CN105770898A - Method for preparing enrofloxacin pillared hydrotalcite - Google Patents
Method for preparing enrofloxacin pillared hydrotalcite Download PDFInfo
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- CN105770898A CN105770898A CN201610204964.7A CN201610204964A CN105770898A CN 105770898 A CN105770898 A CN 105770898A CN 201610204964 A CN201610204964 A CN 201610204964A CN 105770898 A CN105770898 A CN 105770898A
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- enrofloxacin
- hydrotalcite
- preparation
- pillared hydrotalcite
- ldhs
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Links
- 229960000740 enrofloxacin Drugs 0.000 title claims abstract description 82
- SPFYMRJSYKOXGV-UHFFFAOYSA-N Baytril Chemical compound C1CN(CC)CCN1C(C(=C1)F)=CC2=C1C(=O)C(C(O)=O)=CN2C1CC1 SPFYMRJSYKOXGV-UHFFFAOYSA-N 0.000 title claims abstract description 78
- GDVKFRBCXAPAQJ-UHFFFAOYSA-A dialuminum;hexamagnesium;carbonate;hexadecahydroxide Chemical compound [OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Al+3].[Al+3].[O-]C([O-])=O GDVKFRBCXAPAQJ-UHFFFAOYSA-A 0.000 title claims abstract description 53
- 229960001545 hydrotalcite Drugs 0.000 title claims abstract description 52
- 229910001701 hydrotalcite Inorganic materials 0.000 title claims abstract description 52
- 238000000034 method Methods 0.000 title claims abstract description 21
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims abstract description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 21
- 239000008367 deionised water Substances 0.000 claims abstract description 11
- 229910021641 deionized water Inorganic materials 0.000 claims abstract description 11
- 230000032683 aging Effects 0.000 claims abstract description 4
- 238000001291 vacuum drying Methods 0.000 claims abstract description 3
- 238000002360 preparation method Methods 0.000 claims description 27
- 229910052599 brucite Inorganic materials 0.000 claims description 18
- 238000009835 boiling Methods 0.000 claims description 9
- YIXJRHPUWRPCBB-UHFFFAOYSA-N magnesium nitrate Chemical compound [Mg+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O YIXJRHPUWRPCBB-UHFFFAOYSA-N 0.000 claims description 6
- 239000000203 mixture Substances 0.000 claims description 5
- 238000002156 mixing Methods 0.000 claims description 4
- BNGXYYYYKUGPPF-UHFFFAOYSA-M (3-methylphenyl)methyl-triphenylphosphanium;chloride Chemical compound [Cl-].CC1=CC=CC(C[P+](C=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 BNGXYYYYKUGPPF-UHFFFAOYSA-M 0.000 claims description 3
- 239000012266 salt solution Substances 0.000 claims description 3
- 230000008961 swelling Effects 0.000 claims description 3
- 239000004576 sand Substances 0.000 claims description 2
- 238000003756 stirring Methods 0.000 claims description 2
- 239000003814 drug Substances 0.000 abstract description 71
- 229940079593 drug Drugs 0.000 abstract description 33
- 230000000694 effects Effects 0.000 abstract description 16
- 239000011229 interlayer Substances 0.000 abstract description 16
- 239000000243 solution Substances 0.000 abstract description 16
- 239000010410 layer Substances 0.000 abstract description 10
- 238000000338 in vitro Methods 0.000 abstract description 8
- 229910003471 inorganic composite material Inorganic materials 0.000 abstract description 4
- 150000002500 ions Chemical class 0.000 abstract description 4
- 241001465754 Metazoa Species 0.000 abstract description 3
- 238000001727 in vivo Methods 0.000 abstract description 3
- 230000001988 toxicity Effects 0.000 abstract description 3
- 231100000419 toxicity Toxicity 0.000 abstract description 3
- 230000003115 biocidal effect Effects 0.000 abstract description 2
- 239000012620 biological material Substances 0.000 abstract description 2
- 230000001186 cumulative effect Effects 0.000 abstract description 2
- 238000009830 intercalation Methods 0.000 abstract description 2
- 230000002687 intercalation Effects 0.000 abstract description 2
- 239000012670 alkaline solution Substances 0.000 abstract 1
- 239000003242 anti bacterial agent Substances 0.000 abstract 1
- 230000001276 controlling effect Effects 0.000 abstract 1
- 230000001105 regulatory effect Effects 0.000 abstract 1
- 239000002002 slurry Substances 0.000 abstract 1
- 238000005406 washing Methods 0.000 abstract 1
- 239000000047 product Substances 0.000 description 30
- 239000003070 absorption delaying agent Substances 0.000 description 14
- 238000010521 absorption reaction Methods 0.000 description 14
- 150000001450 anions Chemical class 0.000 description 12
- 238000011068 loading method Methods 0.000 description 11
- 238000002835 absorbance Methods 0.000 description 10
- 238000006243 chemical reaction Methods 0.000 description 8
- 230000003578 releasing effect Effects 0.000 description 8
- 239000000872 buffer Substances 0.000 description 6
- 229910052739 hydrogen Inorganic materials 0.000 description 6
- 239000001257 hydrogen Substances 0.000 description 6
- 230000008569 process Effects 0.000 description 6
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- 239000003937 drug carrier Substances 0.000 description 5
- -1 enrofloxacin anion Chemical class 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 239000002243 precursor Substances 0.000 description 5
- 238000011160 research Methods 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- MYSWGUAQZAJSOK-UHFFFAOYSA-N ciprofloxacin Chemical compound C12=CC(N3CCNCC3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 MYSWGUAQZAJSOK-UHFFFAOYSA-N 0.000 description 4
- 238000004090 dissolution Methods 0.000 description 4
- 238000005342 ion exchange Methods 0.000 description 4
- 206010059866 Drug resistance Diseases 0.000 description 3
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 3
- 229910002651 NO3 Inorganic materials 0.000 description 3
- 230000000844 anti-bacterial effect Effects 0.000 description 3
- 239000007853 buffer solution Substances 0.000 description 3
- 239000012876 carrier material Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 238000000975 co-precipitation Methods 0.000 description 3
