CN103992219B - Hydroxyl amyl group Potassium Benzoate crystal and preparation method thereof - Google Patents
Hydroxyl amyl group Potassium Benzoate crystal and preparation method thereof Download PDFInfo
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- CN103992219B CN103992219B CN201410056551.XA CN201410056551A CN103992219B CN 103992219 B CN103992219 B CN 103992219B CN 201410056551 A CN201410056551 A CN 201410056551A CN 103992219 B CN103992219 B CN 103992219B
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- 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 hydroxyl amyl group Potassium Benzoate crystal and preparation method thereof.The powder X-ray x ray diffraction of hydroxyl amyl group Potassium Benzoate crystal of the present invention is in 2 θ：There is characteristic peak at 7.0 ± 0.2 °, 20.9 ± 0.2 °.Hydroxyl amyl group Potassium Benzoate crystal mass of the present invention is stable, stable crystal form, is used more suitable for storage and as bulk drug.
Description
Technical field
The invention belongs to pharmaceutical technology field, and in particular to hydroxyl amyl group Potassium Benzoate crystal and preparation method thereof.
Background technology
Cranial vascular disease（Cerebral apoplexy）It is that cerebrovascular occlusion or rupture cause brain blood flow to be obstructed caused illness, point ischemic
Cerebral apoplexy and hemorrhagic apoplexy.It is reported that China cities and towns and rural crowd's sample survey results show that annual morbidity is respectively
219/100000 and 1,85/,100,000, the death rate is 1,16/,100,000 and 141.8/10 ten thousand, and the rejuvenation that becomes.Cerebral apoplexy is newly sent out every year by China
The people of patient about 150 ~ 2,000,000, wherein cerebral arterial thrombosis account for the 60 ~ 80% of cerebral apoplexy case.China's rural and urban population is dead within 1992
Die in reason, cerebral apoplexy comes second, account for the 21.13% and 16.18% of total toll.Beijing area cerebral arterial thrombosis
Ratio 1999 up to 81.6%.China dies from cerebrovascular disease more than heart disease and cancer is died from, first of the three big causes of the death.Brain
Palsy is not only with high incidence, high mortality, high disability rate harm people's health, and in the apoplexy for accounting for 80% survived
In patient, only 10% or so can recover normal function completely, and most patients leave hemiplegia, the sequelae such as aphasia, so that
CR Critical burden is caused to society and family.Other national situations are also substantially similar, but at present both at home and abroad to cerebrovascular disease
Preventing and treating there is no preferable medicine.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) benzoic acid sylvite and its preparation method and purposes.Should
Compound is on the basis for the treatment of cerebral apoplexy medicine butylphenyl phthaleine has been listed, to be developed using principle of pro-drug.Because it is with solid
Body form is provided, and can greatly simplify preparation process.That application discloses two kinds of 2- (Alpha-hydroxy amyl group) benzoic acid sylvite（Following letter
Referred to as hydroxyl amyl group Potassium Benzoate）Purification process, be respectively recrystallized with methanol-chloroform, methanol-diethyl ether, obtain white
Granular crystal, 151 ~ 152 DEG C of fusing point（In the present invention, the hydroxyl amyl group Potassium Benzoate crystal that both the above method is obtained is ordered respectively
Entitled crystal I and crystal II）.Above-mentioned recrystallization solvent toxicity is big, such as chloroform, or low boiling point, dangerous height, and such as ether will not
It is adapted to large-scale production.In addition, Chinese patent application CN1523003A describes the hydroxyl that method preparation is disclosed by CN1382682A
Amyl group Potassium Benzoate draws moist very strong, to moist lability, places easily decompose in normal circumstances.Therefore, to hydroxyl amyl group benzoic acid
Potassium crystallization is further studied, find that property is stable, crystallization condition be adapted to industrialized hydroxyl amyl group Potassium Benzoate and crystallize be pair
Particularly important one work before the medicine is introduced to the market.
