CN107311915A - A kind of salicylic acid organic pharmaceutical co-crystal and preparation method thereof - Google Patents
A kind of salicylic acid organic pharmaceutical co-crystal and preparation method thereof Download PDFInfo
- Publication number
- CN107311915A CN107311915A CN201710509939.4A CN201710509939A CN107311915A CN 107311915 A CN107311915 A CN 107311915A CN 201710509939 A CN201710509939 A CN 201710509939A CN 107311915 A CN107311915 A CN 107311915A
- Authority
- CN
- China
- Prior art keywords
- salicylic acid
- crystal
- eutectic
- pharmaceutical
- acid organic
- 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.)
- Pending
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/06—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom containing only hydrogen and carbon atoms in addition to the ring nitrogen atom
- C07D213/22—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom containing only hydrogen and carbon atoms in addition to the ring nitrogen atom containing two or more pyridine rings directly linked together, e.g. bipyridyl
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/60—Salicylic acid; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/36—Carboxylic acids; Salts or anhydrides thereof
- A61K8/368—Carboxylic acids; Salts or anhydrides thereof with carboxyl groups directly bound to carbon atoms of aromatic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/494—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with more than one nitrogen as the only hetero atom
- A61K8/4953—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with more than one nitrogen as the only hetero atom containing pyrimidine ring derivatives, e.g. minoxidil
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
-
- C—CHEMISTRY; METALLURGY
- 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
- C07C65/03—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 monocyclic and having all hydroxy or O-metal groups bound to the ring
- C07C65/05—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 monocyclic and having all hydroxy or O-metal groups bound to the ring o-Hydroxy carboxylic acids
- C07C65/10—Salicylic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/10—General cosmetic use
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
- A61K2800/52—Stabilizers
- A61K2800/524—Preservatives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Birds (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Emergency Medicine (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention relates to a kind of salicylic acid organic pharmaceutical co-crystal and preparation method thereof, be using salicylic acid as active constituents of medicine, with 4,4' bipyridyls for eutectic presoma, by salicylic acid and 4,4' bipyridyls, water and ethanol, methanol or acetone are put into eutectic container in the lump；Eutectic container is placed on agitator, is stirred at room temperature 2 hours；After stirring stops, eutectic container being placed in after being placed 10 ~ 40 hours in 40~100 DEG C of baking ovens and taken out, dropping to after room temperature has block and sheet clear crystal to separate out.Eutectic of the present invention inherits the pharmacological activity of salicylic acid in itself, and its dissolubility, stability and bioavilability aspect are significantly improved.
Description
Technical field
The invention belongs to technical field of organic pharmaceutical co-crystal, and in particular to a kind of new salicylic acid organic pharmaceutical co-crystal and its
Preparation method.
Background technology
Pharmaceutical co-crystals are to be based on supramolecular chemistry principle, i.e., the molecular recognition carried out by intermolecular mutual synergy
And Supramolecular self assembly.Active constituents of medicine (API) passes through with suitable eutectic formation (Cocrystal Former, CCF)
H-bonding self-assembly, or with saturability and directionality non-covalent bond (Van der Waals force of such as aromatic hydrocarbons or phenyl ring, conjugation and
Halogen key) assemble a kind of new structure formed, i.e. pharmaceutical co-crystals.In November, 2011, FDA is issued《Pharmaceutical co-crystals management classification
Guide》(Guidance Forlndustry:Regulatory Classificat1n Of
PharmaceuticalCocrystals), it is indicated that when medicine and certain auxiliary material formation eutectic after, can using pharmaceutical co-crystals as
" preparation intermediate " is managed and controlled, thus eutectic separately as medicine without be registered.In recent years, pharmaceutical co-crystals were ground
Study carefully and increasingly paid close attention to by people.At this stage, the external research to pharmaceutical co-crystals starts gradually to increase and goed deep into；And it is domestic right
Its research is also relatively fewer.For imitation medicine, the research of pharmaceutical co-crystals can also break Yuan Yan medicines company to drug crystal forms
Patent protection, introduced to the market beneficial to by imitation medicine.Therefore, obtain more with novel, practical and creative pharmaceutical co-crystals
Have important practical significance, in the case where not changing medicines structure and the pharmacological properties of itself, the new crystal of formation can be with
The stability of medicine is improved, changes its fusing point, improve its dissolubility, it is reduced and draws moist, slows down its release and dissolution rate, improves
Its engineering properties etc., particularly some water-insoluble drugs, are conducive to improving the water solubility and bioavilability of medicine.