- 239000002131 composite material Substances 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 239000012153 distilled water Substances 0.000 description 3
- 238000012417 linear regression Methods 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 239000004471 Glycine Substances 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 238000013019 agitation Methods 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 235000019994 cava Nutrition 0.000 description 2
- 229960003405 ciprofloxacin Drugs 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 238000001938 differential scanning calorimetry curve Methods 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000012467 final product Substances 0.000 description 2
- 229960002449 glycine Drugs 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 230000003068 static effect Effects 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 235000012222 talc Nutrition 0.000 description 2
- IVLXQGJVBGMLRR-UHFFFAOYSA-N 2-aminoacetic acid;hydron;chloride Chemical compound Cl.NCC(O)=O IVLXQGJVBGMLRR-UHFFFAOYSA-N 0.000 description 1
- 206010002198 Anaphylactic reaction Diseases 0.000 description 1
- 229910013504 M-O-M Inorganic materials 0.000 description 1
- TZJKHERXIDPDTK-UHFFFAOYSA-N N1=CC=CC2=CC=CC=C12.[F] Chemical compound N1=CC=CC2=CC=CC=C12.[F] TZJKHERXIDPDTK-UHFFFAOYSA-N 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 238000005411 Van der Waals force Methods 0.000 description 1
- 238000002441 X-ray diffraction Methods 0.000 description 1
- 241000276425 Xiphophorus maculatus Species 0.000 description 1
- 239000003929 acidic solution Substances 0.000 description 1
- 230000005260 alpha ray Effects 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 230000036783 anaphylactic response Effects 0.000 description 1
- 208000003455 anaphylaxis Diseases 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 210000000941 bile Anatomy 0.000 description 1
- 230000008033 biological extinction Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 229910021538 borax Inorganic materials 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000007979 citrate buffer Substances 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 230000007797 corrosion Effects 0.000 description 1
- 238000005260 corrosion Methods 0.000 description 1
- 239000003405 delayed action preparation Substances 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 238000007599 discharging Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- UQGFMSUEHSUPRD-UHFFFAOYSA-N disodium;3,7-dioxido-2,4,6,8,9-pentaoxa-1,3,5,7-tetraborabicyclo[3.3.1]nonane Chemical compound [Na+].[Na+].O1B([O-])OB2OB([O-])OB1O2 UQGFMSUEHSUPRD-UHFFFAOYSA-N 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 230000009881 electrostatic interaction Effects 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000004744 fabric Substances 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000009432 framing Methods 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 229960001269 glycine hydrochloride Drugs 0.000 description 1
- 238000009396 hybridization Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 150000004679 hydroxides Chemical class 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000004531 microgranule Substances 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 150000002891 organic anions Chemical class 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 231100000572 poisoning Toxicity 0.000 description 1
- 230000000607 poisoning effect Effects 0.000 description 1
- 229920005597 polymer membrane Polymers 0.000 description 1
- FGIUAXJPYTZDNR-UHFFFAOYSA-N potassium nitrate Chemical compound [K+].[O-][N+]([O-])=O FGIUAXJPYTZDNR-UHFFFAOYSA-N 0.000 description 1
- 244000144977 poultry Species 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical compound C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000008085 renal dysfunction Effects 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 235000010339 sodium tetraborate Nutrition 0.000 description 1
- 239000004328 sodium tetraborate Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000002798 spectrophotometry method Methods 0.000 description 1
- 239000012086 standard solution Substances 0.000 description 1
- 238000010025 steaming Methods 0.000 description 1
- 230000003335 steric effect Effects 0.000 description 1
- 239000004575 stone Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000005979 thermal decomposition reaction Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/02—Inorganic compounds
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Inorganic Chemistry (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a method for preparing enrofloxacin pillared hydrotalcite. The method comprises the following steps: dissolving enrofloxacin in a four-port flask by using a NaOH solution, adding deionized water, and regulating the pH value to 9.66; dropwise adding Mg-Al-NO3-LDHs slurry into an alkaline solution of enrofloxacin under N2 protection conditions, controlling the pH value to 7.5-11, wherein the ratio of enrofloxacin to hydrotalcite is 2:1; and aging under the condition of T=50-70 DEG C for 12 hours, centrifuging, washing, and performing vacuum drying, thereby obtaining the product. According to the method disclosed by the invention, by utilizing exchangeability of negative ions between hydrotalcite layers, enrofloxacin anionic model drug intercalation with functional characteristics is assembled into the interlayer of hydrotalcite, a drug-inorganic composite material is synthesized and has an excellent in-vitro release effect, so that after an antibiotic medicine enrofloxacin is inserted into the hydrotalcite interlayer, cumulative toxicity and side effects of the medicine in vivo are reduced on the basis of reducing raw drug activity, the administration frequency is reduced, compliance in the animal body is increased, and the application range of the hydrotalcite in a biological material is widened.
