CN103992219A - Potassium-hydroxypentyl benzoate crystal and preparation method thereof - Google Patents
Potassium-hydroxypentyl benzoate crystal and preparation method thereof Download PDFInfo
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- CN103992219A CN103992219A CN201410056551.XA CN201410056551A CN103992219A CN 103992219 A CN103992219 A CN 103992219A CN 201410056551 A CN201410056551 A CN 201410056551A CN 103992219 A CN103992219 A CN 103992219A
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- C07—ORGANIC CHEMISTRY
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- C07C65/00—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C65/01—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups containing hydroxy or O-metal groups
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/42—Separation; Purification; Stabilisation; Use of additives
- C07C51/43—Separation; Purification; Stabilisation; Use of additives by change of the physical state, e.g. crystallisation
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Abstract
The invention discloses a potassium-hydroxypentyl benzoate crystal and a preparation method thereof. The potassium-hydroxypentyl benzoate crystal has a characteristic peak in powder X-ray diffraction when 2 theta is 7.0 +/- 0.2 DEG or 20.9 +/- 0.2 DEG. The potassium-hydroxypentyl benzoate crystal has stable quality and a stable crystal form and is more suitable for storage and applicable as a bulk drug.
Description
Technical field
The invention belongs to medical technical field, be specifically related to hydroxyl amylbenzene potassium formiate crystal and preparation method thereof.
Background technology
Cerebrovascular disease (cerebral apoplexy) for the cerebrovascular block or break cause brain blood flow be obstructed due to illness, in point ischemic cerebral apoplexy and hemorrhagic apoplexy.It is reported that China cities and towns and rural crowd's sample survey result show, annual morbidity is respectively 2,19/,100,000 and 1,85/,100,000, and mortality ratio is 1,16/,100,000 and 141.8/10 ten thousand, and the rejuvenation that becomes.Annual new cerebral apoplexy patient approximately 150 ~ 2,000,000 people of China, wherein cerebral infarction accounts for 60 ~ 80% of cerebral apoplexy case.In China's rural and urban population causes of death in 1992, cerebral apoplexy all comes second, accounts for 21.13% and 16.18% of total toll.The ratio of Beijing area cerebral infarction reaches 81.6% in 1999.China dies from cerebro-vascular diseases more than dying from heart trouble and cancer, is positioned at first of the three large causes of the death.Cerebral apoplexy is not only with high incidence, high mortality, high disability rate harm people ' s health, and accounting in 80% paralytic under survival, only there is 10% left and right can recover normal function completely, most patients leave hemiplegia, the sequela such as aphasia, thus society and family are caused to CR Critical burden.Other national situation is also roughly similar, but the control of cerebro-vascular diseases be there is no to desirable medicine both at home and abroad at present.Therefore, the research of such medicine is focus and the forward position of drug development research always.
Chinese patent application CN1382682A discloses 2-(Alpha-hydroxy amyl group) phenylformic acid sylvite and method for making and purposes.This compound is to go on the market on treatment cerebral apoplexy medicine NBP basis, utilizing principle of pro-drug to develop.Because it provides with solid form, can greatly simplify preparation process.This application discloses the purification process of two kinds of 2-(Alpha-hydroxy amyl group) phenylformic acid sylvite (being designated hereinafter simply as hydroxyl amylbenzene potassium formiate), be respectively with methyl alcohol-chloroform, methyl alcohol-ether and carry out recrystallization, obtain white particulate crystallization, 151 ~ 152 DEG C of fusing points (in the present invention, the hydroxyl amylbenzene potassium formiate crystal that above two kinds of methods are obtained is called after crystal I and crystal II respectively).Above-mentioned recrystallization solvent toxicity is large, and as chloroform, or boiling point is low, danger is high, as ether, will be not suitable for large-scale production.In addition, Chinese patent application CN1523003A has recorded the hydroxyl amylbenzene potassium formiate of being prepared by the open method of CN1382682A and has drawn moist very by force, to moist lability, under conventional environment, places easily and decomposes.Therefore, to hydroxyl amylbenzene potassium formiate, crystallization is further studied, and finding stable in properties, crystallization condition to be applicable to the crystallization of industrialized hydroxyl amylbenzene potassium formiate is to a job very important before this medicine is introduced to the market.
