CN110330410A - A kind of honokiol meglumine eutectic and preparation method thereof - Google Patents
A kind of honokiol meglumine eutectic and preparation method thereof Download PDFInfo
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- CN110330410A CN110330410A CN201910783703.9A CN201910783703A CN110330410A CN 110330410 A CN110330410 A CN 110330410A CN 201910783703 A CN201910783703 A CN 201910783703A CN 110330410 A CN110330410 A CN 110330410A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07C215/00—Compounds containing amino and hydroxy groups bound to the same carbon skeleton
- C07C215/02—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C215/04—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being saturated
- C07C215/06—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being saturated and acyclic
- C07C215/10—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being saturated and acyclic with one amino group and at least two hydroxy groups bound to the carbon skeleton
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- C07C39/205—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a six-membered aromatic ring polycyclic, containing only six-membered aromatic rings as cyclic parts with unsaturation outside the rings
- C07C39/21—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a six-membered aromatic ring polycyclic, containing only six-membered aromatic rings as cyclic parts with unsaturation outside the rings with at least one hydroxy group on a non-condensed ring
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Abstract
The invention discloses a kind of honokiol meglumine eutectic and preparation method thereof, the x-ray diffractogram of powder spectrum of the honokiol meglumine eutectic in the present invention has crystal characteristic diffraction maximum at 4.87 °, 12.66 °, 15.50 °, 18.85 °, 19.79 °, 20.39 °, 21.44 ° and 25.57 ° (2 θ)；Differential Scanning Calorimetry has single endothermic fusion peak at 153.7 DEG C；Infrared spectroscopy is in 3426,3202,1589,1481,1435,1281 and 1088cm‑1There is characteristic absorption peak at place.The above eutectic characterization result and honokiol crystal, meglumine crystal and the two physical mixture are different, show that the honokiol meglumine eutectic is a kind of completely new solid forms.Preparation method of the present invention is easy, and easily controllable, the honokiol meglumine eutectic of acquisition is remarkably improved the dissolution dissolution rate of slightly solubility honokiol, and improves its compressibility.
Description
Technical field
The present invention relates to pharmaceutical co-crystals, and in particular to a kind of honokiol meglumine eutectic and preparation method thereof.
Background technique
With the development of High Throughput Screening Assay, more and more active constituents are found, wherein there are about 75% candidates
Drug there are poorly water-soluble, dissolution rate is low, bioavilability is low the problems such as.In the research and development process of Chinese medicine, also often by
Cause its formulation development and clinical application limited in the slightly solubility of active ingredient of Chinese herbs.Pharmaceutical co-crystals refer to active pharmaceutical ingredient
It is assembled in certain proportion under the action of hydrogen bond, pi-pi accumulation, Van der Waals force or other non-covalent bonds with suitable eutectic ligand
The novel crystal structure with single fusing point formed.It can not change medicines structure, retain drug pharmacological properties itself
Improve the physicochemical property of insoluble drug simultaneously, such as solubility, dissolution rate, stability, draws moist and mechanical performance.
Honokiol (Honokiol) is one of Magnoliacea plant Cortex Magnoliae Officinalis lignin compound, and chemistry is entitled
Bis- -2- acrylic -1,1'- biphenyl -2,4'- diphenol of 3', 5-, molecular formula C18H18O2, chemical structural formula is as follows.Research report,
Honokiol antibacterial, it is anti-inflammatory, anti-oxidant, in terms of show very strong pharmacological activity.However, honokiol is water-soluble
Property is poor, and solubility is about 60 μ g/mL in 37 DEG C of water, this largely limits its formulation development and clinical application.To solve
This problem, CN103705469A disclose a kind of honokiol nanoparticle and preparation method thereof；CN104095817A is disclosed
A kind of nanosphere and its preparation method and application containing magnolol or honokiol；CN105012242A discloses a kind of thickness
Plain phenol or honokiol or both mixture amorphous solid dispersion and its hot-melt extruded preparation method.Though patent disclosed above
The water solubility of honokiol can be improved, but the problems such as there are preparation long-time stability difference or low drugloading rates.
Summary of the invention
Goal of the invention: the object of the present invention is to provide a kind of honokiol meglumine eutectic, by honokiol with it is medicinal small
Molecule auxiliary material meglumine forms eutectic, while guaranteeing drugloading rate and stability, improves the dissolution dissolution rate of honokiol, changes
It is apt to its compressibility.