Description
Technical field
The present invention relates to the preparation method of a kind of novel organic drug inorganic composite materials enrofloxacin pillared hydrotalcite.
Background technology
Along with the reach of science, the progress of science and technology, people are to the requirement of the therapeutic effect of disease and treatment means the most day by day
Improve.Raising curative effect, simplification application method, reduction side effect are still emphasis and the striving direction that scientist studies.Especially
It is the medicine that toxicity is the biggest, takes for the ease of patient, while ensureing effectively to treat concentration, reduce the malicious secondary of medicine and make
With, it is to avoid the generation of drug resistance, medicine can be made slow releasing preparation, make patient can continue within the longer time after using medicine
Release medicine.And slow releasing preparation mainly has matrix type and reservoir devices two kinds.Medicine uniformly divides with the form of molecule or crystallite, microgranule
It is dispersed in various carrier material, then forms skeleton type sustained release preparation；Medicine is wrapped in polymer membrane, then form storage
Storehouse type slow releasing preparation.Release principle involved by two kinds of slow releasing preparation mainly have dissolution, diffusion, corrosion, osmotic pressure or
Ion exchange.
In order to extend the action time of medicine, improving its bioavailability, the performance of pharmaceutical carrier and structural research are especially
The key of this system.And LDHs is as the novel inorganic lamellar material of a class, is good drug carrier material, in medicinal load
Body field has a wide range of applications, and can be combined with organic drug, synthesizes new pharmaceutical inorganic hydridization.
Layered double hydroxide (Layered Double Hydroxides is called for short LDHs), also known as houghite,
Refer to the oxide with hydrotalcite laminar crystalline structure being made up of two or more metallic element, be a class in recent years
The stratified material received much concern.LDHs is that a class is made up of the anion of positively charged laminate and interlayer filling tape negative charge
Typical anion type laminated compound.There is strong covalent bond effect in LDHs laminate, interlayer then exists a kind of weak mutual
Effect, i.e. weakens with electrostatic attraction, hydrogen bond or Van der Waals force etc. between interlayer object and main body laminate bonded.Medicine (or
Biomolecule) can be inserted into LDHs interlayer, obtain medicine (or biological)/LDHs (Drug or Bio/LDHs) nano hybridization
Thing, can realize effective controlled release of medicine because there is electrostatic interaction, hydrogen bond action and space steric effect between medicine and laminate, because of
This LDHs is considered as the Organic Nano-Scale Pharmaceutical Carrier of a great application prospect of class.
Enrofloxacin (enrofloxacin, ENRO) has another name called ENR, is the special fluorine quinoline promises of first poultry
Ketone medicine, has has a broad antifungal spectrum, bactericidal activity is strong, distribution in vivo is extensive and other antibacterials are without handing over the justice spy such as drug resistance
Point.
ENRO is widely used on veterinary clinic at present, has been made into multiple dosage form, such as tablet, powder in production
Agent, injection, plain particles agent etc..But these dosage forms are many based on ordinary preparation, and the most often administration number of times is many, internal work
Short with the time, and have blood drug level peak valley phenomenon, side effect is relatively big, and cost is high.
Enrofloxacin be it is generally acknowledged and is not stranded in animal body in recent years, but has certain accumulative during heavy dose of application,
Major metabolite is enrofloxacin prototype and ciprofloxacin in vivo, and ciprofloxacin has antibacterial activity equally, and generate and
Eliminate slowly, widely distributed, apply veterinary the report of produced untoward reaction and drug resistance to get more and more, nerve can be caused
The toxic and side effects such as poisoning, renal dysfunction, anaphylaxis, and enrofloxacin is mainly by kidney, discharges body secondly by bile
Outward, thus be mainly trapped in muscle, liver and kidney.
Enrofloxacin is combined with carrier material the slow releasing preparation made, both can expand the range of application of enrofloxacin,
Improve drug effect and degree of safety, reduce untoward reaction, raiser can be facilitated again to be administered, reduce feeding cost.
Summary of the invention
It is an object of the invention to provide the preparation method of a kind of enrofloxacin pillared hydrotalcite, the method is with Mg-Al-LDHs
As drug carrier material, enrofloxacin is drug model, by anion pillared for enrofloxacin to hydrotalcite layers, synthesized and has had
Machine pharmaceutical inorganic composite, it has good release in vitro effect, produces for theoretical from now on and industrialization and provided
The basic data of effect.