Summary of the invention
In view of the problem of prior art existence, the inventor to hydroxyl amylbenzene potassium formiate crystallization carried out large quantity research, multi-solvents system and crystallization condition are investigated, find this compound in multi-solvents system as ethanol, Virahol, acetone, methyl alcohol-ethyl acetate, acetone-chloroform, ethyl acetate-sherwood oil (normal hexane), toluene, acetonitrile etc., all can not maybe can not obtain well-crystallized by successful crystallization.By accident, contriver has obtained a kind of new hydroxyl amylbenzene potassium formiate crystal, and through study on the stability, finds that this crystal stability is very good, without drawing moist and stable in properties, in the present invention by this crystal called after crystal III.
Therefore, one aspect of the present invention provides a kind of hydroxyl amylbenzene potassium formiate crystal III, it is characterized in that, uses Cu-K α radiation, with 2 θ angles (°) powder x-ray diffraction that represents having characteristic peak with upper/lower positions: 7.0 ± 0.2 °, 20.9 ± 0.2 °.
In the present invention's one preferred embodiment, the hydroxyl amylbenzene potassium formiate crystal III providing
,use Cu-K α radiation, with 2 θ angles (°) powder x-ray diffraction that represents has characteristic peak 7.0 ± 0.2 °, 20.9 ± 0.2 ° positions, other position is relative intensity and is less than 10%, is even less than 5% weak peak.
In another preferred embodiment of the present invention, the hydroxyl amylbenzene potassium formiate crystal III providing
,use Cu-K α radiation, with 2 θ angles (°) powder x-ray diffraction that represents is in 7.0 ± 0.2 °, 20.9 ± 0.2 ° positions and has outside characteristic peak, can further locate characteristic peak at 7.0 ± 0.2 °, 17.4 ± 0.2 °, 20.9 ± 0.2 °, 23.2 ± 0.2 °, 25.5 ± 0.2 °, 26.5 ± 0.2 °.
In another preferred embodiment of the present invention, the hydroxyl amylbenzene potassium formiate crystal III providing
,use Cu-K α radiation, with 2 θ angles (°) powder x-ray diffraction that represents is in 7.0 ± 0.2 °, 20.9 ± 0.2 ° positions and has outside characteristic peak, can further locate characteristic peak at 7.0 ± 0.2 °, 15.6 ± 0.2 °, 17.4 ± 0.2 °, 19.4 ± 0.2 °, 20.9 ± 0.2 °, 23.2 ± 0.2 °, 24.3 ± 0.2 °, 25.5 ± 0.2 °, 26.5 ± 0.2 °, 27.8 ± 0.2 °, 30.6 ± 0.2 °.
Characteristic peak of the present invention generally refers to relative intensity and is not less than 10% peak.
The present invention also provides a kind of preparation method of hydroxyl amylbenzene potassium formiate crystal III on the other hand, comprise the steps: that hydroxyl amylbenzene potassium formiate crude product is placed in to one or more the organic solvent that is selected from ethyl acetate, isopropyl ether or tertiary methyl ether carries out recrystallization, obtains hydroxyl amylbenzene potassium formiate crystal III.
Wherein:
Recrystallization process is that hydroxyl amylbenzene potassium formiate crude product is joined in the mixed solvent of a kind of organic solvent or two or more organic solvents, heating for dissolving, and cooling, crystallization, obtains hydroxyl amylbenzene potassium formiate crystal III.Described Heating temperature is preferably 35 DEG C ~ organic solvent boiling point, more preferably 50 DEG C ~ organic solvent boiling point; Recrystallization temperature is preferably 30 DEG C ~-20 DEG C, more preferably 20 DEG C ~ 0 DEG C; The mass volume ratio of hydroxyl amylbenzene potassium formiate and organic solvent is preferably 1:1 ~ 100, more preferably 1:5 ~ 20.
The present invention also provides a kind of pharmaceutical composition on the other hand, comprises above-mentioned hydroxyl amylbenzene potassium formiate crystal III and pharmaceutically acceptable carrier, and optionally, described pharmaceutical composition also can exist other treatment component.
In the time that described pharmaceutical composition comprises above-mentioned hydroxyl amylbenzene potassium formiate crystal III and pharmaceutically acceptable carrier, can be made into oral preparations, be preferably tablet, capsule, granule; Also can be made into injection formulations, be preferably lyophilized injectable powder or injection liquid, these preparations can adopt the known corresponding auxiliary material of persons skilled in the art, adopt the technology of preparing of corresponding known pharmaceutical preparation to make.
Described other treatment component can produce synergy with hydroxyl amylbenzene potassium formiate, advantageous particularly in the time of prevention and treatment cerebro-vascular diseases.