The content of the invention
In view of the problem of prior art is present, the present inventor has carried out numerous studies to the crystallization of hydroxyl amyl group Potassium Benzoate, it is right
Multi-solvents system and crystallization condition are investigated, and find the compound in multi-solvents system such as ethanol, isopropanol, third
Ketone, methanol-ethyl acetate, acetone-chloroform, ethyl acetate-light petrol（N-hexane）, toluene, acetonitrile etc., can not succeed crystallization
Or well-crystallized can not be obtained.By accident, inventor has obtained a kind of new hydroxyl amyl group Potassium Benzoate crystal, and through stability
Investigate, it is found that the crystal stability is very good, it is stable without moist and property is drawn, the crystal is named as crystal III in the present invention.
Therefore, one aspect of the present invention provides a kind of hydroxyl amyl group Potassium Benzoate crystal III, it is characterised in that use Cu-K α spokes
Penetrate, with 2 θ angles（°）The powder x-ray diffraction of expression has characteristic peak in following position：7.0±0.2°、 20.9±0.2°.
In a preferred embodiment of the invention, the hydroxyl amyl group Potassium Benzoate crystal III provided is radiated using Cu-K α,
With 2 θ angles（°）The powder x-ray diffraction of expression only has characteristic peak, other positions 7.0 ± 0.2 °, 20.9 ± 0.2 ° of positions
It is that relative intensity is less than 10%, even less than 5% weak peak.
In another preferred embodiment of the invention, the hydroxyl amyl group Potassium Benzoate crystal III provided uses Cu-K α spokes
Penetrate, with 2 θ angles（°）The powder x-ray diffraction of expression be in 7.0 ± 0.2 °, 20.9 ± 0.2 ° of positions have outside characteristic peak, can enter
One step has spy 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 °
Levy peak.
In another preferred embodiment of the invention, the hydroxyl amyl group Potassium Benzoate crystal III provided uses Cu-K α spokes
Penetrate, with 2 θ angles（°）The powder x-ray diffraction of expression be in 7.0 ± 0.2 °, 20.9 ± 0.2 ° of positions have outside characteristic peak, can enter
One step 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 ±
There is characteristic peak at 0.2 °, 25.5 ± 0.2 °, 26.5 ± 0.2 °, 27.8 ± 0.2 °, 30.6 ± 0.2 °.
Characteristic peak of the present invention is generally referred to as the peak that relative intensity is not less than 10%.
Another aspect of the present invention also provides a kind of preparation method of hydroxyl amyl group Potassium Benzoate crystal III, comprises the following steps：
Hydroxyl amyl group Potassium Benzoate crude product is placed in organic more than one or both of ethyl acetate, isopropyl ether or tertiary methyl ether
Recrystallized in solvent, obtain hydroxyl amyl group Potassium Benzoate crystal III.
Wherein：
Recrystallization process is that hydroxyl amyl group Potassium Benzoate crude product is added into a kind of organic solvent or two or more organic solvents
In the mixed solvent, dissolve by heating, cooling, crystallization obtains hydroxyl amyl group Potassium Benzoate crystal III.The heating-up 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℃~0℃；The mass volume ratio of hydroxyl amyl group Potassium Benzoate and organic solvent is preferably 1:1 ~ 100, more preferably 1:5~20.
Another aspect of the present invention also provides a kind of pharmaceutical composition, includes above-mentioned hydroxyl amyl group Potassium Benzoate crystal III and pharmacy
Upper acceptable carrier, optionally, other therapeutic components also may be present in described pharmaceutical composition.
, can when described pharmaceutical composition includes above-mentioned hydroxyl amyl group Potassium Benzoate crystal III and pharmaceutically acceptable carrier
It is made into oral formulations, preferably tablet, capsule, granule；Also ejection preparation, preferably freeze drying powder injection can be made into
Or parenteral solution, these preparations can use corresponding auxiliary material known to persons skilled in the art, using corresponding known medicine system
The technology of preparing of agent is made.