Technical solution: honokiol meglumine eutectic of the present invention is honokiol and medicinal small molecule auxiliary material Portugal first
The eutectic that amine is formed.
The honokiol meglumine eutectic, eutectic are using honokiol as active pharmaceutical ingredient, and meglumine is matched for eutectic
Body, 1:1 is combined and is formed in molar ratio.
The honokiol meglumine eutectic, the powder of eutectic indicate for θ ° with x-ray diffraction angle 2,4.87 °,
There is characteristic diffraction peak at 12.66 °, 15.50 °, 18.85 °, 19.79 °, 20.39 °, 21.44 ° and 25.57 °；The eutectic differential is swept
Retouch calorimetric map has single endothermic fusion peak at 153.7 DEG C；The infrared spectroscopy obtained with potassium bromide mixed pressuring plate 3726,
3426、 3202、2970、2916、2353、2315、1898、1636、1589、1481、1435、1319、1281、1227、 1173、
1126,1088,1042,995,949,918,856,787,610,486 and 447cm-1There is absorption peak at place.
A. the preparation method of the honokiol meglumine eutectic, includes the following steps:
(1) honokiol is dissolved in suitable organic solvent；
(2) meglumine of equimolar amounts is dissolved in the water；
(3) aqueous megiumine solution is slowly added dropwise into the resulting honokiol solution of step (1), is held at 10~55 DEG C
20~28h of continuous stirring；
(4) gained emulsion filters, and filter cake is through 25~40 DEG C of 24~48h of vacuum drying removal solvents to get described and thick
Plain phenol meglumine eutectic.
The organic solvent is dehydrated alcohol, methanol, acetonitrile or their mixed solvent.
Preferably, step (3) whipping temp is 25~45 DEG C.
Preferably, organic solvent is dehydrated alcohol or methanol.
B. another preparation method of the honokiol meglumine eutectic, includes the following steps:
(1) meglumine of honokiol and equimolar amounts is dissolved in organic solvent, obtains clear solution；
(2) clear solution obtained by step (1) is depressurized at 30~60 DEG C rotary evaporation and removes solvent, vacuum drying is gone residual
Stay solvent to get the honokiol meglumine eutectic.
The organic solvent is methanol, dehydrated alcohol or their mixed solvent.
Preferably, the temperature of the decompression rotary evaporation is 40~55 DEG C.
Preferably, organic solvent is methanol.
The utility model has the advantages that (1) the invention discloses a kind of honokiol meglumine eutectics, with honokiol crystal, Portugal's first
PXRD, DSC, FTIR map of amine crystal and honokiol meglumine molar ratio 1:1 physical mixture are different, finish for one
It is different from the new solid-state of existing honokiol and meglumine entirely；(2) honokiol meglumine eutectic preparation side disclosed by the invention
Method is easy, at low cost, easily controllable, is conducive to industrialized production.In addition, through studying, it has been found that by honokiol with it is medicinal
Small molecule auxiliary material meglumine forms eutectic, can greatly improve the dissolution dissolution rate of honokiol.With above-mentioned amorphous solid point
Granular media technology is compared, and eutectic technology drugloading rate is high, and has better stability as crystal；Compared with nanotechnology, eutectic
Technology is easier to industrialize, and quality is easier to control.In addition, honokiol meglumine eutectic disclosed by the invention can also significantly improve
The compressibility of honokiol.
Detailed description of the invention
Fig. 1 is the x-ray diffractogram of powder of honokiol；
Fig. 2 is the x-ray diffractogram of powder of meglumine；
Fig. 3 is the x-ray diffractogram of powder of honokiol meglumine molar ratio 1:1 physical mixture；
Fig. 4 is the x-ray diffractogram of powder of honokiol meglumine eutectic；
Fig. 5 is the DSC figure of honokiol；
Fig. 6 is the DSC figure of meglumine；
Fig. 7 is the DSC figure of honokiol meglumine molar ratio 1:1 physical mixture；
Fig. 8 is the DSC figure of honokiol meglumine eutectic；
Fig. 9 is the infrared spectrogram of honokiol；
Figure 10 is the infrared spectrogram of meglumine；
Figure 11 is the infrared spectrogram of honokiol meglumine molar ratio 1:1 physical mixture；
Figure 12 is the infrared spectrogram of honokiol meglumine eutectic；
Figure 13 is the characteristic dissolution comparison diagram of honokiol, honokiol meglumine eutectic in water；
Figure 14 is that honokiol, honokiol meglumine eutectic can tabletting linearity curve comparison diagrams.