Application in the medicine of the disease that the pharmaceutical composition that the present invention also provides on the other hand above-mentioned hydroxyl amylbenzene potassium formiate crystal III or comprises it causes in preparation cerebral ischemia.
Hydroxyl amylbenzene potassium formiate crystal III solvent for use of the present invention is middle low-toxic solvent, and moderate boiling point, will be more suitable in suitability for industrialized production.
By the hydroxyl amylbenzene potassium formiate crystal III of gained of the present invention, be under 75% ± 5% condition, to carry out stability test investigation in 40 DEG C ± 2 DEG C of temperature, relative humidity, test-results shows, hydroxyl amylbenzene potassium formiate crystal III of the present invention is moist without drawing, stable in properties, is more suitable for storage and develops as bulk drug.
Brief description of the drawings
The testing conditions of powder x-ray diffraction spectrum accompanying drawing is as follows:
Device name: D8ADVANCE x-ray diffractometer
Leather bar: Cu-K α radiation
Step angle: 0. 02 ° of o
Sweep limit: 5 ~ 60 °.
The powder x-ray diffraction figure of Fig. 1: embodiment 1 gained crystal prototype.Length axis represents diffracted intensity (cps), and axis of abscissa represents diffraction angle (2 θ).
Fig. 2: embodiment 1 gained crystal prototype accelerates the powder x-ray diffraction figure of 6 months.Length axis represents diffracted intensity (cps), and axis of abscissa represents diffraction angle (2 θ).
The powder x-ray diffraction figure of Fig. 3: embodiment 2 gained crystal prototypes.Length axis represents diffracted intensity (cps), and axis of abscissa represents diffraction angle (2 θ).
Fig. 4: embodiment 2 gained crystal prototypes accelerate the powder x-ray diffraction figure of 6 months.Length axis represents diffracted intensity (cps), and axis of abscissa represents diffraction angle (2 θ).
The powder x-ray diffraction figure of Fig. 5: embodiment 3 gained crystal prototypes.Length axis represents diffracted intensity (cps), and axis of abscissa represents diffraction angle (2 θ).
Fig. 6: embodiment 3 gained crystal prototypes accelerate the powder x-ray diffraction figure of 6 months.Length axis represents diffracted intensity (cps), and axis of abscissa represents diffraction angle (2 θ).
The powder x-ray diffraction figure of Fig. 7: embodiment 5 gained crystal prototypes.Length axis represents diffracted intensity (cps), and axis of abscissa represents diffraction angle (2 θ).
The powder x-ray diffraction figure of Fig. 8: embodiment 6 gained crystal prototypes.Length axis represents diffracted intensity (cps), and axis of abscissa represents diffraction angle (2 θ).
Embodiment
preparation example: the preparation of hydroxyl amylbenzene potassium formiate crude product
1kg NBP is dissolved in 5L methyl alcohol, the aqueous solution that then adds 5L to contain 0.3kg potassium hydroxide, reflux, to reacting completely, obtains spumescence solid 1.3kg by reaction solution concentrating under reduced pressure, i.e. hydroxyl amylbenzene potassium formiate crude product at 85 DEG C.
embodiment 1: the preparation of hydroxyl amylbenzene potassium formiate crystal III
hydroxyl amylbenzene potassium formiate crude product 10g is joined in 50mL isopropyl ether, and reflux is dissolved, and is cooled to room temperature, and stirring and crystallizing 1h filters, is dried, and obtains white crystal 9.3g.Gained crystal prototype is carried out to powder x-ray diffraction, and accompanying drawing 1 is shown in by gained collection of illustrative plates, and spectrum data is in table 1.
embodiment 2: the preparation of hydroxyl amylbenzene potassium formiate crystal III
hydroxyl amylbenzene potassium formiate crude product 10g is joined in 100mL ethyl acetate, and heating for dissolving, is cooled to 5 DEG C, and stirring and crystallizing 2h filters, is dried, and obtains white crystal 8.5g.Gained crystal prototype is carried out to powder x-ray diffraction, and accompanying drawing 3 is shown in by gained collection of illustrative plates, and spectrum data is in table 1.
embodiment 3: the preparation of hydroxyl amylbenzene potassium formiate crystal III
Hydroxyl amylbenzene potassium formiate crude product 10g is joined in the tertiary methyl ether of 200mL, and reflux is dissolved, and is cooled to 0 DEG C, and stirring and crystallizing 2h filters, is dried, and obtains white crystal 8.2g.Gained crystal prototype is carried out to powder x-ray diffraction, and accompanying drawing 5 is shown in by gained collection of illustrative plates, and spectrum data is in table 1.