Other therapeutic components can produce synergy with hydroxyl amyl group Potassium Benzoate, when preventing and treating cerebrovascular disease
It is particularly advantageous.
Another aspect of the present invention also provides above-mentioned hydroxyl amyl group Potassium Benzoate crystal III or the pharmaceutical composition comprising it in system
Application in the medicine of disease caused by standby cerebral ischemia.
The solvent for use of hydroxyl amyl group Potassium Benzoate crystal III of the present invention is middle low-toxic solvent, and moderate boiling point will be more suitable for
In industrialized production.
It is 75% ± 5% in 40 DEG C ± 2 DEG C of temperature, relative humidity by the hydroxyl amyl group Potassium Benzoate crystal III obtained by the present invention
Under the conditions of carry out stability test investigation, result of the test shows that hydroxyl amyl group Potassium Benzoate crystal III of the invention is moist without drawing, property
Matter is stable, is more suitable for storing and developing as bulk drug.
Brief description of the drawings
The testing conditions of powder x-ray diffraction spectrum accompanying drawing are as follows：
Device name：D8ADVANCE x-ray diffractometers
Remove from office bar：Cu-K α are radiated
Step angle：0. 02°º
Scanning range：5~60°.
Fig. 1：The powder x-ray diffraction figure of the gained crystal prototype of embodiment 1.Axis of ordinates represents diffracted intensity（cps）,
Axis of abscissas represents the angle of diffraction（2θ）.
Fig. 2：The gained crystal prototype of embodiment 1 accelerates the powder x-ray diffraction figure of 6 months.Axis of ordinates represents that diffraction is strong
Degree（cps）, axis of abscissas represents the angle of diffraction（2θ）.
Fig. 3：The powder x-ray diffraction figure of the gained crystal prototype of embodiment 2.Axis of ordinates represents diffracted intensity（cps）,
Axis of abscissas represents the angle of diffraction（2θ）.
Fig. 4：The gained crystal prototype of embodiment 2 accelerates the powder x-ray diffraction figure of 6 months.Axis of ordinates represents that diffraction is strong
Degree（cps）, axis of abscissas represents the angle of diffraction（2θ）.
Fig. 5：The powder x-ray diffraction figure of the gained crystal prototype of embodiment 3.Axis of ordinates represents diffracted intensity（cps）,
Axis of abscissas represents the angle of diffraction（2θ）.
Fig. 6：The gained crystal prototype of embodiment 3 accelerates the powder x-ray diffraction figure of 6 months.Axis of ordinates represents that diffraction is strong
Degree（cps）, axis of abscissas represents the angle of diffraction（2θ）.
Fig. 7：The powder x-ray diffraction figure of the gained crystal prototype of embodiment 5.Axis of ordinates represents diffracted intensity（cps）,
Axis of abscissas represents the angle of diffraction（2θ）.
Fig. 8：The powder x-ray diffraction figure of the gained crystal prototype of embodiment 6.Axis of ordinates represents diffracted intensity（cps）,
Axis of abscissas represents the angle of diffraction（2θ）.
Embodiment
Preparation example：The preparation of hydroxyl amyl group Potassium Benzoate crude product
1kg butylphenyl phthaleines are dissolved in 5L methanol, then adds and adds at the aqueous solution that 5L contains 0.3kg potassium hydroxide, 85 DEG C
Heat is back to reaction completely, and reaction solution is concentrated under reduced pressure to give into foaming solid 1.3kg, i.e. hydroxyl amyl group Potassium Benzoate crude product.
Embodiment 1：The preparation of hydroxyl amyl group Potassium Benzoate crystal III
Hydroxyl amyl group Potassium Benzoate crude product 10g is added in 50mL isopropyl ethers, dissolving is heated to reflux, is cooled to room temperature, stirs
Crystallization 1h is mixed, filters, dry, obtain white crystal 9.3g.Gained crystal prototype is subjected to powder x-ray diffraction, gained collection of illustrative plates
See accompanying drawing 1, spectrum data is shown in Table 1.