It is an object of the invention to be achieved through the following technical solutions:
The preparation method of a kind of enrofloxacin pillared hydrotalcite, using Mg-Al-LDHs as main body, the interlayer utilizing brucite is cloudy
The interchangeability of ion, uses co-precipitation and ion exchange that enrofloxacin is inserted into Mg-Al-LDHs interlayer, is prepared for one
Plant novel Drug-inorganic composite.Specifically comprise the following steps that
One, Mg-Al-NO3The preparation of-LDHs
The double dripping method in coprecipitation are utilized to complete hydrotalcite precursor Mg-Al-NO3The preparation of-LDHs:
In four-hole boiling flask, add the deionized water of 300mL, the magnesium nitrate of 0.17mo1 and the aluminum nitrate of 0.09mo1 are dissolved in
300mL deionized water is configured to mixing salt solution in separatory funnel, is added dropwise in four-hole boiling flask, and at N2Protection is lower strong
Strong stirring, regulates pH to 10 ± 0.3 with 2mol NaOH simultaneously, and gelatinous mixture is stirred continuously ageing 24h hydro-thermal 70 DEG C,
It is subsequently poured in the conical flask of 1000ml swelling 5 days, obtains hydrotalcite precursor Mg-Al-NO to be prepared3-LDHs。
Two, the preparation of enrofloxacin pillared hydrotalcite
Enrofloxacin NaOH is dissolved in four-hole boiling flask, adds deionized water and pH value is adjusted to 9.66, at N2Ceiling
Under part, take Mg-Al-NO3-LDHs serosity is added dropwise in the aqueous slkali of enrofloxacin, is controlled by pH value between 7.5 ~ 11,
Enrofloxacin: brucite=2:1(mol ratio), under conditions of 50 ~ 70 DEG C, then it is aged 12h, is then centrifuged for, washes, is dried,
Obtain product.
Present invention have the advantage that
1, by the analysis to collection of illustrative plates and data, enrofloxacin anion is inserted into hydrotalcite layers first, at pH=3.6
Time have preferable releasing effect.
The meansigma methods of the drug loading 2, being recorded product by test is 36.71%.
3, the present invention utilizes the interchangeability of hydrotalcite layers anion, will have the enrofloxacin anion of functional characteristic
Model drug intercalation is assembled into the interlayer of brucite, has synthesized Drug-inorganic composite, and it has good release in vitro effect
Really, make antibiotic medicine enrofloxacin after inserting hydrotalcite layers, on the basis of the activity keeping former medicine, reduce medicine at body
Interior cumulative toxicity, side effect, reduces administration number of times, increases compliance in animal body, extend brucite at biological material
Range of application in material, the structure and performance study for preparing organic anion pillared hydrotalcite from now on provides theoretical basic number
According to.
Accompanying drawing explanation
Fig. 1 is the XRD spectrum of product, B: enrofloxacin pillared hydrotalcite, C:LDHs；
Fig. 2 is hydrotalcite structure schematic diagram before and after reaction；
Fig. 3 is nitrate anion brucite, the former medicine of enrofloxacin, the Fourier infrared spectrum figure of enrofloxacin pillared hydrotalcite, B: grace
Promise sand star former medicine C: enrofloxacin pillared hydrotalcite D: nitrate anion brucite；
Fig. 4 is the scanning electron microscope of enrofloxacin pillared hydrotalcite, a: crystallite dimension 1 m(25kv × 10000), b: crystallite dimension 1
M(25kv × 10000), c: crystallite dimension 5 m(25kv × 5000), d: crystallite dimension 5 m(25kv × 2000) and, e: crystallite dimension
50 m(25kv × 500), f: crystallite dimension 100 m(25kv × 100)；
Fig. 5 is TG and the DSC curve of enrofloxacin pillared hydrotalcite；
Fig. 6 is enrofloxacin concentration absorbance standard curve in the absorption delaying agents of pH=2.0；
Fig. 7 is enrofloxacin concentration absorbance standard curve in the absorption delaying agents of pH=3.6；
Fig. 8 is enrofloxacin pillared hydrotalcite release rate-time graph in the buffer medium of pH=2.0；
Fig. 9 is enrofloxacin pillared hydrotalcite release rate-time graph in the buffer medium of pH=3.6.
Detailed description of the invention
Below in conjunction with the accompanying drawings technical scheme is further described, but is not limited thereto, every to this
Inventive technique scheme is modified or equivalent, without deviating from the spirit and scope of technical solution of the present invention, all should contain
In protection scope of the present invention.
The invention provides the preparation method of a kind of enrofloxacin pillared hydrotalcite, mainly using Mg-Al-LDHs as medicine
Carrier material, enrofloxacin is drug model, carries out prepared by enrofloxacin pillared hydrotalcite newtype drug inorganic composite materials
Research.Particular content is as follows:
1 experimental technique
1.1 Mg-Al-NO3The preparation of-LDHs
First by the distilled water heated and boiled of 500ml, the preparation of deionized water is completed, in order to experiment is required.
