CN106389342B - A kind of hydroxyapatite/tannic acid composite particles preparation method of controllable methylene blue monomer rate of release - Google Patents
A kind of hydroxyapatite/tannic acid composite particles preparation method of controllable methylene blue monomer rate of release Download PDFInfo
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- CN106389342B CN106389342B CN201610833387.8A CN201610833387A CN106389342B CN 106389342 B CN106389342 B CN 106389342B CN 201610833387 A CN201610833387 A CN 201610833387A CN 106389342 B CN106389342 B CN 106389342B
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- methylene blue
- hydroxyapatite
- tannic acid
- aqueous solution
- solution containing
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- RBTBFTRPCNLSDE-UHFFFAOYSA-N 3,7-bis(dimethylamino)phenothiazin-5-ium Chemical compound C1=CC(N(C)C)=CC2=[S+]C3=CC(N(C)C)=CC=C3N=C21 RBTBFTRPCNLSDE-UHFFFAOYSA-N 0.000 title claims abstract description 77
- 229960000907 methylthioninium chloride Drugs 0.000 title claims abstract description 77
- 229910052588 hydroxylapatite Inorganic materials 0.000 title claims abstract description 41
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 title claims abstract description 41
- TUSDEZXZIZRFGC-UHFFFAOYSA-N 1-O-galloyl-3,6-(R)-HHDP-beta-D-glucose Natural products OC1C(O2)COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC1C(O)C2OC(=O)C1=CC(O)=C(O)C(O)=C1 TUSDEZXZIZRFGC-UHFFFAOYSA-N 0.000 title claims abstract description 29
- 239000001263 FEMA 3042 Substances 0.000 title claims abstract description 29
- LRBQNJMCXXYXIU-PPKXGCFTSA-N Penta-digallate-beta-D-glucose Natural products OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@@H]2[C@H]([C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-PPKXGCFTSA-N 0.000 title claims abstract description 29
- LRBQNJMCXXYXIU-NRMVVENXSA-N tannic acid Chemical compound OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@@H]2[C@H]([C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-NRMVVENXSA-N 0.000 title claims abstract description 29
- 229940033123 tannic acid Drugs 0.000 title claims abstract description 29
- 235000015523 tannic acid Nutrition 0.000 title claims abstract description 29
- 229920002258 tannic acid Polymers 0.000 title claims abstract description 29
- 239000011246 composite particle Substances 0.000 title claims abstract description 19
- 239000000178 monomer Substances 0.000 title claims abstract description 16
- 238000002360 preparation method Methods 0.000 title claims abstract description 6
- 239000000243 solution Substances 0.000 claims abstract description 48
- 239000007864 aqueous solution Substances 0.000 claims abstract description 21
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims abstract description 21
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims abstract description 8
- 238000003756 stirring Methods 0.000 claims abstract description 7
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 claims abstract description 6
- 239000000920 calcium hydroxide Substances 0.000 claims abstract description 6
- 229910001861 calcium hydroxide Inorganic materials 0.000 claims abstract description 6
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims abstract description 4
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 claims abstract 4
- 229910021578 Iron(III) chloride Inorganic materials 0.000 claims abstract 4
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 claims abstract 4
- 235000019270 ammonium chloride Nutrition 0.000 claims abstract 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- 239000000725 suspension Substances 0.000 claims description 6
- 238000006243 chemical reaction Methods 0.000 claims description 4
- 239000013049 sediment Substances 0.000 claims description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 2
- 238000005119 centrifugation Methods 0.000 claims 1
- 239000008367 deionised water Substances 0.000 claims 1
- 229910021641 deionized water Inorganic materials 0.000 claims 1
- 239000002245 particle Substances 0.000 abstract description 13
- 238000000034 method Methods 0.000 abstract description 7
- 230000001105 regulatory effect Effects 0.000 abstract description 3
- 238000009776 industrial production Methods 0.000 abstract 1
- 239000000203 mixture Substances 0.000 abstract 1
- 239000002994 raw material Substances 0.000 abstract 1
- 238000000926 separation method Methods 0.000 abstract 1
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 10
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 9
- 239000011574 phosphorus Substances 0.000 description 9
- 229910052698 phosphorus Inorganic materials 0.000 description 9
- 239000008351 acetate buffer Substances 0.000 description 7
- 239000000872 buffer Substances 0.000 description 7
- 239000000084 colloidal system Substances 0.000 description 7
- 238000002835 absorbance Methods 0.000 description 6
- 239000000539 dimer Substances 0.000 description 5
- 150000002500 ions Chemical class 0.000 description 5
- 229910052742 iron Inorganic materials 0.000 description 5