Embodiment 2：The preparation of hydroxyl amyl group Potassium Benzoate crystal III
Hydroxyl amyl group Potassium Benzoate crude product 10g is added in 100mL ethyl acetate, dissolved by heating, 5 DEG C, stirring are cooled to
Crystallization 2h, filters, dries, obtain white crystal 8.5g.Gained crystal prototype is subjected to powder x-ray diffraction, gained collection of illustrative plates is shown in
Accompanying drawing 3, spectrum data is shown in Table 1.
Embodiment 3：The preparation of hydroxyl amyl group Potassium Benzoate crystal III
Hydroxyl amyl group Potassium Benzoate crude product 10g is added in the tertiary methyl ethers of 200mL, dissolving is heated to reflux, is cooled to 0 DEG C, stirs
Crystallization 2h is mixed, filters, dry, obtain white crystal 8.2g.Gained crystal prototype is subjected to powder x-ray diffraction, gained collection of illustrative plates
See accompanying drawing 5, spectrum data is shown in Table 1.
The crystal prototype powder x-ray diffraction characteristic peak data of 1 embodiment of table 1 ~ 3
。
Embodiment 4：Other crystallization solvent systems are investigated
In order to obtain, property is stable and crystallization condition is adapted to industrialized hydroxyl amyl group Potassium Benzoate crystal, except above-mentioned implementation
Outside example crystallization solvent system, the present inventor is also investigated to some other solvent system, and experimental result is as follows.
1. ethanol
Hydroxyl amyl group Potassium Benzoate crude product 10g is added in 150mL ethanol, dissolved by heating, stirring is cooled to after room temperature, is put
Enter refrigeration crystallization 24h in refrigerator, solid is not separated out.Solution is concentrated into 80mL, continues to be put into refrigeration crystallization 24h in refrigerator, still
Solid is not separated out.
2. isopropanol
Hydroxyl amyl group Potassium Benzoate crude product 10g is added in 20mL isopropanols, heated, solid can not dissolve, and add solvent
When to total solvent amount being 50ml, solid is completely dissolved, and stirring is cooled to after room temperature, is put into refrigerator refrigeration crystallization 24h, is not separated out
Solid.
3. acetone
Hydroxyl amyl group Potassium Benzoate crude product 10g is added in 100mL acetone, dissolved by heating, stirring is cooled to after room temperature, is put
Enter refrigeration crystallization 24h in refrigerator, solid is not separated out.Solution is concentrated into 50mL, continues to be put into refrigeration crystallization 24h in refrigerator, still
Solid is not separated out.
4. methanol-ethyl acetate
Hydroxyl amyl group Potassium Benzoate crude product 10g is added in 10ml methanol, dissolving is heated to reflux, 20ml acetic acid is then added
Ethyl ester, is down to room temperature, is put into refrigerator cold-storage crystallization overnight.Solid filtering will be separated out, solid is tacky, is particularly easy to the moisture absorption.Sampling
Product carry out powder x-ray diffraction test, are amorphous form.
5. acetone-chloroform
Hydroxyl amyl group Potassium Benzoate crude product 10g is added in 100mL acetone, dissolved by heating, stirring is cooled to 0-5 DEG C, drop
Chlorination imitates 50mL, separates out thick yellow solid, it is impossible to be successfully filtrated to get blocks of solid.
6. ethyl acetate-light petrol（Or n-hexane）
Hydroxyl amyl group Potassium Benzoate crude product 10g is added in 100mL ethyl acetate, dissolved by heating, stirring is cooled to 0-5
DEG C, petroleum ether is added dropwise（Or n-hexane）50mL, separates out thick yellow solid, it is impossible to be successfully filtrated to get blocks of solid.
In addition, inventor have also been attempted toluene, acetonitrile equal solvent system, well-crystallized can not be obtained.