Table 1 embodiment 1 ~ 3 crystal prototype powder x-ray diffraction characteristic peak data
。
embodiment 4: other crystallization solvent system is investigated
Be applicable to industrialized hydroxyl amylbenzene potassium formiate crystal in order to obtain stable in properties and crystallization condition, except above-described embodiment crystallization solvent system, the inventor also investigates some other solvent systems, and experimental result is as follows.
1. ethanol
Hydroxyl amylbenzene potassium formiate crude product 10g is joined in 150mL ethanol, and heating for dissolving, stirs and is cooled to after room temperature, puts into refrigerator and cooled and hides crystallization 24h, does not separate out solid.Solution is concentrated into 80mL, continues to put into refrigerator and cooled and hide crystallization 24h, do not separate out yet solid.
2. Virahol
Hydroxyl amylbenzene potassium formiate crude product 10g is joined in 20mL Virahol, heating, solid can not dissolve, and when adding solvent to total solvent amount and being 50ml, solid dissolves completely, stirs and is cooled to after room temperature, puts into refrigerator and cooled and hides crystallization 24h, does not separate out solid.
3. acetone
Hydroxyl amylbenzene potassium formiate crude product 10g is joined in 100mL acetone, and heating for dissolving, stirs and is cooled to after room temperature, puts into refrigerator and cooled and hides crystallization 24h, does not separate out solid.Solution is concentrated into 50mL, continues to put into refrigerator and cooled and hide crystallization 24h, do not separate out yet solid.
4. methyl alcohol-ethyl acetate
Hydroxyl amylbenzene potassium formiate crude product 10g is joined in 10ml methyl alcohol, and reflux is dissolved, and then adds 20ml ethyl acetate, is down to room temperature, puts into the refrigerator cold-storage crystallization that spends the night.To separate out solid filtering, solid is clamminess, especially easily the moisture absorption.Sample thief carries out powder x-ray diffraction test, is amorphous form.
5. acetone-chloroform
Hydroxyl amylbenzene potassium formiate crude product 10g is joined in 100mL acetone, and heating for dissolving, stirs and is cooled to 0-5 DEG C, drips chloroform 50mL, separates out thick yellow solid, can not successfully filter and obtain blocks of solid.
6. ethyl acetate-sherwood oil (or normal hexane)
Hydroxyl amylbenzene potassium formiate crude product 10g is joined in 100mL ethyl acetate, and heating for dissolving, stirs and is cooled to 0-5 DEG C, drips sherwood oil (or normal hexane) 50mL, separates out thick yellow solid, can not successfully filter and obtain blocks of solid.
In addition, contriver has also attempted toluene, acetonitrile equal solvent system, all can not obtain well-crystallized.
Above-mentioned experimental result shows, hydroxyl amylbenzene potassium formiate can not maybe can not obtain well-crystallized by successful crystallization under multi-solvents system.Hydroxyl amylbenzene potassium formiate crystal III of the present invention is that contriver obtains through lot of experiments.
embodiment 5: the preparation of the existing crystal I of hydroxyl amylbenzene potassium formiate
Hydroxyl amylbenzene potassium formiate crude product 10g is joined in 10ml methyl alcohol, and reflux is dissolved, and then adds 20ml chloroform, is down to room temperature, puts into the refrigerator cold-storage crystallization that spends the night.Filter, be dried 12h, obtain white solid 5.2g.Gained crystal prototype is carried out to powder x-ray diffraction, and accompanying drawing 7 is shown in by gained collection of illustrative plates, and spectrum data is in table 2.
Table 2 embodiment 5 crystal prototype powder x-ray diffraction peak data
。
embodiment 6: the preparation of the existing crystal II of hydroxyl amylbenzene potassium formiate
10g NBP adds 40ml water, stirs into dirty solution, adds 2.12g sodium hydroxide, under 85 DEG C of conditions, reacts completely.In 10 DEG C ~ 0 DEG C cold-trap cooling of ﹣, after constant temperature, slowly drip hydrochloric acid, pH value is adjusted to 2-3, reaction 10min, separates out a large amount of white solid 2-(Alpha-hydroxy amyl groups) phenylformic acid.Filtration obtains white solid, uses 100ml ether dissolution, and the large quantity of moisture that extracting and separating product carries obtains 2-(Alpha-hydroxy amyl group) phenylformic acid diethyl ether solution, anhydrous magnesium sulfate drying 1h, filters;
By dried in advance 100ml 2-(Alpha-hydroxy amyl group) phenylformic acid diethyl ether solution is diluted to 700ml with anhydrous diethyl ether, be placed in the mixture of ice and water of 0 DEG C, after constant temperature, the 140ml salt of wormwood methanol solution (3.66g salt of wormwood is dissolved in 140ml methyl alcohol) configuring is slowly dropped to 2-(Alpha-hydroxy amyl group) in phenylformic acid diethyl ether solution, stirring and crystallizing.Filter, be dried, obtain white solid 4.2g.Gained crystal prototype carries out powder x-ray diffraction, and accompanying drawing 8 is shown in by gained collection of illustrative plates, and spectrum data is in table 3.