Salicylic acid (generally with sodium salicylate or aspirin form given by the composition in aspirin and many anodyne
Medicine) it is a kind of fat-soluble organic acid, it is one of clinical the most frequently used medicine.Not only in analgesic, anti-inflammatory, bring down a fever and treat gout etc.
Aspect has critical role, and due to there is anticoagulation, may also have in terms of prevention phlebothrombosis, coronary artery thrombus and pulmonary embolism
Certain effect.Salicylic acid may further be used to the long-term concurrent cardiopathic risk of reduction diabetic, and newest research is requirement institute
There is the IDDM patient for having had heart disease to take, while salicylic treatment is also proposed as prevention concurrently
The method of disease.The diabetic of 30 years old is had more than, as long as no special medical reason, all this is taken.
Salicylic acid also acts as cosmetics preservative simultaneously.It is mainly used in the water classes such as floral water, miliaria lotion, quinine head water
Cosmetic.In addition to antisepsis and sterilization is acted on, the functions such as bad smell of perspiration, relieving itching and eliminating swelling, analgesic antiphlogistic are also dispelled.It is a small amount of to be also used for braking
The daily essences such as thing flavor essence.It is micro to be used in food, play a part of preservative.
2016, the researcher from Grice research institute (Gladstone Institutes) was sent out by studying
Existing, salicylic acid can block body inflammatory and cancer to occur, and correlative study is published on eLife magazines.
The subject matter clinically existed using Genprin is that stomach is stimulated, or even can cause gastrorrhagia or brain
The danger of bleeding, in order to efficiently control drug release rate, reduces the toxic side effect to stomach and intestinal mucosa, each preparation unit is confused
The slow release method of confused research aspirin.Most producers obtain fine crystallization by crushing, but crushing destroys crystal formation and crushing process
Adverse effect is generated to product quality.Therefore, drugloading rate height how is prepared, carrier auxiliary material is few and preparation process does not influence medicine
Stable and formulation simple and easy to apply just turns into one of target of researcher, and now eutectic becomes one of scheme preferably.
The content of the invention
The purpose of the present invention aims to provide a kind of salicylic acid organic pharmaceutical co-crystal and preparation method thereof, salicylic acid and 4,4'-
The pharmaceutical co-crystals body and its preparation technology of bipyridyl formation, had both remained the pharmacological properties of salicylate agent in itself, can change again
The physicochemical properties such as stability, the solubility of kind medicine, improve drug effect and bioavilability.The present invention and to its crystal structure
Tested, its property is characterized.
The active constituents of medicine (API) that the present invention is selected is salicylic acid, 4,4'-Bipyridine as eutectic presoma (CCF),
Solvent selects water and ethanol, methanol or acetone, prepares a kind of pharmaceutical co-crystals of new structure.
Salicylic acid (generally with sodium salicylate or aspirin form given by the composition in aspirin and many anodyne
Medicine) as the active constituents of medicine of the present invention, chemical name is：Septichen, molecular formula is：C7H6O3, its structural formula is such as
Shown in formula a.With 4,4'-Bipyridine as eutectic presoma in the present invention, molecular formula is C10H8N2, its structural formula is as shown in formula b.
Salicylic acid organic pharmaceutical co-crystal of the present invention is by a bigcatkin willow acid molecule and two 4,4'-Bipyridine molecules
Constitute the basic structural unit of salicylic acid organic pharmaceutical co-crystal, among eutectic structure, salicylic acid carboxyl and bipyridyl hexatomic ring
Upper three hydrogen atoms are used as hydrogen-bond donor；Salicylic acid carboxyl oxygen atom, salicylic acid hydroxyl oxygen atom and the hexa-atomic theheterocyclic nitrogen atom of pyridine
It is used as the three-D space structure of hydrogen bond receptor formation hydrogen bond.The actual crystal data of the pharmaceutical co-crystals are as follows：C10H8N2·2
(C7H6O3),Triclinic,P1, α=87.446
(3) °, β=82.198 (3), γ=65.780 (2) °, Z=1.
The bigcatkin willow acid molecule and 4,4 '-bipyridyl molecule press 1:2 mol ratio is combined.
Application of the described salicylic acid organic pharmaceutical co-crystal in preparing analgesic, anti-inflammatory, bringing down a fever and treat gout medicine.
Described salicylic acid organic pharmaceutical co-crystal is preparing anticoagulation, prevention phlebothrombosis, coronary artery thrombus and pulmonary embolism
Application in medicine.
Application of the described salicylic acid organic pharmaceutical co-crystal in cosmetics and preservative are prepared.
Described salicylic acid organic pharmaceutical co-crystal is preparing the application in blocking body inflammatory and pre- anti-cancer to occur medicine.