2. pH value is positioned with pH precision instrument, calibrates: the slope button on instrument is transferred to maximum, then with mixing phosphorus
Hydrochlorate location pH=6.86；Use sodium tetraborate solution instead to be adjusted to slope into pH=9.18.
3. utilize the double dripping method in coprecipitation to complete the preparation of hydrotalcite precursor, in four-hole boiling flask, add 300mL's
Deionized water, is dissolved in 300mL deionized water by the magnesium nitrate of 0.17mo1 and the aluminum nitrate of 0.09mo1 and is configured to mixing salt solution
In separatory funnel, it is added dropwise in four-hole boiling flask, and at N2The lower strong agitation of protection, regulates pH with 2mol NaOH simultaneously
It is stirred continuously ageing 24h to 10 ± 0.3 gelatinous mixtures hydro-thermal 70 DEG C, is subsequently poured in the conical flask of 1000ml swelling 5
My god, obtain hydrotalcite precursor to be prepared.
The preparation of enrofloxacin pillared hydrotalcite
The NaOH10mL of 0.7615g enrofloxacin 1mol/L is dissolved in four-hole boiling flask, adds deionized water and pH value is adjusted
To 9.66, in magnetic agitation N2Protective condition under, take the Mg-Al-NO of the above-mentioned preparation of 50ml3-LDHs serosity is added dropwise to
In the aqueous slkali of the enrofloxacin of excess, pH value is controlled between 7.5 ~ 11, under conditions of 50 DEG C, be then aged 12h, so
It is centrifuged afterwards, washes repeatedly, under the conditions of 20 DEG C, vacuum drying oven is dried, obtains product.
The sign of product
1.3.1 the XRD of product characterizes
Use Germany D8 ADVANCE type X-ray diffractometer (Cu target k alpha ray, λ=1.5406, tube voltage 40kV, tube current
20mA, scanning speed 0.05second/step, 2 θ scope 2 ° ~ 70 °) crystal structure of assay products.
The FT-IR of product characterizes
The FT-IR using Germany's Brooker company VERTEX type Fourier transformation infrared spectrometer to measure sample composes, KBr tabletting,
Sweep limits 4000-400cm-1, determine functional group that may be present in compound.
The SEM of product characterizes
Use JSM-6360 scanning electron microscope analysis product crystalline substance looks feature.
The TG-DSC of product characterizes
NETZSCH STA 409 PC/PG type is used to synchronize TG-DSC analyser (programming rate 20k/min) steady to the heat of product
Qualitative being measured is analyzed.
1.3.5 ultraviolet and visible spectrophotometry
Use Shanghai Precision Scientific Apparatus Co., Ltd's UV757CRT ultraviolet-uisible spectrophotometer detection product at different pH value
Buffer solution in the burst size of maximum absorption wave strong point.
The research of enrofloxacin pillared hydrotalcite release in vitro performance
1.4.1 the selection of vitro Release Medium
Have chosen the absorption delaying agents of two kinds of different pH value
1. pH=2.0: measure the hydrochloric acid solution 440m1 of glycine solution 500ml and 0.2mo1/L of 0.2mo1/L, add distilled water
It is diluted to 2000m1, stands, to obtain final product.
2. pH=3.6: measure the hydrochloric acid solution 500ml of glycine solution 500ml and 0.2mo1/L of 0.2mo1/L, add steaming
Distilled water is diluted to 2000m1, stands, to obtain final product.
The determination of standard curve
With absorption delaying agents as solvent, prepare the standard solution of a series of purely medical compounds, utilize UV-Vis spectrophotometer,
With absorption delaying agents as reference liquid, measure A-C working curve in maximum absorption wave strong point.
The mensuration of drug loading
The glycine hydrochloride buffer solution taking appropriate product pH=2.0 is settled in the volumetric flask of 250ml, and static 24h makes
Drug release is complete, measures absorbance A in maximum absorption wave strong point, goes out medicine by the linearity of regression Equation for Calculating of pH=2.0
Concentration (c), according to computing formula: drug loading (%)=cv/m × 100% calculates the drug loading of medicine.
Release in vitro
Enrofloxacin pillared hydrotalcite is the mensuration of dissolution in pH=2.0 absorption delaying agents.Analyzer is used in 78X-2 matrix agent four
Middle addition 500ml pH=2.0 absorption delaying agents, constant temperature to 37 DEG C, take enrofloxacin pillared hydrotalcite and put in right amount and turn in basket, start
Rotating switch, takes out 3ml solution for every 2 minutes and uses ultraviolet spectrophotometer to measure it under this absorption delaying agents maximum absorption wavelength
Absorbance, after mensuration, solution is refunded intelligence dissolving-out tester in, after numerical value is basicly stable some minutes measure once, extremely
Till numerical value is almost unchanged.Record data above, makes Dissolution profiles.According to said method, measure medicine pH=3.6 respectively
Time absorbance, record and process data, making Dissolution profiles.
