CN103751196A - Ceftiofur hydroxypropyl-beta-cyclodextrin inclusion compound and preparation method thereof - Google Patents
Ceftiofur hydroxypropyl-beta-cyclodextrin inclusion compound and preparation method thereof Download PDFInfo
- Publication number
- CN103751196A CN103751196A CN201410008732.5A CN201410008732A CN103751196A CN 103751196 A CN103751196 A CN 103751196A CN 201410008732 A CN201410008732 A CN 201410008732A CN 103751196 A CN103751196 A CN 103751196A
- Authority
- CN
- China
- Prior art keywords
- ceftiofur
- beta
- hydroxypropyl
- inclusion compound
- preparation
- 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.)
- Granted
Links
- ZBHXIWJRIFEVQY-IHMPYVIRSA-N ceftiofur Chemical compound S([C@@H]1[C@@H](C(N1C=1C(O)=O)=O)NC(=O)\C(=N/OC)C=2N=C(N)SC=2)CC=1CSC(=O)C1=CC=CO1 ZBHXIWJRIFEVQY-IHMPYVIRSA-N 0.000 title claims abstract description 55
- 229960005229 ceftiofur Drugs 0.000 title claims abstract description 55
- ODLHGICHYURWBS-LKONHMLTSA-N trappsol cyclo Chemical compound CC(O)COC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)COCC(O)C)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1COCC(C)O ODLHGICHYURWBS-LKONHMLTSA-N 0.000 title claims abstract description 47
- 238000002360 preparation method Methods 0.000 title claims abstract description 13
- 150000001875 compounds Chemical class 0.000 title abstract description 10
- 238000006243 chemical reaction Methods 0.000 claims abstract description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 9
- 239000002994 raw material Substances 0.000 claims abstract description 8
- 239000000843 powder Substances 0.000 claims abstract description 4
- WCZBUQIZTSIQFE-UHFFFAOYSA-N furan;thiophene Chemical compound C=1C=COC=1.C=1C=CSC=1 WCZBUQIZTSIQFE-UHFFFAOYSA-N 0.000 claims description 4
- 238000000034 method Methods 0.000 claims description 3
- 238000001291 vacuum drying Methods 0.000 claims description 3
- 238000003801 milling Methods 0.000 claims description 2
- 239000003814 drug Substances 0.000 abstract description 13
- 229940079593 drug Drugs 0.000 abstract description 6
- 230000000694 effects Effects 0.000 abstract description 6
- 238000007254 oxidation reaction Methods 0.000 abstract description 5
- 239000007787 solid Substances 0.000 abstract description 5
- 230000003647 oxidation Effects 0.000 abstract description 4
- 238000006460 hydrolysis reaction Methods 0.000 abstract description 3
- 231100000331 toxic Toxicity 0.000 abstract description 3
- 230000002588 toxic effect Effects 0.000 abstract description 3
- 238000001035 drying Methods 0.000 abstract 1
- 230000002708 enhancing effect Effects 0.000 abstract 1
- 238000001914 filtration Methods 0.000 abstract 1
- 238000000227 grinding Methods 0.000 abstract 1
- 238000002441 X-ray diffraction Methods 0.000 description 10
- 239000006069 physical mixture Substances 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 5
- 238000002156 mixing Methods 0.000 description 5
- 229920000858 Cyclodextrin Polymers 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 4
- 230000000844 anti-bacterial effect Effects 0.000 description 3
- 230000031700 light absorption Effects 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 230000008685 targeting Effects 0.000 description 2
- 229930186147 Cephalosporin Natural products 0.000 description 1
- 229910016523 CuKa Inorganic materials 0.000 description 1
- 108090000279 Peptidyltransferases Proteins 0.000 description 1
- 206010057190 Respiratory tract infections Diseases 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 229950005162 benexate Drugs 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 210000002421 cell wall Anatomy 0.000 description 1
- 229940124587 cephalosporin Drugs 0.000 description 1
- 150000001780 cephalosporins Chemical class 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 229910052593 corundum Inorganic materials 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 238000000113 differential scanning calorimetry Methods 0.000 description 1
- 238000004455 differential thermal analysis Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 229910001845 yogo sapphire Inorganic materials 0.000 description 1
Images
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses a preparation method of a solid inclusion compound of ceftiofur and hydroxypropyl-beta-cyclodextrin (CD). The preparation method comprises the following steps of taking ceftiofur and hydroxypropyl-beta-cyclodextrin in a molar ratio of 1: (1 to 3) as reaction raw materials; adding water which is 5 times the total weight of the reaction raw materials under a temperature of 20 to 50 DEG C; grinding for 2 to 5 hours; drying for 12 hours under vacuum; and filtering to obtain white powder which is the inclusion compound. The prepared inclusion compound has the effects of effectively preventing a chemical compound from oxidation reaction or hydrolysis reaction and other reactions, improving the water solubility of a medicine, enhancing the stability, reducing the toxic and side effects, controlling the medicine release, and improving the bioavailability. The prepared hydroxypropyl-beta-CD inclusion compound improves the solubility and bioavailability of ceftiofur serving as a raw medicine. The prepared inclusion compound shows remarkable capacity of improving oxidation resistance of the raw medicines under light, high temperature, humidity and other conditions, and brings effective means for developing a novel form of ceftiofur.