Table 3 embodiment 6 crystal prototype powder x-ray diffraction characteristic peak data
。
Can find out from table 1 ~ 3 data, gained hydroxyl amylbenzene potassium formiate crystal of the present invention is different from existing crystal, is a kind of new crystal.
The inventor to hydroxyl amylbenzene potassium formiate crystallization carried out large quantity research, in order to obtain stay-in-grade hydroxyl amylbenzene potassium formiate new crystal, contriver has carried out stability test to gained hydroxyl amylbenzene potassium formiate crystal of the present invention.
embodiment 7: stability test
Respectively get embodiment 1 ~ 3 sample appropriate, simulation listing packaging, is to place 6 months under 75% ± 5% condition in 40 DEG C ± 2 DEG C of temperature, relative humidity, respectively at the 1st, 2,3,6 samplings at the end of month, relatively after outward appearance, test other and investigate index, result and data comparison in 0 month.Will speed up sample after 6 months carries out powder x-ray diffraction analysis and (is called for short: whether XRD), observe unanimously with 0 month crystal formation, accelerated test the results are shown in Table 4-1, shows 4-2.
Table 4-1: embodiment 1 ~ 3 crystal prototype accelerated test stability result
。
Accelerated test result shows: hydroxyl amylbenzene potassium formiate crystal prototype of the present invention is to place 6 months under 75% ± 5% condition in 40 DEG C ± 2 DEG C of temperature, relative humidity, every detection index there are no significant change, stable in properties.
Table 4-2 embodiment 1 ~ 3 crystal prototype accelerates powder x-ray diffraction characteristic peak data after 6 months
。
Powder x-ray diffraction analytical results shows: powder x-ray diffraction collection of illustrative plates and the 0 month collection of illustrative plates of hydroxyl amylbenzene potassium formiate crystal acceleration of the present invention after 6 months is basically identical, shows that crystal formation of the present invention, acceleration environment placement 6 months, has good stability; And Chinese patent application CN1523003A has recorded the hydroxyl amylbenzene potassium formiate (being crystal I and crystal II) being prepared by CN1382682A method and draws moist very by force, to moist lability, under conventional environment, place easily and decompose.
Above result shows: hydroxyl amylbenzene potassium formiate crystal mass of the present invention is stable, stable crystal form, is more suitable in storage and uses as bulk drug.
Claims (10)
1. hydroxyl amylbenzene potassium formiate crystal, is characterized in that, uses Cu-K α radiation, with 2 θ angles (°) powder x-ray diffraction that represents having characteristic peak with upper/lower positions: 7.0 ± 0.2 °, 20.9 ± 0.2 °.
2. hydroxyl amylbenzene potassium formiate crystal as claimed in claim 1, it is characterized in that, use Cu-K α radiation, with 2 θ angles (°) powder x-ray diffraction that represents, further having characteristic peak with upper/lower positions: 17.4 ± 0.2 °, 23.2 ± 0.2 °, 25.5 ± 0.2 °, 26.5 ± 0.2 °.
3. hydroxyl amylbenzene potassium formiate crystal as claimed in claim 1, it is characterized in that, use Cu-K α radiation, with 2 θ angles (°) powder x-ray diffraction that represents, further having characteristic peak with upper/lower positions: 7.0 ± 0.2 °, 15.6 ± 0.2 °, 17.4 ± 0.2 °, 19.4 ± 0.2 °, 20.9 ± 0.2 °, 23.2 ± 0.2 °, 24.3 ± 0.2 °, 25.5 ± 0.2 °, 26.5 ± 0.2 °, 27.8 ± 0.2 °, 30.6 ± 0.2 °.