The preparation method of the salicylic acid organic pharmaceutical co-crystal of the present invention, step is as follows：
1) by the salicylic acid and 4,4 '-bipyridyl of mass ratio 1: 0.5~1: 5 and the water and second of volume ratio 4: 1~1: 4
Alcohol, methanol or acetone, are added in eutectic container in the lump.
2) eutectic container is placed on agitator, be stirred at room temperature 2 hours；
3) after stirring stops, eutectic container being placed in after being placed 10~40 hours in 40~100 DEG C of baking ovens and taken out, drop to room
There is block and sheet clear crystal to separate out after temperature, as salicylic acid organic pharmaceutical co-crystal.
Eutectic prepared by the present invention inherits the pharmacological activity of salicylic acid in itself, and to its dissolubility, stability and biology
It is significantly improved in terms of availability.
Brief description of the drawings
Fig. 1：Salicylic acid organic pharmaceutical co-crystal construction unit schematic diagram；
Fig. 2：The hydrogen bond network figure of salicylic acid organic pharmaceutical co-crystal；
Fig. 3：The simulation of salicylic acid organic pharmaceutical co-crystal obtains XRD spectra.
Embodiment
Below in conjunction with the embodiment of the present invention and accompanying drawing, the technical scheme in the embodiment of the present invention is carried out clear, complete
Ground is described, it is clear that described embodiment is only a part of embodiment of the invention, rather than whole embodiments.Based on this
Embodiment in invention, the every other reality that those of ordinary skill in the art are obtained under the premise of creative work is not paid
Example is applied, the scope of protection of the invention is belonged to.
The preparation of the salicylic acid organic pharmaceutical co-crystal of embodiment 1
0.1mmol salicylic acids, 0.2mmol4,4'- bipyridyls add the mixed solvent juxtaposition of 4ml water and 2ml ethanol composition
In eutectic container, it is stirred at room temperature 2 hours；After stirring stops, eutectic container being placed in after being placed 20 hours in 80 DEG C of baking ovens and taken
Go out, dropping to after room temperature has block and sheet clear crystal to separate out, molar yield 85%.
The preparation of the salicylic acid organic pharmaceutical co-crystal of embodiment 2
0.1mmol salicylic acids, 0.2mmol4,4'- bipyridyls add the mixed solvent juxtaposition of 4ml water and 2ml methanol composition
In eutectic container, it is stirred at room temperature 2 hours；After stirring stops, eutectic container being placed in after being placed 20 hours in 80 DEG C of baking ovens and taken
Go out, dropping to after room temperature has block and sheet clear crystal to separate out, molar yield 80%.
The preparation of the salicylic acid organic pharmaceutical co-crystal of embodiment 3
0.1mmol salicylic acids, 0.2mmol4,4'- bipyridyls add the mixed solvent juxtaposition of 4ml water and 2ml acetone composition
In eutectic container, it is stirred at room temperature 2 hours；After stirring stops, eutectic container being placed in after being placed 20 hours in 80 DEG C of baking ovens and taken
Go out, dropping to after room temperature has block and sheet clear crystal to separate out, molar yield 88%.
The eutectic structure of the salicylic acid organic pharmaceutical co-crystal of embodiment 4 is characterized
Crystal structure determination uses Bruker Apex II CCD diffractometers, under 296 (2) K, with through graphite monochromatised
MoK alpha raysPoint diffraction is collected with ω scan modes, the data of collection are used in combination by SAINT programe reductions
SADABS methods carry out semiempirical absorption correction.Structure elucidation and refine be respectively adopted SHELXTL programs SHELXS and
SHELXL is completed, by complete matrix least square method to F2It is modified the coordinate that obtains whole non-hydrogen atoms and each to different
Property parameter.All hydrogen atoms are fixed on parent during structure refinement by theory, are assigned than parent displacement parameter slightly
The isotropism displacement parameter of (C-H, 1.2 or O/N-H, 1.5 times) greatly.Detailed axonometry data are shown in Table 1, and construction unit shows
It is intended to such as Fig. 1, hydrogen bond network figure such as Fig. 2 of salicylic acid organic pharmaceutical co-crystal, the simulation powder of salicylic acid organic pharmaceutical co-crystal spreads out
Penetrate figure such as Fig. 3.
The eutectic predominant crystal data of table 1
The foregoing is merely illustrative of the preferred embodiments of the present invention, is not intended to limit the invention, all essences in the present invention
God is with principle, and any modification, equivalent substitution and improvements made etc. should be included in the scope of the protection.