It is above-mentioned test result indicates that, hydroxyl amyl group Potassium Benzoate can not succeed under multi-solvents system and crystallization or can not obtain
To well-crystallized.The hydroxyl amyl group Potassium Benzoate crystal III of the present invention is that inventor obtains by lot of experiments.
Embodiment 5：The preparation of the existing crystal I of hydroxyl amyl group Potassium Benzoate
Hydroxyl amyl group Potassium Benzoate crude product 10g is added in 10ml methanol, dissolving is heated to reflux, 20ml chlorine is then added
It is imitative, room temperature is down to, refrigerator cold-storage crystallization overnight is put into.Filtering, dry 12h, obtain white solid 5.2g.Gained crystal prototype is entered
Row powder x-ray diffraction, gained collection of illustrative plates is shown in accompanying drawing 7, and spectrum data is shown in Table 2.
The crystal prototype powder X-ray diffraction peak data of 2 embodiment of table 5
。
Embodiment 6：The preparation of the existing crystal II of hydroxyl amyl group Potassium Benzoate
10g butylphenyl phthaleines add 40ml water, stir into dirty solution, add under the conditions of 2.12g sodium hydroxides, 85 DEG C and have reacted
Entirely.In hydrochloric acid is slowly added dropwise after 10 DEG C ~ 0 DEG C cold-trap cooling of ﹣, constant temperature, pH value is adjusted to 2-3,10min is reacted, separated out a large amount of
White solid 2-（Alpha-hydroxy amyl group）Benzoic acid.White solid is filtrated to get, 100ml ether dissolutions are used, extract and separate product is taken
The large quantity of moisture of band, obtains 2-（Alpha-hydroxy amyl group）Benzoic acid diethyl ether solution, anhydrous magnesium sulfate dries 1h, filtering；
By the 100ml 2- being pre-dried（Alpha-hydroxy amyl group）Benzoic acid diethyl ether solution is diluted to absolute ether
In 700ml, the mixture of ice and water for being placed in 0 DEG C, after constant temperature, by the 140ml potassium carbonate methanol solutions configured（3.66g potassium carbonate
It is dissolved in 140ml methanol）It is slowly added dropwise to 2-（Alpha-hydroxy amyl group）In benzoic acid diethyl ether solution, stirring and crystallizing.Filter, dry, obtain
To white solid 4.2g.Gained crystal prototype carries out powder x-ray diffraction, and gained collection of illustrative plates is shown in accompanying drawing 8, and spectrum data is shown in Table 3.
The crystal prototype powder x-ray diffraction characteristic peak data of 3 embodiment of table 6
。
Hydroxyl amyl group Potassium Benzoate crystal obtained by the present invention is can be seen that from the data of table 1 ~ 3 different from existing crystal, be one kind
Novel crystal forms.
The present inventor has carried out numerous studies to the crystallization of hydroxyl amyl group Potassium Benzoate, in order to obtain the hydroxyl amylbenzene of steady quality
Potassium formate novel crystal forms, inventor has carried out stability test to hydroxyl amyl group Potassium Benzoate crystal obtained by the present invention.
Embodiment 7：Stability test
Each sample of Example 1 ~ 3 is appropriate, simulation listing packaging, is 75% ± 5% in 40 DEG C ± 2 DEG C of temperature, relative humidity
Under the conditions of place 6 months, respectively at the 1st, 2,3,6 the end of month samplings, compare and other inspection targets tested after outward appearance, as a result with 0
Month data compare.Sample after accelerating 6 months is subjected to powder x-ray diffraction analysis（Referred to as：XRD）, observe and 0 month crystal formation
Whether consistent, accelerated test the results are shown in Table 4-1, table 4-2.
Table 4-1：The crystal prototype accelerated test stability result of embodiment 1 ~ 3
。
Accelerated test result shows：Hydroxyl amyl group Potassium Benzoate crystal prototype of the present invention is in 40 DEG C ± 2 DEG C of temperature, relative humidity
To place 6 months under the conditions of 75% ± 5%, every Testing index there are no significant change, property is stable.