- 241001062009 Indigofera Species 0.000 description 4
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
- 238000002441 X-ray diffraction Methods 0.000 description 3
- 239000004575 stone Substances 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
- 235000019738 Limestone Nutrition 0.000 description 2
- DMGNFLJBACZMRM-UHFFFAOYSA-N O[P] Chemical compound O[P] DMGNFLJBACZMRM-UHFFFAOYSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 230000000996 additive effect Effects 0.000 description 2
- 229910052586 apatite Inorganic materials 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 239000003292 glue Substances 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- FBAFATDZDUQKNH-UHFFFAOYSA-M iron chloride Chemical compound [Cl-].[Fe] FBAFATDZDUQKNH-UHFFFAOYSA-M 0.000 description 2
- 239000006028 limestone Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- MCPLVIGCWWTHFH-UHFFFAOYSA-L methyl blue Chemical compound [Na+].[Na+].C1=CC(S(=O)(=O)[O-])=CC=C1NC1=CC=C(C(=C2C=CC(C=C2)=[NH+]C=2C=CC(=CC=2)S([O-])(=O)=O)C=2C=CC(NC=3C=CC(=CC=3)S([O-])(=O)=O)=CC=2)C=C1 MCPLVIGCWWTHFH-UHFFFAOYSA-L 0.000 description 2
- VSIIXMUUUJUKCM-UHFFFAOYSA-D pentacalcium;fluoride;triphosphate Chemical compound [F-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O VSIIXMUUUJUKCM-UHFFFAOYSA-D 0.000 description 2
- 229920001864 tannin Polymers 0.000 description 2
- 239000001648 tannin Substances 0.000 description 2
- 235000018553 tannin Nutrition 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- RNKMOGIPOMVCHO-SJMVAQJGSA-N 1,3,6-trigalloyl glucose Chemical compound C([C@@H]1[C@H]([C@@H]([C@@H](O)[C@H](OC(=O)C=2C=C(O)C(O)=C(O)C=2)O1)OC(=O)C=1C=C(O)C(O)=C(O)C=1)O)OC(=O)C1=CC(O)=C(O)C(O)=C1 RNKMOGIPOMVCHO-SJMVAQJGSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000011260 aqueous acid Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- XAAHAAMILDNBPS-UHFFFAOYSA-L calcium hydrogenphosphate dihydrate Chemical compound O.O.[Ca+2].OP([O-])([O-])=O XAAHAAMILDNBPS-UHFFFAOYSA-L 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 239000013064 chemical raw material Substances 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000011010 flushing procedure Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000006193 liquid solution Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000001000 micrograph Methods 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 238000006552 photochemical reaction Methods 0.000 description 1
- 230000002215 photochemotherapeutic effect Effects 0.000 description 1
- 230000002468 redox effect Effects 0.000 description 1
- 238000002798 spectrophotometry method Methods 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- ISIJQEHRDSCQIU-UHFFFAOYSA-N tert-butyl 2,7-diazaspiro[4.5]decane-7-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCCC11CNCC1 ISIJQEHRDSCQIU-UHFFFAOYSA-N 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
Classifications
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1611—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
- A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
- A61K31/5415—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with carbocyclic ring systems, e.g. phenothiazine, chlorpromazine, piroxicam
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1617—Organic compounds, e.g. phospholipids, fats
- A61K9/1623—Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules
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- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Inorganic Chemistry (AREA)
- Medicinal Preparation (AREA)
Abstract
本发明提供一种可调控亚甲基蓝单体释放速度的的羟基磷灰石/单宁酸复合颗粒的制备方法，即在含柠檬酸和氢氧化钙的水溶液中逐滴加入磷酸溶液，当pH值降至10时停止滴加，静置后用氯化铵溶液洗涤，再在分离得到的胶体溶液中加入亚甲基蓝后配成含亚甲基蓝的羟基磷灰石胶体溶液；在含单宁酸的溶液中加入含亚甲基蓝的羟基磷灰石胶体溶液，搅拌5分钟后，再加入含氯化铁的水溶液，搅拌反应5分钟后分离、干燥，即得到含亚甲基蓝的羟基磷灰石/单宁酸复合颗粒。本方法工艺简单、原料价格低，易于工业化生产。本方法制备得到的颗粒生物相容性好，易降解。亚甲基蓝主要以单体分子的形式自颗粒内部释放至溶液中，释放行为可方便调控。The invention provides a preparation method of hydroxyapatite/tannic acid composite particles capable of regulating the release rate of methylene blue monomer, namely adding phosphoric acid solution dropwise to an aqueous solution containing citric acid and calcium hydroxide, and when the pH value drops Stop dripping at 10:00, wash with ammonium chloride solution after standing, and then add methylene blue to the colloidal solution obtained by separation to prepare a hydroxyapatite colloidal solution containing methylene blue; The hydroxyapatite colloidal solution of methylene blue is stirred for 5 minutes, then an aqueous solution containing ferric chloride is added, and the mixture is separated and dried after stirring for 5 minutes to obtain the hydroxyapatite/tannic acid composite particles containing methylene blue. The method has the advantages of simple process, low raw material price and easy industrial production. The particles prepared by the method have good biocompatibility and are easy to degrade. Methylene blue is mainly released from the inside of the particles into the solution in the form of monomer molecules, and the release behavior can be easily regulated.
