CN109970594B - Eutectic product of 2-aminobenzamide and oxalic acid and microwave radiation-assisted preparation method thereof - Google Patents
Eutectic product of 2-aminobenzamide and oxalic acid and microwave radiation-assisted preparation method thereof Download PDFInfo
- Publication number
- CN109970594B CN109970594B CN201910308208.2A CN201910308208A CN109970594B CN 109970594 B CN109970594 B CN 109970594B CN 201910308208 A CN201910308208 A CN 201910308208A CN 109970594 B CN109970594 B CN 109970594B
- Authority
- CN
- China
- Prior art keywords
- aminobenzamide
- oxalic acid
- product
- crystal
- eutectic
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/12—Preparation of carboxylic acid amides by reactions not involving the formation of carboxamide groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
- C07C237/28—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton
- C07C237/30—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton having the nitrogen atom of the carboxamide group bound to hydrogen atoms or to acyclic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/41—Preparation of salts of carboxylic acids
- C07C51/412—Preparation of salts of carboxylic acids by conversion of the acids, their salts, esters or anhydrides with the same carboxylic acid part
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C55/00—Saturated compounds having more than one carboxyl group bound to acyclic carbon atoms
- C07C55/02—Dicarboxylic acids
- C07C55/06—Oxalic acid
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C55/00—Saturated compounds having more than one carboxyl group bound to acyclic carbon atoms
- C07C55/02—Dicarboxylic acids
- C07C55/06—Oxalic acid
- C07C55/07—Salts thereof
Abstract
The invention discloses a eutectic product of 2-aminobenzamide and oxalic acid, wherein an X-ray powder diffraction pattern of a crystal of the eutectic product has characteristic peaks at diffraction angles 2 theta of 7.8 +/-0.1, 8.1 +/-0.1, 12.7 +/-0.1, 15.9 +/-0.1, 17.3 +/-0.1, 19.8 +/-0.1, 23.2 +/-0.1, 25.6 +/-0.1 and 29.7 +/-0.1 degrees, and further discloses a microwave radiation-assisted preparation method of the eutectic product of the 2-aminobenzamide and the oxalic acid. The invention has the beneficial effects of improving the solubility of the 2-aminobenzamide eutectic product, improving the crystal morphology of the eutectic product and increasing the grain diameter and bulk density of the eutectic product.
Description
Technical Field
The invention relates to the technical field of chemical engineering crystallization. More specifically, the invention relates to a microwave radiation-assisted preparation method of a 2-aminobenzamide and oxalic acid eutectic product.
Background
2-aminobenzamide (C)7H8N2O, 136.15g/mol, CAS NO:88-68-6), also known as anthranilamide, English name 2-Aminobenzamide, usually light brown to gray-brown crystal powder or tablet, odorless, slightly bitter in taste, slightly soluble in water, slightly soluble in ethanol, melting point 111-113 ℃, 2-Aminobenzamide is used as an organic synthesis intermediate for synthesizing bulk drugs, has NO selectivity and effective polysaccharide fluorescent marker, the particle size of the currently prepared 2-Aminobenzamide is small and is only 150 mu m, the morphology is shown in figure 1, the coalescence degree is large, the bulk density is small and is only 300g/L, the water solubility is poor, the solubility in water at normal temperature is only 0.2g/L, the increase of the solubility is not obvious along with the increase of the temperature, and the solubility is not obviousThe temperature dependence of the temperature curve is shown in fig. 2. Oxalic acid (C)2H2O490.04g/mol, CAS NO:144-62-7), also known as Oxalic acid, having the English name of Oxalic acid and a melting point of 101 ℃, the Oxalic acid is usually colorless monoclinic sheet-like or prism-like crystals or white powder, and is widely present in plant-derived foods, is easy to dissolve in water and is not soluble in organic solvents such as diethyl ether. The molecular structural formula of the 2-aminobenzamide and the oxalic acid is as follows:
the pharmaceutical cocrystal is a novel solid form of a pharmaceutical active ingredient, and has the effects of improving the bioavailability and storage stability of insoluble drugs and the physicochemical properties of the drugs, so that the pharmaceutical cocrystal is widely applied to the pharmaceutical industry.