Description
Technical field
The present invention relates to a kind of clathrate of ceftiofur.
Background technology
Ceftiofur is the main confession third generation cephalosporin for animals of the exploitation eighties in 20th century.Its mechanism of action is to act on antibacterial transpeptidase and block the synthetic of cell wall, presents bactericidal action, is used for the treatment of and controls the bacillary intestinal of domestic animal and respiratory tract infection.Because the water solublity of ceftiofur is very poor, and there are a lot of problems in existing ceftiofur preparation, thereby development has the focus that good ceftiofur novel formulation is researcher concern always.Development along with related science technical field, the research of antibacterials dosage form is just towards efficient, targeting, intelligentized future development, desirable dosage form should have the advantage that dosage is little, toxicity is little, side effect is little, the good news is that take the drug-supplying system that slow release, controlled release, targeting be representative has shown good development prospect.Because cyclodextrin has unique interior hydrophobic outer hydrophilic structure, the guest molecule formation clathrate suitable with many sizes can form liquid inclusion complex by cyclodextrin to ceftiofur enclose.The formation of clathrate can effectively protect compound to avoid the reactions such as oxidation or hydrolysis, also increases the water solublity of medicine simultaneously, and enhanced stability reduces toxic and side effects, controls drug release and improves bioavailability.Recently, cyclodextrin is used for improving the concern that the physical chemistry of medicine and the research of biological property aspect application are more and more subject to people.Particularly be used for improving stability and the bioavailability of dewatering medicament, have the report of clathration in some solution, and the preparation of cyclodextrin ceftiofur solid clathrates and the research of character thereof have no report.Ceftiofur is atomic water-soluble, limits its range of application.The construction features of utilizing beta-schardinger dextrin-, is prepared into ceftiofur-Benexate Hydrochloride by both, can improve the dissolubility of ceftiofur in water, has good clinical value.
Summary of the invention
The technical problem to be solved in the present invention is to overcome existing defect, and a kind of ceftiofur HP-β-CD solid clathrates is provided;
The preparation method of the above-mentioned ceftiofur HP-β-CD of another object of the present invention solid clathrates.
Object of the present invention is carried out specific implementation by the following technical programs:
The preparation method of the clathrate of a kind of ceftiofur and HP-β-CD (HP-β-CD), ceftiofur and HP-β-CD are usingd to the mol ratio of 1:1 ~ 3 as reaction raw materials, at 20-50 ℃, add the water of 5 times of amounts of reaction raw materials gross weight and grind 2-5h, then vacuum drying 12h, filter, obtain white powder.
Preferably, ceftiofur: the mol ratio of HP-β-CD is 1:2.
Preferably, temperature is 40 ℃.
Preferably, milling time is 4h.
A ceftiofur hydroxypropyl-beta-cyclodextrin inclusion, take HP-β-CD as outer casing framework, and ceftiofur molecule by enclose wherein.
As preferred version, above-mentioned ceftiofur hydroxypropyl-beta-cyclodextrin inclusion, is prepared from according to above-mentioned method.
Beneficial effect:
The formation of clathrate of the present invention can effectively protect compound to avoid the reactions such as oxidation or hydrolysis, also increases the water solublity of medicine simultaneously, and enhanced stability reduces toxic and side effects, controls drug release and improves bioavailability.Ceftiofur-beta-CD inclusion prepared by the present invention can improve dissolubility and the bioavailability of ceftiofur crude drug.The clathrate of preparing is in illumination, and high temperature can significantly improve the oxidation resistance of crude drug under damp condition, and this exploitation for ceftiofur novel form provides a kind of very effective means.Meanwhile, the present invention has realized solid clathrates formation, can effectively open up the application of ceftiofur.