Description
Technical field
The present invention provides a kind of hydroxyapatite/tannic acid composite particles of controllable methylene blue monomer rate of release
Preparation method belongs to technical field of chemical raw material production.
Background technique
Under solution condition, methylene blue molecule is difficult to exist with monomeric form, because having the shape of dimer in solution
Formula exists, and when using higher concentration dosage especially for realization therapeutic effect, monomer is often gathered into dimer molecule,
The performances such as its photochemo-therapeutic effect, redox property and cell membrane span ability are had a significant impact, and then influence methylene
The therapeutic effect of base indigo plant also influences the photochemical reaction efficiency and fluorescence property of methylene blue.In addition, due to methylene blue monomer
The ability being reduced in vivo is very strong, is easily excreted, and circulation time in vivo is short, therefore reaches the methylene of pathological tissues
The negligible amounts of base indigo plant monomer, it is self-contained intracorporal to regulate and control methylene blue that this just needs pharmaceutical carrier to adsorb methylene blue
Release behavior, such as slow release, quick release and pH sensitive release etc..
Researcher (S. Zhang, Z. Chu, C. Yin, C. Zhang, G. Lin, Q. Li, J. Am.
Chem. 2013,135,5709-5716 Soc.) by the way of wrapping up methylene blue molecule in pharmaceutical carrier, it can ensure
The sustained release of methylene blue molecule, there are the times in extension body, but the rate of release of methylene blue in the solution is excessively slow and main
To exist in the form of dimer, need to increase dosage when needing quick release methylene blue, but carrier silicas
It is still necessary to increase substantially for biocompatibility.The calcium phosphate similar with human body hard tissue inorganic constituents, such as hydroxyapatite, phosphorus
The sour biocompatibilities such as eight calcium and calcium phosphate dibasic dihydrate are good, and catabolite is internal friendly ion, but these particles are molten
It is main positively charged in liquid, it is very weak with the suction-operated of methylene blue (in aqueous solution positively charged), easily cause methylene blue to inhale
The too low problem of attached amount because prepare drug granule kimonos with during solution the methylene blue of absorption can be washed easily
Fall.As it can be seen that methylene blue is from carrier inside initial stage quick release, middle and later periods slow release and mainly existing for monomeric form
Correlative study needs to carry out, and the pharmaceutical preparation of quick release methylene blue monomer is in the field for needing to fast implement curative effect of medication after all
There is very urgent demand in conjunction, however up to the present, there is not been reported for correlative study.
Summary of the invention
The object of the present invention is to provide a kind of hydroxyapatite/tannic acid of controllable methylene blue monomer rate of release is multiple
The preparation method of particle is closed, to achieve the above object, steps are as follows for the technical solution adopted in the present invention:
(1) aqueous solution containing citric acid and calcium hydroxide is prepared, is stirred to get the water of phosphoric acid after uniform suspension
Solution is added dropwise, and stops being added dropwise when the pH value of suspension is down to 10, the chlorination for being 4% with mass fraction after standing 18 hours
Aqueous ammonium washing will be added methylene blue, be made after stirring 2 hours in the hydroxyapatite colloid solution being centrifugally separating to obtain
Hydroxyapatite colloid solution containing methylene blue；
(2) in the aqueous solution containing tannic acid, the hydroxyapatite glue containing methylene blue that step (1) is prepared is added
Liquid solution is stirred to react the aqueous solution for adding chloride containing iron after five minutes, is stirred to react 5 minutes；
(3) reaction solution for obtaining step (2) is centrifuged, and with drying 12 is small at 60oC after ethanol washing sediment
When to get arrive the hydroxyapatite containing methylene blue/tannic acid composite particles.