Claims (10)
1. a kind of salicylic acid organic pharmaceutical co-crystal, it is characterised in that：Using salicylic acid as active constituents of medicine, with 4,4 '-bipyridyl
For eutectic presoma；One bigcatkin willow acid molecule and two 4,4 '-bipyridyl molecular composition salicylic acid organic pharmaceutical co-crystals it is basic
Construction unit；Among eutectic structure, three hydrogen atoms are used as hydrogen-bond donor on salicylic acid carboxyl and bipyridyl hexatomic ring；Bigcatkin willow
Sour carboxyl oxygen atom, salicylic acid hydroxyl oxygen atom and the hexa-atomic theheterocyclic nitrogen atom of pyridine form the three dimensions of hydrogen bond as hydrogen bond receptor
Structure；The crystallographic data of the pharmaceutical co-crystals is as follows：C10H8N2·2(C7H6O3) , Triclinic, P-1, a=7.8525
(14), b=8.2731 (15), c=8.5037 (16), α=87.446 (3) °, β=82.198 (3), γ=65.780 (2) °,
V = 499.11（16）Å3, Z =1。
2. salicylic acid organic pharmaceutical co-crystal according to claim 1, it is characterised in that：The bigcatkin willow acid molecule and 4,4 '-
Bipyridyl molecule presses 1:2 mol ratio is combined.
3. salicylic acid organic pharmaceutical co-crystal described in claim 1 preparing analgesic, anti-inflammatory, bring down a fever and treat in gout medicine
Using.
4. salicylic acid organic pharmaceutical co-crystal described in claim 1 prepare anticoagulation, prevention phlebothrombosis, coronary artery thrombus and
Application in pulmonary embolism medicine.
5. application of the salicylic acid organic pharmaceutical co-crystal in cosmetics and preservative are prepared described in claim 1.
6. the salicylic acid organic pharmaceutical co-crystal described in claim 1 is in blocking body inflammatory and pre- anti-cancer generation medicine is prepared
Application.
7. the preparation method of a kind of salicylic acid organic pharmaceutical co-crystal described in claim, it is characterised in that step is as follows：
1) by the water of the salicylic acid and 4,4 '-bipyridyl of mass ratio 1: 0.5~1: 5 and volume ratio 4: 1~1: 4 and organic
Solvent, is added in eutectic container in the lump；
2) eutectic container is placed on agitator, be stirred at room temperature 2 hours；
3) after stirring stops, eutectic container being placed in after being placed 10~40 hours in 40~100 DEG C of baking ovens and taken out, drop to room temperature
After there is block and sheet clear crystal to separate out, as salicylic acid organic pharmaceutical co-crystal.
8. preparation method according to claim 7, it is characterised in that：Described organic solvent is selected from methanol, ethanol, isopropyl
Mixture more than one or both of alcohol, ethyl acetate, acetone and acetonitrile.
9. preparation method according to claim 7, it is characterised in that：Described mixing time is 30min~4h.
10. preparation method according to claim 7, it is characterised in that：Reaction temperature is 80~100 DEG C.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710509939.4A CN107311915A (en) | 2017-06-28 | 2017-06-28 | A kind of salicylic acid organic pharmaceutical co-crystal and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710509939.4A CN107311915A (en) | 2017-06-28 | 2017-06-28 | A kind of salicylic acid organic pharmaceutical co-crystal and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN107311915A true CN107311915A (en) | 2017-11-03 |
Family
ID=60180819
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710509939.4A Pending CN107311915A (en) | 2017-06-28 | 2017-06-28 | A kind of salicylic acid organic pharmaceutical co-crystal and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107311915A (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108358904A (en) * | 2018-03-28 | 2018-08-03 | 梧州学院 | A kind of eutectic and preparation method thereof of Azilsartan and 4,4 '-bipyridyls |
| CN110183310A (en) * | 2019-06-05 | 2019-08-30 | 西北师范大学 | Utilize the method for ultrasonic wave added cocrystallization method preparation resveratrol medicament eutectic |
| CN111574435A (en) * | 2019-02-19 | 2020-08-25 | 鲁南制药集团股份有限公司 | 4,4' -bipyridine methylpyrazine derivative eutectic |
| WO2023274401A1 (en) * | 2021-07-02 | 2023-01-05 | 深圳市萱嘉生物科技有限公司 | Betaine salicylic acid eutectic, preparation method therefor, and application thereof |