Zhang Xiaopeng et al [ anthranilamide compounds, chemical evolution, 2017, 29 (11): 1351-1356 ] summarizes the progress of the synthesis research of anthranilamide compounds, and mainly introduces several methods for synthesizing anthranilamide, for example, anthranilamide is directly synthesized by nucleophilic substitution reaction with anthranilamide halide as a substrate and organic amine as a nucleophilic reagent, but the prepared anthranilamide product has problems, such as uneven product particle size distribution, coalescence phenomenon, and impurity of crystal product, so that a new eutectic ligand is urgently needed to be searched to form a eutectic product with 2-aminobenzamide.
Disclosure of Invention
An object of the present invention is to solve at least the above problems and to provide at least the advantages described later.
The invention also aims to provide a eutectic product of 2-aminobenzamide and oxalic acid and a microwave radiation auxiliary preparation method of the eutectic product of 2-aminobenzamide and oxalic acid, which can effectively improve the solubility of the eutectic product of 2-aminobenzamide, improve the crystal morphology, increase the crystal grain size and improve the bulk density of the crystal.
To achieve these objects and other advantages in accordance with the present invention, there is provided a co-crystal product of 2-aminobenzamide and oxalic acid, which crystal has an X-ray powder diffraction pattern having characteristic peaks at diffraction angles 2 θ of 7.8 ± 0.1, 8.1 ± 0.1, 12.7 ± 0.1, 15.9 ± 0.1, 17.3 ± 0.1, 19.8 ± 0.1, 23.2 ± 0.1, 25.6 ± 0.1, 29.7 ± 0.1 degrees.
Further, the DSC spectrum of the crystal of the eutectic product has a characteristic melting point peak at 182 +/-1 ℃.
Furthermore, the crystal morphology of the eutectic product is in a long rod shape.
Also provides a microwave radiation-assisted preparation method of the eutectic product of 2-aminobenzamide and oxalic acid, which comprises the following steps:
(1) adding 2-aminobenzamide and a solvent into a microwave reactor under the stirring condition and at the temperature of 10-40 ℃ to ensure that the mass fraction of the 2-aminobenzamide is 10-30%, and stirring at a constant temperature for 10-30 min to completely dissolve solids;
(2) adding oxalic acid with the mass equal to that of 2-aminobenzamide into a microwave reactor at the temperature of 10-40 ℃, and stirring until the oxalic acid is completely dissolved and becomes a clear solution;
(3) setting the microwave radiation power in a microwave reactor to be 100-400W at the temperature of 10-40 ℃, and carrying out microwave reaction for 2-4 h to obtain crystal slurry;
(4) and washing, filtering and freeze-drying the crystal slurry to obtain the 2-aminobenzamide and oxalic acid eutectic product.
Further, the organic solvent in step (1) is selected from one of methanol, dimethylformamide, methyl ethyl ketone, dimethyl sulfoxide or acetone.
Further, the stirring speed in the step (1) and the stirring speed in the step (2) are both 200-400 rpm.
Further, the freeze drying temperature in the step (4) is-15 to-5 ℃, the vacuum degree is 0.02 to 0.08MPa, and the freeze drying time is 24 to 48 hours.
The invention at least comprises the following beneficial effects: the preparation method of the eutectic product improves the crystal morphology of the eutectic product, increases the grain diameter of the eutectic product, improves the bulk density of the eutectic product, increases the grain diameter, enhances the dispersibility and reduces the coalescence degree of the crystal product.
Additional advantages, objects, and features of the invention will be set forth in part in the description which follows and in part will become apparent to those having ordinary skill in the art upon examination of the following or may be learned from practice of the invention.
Drawings
FIG. 1 is a photomicrograph of a 2-aminobenzamide starting material of the present invention;
FIG. 2 is a graph of the solubility of a 2-aminobenzamide starting material in water as a function of temperature in accordance with the present invention;
FIG. 3 is an XRD pattern of the eutectic product of 2-aminobenzamide and oxalic acid of the invention;
FIG. 4 is a DSC of the eutectic product of 2-aminobenzamide and oxalic acid of the present invention;
FIG. 5 is a photomicrograph of a 2-aminobenzamide and oxalic acid co-crystal product of the present invention;
FIG. 6 is a curve of the solubility of the 2-aminobenzamide and oxalic acid eutectic product in water along with the change of temperature.