Accompanying drawing explanation
Accompanying drawing is used to provide a further understanding of the present invention, and forms a part for description, for explaining the present invention, is not construed as limiting the invention together with embodiments of the present invention.In the accompanying drawings:
Fig. 1 is the standard curve of variable concentrations ceftiofur uv absorption, wherein, and A trap, C drug level;
Fig. 2 is means of differential scanning calorimetry figure (DTA curve), wherein, and a. ceftiofur; B. HP-β-CD; C. physical mixture; D. clathrate;
Fig. 3 is ceftiofur (a) x-ray diffraction pattern, horizontal be designated as x-ray diffraction angle/(°);
Fig. 4 is HP-β-CD (b) x-ray diffraction pattern, horizontal be designated as x-ray diffraction angle/(°);
Fig. 5 is physical mixture (c) x-ray diffraction pattern, horizontal be designated as x-ray diffraction angle/(°);
Fig. 6 is clathrate (d) x-ray diffraction pattern, horizontal be designated as x-ray diffraction angle/(°).
The specific embodiment
Below in conjunction with accompanying drawing, the preferred embodiments of the present invention are described, should be appreciated that preferred embodiment described herein, only for description and interpretation the present invention, is not intended to limit the present invention.
One, phase solubility method research
Low concentration system, dilution effect makes HP-β-CD (HP-β-CD) can ignore the impact of ceftiofur uv absorption.Gained standard curve is Y=0.0279X+0.0118 (R
2=0.9997) (Fig. 1).
According to standard curve result, when HP-β-CD concentration is 0, ceftiofur intrinsic solubility equals 4.70 * 10
-7mol/L.
Two, enclose condition optimizing
1, the impact of raw material different proportion on enclose
Ceftiofur and HP-β-CD (HP-β-CD), temperature is 40 ℃, time 4h, during with 1:2 mixed in molar ratio, it is maximum that light absorption value differs, and both probabilities of carrying out enclose with 1:2 ratio of results suggest are maximum thus.In Table 1.
The different proportion HP-β-cdinclusion ultraviolet absorptivity of table 1 ceftiofur is poor
。
2, the impact of reaction temperature on enclose
Ceftiofur and HP-β-CD be during with 1:2 mixed in molar ratio, time 4h, and it is maximum that 40 ℃ of light absorption values of mixing temperature differ, and 40 ℃ of probabilities of carrying out enclose of results suggest mixing temperature are maximum thus, in Table 2.
When table 2 ceftiofur is 1:2 than HP-β-CD, mixing temperature enclose ultraviolet absorptivity is poor
3, the impact of response time on enclose
Ceftiofur and HP-β-CD be during with 1:2 mixed in molar ratio, 40 ℃ of mixing temperatures, and it is maximum that the response time is that 4h light absorption value differs, to be that 4h carries out the probability of enclose maximum the results suggest hybrid reaction time thus, in Table 3.
Table 3 ceftiofur and HP-β-CD are that response time enclose ultraviolet absorptivity is poor
Note: when ceftiofur is 1:2 than HP-β-CD, mixing temperature is 40 ℃.
Three, the thing identification of phases of clathrate
1, differential thermal analysis
Get ceftiofur, HP-β-CD, clathrate, four kinds of samples of physical mixture and carry out differential scanning calorimeter: take Al2O3 as reference; take 5.0mg left and right sample; range is ± 25 μ V; intensification scope is 40-400 ℃; heating rate is 10 ℃/min, makes DTA collection of illustrative plates, referring to Fig. 2; wherein, a. ceftiofur; B. HP-β-CD; C. the physical mixture of ceftiofur and HP-β-CD; D. the clathrate of spore thiophene furan and HP-β-CD.
As shown in Fig. 2, ceftiofur has a melting peak 203.8 ℃ of left and right, and HP-β-CD locates respectively to have a peak at 80.6 ℃ and 310.6 ℃, is respectively dehydration endothermic peak and the melting-decomposition peak of HP-β-CD.Mixture has kept the endothermic peak of HP-β-CD and ceftiofur, is the stack of single compound collection of illustrative plates substantially, and on the collection of illustrative plates of clathrate, variation has all occurred for the position at each peak and shape, infers that clathrate forms.
2, X-ray diffraction analysis
Test condition is: CuKa target, high pressure 5kV, pipe flow 20mA, 4 ° of min-1 of scanning speed, sweep limits 5-40 °.
X x ray diffraction the results are shown in Figure 3-6, ceftiofur (a) and HP-β-CD (b) have visibly different diffraction maximum, the diffraction maximum of existing HP-β-CD in physical mixture (c), the diffraction maximum that has again ceftiofur is the diffraction maximum stack of ceftiofur and HP-β-CD.Clathrate (d) is different from physical mixture, and the Partial Feature diffraction maximum of ceftiofur disappears or displacement, show really to have formed clathrate, and d has the crystal formation different from a and b.