Experimental result
The characterization result analysis of 2.1 products
2.1.1 the XRD analysis of product
Fig. 1 shows: can be seen that in XRD figure C that 2 θ relative diffracted intensity occur relatively at 9.89 °, 19.74 °, 34.52 °, 60.71 °
The characteristic diffraction peak in big (003) (006) (009) (110) face, does not find other diffraction maximum, and its baseline is low and steady,
Diffraction maximum peak shape is narrow and sharp.In B, can be seen that product shows the characteristic diffraction peak of layer structure, locate 2 θ its (003)
(006) a series of corresponding characteristic diffraction peak in (009) (110) face is respectively 3.79 °, 11.25 °, 23.49 °, 60.54 °.
(003) and (006) diffraction maximum of column-supporting product the most all moves to low-angle direction compared with nitrate anion brucite simultaneously, shows nitre
The interlamellar spacing of acid group brucite increases, and medicine anion has been inserted between brucite laminate.Through scherrer formula D=R λ/β cos θ
The interlamellar spacing calculating gained is 2.33nm, owing to laminate thickness is about 0. 48nm, deducts by interlamellar spacing in the thickness resultant layer of layer
Spatial altitude about 1.85 nm(is consistent with actual size 1.2nm-1.87nm), it was demonstrated that enrofloxacin anion is vertically oriented
Insert interlayer, see Fig. 2.It addition, compose it will be seen that the good crystallinity of product from the XRD of product, and Rotating fields is regular in order.
The FT-IR of product analyzes
Fig. 3 is nitrate anion brucite, the former medicine of enrofloxacin, the infared spectrum of enrofloxacin pillared hydrotalcite.Figure shows: B schemes
The former medicine of middle enrofloxacin is at 3441 cm-1Place occurs that a broad peak is the stretching vibration of the O-H of carboxyl, at 2822cm-1Vicinity goes out
Existing several little and weak spikes are considered as the stretching vibration of C-H, it may be possible to the ethyl peak on enrofloxacin molecule, phenyl ring
On hydrogen and the overlap of hydrogen on piperazinyl；At 1624 cm-1It it is the carbonyl characteristic absorption peak of the former medicine of enrofloxacin；1464cm-1
It it is the characteristic absorption peak of the basic framework of phenyl ring in the former medicine of enrofloxacin.After drug molecule inserts laminate, C figure is in
3441cm-1The characteristic absorption peak at place is to high wave number 3460cm-1Position be moved, this is by 3464cm in D figure-1Place's neatly
The intermediary water of stone, the stretching vibration overlap of the O-H of laminate hydroxyl and crude drug carboxyl produces, and enrofloxacin is former in C figure
The basic feature peak of medicine is most of to be moved to lower wave number, due to hydrogen bond inducing action and intermolecular electrostatic captivation between anion,
Although making part peak be weakened by hydrotalcite layers anion, but still exist.This external C figure low frequency range, wave number is 781cm-1,
500 cm-1Be below M-O and M-O-M(M=Mg, Al) lattice vibration, this explanation in the conjunction carrying out enrofloxacin pillared hydrotalcite
During one-tenth, the basic structure of brucite is not destroyed.
The sem analysis of product
Fig. 4 shows: uses JSM-6360 scanning electron microscope analysis sample surface morphology, is to be all between 1 ~ 100 m at crystallite dimension
Typical brucite pattern, it may be assumed that non-homogeneous, irregular gathering platy structure.
The TG-DSC of product analyzes
Fig. 5 be enrofloxacin pillared hydrotalcite TG-DSC curve, from figure, curve can be seen that product thermal decomposition process can
It was divided into for three stages.First stage is room temperature near 234 DEG C, and present in DSC figure is the endothermic process of product, its mass loss
Belong to the hydrone of sample surfaces physical absorption and sloughing of intermediary water molecule；Second stage is near 234 DEG C to 359 DEG C；
Present in DSC figure is that product is in shorter exothermic process, and its mass loss belongs to dividing of interlayer organic drug anion
Solve and burning；Phase III is 359 DEG C to 520 DEG C, and start in DSC figure to present is the endothermic process of fraction, finally releases
Substantial amounts of heat, mass loss belongs to the burning of sample interlayer drug molecule, releases CO2And water；Next laminate finally quilt
Destroying, framing structure is caved in.
The research of enrofloxacin pillared hydrotalcite release in vitro
2.2.1 the standard curve of the former medicine of enrofloxacin and the foundation of equation of linear regression
1. the glycine-HCI buffer of pH=2.0
Being dissolved by the absorption delaying agents of enrofloxacin pH=2.0, the enrofloxacin solution of five kinds of variable concentrations of accurate formulation, at purple
200 ~ 400nm length scanning is carried out on outer visible spectrophotometer.Select maximum absorption wavelength 277nm, measure different dense respectively
The enrofloxacin solution of degree absorbance at this wavelength, draws concentration one absorbance standard curve under 277nm wavelength also
Determine that equation of linear regression is Y=0.1169x-0.0189, coefficient R2=0.9991, its standard curve is shown in Fig. 6.