Detailed Description
The present invention is further described in detail below with reference to the drawings and examples so that those skilled in the art can practice the invention with reference to the description.
It should be noted that the experimental methods described in the following embodiments are all conventional methods unless otherwise specified, and the reagents and materials described therein are commercially available unless otherwise specified.
Example 1
The microwave radiation assisted preparation method of the eutectic product of 2-aminobenzamide and oxalic acid comprises the following steps:
(1) under the conditions that the stirring speed is 200rpm and the temperature is 10 ℃, adding 1g of 2-aminobenzamide into a microwave reactor containing 10g of methanol solvent, and stirring at constant temperature for 10min until the 2-aminobenzamide is completely dissolved to obtain a dissolved solution, wherein the mass fraction of the 2-aminobenzamide in the dissolved solution is 10%;
(2) continuously adding 1g of oxalic acid into the microwave reactor at the temperature of 10 ℃, and stirring at constant temperature until the oxalic acid is completely dissolved and becomes a clear solution;
(3) setting the microwave radiation power in the microwave reactor to be 100W at the temperature of 10 ℃, and starting the microwave radiation reaction for 2h to obtain crystal mush;
(4) carrying out suction filtration and washing on the crystal slurry to obtain a filter cake, and drying the filter cake for 24h at the temperature of-15 ℃ and the vacuum degree of 0.02MPa to obtain a 2-aminobenzamide and oxalic acid eutectic product with the yield of;
the morphology of the 2-aminobenzamide and oxalic acid eutectic product is shown in fig. 5, the magnifications of fig. 1 and fig. 5 are the same, the XRD spectrum is shown in fig. 3, and the characteristic peaks exist at diffraction angles 2 theta of 7.8 +/-0.1, 8.1 +/-0.1, 12.7 +/-0.1, 15.9 +/-0.1, 17.3 +/-0.1, 19.8 +/-0.1, 23.2 +/-0.1, 25.6 +/-0.1 and 29.7 +/-0.1 degrees, and the DSC spectrum is shown in fig. 4 and has the characteristic peak at 182 ℃.
Example 2
The microwave radiation assisted preparation method of the eutectic product of 2-aminobenzamide and oxalic acid comprises the following steps:
(1) under the conditions that the stirring speed is 300rpm and the temperature is 20 ℃, 2g of 2-aminobenzamide is added into a microwave reactor containing 10g of dimethylformamide solvent, and the mixture is stirred at constant temperature for 20min until the mixture is completely dissolved to obtain a dissolved solution, wherein the mass fraction of the 2-aminobenzamide in the dissolved solution is 20%;
(2) continuously adding 2g of oxalic acid into the microwave reactor at the temperature of 20 ℃, and stirring at constant temperature until the oxalic acid is completely dissolved and becomes a clear solution;
(3) setting the microwave radiation power in the microwave reactor to be 200W at the temperature of 20 ℃, and starting the microwave reaction for 3h to obtain crystal mush;
(4) carrying out suction filtration and washing on the crystal slurry to obtain a filter cake, and drying the filter cake for 30h at the temperature of-12 ℃ and the vacuum degree of 0.04MPa to obtain a 2-aminobenzamide and oxalic acid eutectic product with the yield of 91.1%;
the appearance, XRD pattern data and DSC pattern data of the eutectic product of the 2-aminobenzamide and the oxalic acid are close to those of the eutectic product of the 2-aminobenzamide and the oxalic acid in example 1.