Powder x-ray diffraction characteristic peak data after the crystal prototype of table 4-2 embodiments 1 ~ 3 accelerates 6 months
。
Powder x-ray diffraction analysis result shows：Hydroxyl amyl group Potassium Benzoate crystal of the present invention accelerate 6 months after powder
X-ray diffracting spectrum and 0 month collection of illustrative plates are basically identical, show that the crystal formation of the present invention is placed 6 months in acceleration environment, stability is good
It is good；And Chinese patent application CN1523003A describes the hydroxyl amyl group Potassium Benzoate prepared by CN1382682A methods（I.e.
Crystal I and crystal II）Draw moist very strong, to moist lability, place easily decompose in normal circumstances.
Result above shows：Hydroxyl amyl group Potassium Benzoate crystal mass of the present invention is stable, stable crystal form, more suitable for storage and
Used as bulk drug.
Claims (10)
1. hydroxyl amyl group Potassium Benzoate crystal, it is characterised in that radiated using Cu-K α, with 2 θ angles（°）The powder X-ray of expression
Diffraction has characteristic peak in following position：7.0±0.2°、17.4±0.2°、20.9±0.2°、23.2±0.2°、25.5±0.2°、
26.5±0.2°。
2. hydroxyl amyl group Potassium Benzoate crystal as claimed in claim 1, it is characterised in that radiated using Cu-K α, with 2 θ angles
（°）The powder x-ray diffraction of expression has characteristic peak in following position：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°。
3. hydroxyl amyl group Potassium Benzoate crystal, it is characterised in that substantially show powder x-ray diffraction figure as shown in Figure 1
Spectrum.
4. a kind of preparation method of the hydroxyl amyl group Potassium Benzoate crystal described in claim 1, comprises the following steps：By hydroxyl amylbenzene
Potassium formate crude product is placed in the organic solvent more than one or both of ethyl acetate, isopropyl ether or tertiary methyl ether and carried out
Recrystallization, obtains hydroxyl amyl group Potassium Benzoate crystal.
5. a kind of pharmaceutical composition, includes hydroxyl amyl group Potassium Benzoate crystal as claimed any one in claims 1 to 3 and pharmacy
Upper acceptable carrier, optionally, other therapeutic components also may be present in described pharmaceutical composition.
6. pharmaceutical composition as claimed in claim 5, it is characterised in that it is oral formulations.
7. pharmaceutical composition as claimed in claim 6, it is characterised in that the oral formulations are capsule, tablet, granule.
8. pharmaceutical composition as claimed in claim 5, it is characterised in that it is ejection preparation.
9. pharmaceutical composition as claimed in claim 8, it is characterised in that the ejection preparation is freeze drying powder injection, parenteral solution.
Any one of 10. hydroxyl amyl group Potassium Benzoate crystal as claimed any one in claims 1 to 3, or claim 5 to 9
Described pharmaceutical composition, the application in the medicine of disease caused by treatment cerebral ischemia is prepared.
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| CN201310052869.6 | 2013-02-19 | ||
| CN201410056551.XA CN103992219B (en) | 2013-02-19 | 2014-02-19 | Hydroxyl amyl group Potassium Benzoate crystal and preparation method thereof |
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| 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 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| 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 |
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| CN1243541C (en) * | 2002-05-09 | 2006-03-01 | 中国医学科学院药物研究所 | 2-(alpha-hydroxypentyl) benzoate and its preparing process and usage |
| WO2010003287A1 (en) * | 2008-07-08 | 2010-01-14 | 中国医学科学院药物研究所 | THE USE OF POTASSIUM 2-(α- HYDROXYPENTYL) BENZOATE IN THE MANUFACTURE OF MEDICAMENTS FOR PREVENTING AND/OR TREATING SENILE DEMENTIA |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
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