Table 1 enrofloxacin UV absorption of concentration under pH=2.0
2. disodium hydrogen phosphate-the citrate buffer solution of pH=3.6
Method ibid, selects enrofloxacin maximum absorption wavelength 277nm in pH=3.6 absorption delaying agents, and draws under this wavelength
Concentration one absorbance standard curve also determines that equation of linear regression is Y=0.1154x+0.0008, coefficient R2=0.9989, its
Standard curve is shown in Fig. 7.
Table 2 enrofloxacin ultraviolet absorption value of concentration under pH=3.6
Result shows, has good linear relationship, extinction between absorbance and the drug level in the range of finite concentration
Degree is little affected by the impact of absorption delaying agents solution type.
The mensuration of drug loading
The glycine-HCI buffer solution taking m=0.0104g pH=2.0 is settled in the volumetric flask of 250ml, and static 24h makes medicine
Thing release is completely.
The measurement result of table 3 product drug loading
Measurement result according to table 3: measuring absorbance in maximum absorption wave strong point is 1.785, with the regression equation meter of pH=2.0
Calculate concentration c=15.27 g/ml of medicine, calculate the flat of drug loading according to the computing formula of drug loading (%)=cv/m × 100%
Average is 36.71%.
2.2.3 release in vitro interpretation of result
Fig. 8 is enrofloxacin pillared hydrotalcite A in the buffer medium of pH=2.0-The release rate of (interlayer anion)-time is bent
Line.As can be seen from Figure 8, when 10min, A-Release rate be 69.15%；Tend to balance when 30min, the release rate of A-
It is 91.27%；A during 92 min-Release rate be 92.11%.
Fig. 9 is enrofloxacin pillared hydrotalcite A in the buffer medium of pH=3.6-(interlayer anion) release rate-time
Half interval contour.It can be seen in figure 9 that when 10min A-Release rate be 49.18%；A during 60min-Release rate be 71%
Tend to balance during 136min, A-Release rate be 92.43%；A during 200min-Release rate be 92.81%.
Known according to figure: in the solution of suitable acidity, interlayer medicine anion forms electric neutrality molecule after being protonated, by
In the reaction force attenuation with laminate, thus departing from interlayer and produce release phenomenon, this exchanged form can be referred to as active ion
Exchange, active exchange driving force is big, and drug release rate is fast.For carboxylate anion type medicament intercalated houghite complex
For, in weakly acidic solution, the exchange of active ion plays a leading role.Enrofloxacin in the buffer medium of pH=2.0, water
It is fast that Talcum laminate caves in, and medicine discharges the most completely, and in the absorption delaying agents of pH=3.6, it is slow that drug molecule discharges, energy
Playing slow releasing function, and the increase medicine of release rate discharges the most completely therewith, preliminary explanation enrofloxacin pillared hydrotalcite exists
The absorption delaying agents of pH=3.6 has slow release trend.
3 discuss
(1) in course of reaction, produce the factor of error, first, under conditions of meta-alkalescence, the only simple exchange of ion, this
Individual process is relatively slower, and in acid condition, the nitrate ion of hydrotalcite layers is activated, it is possible to hand over faster
Change；Secondly, in the whole experimentation preparing medicament intercalated houghite, it is necessary to carry out under strict nitrogen protection.Because
Protect without nitrogen, the CO in air2Reaction system will be entered, form carbanion, brucite will be swapped out
Anion in laminate, causes product impure；Further, since quinolone medicine major part is all insoluble in water, so reaction
Temperature should control to carry out between 50 ~ 70 DEG C, and temperature is not so high, and otherwise medicine can decompose when temperature is too high.
(2) mensuration of drug loading: due to enrofloxacin in water insoluble, in absorption delaying agents release incomplete, at drug loading
During mensuration, should be longer than the time that other class medicines discharge completely, therefore divide some stages to measure the suction in maximum absorption wave strong point
Luminosity, until discharging completely, or in order to shorten the method that the time can use heated and stirred.
(3) solution measured with cuvette should be refunded in system, and all should position sampling every time, reduces reality as far as possible
Test error.
4 conclusions
With Mg-Al-NO3-LDHs is precursor, uses ion exchange, at T=50 DEG C, pH=10.17, enrofloxacin/brucite
In the environment of proportioning is 2:1, through the reaction of about 12h, the preparation of expection research enrofloxacin pillared hydrotalcite can be completed, logical
The chemical composition of the product obtained by the preliminary identification of sign crossing IR, XRD, scanning electron microscope is clear and definite, and good crystallinity, crystal particle diameter divides
Cloth is uniform.The meansigma methods of the drug loading being recorded product by test is 36.71%.Utilize TG-DSC to measure and analyze medicament intercalated water
The good thermal stability of Talcum.
Detect its release in vitro effect by ultraviolet spectrophotometer and tablet four with analyzer to show: enrofloxacin is pillared
Brucite discharges rapidly in the release medium of pH=2.0, brucite laminate caves in；The release medium of pH=3.6 discharges
196min, releasing effect is preferable, and preliminary identification enrofloxacin pillared hydrotalcite absorbs in the environment of pH=3.6 and can play slow release
Effect, brucite is good pharmaceutical carrier, and produces carry for preparing organic drug-inorganic composite materials and industrialization from now on
For basic data.