Specific embodiment
Embodiment 1: the preparation of honokiol meglumine eutectic
(1) prepare honokiol ethanol solution: 6.0g honokiol, which is dissolved in 10mL dehydrated alcohol, to be clarified
Solution；
(2) it prepares aqueous megiumine solution: 4.4g meglumine being dissolved in 10mL water and obtains clear solution；
Under the conditions of (3) 10 DEG C of magnetic agitations, aqueous megiumine solution is slowly added dropwise in honokiol ethanol solution, holds
Continuous stirring for 24 hours, obtains white " milky " liquid；
(4) above-mentioned emulsion is filtered, for gained filter cake in 25 DEG C of vacuum drying 48h, it is described and thick for obtaining white solid
Plain phenol meglumine eutectic.
Embodiment 2: the preparation of honokiol meglumine eutectic
(1) it prepares honokiol methanol solution: 6.0g honokiol being dissolved in 10mL methanol and obtains clear solution；
(2) it prepares aqueous megiumine solution: 4.4g meglumine being dissolved in 10mL water and obtains clear solution；
Under the conditions of (3) 25 DEG C of stirring in water bath, aqueous megiumine solution is slowly added dropwise in honokiol methanol solution, persistently stirs
20h is mixed, white " milky " liquid is obtained；
(4) above-mentioned emulsion is filtered, 30 DEG C of vacuum drying 48h of gained filter cake, obtaining white solid is the magnolia obovata
Phenol meglumine eutectic.
Embodiment 3: the preparation of honokiol meglumine eutectic
(1) it prepares honokiol acetonitrile solution: 6.0g honokiol being dissolved in 6mL acetonitrile and obtains clear solution；
(2) it prepares aqueous megiumine solution: 4.4g meglumine being dissolved in 6mL water and obtains clear solution；
Under the conditions of (3) 45 DEG C of magnetic agitations, aqueous megiumine solution is slowly added dropwise in honokiol acetonitrile solution, persistently stirs
28h is mixed, white " milky " liquid is obtained；
(4) above-mentioned emulsion is filtered, 40 DEG C of vacuum drying 48h of gained filter cake, obtaining white solid is the magnolia obovata
Phenol meglumine eutectic.
Embodiment 4: the preparation of honokiol meglumine eutectic
(1) it prepares honokiol solution: 6.0g honokiol is dissolved in 10mL methanol and dehydrated alcohol in the mixed solvent
Clear solution is obtained in (50:50, V:V)；
(2) it prepares aqueous megiumine solution: 4.4g meglumine being dissolved in 10mL water and obtains clear solution；
Under the conditions of (3) 55 DEG C of magnetic agitations, aqueous megiumine solution is slowly added dropwise in honokiol solution, it is lasting to stir
For 24 hours, white " milky " liquid is obtained；
(4) above-mentioned emulsion is filtered, 25 DEG C of vacuum drying 48h of gained filter cake, obtaining white solid is the magnolia obovata
Phenol meglumine eutectic.
Embodiment 5: the preparation of honokiol meglumine eutectic
665.0mg honokiol and 487.5mg meglumine (molar ratio 1:1) are added in 50mL methanol, room temperature ultrasound is molten
Solve clear solution, at 60 DEG C depressurize rotary evaporation of solvent after, by product in 25 DEG C vacuum drying for 24 hours to get.
Embodiment 6: the preparation of honokiol meglumine eutectic
163.7mg honokiol and 120.0mg meglumine (molar ratio 1:1) are added in 50mL dehydrated alcohol, room temperature is super
Sound dissolves to obtain clear solution, at 30 DEG C depressurize rotary evaporation of solvent after, by product in 25 DEG C vacuum drying for 24 hours to get.