Example 3
The microwave radiation assisted preparation method of the eutectic product of 2-aminobenzamide and oxalic acid comprises the following steps:
(1) under the conditions that the stirring speed is 300rpm and the temperature is 30 ℃, adding 3g of 2-aminobenzamide into a microwave reactor containing 10g of methyl ethyl ketone solvent, and stirring at constant temperature for 30min until the 2-aminobenzamide is completely dissolved to obtain a dissolved solution, wherein the mass fraction of the 2-aminobenzamide in the dissolved solution is 30%;
(2) continuously adding 3g of oxalic acid into the microwave reactor at the temperature of 30 ℃, and stirring at constant temperature until the oxalic acid is completely dissolved and becomes a clear solution;
(3) setting the microwave radiation power in the microwave reactor to be 300W at the temperature of 30 ℃, and starting the microwave reaction for 4h to obtain crystal mush;
(4) carrying out suction filtration and washing on the crystal mush to obtain a filter cake, and drying the filter cake for 30h at the temperature of minus 10 ℃ and the vacuum degree of 0.06MPa to obtain a 2-aminobenzamide and oxalic acid eutectic product with the yield of 93.1 percent;
the appearance, XRD pattern data and DSC pattern data of the eutectic product of the 2-aminobenzamide and the oxalic acid are close to those of the eutectic product of the 2-aminobenzamide and the oxalic acid in example 1.
Example 4
The microwave radiation assisted preparation method of the eutectic product of 2-aminobenzamide and oxalic acid comprises the following steps:
(1) under the conditions that the stirring speed is 400rpm and the temperature is 40 ℃, 3g of 2-aminobenzamide is added into a microwave reactor containing 10g of dimethyl sulfoxide solvent, and the mixture is stirred at constant temperature for 30min until the mixture is completely dissolved to obtain a dissolved solution, wherein the mass fraction of the 2-aminobenzamide in the dissolved solution is 30%;
(2) continuously adding 3g of oxalic acid into the microwave reactor at 40 ℃, and stirring at constant temperature until the oxalic acid is completely dissolved and becomes a clear solution;
(3) setting the microwave radiation power in the microwave reactor to be 400W at 40 ℃, and starting the microwave reaction for 4h to obtain crystal mush;
(4) carrying out suction filtration and washing on the crystal mush to obtain a filter cake, and drying the filter cake for 36h at the temperature of minus 5 ℃ and the vacuum degree of 0.08MPa to obtain a 2-aminobenzamide and oxalic acid eutectic product with the yield of 91.3%;
the appearance, XRD pattern data and DSC pattern data of the eutectic product of the 2-aminobenzamide and the oxalic acid are close to those of the eutectic product of the 2-aminobenzamide and the oxalic acid in example 1.
Example 5
The microwave radiation assisted preparation method of the eutectic product of 2-aminobenzamide and oxalic acid comprises the following steps:
(1) under the conditions that the stirring speed is 350rpm and the temperature is 30 ℃, adding 3g of 2-aminobenzamide into a microwave reactor containing 10g of acetone solvent, and stirring at constant temperature for 30min until the 2-aminobenzamide is completely dissolved to obtain a dissolved solution, wherein the mass fraction of the 2-aminobenzamide in the dissolved solution is 30%;
(2) continuously adding 3g of oxalic acid into the microwave reactor at the temperature of 30 ℃, and stirring at constant temperature until the oxalic acid is completely dissolved and becomes a clear solution;
(3) setting the microwave radiation power in the microwave reactor to be 400W at the temperature of 30 ℃, and starting the microwave reaction for 3h to obtain crystal mush;
(4) carrying out suction filtration and washing on the crystal slurry to obtain a filter cake, and drying the filter cake for 36h at-8 ℃ and under the vacuum degree of 0.06MPa to obtain a 2-aminobenzamide and oxalic acid eutectic product with the yield of 91.5%;
the appearance, XRD pattern data and DSC pattern data of the eutectic product of the 2-aminobenzamide and the oxalic acid are close to those of the eutectic product of the 2-aminobenzamide and the oxalic acid in example 1.
< evaluation test of Co-Crystal product of 2-aminobenzamide with oxalic acid >
Taking the eutectic products obtained in the embodiments 1-5, determining the purity of the products by adopting a liquid phase analysis method, determining the granularity by adopting a granularity analyzer, determining the solubility and the solubility at room temperature (25 ℃) by adopting a shaking flask method, determining the bulk density by adopting a measuring cylinder tapping method, and determining the detection results as shown in the following table;
as can be seen from the above table, the purity of the eutectic product in the embodiments 1-5 reaches more than 99.3%; the solubility of the eutectic products in the embodiments 1-5 at normal temperature is more than 6g/L, the solubility at normal temperature is improved by about 30 times compared with that of the commercially available 2-aminobenzamide, and the solubility is obviously increased along with the temperature rise, as shown in FIG. 6; the average particle size of the eutectic product in the embodiments 1-5 is over 600 microns, which is improved by 4 times compared with the commercially available 2-aminobenzamide, and the dispersibility is better; the bulk density of the eutectic product in the embodiments 1-5 is 900g/L, the bulk density of the commercially available 2-aminobenzamide is 300g/L, the bulk density is improved by nearly 3 times, and the increase of the average grain size and the bulk density can increase the fluidity of the eutectic product, thereby being beneficial to industrialization.