Claims (6)
1. the preparation method of an enrofloxacin pillared hydrotalcite, it is characterised in that described method step is as follows:
Enrofloxacin NaOH is dissolved in four-hole boiling flask, adds deionized water and pH value is adjusted to 9.66, at N2Protective condition
Under, take Mg-Al-NO3-LDHs serosity is added dropwise in the aqueous slkali of enrofloxacin, is controlled by pH value between 7.5 ~ 11, grace
Promise sand star: brucite=2:1(mol ratio), under conditions of T=50 ~ 70 DEG C, then it is aged 12h, is then centrifuged for, washes, vacuum is done
Dry, obtain product.
The preparation method of enrofloxacin pillared hydrotalcite the most according to claim 1, it is characterised in that described Mg-Al-NO3-
The preparation method of LDHs is as follows:
In four-hole boiling flask, add the deionized water of 300mL, the magnesium nitrate of 0.17mo1 and the aluminum nitrate of 0.09mo1 are dissolved in
300mL deionized water is configured to mixing salt solution in separatory funnel, is added dropwise in four-hole boiling flask, and at N2Protection is lower strong
Strong stirring, regulates pH to 10 ± 0.3 with 2mol NaOH simultaneously, and gelatinous mixture is stirred continuously ageing 24h hydro-thermal 70 DEG C,
It is subsequently poured in the conical flask of 1000ml swelling 5 days, obtains Mg-Al-NO3-LDHs。
The preparation method of enrofloxacin pillared hydrotalcite the most according to claim 1, it is characterised in that described pH=10.17.
The preparation method of enrofloxacin pillared hydrotalcite the most according to claim 1, it is characterised in that described T=50 DEG C.
The preparation method of enrofloxacin pillared hydrotalcite the most according to claim 1, it is characterised in that described NaOH's is dense
Degree is 1mol/L.
The preparation method of enrofloxacin pillared hydrotalcite the most according to claim 1, it is characterised in that described vacuum drying
Temperature is 20 DEG C.
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1468913A (en) * | 2003-03-14 | 2004-01-21 | 北京化工大学 | Borate radical intercalated hydrotalcite and its prepn process and application as fire retardant |
| WO2007058630A1 (en) * | 2005-11-17 | 2007-05-24 | Agency For Science, Technology And Research | Novel bis(amino)-ortho-dicarbaborane cluster compounds |
| CN101664386A (en) * | 2009-09-30 | 2010-03-10 | 北京大北农动物保健科技有限责任公司 | Enrofloxacin double emulsion for livestock and preparation method thereof |
| US20120288553A1 (en) * | 2010-03-26 | 2012-11-15 | National Taiwan University | Method for controlling toxicity of metallic particle and low-toxicity composite of metallic nanoparticle and inorganic clay |
| CN103222975A (en) * | 2013-05-03 | 2013-07-31 | 广州英赛特生物技术有限公司 | Application of enrofloxacin salt in preparation of swine oral preparation |
-
2016
- 2016-04-05 CN CN201610204964.7A patent/CN105770898A/en active Pending
Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1468913A (en) * | 2003-03-14 | 2004-01-21 | 北京化工大学 | Borate radical intercalated hydrotalcite and its prepn process and application as fire retardant |
| WO2007058630A1 (en) * | 2005-11-17 | 2007-05-24 | Agency For Science, Technology And Research | Novel bis(amino)-ortho-dicarbaborane cluster compounds |
| CN101664386A (en) * | 2009-09-30 | 2010-03-10 | 北京大北农动物保健科技有限责任公司 | Enrofloxacin double emulsion for livestock and preparation method thereof |
| CN101664386B (en) * | 2009-09-30 | 2011-05-25 | 北京大北农动物保健科技有限责任公司 | Enrofloxacin double emulsion for livestock and preparation method thereof |
| US20120288553A1 (en) * | 2010-03-26 | 2012-11-15 | National Taiwan University | Method for controlling toxicity of metallic particle and low-toxicity composite of metallic nanoparticle and inorganic clay |
| US20130189326A1 (en) * | 2010-03-26 | 2013-07-25 | National Taiwan University | Method for controlling toxicity of metallic particle and low-toxicity composite of metallic nanoparticle and inorganic clay |
| CN103222975A (en) * | 2013-05-03 | 2013-07-31 | 广州英赛特生物技术有限公司 | Application of enrofloxacin salt in preparation of swine oral preparation |
| CN103222975B (en) * | 2013-05-03 | 2014-12-17 | 广州英赛特生物技术有限公司 | Application of enrofloxacin salt in preparation of swine oral preparation |
Non-Patent Citations (2)
| Title |
|---|
| FRANZISKA DUDA，ET AL: ""Highly biocompatible behaviour and slow degradation of a LDH (layered double hydroxide)-coating on implants in the middle ear of rabbits"", 《JOURNAL OF MATERIALS SCIENCE: MATERIALS IN MEDICINE》 * |
| 姬海婷: ""依诺沙星-水滑石纳米复合材料的制备、表征及热稳定性"", 《沈阳药科大学学报》 * |
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