Honokiol and the honokiol meglumine eutectic are detected, specific as follows:
1, honokiol ratio measuring in conjunction with meglumine in honokiol meglumine eutectic
(1) content determination (HPLC) of honokiol: 1260 high performance liquid chromatograph of Agilent is used, with Ultimate
XB-C18 column (4.6mm × 250mm, 5 μm) is chromatographic column；Methanol-water (85:15, V/V) is mobile phase；Detection wavelength is
291nm；Column temperature is 30 DEG C；Flow velocity is 1.0mL/min.
(2) test solution: taking honokiol meglumine eutectic 21.98mg, accurately weighed, sets in 50mL measuring bottle, adds first
Alcohol dissolves and is diluted to scale, shakes up, 0.22 μm of filtering with microporous membrane, take 20 μ L of subsequent filtrate inject liquid chromatograph, record and
Magnolol peak area is 7881945.
(3) reference substance solution: taking honokiol reference substance 12.61mg, accurately weighed, sets in 50mL measuring bottle, adds methanol molten
Scale is solved and be diluted to, is shaken up, 0.22 μm of filtering with microporous membrane takes 20 μ L of subsequent filtrate to inject liquid chromatograph, records magnolia obovata
Phenol peak area is 7785037.
(4) in honokiol meglumine eutectic honokiol and meglumine molar ratio are as follows:
(12.61/7785037×7881945/266.33):((21.98-12.61/7785037×7881945)/
195.22)≌1:1
2, powder x-ray diffraction
Instrument: D8 Advance X-ray diffractometer (Bruker, Germany)
Target: Cu-K α radiation
Wavelength:
Pipe pressure: 40KV
Guan Liu: 40mA
Step-length: 0.02 °
Scanning speed: 4 °/min
As a result: honokiol, meglumine, honokiol meglumine molar ratio 1:1 physical mixture and honokiol Portugal
The x-ray diffractogram of powder of methylamine eutectic is as shown in attached drawing 1~4.Know what the honokiol meglumine eutectic was indicated with 2 θ
Powder x-ray diffraction spectrum is at 4.87 °, 12.66 °, 15.50 °, 18.85 °, 19.79 °, 20.39 °, 21.44 ° and 25.57 °
There is the characteristic diffraction peak different from honokiol crystal, meglumine crystal and the two molar ratio 1:1 physical mixture.
3, differential scanning calorimetry
Instrument: 204 differential scanning calorimetric analysis instrument (Netzsch, Germany) of NETZSCH DSC
Temperature range: 45~250 DEG C
Heating rate: 10 DEG C/min
As a result: honokiol, meglumine, honokiol meglumine molar ratio 1:1 physical mixture and honokiol Portugal
The DSC of methylamine eutectic schemes as shown in attached drawing 5~8.Know that the honokiol meglumine eutectic only has single suction at 153.7 DEG C
Heat fusing peak.
4, infrared spectroscopy
Instrument: IRAffinity-1S Fourier Transform Infrared Spectrometer (Shimadzu, Japan)
Scanning range: 4000~400cm-1
As a result: the infrared spectrum absorpting peak of honokiol meglumine eutectic (pressing potassium bromide troche) 3726,3426,3202,
2970、2916、2353、2315、1898、1636、1589、1481、1435、1319、1281、1227、1173、 1126、1088、
1042,995,949,918,856,787,610,486 and 447cm-1Place is different from honokiol crystal, meglumine crystal and two
Person's molar ratio 1:1 physical mixture, especially in 3426,3202,1589,1481,1435,1281,1088cm-1Place.
5, solubility test
Test solution: 5mL water is measured in cillin bottle, is separately added into excessive honokiol and honokiol Portugal first
Amine eutectic (cross 80 meshes), cillin bottle is sealed, and is placed in 37 DEG C of stirring in water bath and is reached after balance (for 24 hours), crosses 0.22 μm of micropore filter
Film to get.
Reference substance solution: taking honokiol reference substance 10.0mg, accurately weighed, sets in 100mL measuring bottle, adds methanol dissolution simultaneously
Be diluted to scale, shake up, 0.22 μm of filtering with microporous membrane to get.
The measurement of honokiol HPLC method in ratio measuring in conjunction with meglumine using honokiol: it takes respectively above two
20 μ L of solution injects liquid chromatograph, records peak area.
The result shows that solubility (143.73 μ g/mL) is significantly higher than honokiol to honokiol meglumine eutectic in water
Crystal (59.02 μ g/mL).