While embodiments of the invention have been described above, it is not limited to the applications set forth in the description and the embodiments, which are fully applicable to various fields of endeavor for which the invention may be embodied with additional modifications as would be readily apparent to those skilled in the art, and the invention is therefore not limited to the details given herein and to the embodiments shown and described without departing from the generic concept as defined by the claims and their equivalents.
Claims (7)
- A eutectic product of 2-aminobenzamide and oxalic acid, characterized in that the crystal of the eutectic product has an X-ray powder diffraction pattern having characteristic peaks at diffraction angles 2 theta of 7.8 + -0.1, 8.1 + -0.1, 12.7 + -0.1, 15.9 + -0.1, 17.3 + -0.1, 19.8 + -0.1, 23.2 + -0.1, 25.6 + -0.1, 29.7 + -0.1 degrees.
- 2. The co-crystal product of 2-aminobenzamide and oxalic acid according to claim 1, characterized in that the DSC profile of the crystal of the co-crystal product has a characteristic melting point peak at 182 ± 1 ℃.
- 3. The co-crystal product of 2-aminobenzamide with oxalic acid according to claim 1, characterized in that the crystal morphology of the co-crystal product is long-rod shaped.
- 4. The microwave radiation assisted preparation method of a co-crystal product of 2-aminobenzamide with oxalic acid according to claim 1, characterized in that it comprises the following steps:(1) adding 2-aminobenzamide and a solvent into a microwave reactor under the stirring condition and at the temperature of 10-40 ℃ to ensure that the mass fraction of the 2-aminobenzamide is 10-30%, and stirring at a constant temperature for 10-30 min to completely dissolve solids;(2) adding oxalic acid with the mass equal to that of 2-aminobenzamide into a microwave reactor at the temperature of 10-40 ℃, and stirring until the oxalic acid is completely dissolved and becomes a clear solution;(3) setting the microwave radiation power of a microwave reactor to be 100-400W at the temperature of 10-40 ℃, and carrying out microwave reaction for 2-4 h to obtain crystal slurry;(4) and washing, filtering and freeze-drying the crystal slurry to obtain the 2-aminobenzamide and oxalic acid eutectic product.
- 5. The microwave radiation-assisted preparation method of a 2-aminobenzamide and oxalic acid eutectic product according to claim 4, characterized in that the organic solvent in step (1) is selected from one of methanol, dimethylformamide, methyl ethyl ketone, dimethyl sulfoxide or acetone.
- 6. The microwave radiation assisted preparation method of the eutectic product of 2-aminobenzamide and oxalic acid according to claim 4, characterized in that the stirring speed in step (1) and step (2) is 200-400 rpm.