Four, brief summary:
The HYDROXYPROPYL BETA-CYCLODEXTRIN of ceftiofur (HP-β-CD) according to above result: ceftiofur is raw material, by with HP-β-CD with suitable mol ratio 1:2,40
0under C, add a small amount of water and grind 4h, then vacuum drying 12h, filters, and obtains white powder, is optimum condition, completes the preparation of enclose and clathrate.
The foregoing is only the preferred embodiments of the present invention, be not limited to the present invention, although the present invention is had been described in detail with reference to previous embodiment, for a person skilled in the art, its technical scheme that still can record aforementioned each embodiment is modified, or part technical characterictic is wherein equal to replacement.Within the spirit and principles in the present invention all, any modification of doing, be equal to replacement, improvement etc., within all should being included in protection scope of the present invention.
Claims (6)
1. the preparation method of the clathrate of a ceftiofur and HP-β-CD, it is characterized in that: ceftiofur and HP-β-CD are usingd to the mol ratio of 1:1 ~ 3 as reaction raw materials, at 20-50 ℃, add the water of 5 times of amounts of reaction raw materials gross weight and grind 2-5h, then vacuum drying 12h, filter, obtain white powder.
2. the preparation method of the clathrate of spore thiophene furan according to claim 1 and HP-β-CD, is characterized in that: ceftiofur: the mol ratio of HP-β-CD is 1:2.
3. the preparation method of the clathrate of spore thiophene furan according to claim 1 and HP-β-CD, is characterized in that: temperature is 40 ℃.
4. the preparation method of the clathrate of spore thiophene furan according to claim 1 and HP-β-CD, is characterized in that: milling time is 4h.
5. a ceftiofur hydroxypropyl-beta-cyclodextrin inclusion, is characterized in that: take HP-β-CD as outer casing framework, ceftiofur molecule by enclose wherein.
6. according to ceftiofur hydroxypropyl-beta-cyclodextrin inclusion claimed in claim 5, it is characterized in that: described clathrate is prepared from according to the method described in claim 1 to 5 any one.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410008732.5A CN103751196B (en) | 2014-01-08 | 2014-01-08 | Ceftiofur hydroxypropyl-beta-cyclodextrin inclusion and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410008732.5A CN103751196B (en) | 2014-01-08 | 2014-01-08 | Ceftiofur hydroxypropyl-beta-cyclodextrin inclusion and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103751196A true CN103751196A (en) | 2014-04-30 |
| CN103751196B CN103751196B (en) | 2016-08-17 |
Family
ID=50518625
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410008732.5A Active CN103751196B (en) | 2014-01-08 | 2014-01-08 | Ceftiofur hydroxypropyl-beta-cyclodextrin inclusion and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103751196B (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104489268A (en) * | 2014-12-09 | 2015-04-08 | 中国农业科学院兰州畜牧与兽药研究所 | Micro-ecological preparation and preparation method thereof |
| CN104524585A (en) * | 2014-12-08 | 2015-04-22 | 悦康药业集团有限公司 | Cefathiamidine composition |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102462686A (en) * | 2010-11-05 | 2012-05-23 | 天津瑞普生物技术股份有限公司 | Pharmaceutical composition used for preventing and treating colibacillosis in livestock and poultry |
| CN103230364A (en) * | 2013-05-13 | 2013-08-07 | 青岛农业大学 | Preparation method of ceftiofur acid long-acting injection |
-
2014
- 2014-01-08 CN CN201410008732.5A patent/CN103751196B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102462686A (en) * | 2010-11-05 | 2012-05-23 | 天津瑞普生物技术股份有限公司 | Pharmaceutical composition used for preventing and treating colibacillosis in livestock and poultry |
| CN103230364A (en) * | 2013-05-13 | 2013-08-07 | 青岛农业大学 | Preparation method of ceftiofur acid long-acting injection |
Non-Patent Citations (1)
| Title |
|---|
| 姜静等: "β-环糊精对头孢噻呋盐酸盐的增溶作用", 《中国兽医杂志》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104524585A (en) * | 2014-12-08 | 2015-04-22 | 悦康药业集团有限公司 | Cefathiamidine composition |
| CN104524585B (en) * | 2014-12-08 | 2018-11-09 | 悦康药业集团有限公司 | Cefathiamidine composition |
| CN104489268A (en) * | 2014-12-09 | 2015-04-08 | 中国农业科学院兰州畜牧与兽药研究所 | Micro-ecological preparation and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN103751196B (en) | 2016-08-17 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN105753789B (en) | The eutectic and preparation method thereof of olaparib and urea | |
| Kohay et al. | Developing polycation-clay sorbents for efficient filtration of diclofenac: effect of dissolved organic matter and comparison to activated carbon | |
| WO2023065752A1 (en) | Preparation method for and use of clay/tannic acid/metal ion composite material for efficiently adsorbing antibiotics | |
| CN105153198B (en) | A kind of preparation method of Ceftibuten | |
| CN103221411A (en) | A crystalline form of (R)-7-chloro-n-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide hydrochloride monohydrate | |
| CN102276594B (en) | Iloperidone medicinal cocrystal and preparation method thereof | |
| CN106187888A (en) | FG 4592 monocrystalline and preparation method thereof | |
| CN102875531B (en) | A kind of (R)-lansoprazole anhydrous crystal forms and preparation method thereof | |
| CN103751196A (en) | Ceftiofur hydroxypropyl-beta-cyclodextrin inclusion compound and preparation method thereof | |
| Nguyen et al. | Efficient removal of chromium (VI) anionic species and dye anions from water using MOF-808 materials synthesized with the assistance of formic acid | |
| CN103102357B (en) | A kind of synthetic method of Cefuroxime sodium | |
| Lestari et al. | Composite material consisting of HKUST-1 and Indonesian activated natural zeolite and its application in CO2 capture | |
| CN106146603A (en) | A kind of preparation method of Cleistanone derivant | |
| Alhaddad et al. | Nonisothermal cold crystallization kinetics of poly (lactic acid)/bacterial poly (hydroxyoctanoate)(PHO)/talc | |
| CN103910769B (en) | The compound of glucosan derivative and proline, crystal, preparation method and application | |
| Ernawati et al. | Hierarchically 3-D porous structure of silk fibroin-based biocomposite adsorbent for water pollutant removal | |
| CN104961749A (en) | Novel industrial crystallizing technology for cefuroxime sodium | |
| Kahilu et al. | Coal discards and sewage sludge derived-hydrochar for HIV antiretroviral pollutant removal from wastewater and spent adsorption residue evaluation for sustainable carbon management | |
| CN109705101B (en) | Pyrazole triazole sulfonamide compound and solvothermal synthesis method and application thereof | |
| CN108864072B (en) | Coumarin thiadione compound and preparation method and application thereof | |
| CN103044364A (en) | Cabazitaxel amorphous crystal and preparation method thereof | |
| CN103819490A (en) | Cefuroxime sodium compound | |
| Sanad et al. | Radioiodination and Biological Evaluation of Novel Quinoline Derivative for Infective Inflammation Diagnosis | |
| CN109160901A (en) | A kind of metronidazole pharmaceutical co-crystals and preparation method thereof | |
| Chai et al. | Use of Typical Wastes as Biochars in Removing Diethyl Phthalate (Det) from Water |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20201106 Address after: 473000 East of Fumin Road, Suburb Township, Sheqi County, Nanyang City, Henan Province Patentee after: HENAN HUA MU BIOLOGICAL TECHNOLOGY Co.,Ltd. Address before: 730000 Gansu city of Lanzhou province West Lake Qilihe district along the 335 base Patentee before: LANZHOU INSTITUTE OF HUSBANDRY AND PHARMACEUTICAL SCIENCES OF CAAS |
|
| PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: Cefotaxifur hydroxypropyl- b- Cyclodextrin inclusion complex and its preparation method Effective date of registration: 20231115 Granted publication date: 20160817 Pledgee: Bank of China Limited Sheqi Branch Pledgor: HENAN HUA MU BIOLOGICAL TECHNOLOGY Co.,Ltd. Registration number: Y2023980065582 |
|
| PE01 | Entry into force of the registration of the contract for pledge of patent right | ||
| PC01 | Cancellation of the registration of the contract for pledge of patent right |
Granted publication date: 20160817 Pledgee: Bank of China Limited Sheqi Branch Pledgor: HENAN HUA MU BIOLOGICAL TECHNOLOGY Co.,Ltd. Registration number: Y2023980065582 |
|
| PC01 | Cancellation of the registration of the contract for pledge of patent right | ||
| PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: Cefotaxifur hydroxypropyl - b - cyclodextrin inclusion complex and its preparation method Granted publication date: 20160817 Pledgee: Bank of China Limited Sheqi Branch Pledgor: HENAN HUA MU BIOLOGICAL TECHNOLOGY Co.,Ltd. Registration number: Y2024980021100 |
|
| PE01 | Entry into force of the registration of the contract for pledge of patent right |