6, characteristic dissolution measurement
Test solution: weighing honokiol respectively and the honokiol meglumine eutectic (crossing 80 meshes) powder is each
200mg carries out pressed powder at the same pressure, is pressed into the fine and close regular tablet of diameter 13mm, by the bottom surface of tablet and
Side is wrapped up with beeswax, makes it only one circular surface is exposed to contact with dissolution medium.Test is intelligently dissolved out using RC806D
Instrument (Tianjin Tianda Tianfa Science and Technology Co. Ltd.), according to " Chinese Pharmacopoeia " 2015 editions 0931 dissolution rates of general rule and drug release determination the
Two methods (paddle method), using 500mL water as dissolution medium, 37 ± 0.5 DEG C of test temperature, revolving speed 50rpm.After starting test, respectively at
15,20,30,45,60,90,120,180min sampling, and the mutually synthermal medium of same volume, the dissolution of taking-up is replenished in time
Liquid cross 0.22 μm of miillpore filter to get.
Reference substance solution: taking honokiol reference substance 10.0mg, accurately weighed, sets in 100mL measuring bottle, adds methanol dissolution simultaneously
Be diluted to scale, shake up, 0.22 μm of filtering with microporous membrane to get.
The measurement of honokiol HPLC method in ratio measuring in conjunction with meglumine using honokiol: it takes respectively above two
20 μ L of solution injects liquid chromatograph, records peak area.
Characteristic dissolution curve is as shown in Fig. 13, the results showed that, compared with honokiol, the honokiol meglumine is total
Brilliant intrinsic dissolution rate improves 6.7 times.
7, tensile strength measures
Honokiol and the honokiol meglumine eutectic (crossing 80 meshes) each 200mg of powder are weighed respectively, use 4235L
Each sample in 75,100,125,175,225,275,375MPa pressure lower sheeting, is reached mesh by type hydraulic machine (Carver, USA)
Pressure 10s is kept after marking pressure, the fine and close regular disk of gained diameter 13mm is placed in after drying at room temperature condition places 48h and measures circle
Piece thickness and hardness, are calculated as follows tensile strength.
Wherein, Q is tensile strength (MPa), and H is disk hardness (N), and d is disc diameter (mm), and t is wafer thickness (mm).
Can the comparison of tabletting linearity curve it is as shown in Fig. 14, the results showed that, honokiol meglumine eutectic significantly improve and
The compressibility of magnolol.
Claims (10)
1. a kind of honokiol meglumine eutectic, it is characterised in that the eutectic is the Portugal using honokiol as active pharmaceutical ingredient
Methylamine is eutectic ligand, and 1:1 is combined and formed in molar ratio.
2. honokiol meglumine eutectic according to claim 1, it is characterised in that the powder of the eutectic is spread out with X-ray
θ ° of firing angle 2 expression, has feature at 4.87 °, 12.66 °, 15.50 °, 18.85 °, 19.79 °, 20.39 °, 21.44 ° and 25.57 °
Diffraction maximum；The eutectic Differential Scanning Calorimetry has single endothermic fusion peak at 153.7 DEG C；It is obtained with potassium bromide mixed pressuring plate
Infrared spectroscopy 3726,3426,3202,2970,2916,2353,2315,1898,1636,1589,1481,1435,1319,
1281,1227,1173,1126,1088,1042,995,949,918,856,787,610,486 and 447cm-1There is absorption peak at place.
3. the preparation method of honokiol meglumine eutectic as described in claim 1, it is characterised in that include the following steps:
(1) honokiol is dissolved in suitable organic solvent；
(2) meglumine of equimolar amounts is dissolved in the water；
(3) aqueous megiumine solution is slowly added dropwise into the resulting honokiol solution of step (1), is persistently stirred at 10~55 DEG C
Mix 20~28h；
(4) gained emulsion filters, and filter cake is through 25~40 DEG C of 24~48h of vacuum drying removal solvents to get the honokiol
Meglumine eutectic.
4. the preparation method of honokiol meglumine eutectic according to claim 3, it is characterised in that the organic solvent
For dehydrated alcohol, methanol, acetonitrile or their mixed solvent.
5. the preparation method of honokiol meglumine eutectic according to claim 3, it is characterised in that step (3) is described to be stirred
Mixing temperature is 25~45 DEG C.