- 7. The microwave radiation assisted preparation method of the eutectic product of 2-aminobenzamide and oxalic acid according to claim 4, characterized in that the freeze drying temperature in the step (4) is-15 to-5 ℃, the vacuum degree is 0.02 to 0.08MPa, and the freeze drying time is 24 to 48 hours.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201910308208.2A CN109970594B (en) | 2019-04-17 | 2019-04-17 | Eutectic product of 2-aminobenzamide and oxalic acid and microwave radiation-assisted preparation method thereof |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201910308208.2A CN109970594B (en) | 2019-04-17 | 2019-04-17 | Eutectic product of 2-aminobenzamide and oxalic acid and microwave radiation-assisted preparation method thereof |
Publications (2)
Publication Number | Publication Date |
---|---|
CN109970594A CN109970594A (en) | 2019-07-05 |
CN109970594B true CN109970594B (en) | 2022-05-20 |
Family
ID=67084973
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201910308208.2A Active CN109970594B (en) | 2019-04-17 | 2019-04-17 | Eutectic product of 2-aminobenzamide and oxalic acid and microwave radiation-assisted preparation method thereof |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN109970594B (en) |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3919314A (en) * | 1973-11-27 | 1975-11-11 | Ici Ltd | Chemical process |
US3970648A (en) * | 1974-09-06 | 1976-07-20 | Diamond Shamrock Corporation | 2-[2-(5-Nitro-2-furyl)vinyl]-4-(anilino)quinazolines |
-
2019
- 2019-04-17 CN CN201910308208.2A patent/CN109970594B/en active Active
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3919314A (en) * | 1973-11-27 | 1975-11-11 | Ici Ltd | Chemical process |
US3970648A (en) * | 1974-09-06 | 1976-07-20 | Diamond Shamrock Corporation | 2-[2-(5-Nitro-2-furyl)vinyl]-4-(anilino)quinazolines |
Non-Patent Citations (3)
Title |
---|
Microwave-assisted synthesis and antibacterial activity of some quinazolinone derivatives;Temitope O. Olomola等;《journal of pharmacy research》;20130621(第6期);第633-637页 * |
Transfer Catalysis Between Two Solids:Application to the Reduction of Nitroarenes;Anitha Hari,Benjamin L. Miller;《Angew. Chem. Int. Ed.》;19991231;第38卷(第18期);第2777-2779页 * |
药物共晶的最新研究进展;王义成等;《药学进展》;20131231;第37卷(第3期);第120-130页 * |
Also Published As
Publication number | Publication date |
---|---|
CN109970594A (en) | 2019-07-05 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US11084791B2 (en) | Solid state forms of Lenvatinib Mesylate | |
JPH05208943A (en) | Crystal of n-@(3754/24)trans-4-isopropylcyclohexylcarbonyl)-d-phenylalanine and its production | |
WO2013134534A2 (en) | Solid state forms of cabazitaxel and processes for preparation thereof | |
Wang et al. | pH-Switchable vitamin B 9 gels for stoichiometry-controlled spherical co-crystallization | |
CN109970594B (en) | Eutectic product of 2-aminobenzamide and oxalic acid and microwave radiation-assisted preparation method thereof | |
CN113264817A (en) | Curcumin crystallization method and application thereof | |
EP0135044A1 (en) | Tripamide inclusion compound, process for the preparation thereof and pharmaceutical composition | |
CN102924474B (en) | Preparation method of crystal form I of clopidogrel hydrogen sulfate | |
CN102408423B (en) | Method for preparing large particle size dasatinib | |
CN110041320B (en) | Preparation method of azilsartan crystals | |
WO2018215002A1 (en) | Amorphous forms of obeticholic acid | |
Han et al. | Self-gelation involved in the transformation of resveratrol and piperine from a co-amorphous system into a co-crystal system | |
CN111303003B (en) | Olive-shaped N-methyl-4-nitrophthalimide crystal and preparation method thereof | |
EP4303212A1 (en) | Hydroxytyrosol nicotinamide eutectic crystal, and preparation method therefor and composition thereof | |
WO2012071425A1 (en) | Solid state forms of sorafenib besylate, and processes for preparations thereof | |
CN109970664B (en) | Co-crystal product of pyrazinamide and fumaric acid and ultrasonic-microwave coupling preparation method thereof | |
CA2483862A1 (en) | Process for the preparation of the amorphous form of atorvastatin calcium salt | |
CN113004126A (en) | Hydroxytyrosol betaine eutectic crystal, preparation method and composition thereof | |
CN111635327A (en) | Amorphous crystal form of methacholine chloride and preparation method thereof | |
KR102466729B1 (en) | Hexadecyl treprostinil crystals and methods for preparation thereof | |
CN104844669B (en) | A kind of scutelloside A crystal formations, its preparation method and its application | |
CN114057643B (en) | Rosemastat eutectic crystal and preparation method thereof | |
CN107337708A (en) | Pidotimod novel crystal forms and preparation method thereof | |
WO2018078383A1 (en) | Pharmaceutical composition comprising amorphous selexipag | |
CN110218173B (en) | Preparation method of bar-shaped bisphenol A type diether diphthalimide |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant |