylene glycol etc.; The ketone reagent such as acetone; The ethers reagent such as ether and diisopropyl ether; Esters, such as ethyl acetate, methyl acetate, isopropyl acetate, butyl acetate, ethyl n-butyrate., methyl butyrate etc.; Acetonitrile; Dichloromethane, chloroform, hexane, heptane, toluene, oxolane, DMF etc. Using the single of them or mixed solvent, mixed solvent can be two kinds, and three kinds or four kinds of solvent mixing, in mixed solvent, the ratio of various solvents is different.
Specifically include the following step: Te Lawan star adds in the mixed liquor of 2-3 times of (w/v) alcohol, acetic acid water=5-9:0.5-1:1-2, heating is to 50 DEG C-55 DEG C, filtered while hot, filtrate 30 DEG C-35 DEG C is incubated 3-4 hour, 10 DEG C-15 DEG C, then it is incubated 3-4 hour, crystallization, filtering, namely drying obtains above-mentioned Te Lawan star compound crystal.
Te Lawan star used, according to the method synthesis that existing document provides, the chemical constitution of the Te Lawan star of synthesis is through proton nmr spectra, elementary analysis, it was demonstrated that chemical constitution is correct.
Another purpose of the present invention, it is provided that comprise the compositions of Te Lawan star compound crystal and the Te Lawan star of one or more pharmaceutically acceptable carriers composition.
The pharmaceutical composition preparation of the present invention is as follows: use standard and conventional technology; make the compounds of this invention acceptable solid or liquid-carrier on galenic pharmacy be combined, and so as at random acceptable adjuvant and excipient are combined and prepare into microgranule or microsphere on galenic pharmacy. Said composition is used for preparing oral formulations.
The amount of the active ingredient (the compounds of this invention) contained in pharmaceutical composition and unit dosage form specifically can be applied according to the situation of the state of an illness of patient, diagnosis, amount or the concentration of compound used regulate in a wider scope, and the weight range of reactive compound is 1%��50%(weight of compositions).
Stability test
The chemical stability of the Te Lawan star compound crystal of the present invention has been studied by inventor, investigation condition is high temperature (60 DEG C �� 2 DEG C), strong illumination (4500Lx �� 500lx), high humidity (92.5%, RH) inspection target is outward appearance, content and have related substance (optical isomer).
Outward appearance, content is without change.
Result: from 0 10 days under high light, high temperature, super-humid conditions, outward appearance, optical isomer, content do not change, and illustrate that chemical stability is good, are suitable for manufacture and the long term storage of pharmaceutical preparation.
Detailed description of the invention:
Below in conjunction with 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 indicative, is in no way to be construed as the scope that it is intended to limit the present invention in any manner.
Embodiment 1
Equipped with stirring, thermometer, condenser 3000ml reaction bulb in, adding 200 cuts and draw Ethanol-Acetic Acid-water (5:0.5:1) mixed liquor of ten thousand stars and 400ml, start stirring, heat temperature raising heats to 50 DEG C-55 DEG C, filtered while hot, filtrate 30 DEG C-35 DEG C is incubated 3 hours, 10 DEG C-15 DEG C, then is incubated 3 hours, crystallization, filtering, namely drying obtains above-mentioned Te Lawan star compound crystal, 172.6 grams. Purity 99.94%.
Embodiment 2
Equipped with stirring, thermometer, condenser 3000ml reaction bulb in, adding 200 cuts and draw Ethanol-Acetic Acid-water (8:1:2) mixed liquor of ten thousand stars and 600ml, start stirring, heat temperature raising heats to 50 DEG C-55 DEG C, filtered while hot, filtrate 30 DEG C-35 DEG C is incubated 3 hours, 10 DEG C-15 DEG C, then is incubated 3 hours, crystallization, filtering, namely drying obtains above-mentioned Te Lawan star compound crystal, 173 grams.Purity 99.99%.
Claims (5)
1. the compound of Te Lawan star shown in formula I,
(I)
The crystal of described Te Lawan star compound, in measuring as characteristic X-ray powder with CuKa ray, its collection of illustrative plates has the following 2 �� angles of diffraction and D value,
The error of the 2 �� angles of diffraction is �� 0.2.
2. the preparation method of Te Lawan star compound crystal described in claim 1, by being dissolved in alcohol, acetic acid heated in water solution by Te Lawan star, then cooling obtains stage by stage.
3. the preparation method of Te Lawan star compound crystal described in claim 2, it is characterized in that comprising the following steps: in the mixed liquor that Te Lawan star adds 2-3 times of (w/v) alcohol, acetic acid water=5-9:0.5-1:1-2, heating is to 50 DEG C-55 DEG C, filtered while hot, filtrate 30 DEG C-35 DEG C is incubated 3-4 hour, 10 DEG C-15 DEG C, it is incubated 3-4 hour again, crystallization, filters, and namely drying obtains above-mentioned Te Lawan star compound crystal.
4. the compositions containing Te Lawan star compound crystal described in claim 1 with the Te Lawan star of one or more pharmaceutically acceptable carriers composition.
5. the compositions described in claim 4, it is characterised in that said composition is used for preparing oral formulations.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410632228.2A CN105646673A (en) | 2014-11-12 | 2014-11-12 | Telavancin compound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410632228.2A CN105646673A (en) | 2014-11-12 | 2014-11-12 | Telavancin compound |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN105646673A true CN105646673A (en) | 2016-06-08 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410632228.2A Pending CN105646673A (en) | 2014-11-12 | 2014-11-12 | Telavancin compound |
Country Status (1)
| Country | Link |
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| CN (1) | CN105646673A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107629116A (en) * | 2017-09-08 | 2018-01-26 | 福建省微生物研究所 | A kind of purification process of Te Lawan stars |
| CN107629115A (en) * | 2017-09-08 | 2018-01-26 | 福建省微生物研究所 | A kind of purification process of Te Lawan stars |
| CN109725101A (en) * | 2017-10-31 | 2019-05-07 | 正大天晴药业集团股份有限公司 | Detection method in relation to substance in hydrochloric acid Te Lawan star raw material |
-
2014
- 2014-11-12 CN CN201410632228.2A patent/CN105646673A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107629116A (en) * | 2017-09-08 | 2018-01-26 | 福建省微生物研究所 | A kind of purification process of Te Lawan stars |
| CN107629115A (en) * | 2017-09-08 | 2018-01-26 | 福建省微生物研究所 | A kind of purification process of Te Lawan stars |
| CN109725101A (en) * | 2017-10-31 | 2019-05-07 | 正大天晴药业集团股份有限公司 | Detection method in relation to substance in hydrochloric acid Te Lawan star raw material |
| CN109725101B (en) * | 2017-10-31 | 2021-11-19 | 正大天晴药业集团股份有限公司 | Method for detecting related substances in telavancin hydrochloride raw material |
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| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20160608 |
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| WD01 | Invention patent application deemed withdrawn after publication |