6. the preparation method of honokiol meglumine eutectic according to claim 4, it is characterised in that organic solvent is nothing
Water-ethanol or methanol.
7. the preparation method of honokiol meglumine eutectic as described in claim 1, it is characterised in that include the following steps:
(1) meglumine of honokiol and equimolar amounts is dissolved in organic solvent, obtains clear solution；
(2) clear solution obtained by step (1) is depressurized at 30~60 DEG C rotary evaporation and removes solvent, vacuum drying is gone to remain molten
Agent is to get the honokiol meglumine eutectic.
8. the preparation method of honokiol meglumine eutectic according to claim 7, it is characterised in that the organic solvent
For methanol, dehydrated alcohol or their mixed solvent.
9. the preparation method of honokiol meglumine eutectic according to claim 7, it is characterised in that the decompression rotation
The temperature of evaporation is 40~55 DEG C.
10. the preparation method of honokiol meglumine eutectic according to claim 8, it is characterised in that organic solvent is first
Alcohol.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115403450A (en) * | 2022-01-27 | 2022-11-29 | 化学与精细化工广东省实验室 | Magnolol and amino acid eutectic crystal and preparation method and application thereof |
| CN115403449A (en) * | 2022-01-27 | 2022-11-29 | 化学与精细化工广东省实验室 | Magnolol eutectic crystal and preparation method and application thereof |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1748673A (en) * | 2004-09-16 | 2006-03-22 | 山东绿叶天然药物研究开发有限公司 | Medicinal composition and its use in preparing medicine for treating or preventing cardio-cerebral vascular diseases |
| CN109369343A (en) * | 2018-10-29 | 2019-02-22 | 中国药科大学 | A kind of preparation method of honokiol nano-crystal |
| CN109627147A (en) * | 2018-11-27 | 2019-04-16 | 中南民族大学 | A kind of honokiol crystal and preparation method thereof |
| CN109771431A (en) * | 2018-02-10 | 2019-05-21 | 成都贝诺科成生物科技有限公司 | The new application of honokiol derivative |
| CN109966303A (en) * | 2018-03-06 | 2019-07-05 | 成都贝诺科成生物科技有限公司 | The purposes of honokiol derivative in the preparation of antitumor drugs |
-
2019
- 2019-08-23 CN CN201910783703.9A patent/CN110330410B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1748673A (en) * | 2004-09-16 | 2006-03-22 | 山东绿叶天然药物研究开发有限公司 | Medicinal composition and its use in preparing medicine for treating or preventing cardio-cerebral vascular diseases |
| CN109771431A (en) * | 2018-02-10 | 2019-05-21 | 成都贝诺科成生物科技有限公司 | The new application of honokiol derivative |
| CN109966303A (en) * | 2018-03-06 | 2019-07-05 | 成都贝诺科成生物科技有限公司 | The purposes of honokiol derivative in the preparation of antitumor drugs |
| CN109369343A (en) * | 2018-10-29 | 2019-02-22 | 中国药科大学 | A kind of preparation method of honokiol nano-crystal |
| CN109627147A (en) * | 2018-11-27 | 2019-04-16 | 中南民族大学 | A kind of honokiol crystal and preparation method thereof |
Non-Patent Citations (4)
| Title |
|---|
| 朱骤海: "厚朴酚磷脂复合物的制备、理化性质与生物利用度研究", 《中国优秀博硕士学位论文全文数据库(博士)工程科技Ⅰ辑》 * |
| 赵燕娜: "基于新型树枝状大分子的抗肿瘤纳米给药系统的研究", 《中国优秀博硕士学位论文全文数据库(博士)医药卫生科技辑》 * |
| 邸静: "白藜芦醇纳米粒与和厚朴酚前药纳米粒的制备及体内外研究", 《中国优秀博硕士学位论文全文数据库(硕士)医药卫生科技辑》 * |
| 高缘: "药物共晶研究进展", 《化学进展》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115403450A (en) * | 2022-01-27 | 2022-11-29 | 化学与精细化工广东省实验室 | Magnolol and amino acid eutectic crystal and preparation method and application thereof |
| CN115403449A (en) * | 2022-01-27 | 2022-11-29 | 化学与精细化工广东省实验室 | Magnolol eutectic crystal and preparation method and application thereof |
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| CN110330410B (en) | 2022-01-28 |
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