| KR20230142154A (en) * | 2022-04-01 | 2023-10-11 | 주식회사 엘지생활건강 | Eutectic mixture comprising salicylic acid |
-
2017
- 2017-06-28 CN CN201710509939.4A patent/CN107311915A/en active Pending
Non-Patent Citations (5)
| Title |
|---|
| SRINU TOTHADI: "Polymorphism in cocrystals of urea: 4,4′-bipyridine and salicylic acid: 4,4′-bipyridine", 《CRYSTENGCOMM》 * |
| TIMO RAGER AND ROLF HILFIKER: "Cocrystal Formation from Solvent Mixtures", 《CRYSTAL GROWTH & DESIGN》 * |
| 方亮 主编: "《药剂学(第3版)》", 31 March 2016, 中国医药科技出版社 * |
| 陈嘉媚 等人: "超分子化学在药物共晶中的应用", 《高等学校化学学报》 * |
| 高缘 等人: "药物共晶研究进展", 《化学进展》 * |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108358904A (en) * | 2018-03-28 | 2018-08-03 | 梧州学院 | A kind of eutectic and preparation method thereof of Azilsartan and 4,4 '-bipyridyls |
| CN111574435A (en) * | 2019-02-19 | 2020-08-25 | 鲁南制药集团股份有限公司 | 4,4' -bipyridine methylpyrazine derivative eutectic |
| CN111574435B (en) * | 2019-02-19 | 2023-03-31 | 鲁南制药集团股份有限公司 | 4,4' -dipyridyl methylpyrazine derivative eutectic crystal |
| CN110183310A (en) * | 2019-06-05 | 2019-08-30 | 西北师范大学 | Utilize the method for ultrasonic wave added cocrystallization method preparation resveratrol medicament eutectic |
| WO2023274401A1 (en) * | 2021-07-02 | 2023-01-05 | 深圳市萱嘉生物科技有限公司 | Betaine salicylic acid eutectic, preparation method therefor, and application thereof |
| KR20230142154A (en) * | 2022-04-01 | 2023-10-11 | 주식회사 엘지생활건강 | Eutectic mixture comprising salicylic acid |
| KR102640681B1 (en) | 2022-04-01 | 2024-02-27 | 주식회사 엘지생활건강 | Eutectic mixture comprising salicylic acid |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN107311915A (en) | A kind of salicylic acid organic pharmaceutical co-crystal and preparation method thereof | |
| US20060142374A1 (en) | Crystal for oral solid drug and oral solid drug for dysuria treatment containing the same | |
| CN106916177B (en) | A kind of deuterated dipeptide boronic acid or its ester type compound and its synthetic method and purposes | |
| CN101267810A (en) | Capsule formulation of pirfenidone and pharmaceutically acceptable excipients | |
| CN101616915A (en) | The composition and the method for regulation and control kinase cascade | |
| CN103893184B (en) | Comprise the local medicine composition of activating agent | |
| CN108530382A (en) | A kind of Febuxostat ligustrazine eutectic and its preparation method and application | |
| CN1732151A (en) | 4-nitro-2-[(4 '-methoxyl group)-phenoxy group]-methylsulfonylphenylamine derivative and medicinal use thereof | |
| CN103304500B (en) | Novel anti-diabetic compound, as well as preparation method and application thereof | |
| CN103304501B (en) | Anti-diabetic compound, as well as preparation method and application thereof | |
| JPS6310716A (en) | Beta-stimulation agent for external use | |
| CN118290502A (en) | Erigeron breviscapus-huperzine A co-amorphous substance with synergistic antioxidation effect and preparation method thereof | |
| EP2251328B1 (en) | Crystalline 1-(3-fluorophenyl)-5-methyl-2-(1h)pyridone, the preparation methods, compositions and applications thereof | |
| CN105566314A (en) | Tizanidine hydrochloride compound | |
| CN110054606A (en) | A kind of dihydromyricetin-Halomine pharmaceutical co-crystals and preparation method | |
| CN108191734A (en) | A kind of indole -5-carboxylic acid's organic pharmaceutical co-crystal and preparation method thereof | |
| CN105669543A (en) | Isoliquiritigenin nicotinamide eutectic crystal and preparation method thereof | |
| CN108774220B (en) | For treating compound and its application of myocardial ischemia | |
| CN112390792A (en) | Puerarin-proline eutectic crystal and preparation method thereof | |
| CN104447721A (en) | Canagliflozin anhydrous compound | |
| CN101491523A (en) | Combination containing micronized gliquidone | |
| CN115124420B (en) | Rhein and matrine eutectic hydrate, preparation method, composition and application thereof | |
| CN101172107A (en) | Percutaneous drug administration cream ,ointment of letrozole and preparation method thereof | |
| Zhang et al. | A drug–drug cocrystal and a co-amorphous form, prepared from honokiol and ligustrazine, inspired by Chinese patent medicine | |
| CN102342921A (en) | Pharmaceutical composition of prasugrel hydrobromide acetate compound |
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 | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20171103 |