4. the preparation method of a hydroxyl amylbenzene potassium formiate crystal claimed in claim 1, comprise the steps: that hydroxyl amylbenzene potassium formiate crude product is placed in to one or more the organic solvent that is selected from ethyl acetate, isopropyl ether or tertiary methyl ether carries out recrystallization, obtains hydroxyl amylbenzene potassium formiate crystal.
5. a pharmaceutical composition, comprises hydroxyl amylbenzene potassium formiate crystal and pharmaceutically acceptable carrier as claimed any one in claims 1 to 3, and optionally, described pharmaceutical composition also can exist other treatment component.
6. pharmaceutical composition as claimed in claim 5, is characterized in that, it is oral preparations.
7. pharmaceutical composition as claimed in claim 6, is characterized in that, described oral preparations is capsule, tablet, granule.
8. pharmaceutical composition as claimed in claim 5, is characterized in that, it is injection formulations.
9. pharmaceutical composition as claimed in claim 8, is characterized in that, described injection formulations is lyophilized injectable powder, injection liquid.
10. hydroxyl amylbenzene potassium formiate crystal as claimed any one in claims 1 to 3, or the pharmaceutical composition described in any one in claim 5 to 9, the application in the medicine of the disease causing in preparation treatment cerebral ischemia.
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| CN2013100528696A CN103113210A (en) | 2013-02-19 | 2013-02-19 | Hydroxyl amyl benzoate potassium crystal and preparation method thereof |
| CN201410056551.XA CN103992219B (en) | 2013-02-19 | 2014-02-19 | Hydroxyl amyl group Potassium Benzoate crystal and preparation method thereof |
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| CN104086399B (en) * | 2013-07-17 | 2016-08-24 | 浙江奥翔药业股份有限公司 | 5-bromo-2-(Alpha-hydroxy amyl group) different crystal forms and preparation method thereof of benzoic acid sodium salt |
| CN103896763B (en) * | 2014-03-27 | 2015-11-18 | 云南昊邦制药有限公司 | A kind of 2-(Alpha-hydroxy amyl group) potassium benzoate polymorphic and preparation method thereof, preparation and application |
| CN112679353B (en) * | 2020-12-26 | 2022-09-20 | 郑州大学 | Prodrug based on butylphthalide structure or pharmaceutically acceptable metal salt thereof, and preparation method and application thereof |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1382682A (en) * | 2002-05-09 | 2002-12-04 | 中国医学科学院药物研究所 | 2-(alpha-hydroxypentyl) benzoate and its preparing process and usage |
| CN1523003A (en) * | 2003-09-01 | 2004-08-25 | 北京天衡药物研究院 | Novel 2-(alpha-hydroxyl amyl) and its preparing method and use |
| CN1594270A (en) * | 2004-06-17 | 2005-03-16 | 北京天衡药物研究院 | Novel L-2-(alpha-hydroxy pentyl)benzoate and its preparation method and use |
| CN101054346A (en) * | 2006-04-13 | 2007-10-17 | 温建波 | Preparation method and use for a set of novel compound and composition thereof |
| US20110224300A1 (en) * | 2008-07-08 | 2011-09-15 | Institute Of Mataria Medica, Chinese Academy Of Me | USE OF POTASSIUM 2-(a- HYDROXYPENTYL) BENZOATE IN THE MANUFACTURE OF MEDICAMENTS FOR PREVENTING AND/OR TREATING SENILE DEMENTIA |
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- 2013-02-19 CN CN2013100528696A patent/CN103113210A/en active Pending
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- 2014-02-19 CN CN201410056551.XA patent/CN103992219B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1382682A (en) * | 2002-05-09 | 2002-12-04 | 中国医学科学院药物研究所 | 2-(alpha-hydroxypentyl) benzoate and its preparing process and usage |
| CN1523003A (en) * | 2003-09-01 | 2004-08-25 | 北京天衡药物研究院 | Novel 2-(alpha-hydroxyl amyl) and its preparing method and use |
| CN1594270A (en) * | 2004-06-17 | 2005-03-16 | 北京天衡药物研究院 | Novel L-2-(alpha-hydroxy pentyl)benzoate and its preparation method and use |
| CN101054346A (en) * | 2006-04-13 | 2007-10-17 | 温建波 | Preparation method and use for a set of novel compound and composition thereof |
| US20110224300A1 (en) * | 2008-07-08 | 2011-09-15 | Institute Of Mataria Medica, Chinese Academy Of Me | USE OF POTASSIUM 2-(a- HYDROXYPENTYL) BENZOATE IN THE MANUFACTURE OF MEDICAMENTS FOR PREVENTING AND/OR TREATING SENILE DEMENTIA |
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