Wherein, the molar ratio of citric acid and calcium hydroxide is 0.07 ~ 0.21:1 in step (1), it is still further preferred that 0.14:1.It will
The aqueous solution of phosphoric acid is added drop-wise in suspension, the stopping when pH value of solution is down to 10, to ensure preparation-obtained glue
Body is hydroxyapatite.Methylene blue is added in step (1), makes 0.5 ~ 2 milligram every milliliter of concentration of methylene blue, it is optimal
It is 0.5 milligram every milliliter.The concentration of methylene blue and citric acid can regulate and control the methylene blue of hydroxyapatite surface absorption
Quantity.
The concentration of tannic acid is 40 milligrams every milliliter in step (2), and additive amount is 0.15~0.45 milliliter, optimum addition
It is 0.30 milliliter.The concentration of iron chloride is 10 milligrams every milliliter in the aqueous solution of chloride containing iron in step (2), additive amount 0.15
~0.45 milliliter, optimum addition is 0.30 milliliter.In step (2), the hydroxyl containing methylene blue that is prepared through step (1)
The volume ratio of base apatite colloidal solution and tannin aqueous acid is 100:3, through step (1) be prepared containing methylene blue
The volume ratio of the aqueous solution of hydroxyapatite colloid solution and chloride containing iron is 100:3.Tannin acid ion and iron in solution from
Son can be in the hydroapatite particles Surface Creation complex compound wrapping layer containing methylene blue, and then is prepared containing methylene blue
Hydroxyapatite/tannic acid composite particles.
The beneficial effects of the present invention are:
(1) this method simple process, cost of material are low and easy to industrialized production；
(2) the preparation-obtained hydroxyapatite containing methylene blue/tannic acid composite particles surface is tannic acid and iron
The complex layer of ion, good biocompatibility is degradable in the body fluid environment, and degradation ion is internal friendly ion；
(3) in the solution of different pH value, such as phosphorus buffer (pH=7.2 ~ 7.4) and acetate buffer solution (pH=3.6) Central Asia
Mainly discharged in the form of monomer molecule inside the hydroxyapatite of the self-contained methylene blue of methyl blue/tannic acid composite particles to
In solution, and initial stage rate of release is fast, middle and later periods rate of release is slow, and the behavior of release is different with pH value variation.
Detailed description of the invention
Fig. 1 is the hydroxyapatite containing methylene blue/tannic acid composite particles X that the embodiment of the present invention 1 is prepared
The standard X-ray diffraction spectrogram (b) for the hydroxyapatite that x ray diffraction spectrogram (a) and JCPDS card number are 09-0432.
Fig. 2 is the hydroxyapatite containing methylene blue/tannic acid composite particles that the embodiment of the present invention 1 is prepared
SEM electron scanning micrograph.
Fig. 3 is the hydroxyl phosphorus containing methylene blue being prepared in different solutions Methylene Blue from the embodiment of the present invention 1
The behavior discharged in lime stone/tannic acid composite particles.(a) in phosphorus buffer；(b) in acetate buffer solution.
Fig. 4 is the hydroxyl phosphorus containing methylene blue being prepared in different solutions Methylene Blue from the embodiment of the present invention 1
In lime stone/tannic acid composite particles after release to solution, methylene blue monomer is in 664 nanometers absorbances (A664) and dimer
Ratio (A664/A610) between the absorbance (A610) of 610 nanometers changes with time situation.(a) in phosphorus buffer
In；(b) in acetate buffer solution.
Fig. 5 is that (1) is preparation-obtained containing methylene the step of different solutions Methylene Blue is from through the embodiment of the present invention 1
The behavior discharged in the hydroapatite particles of base indigo plant.(a) in phosphorus buffer；(b) in acetate buffer solution.
Fig. 6 is that (1) is preparation-obtained containing methylene the step of different solutions Methylene Blue is from through the embodiment of the present invention 1
In the hydroapatite particles of base indigo plant after release to solution, absorbance (A664) and two of the methylene blue monomer in 664 nanometers
Ratio (A664/A610) of the aggressiveness between the absorbance (A610) of 610 nanometers changes with time situation.(a) slow in phosphorus
In fliud flushing；(b) in acetate buffer solution.
Specific embodiment
The present invention is further illustrated with reference to embodiments.
Embodiment 1:
(1) 50 milliliters of aqueous solutions containing citric acid and calcium hydroxide are prepared, making its concentration is respectively 0.095 mole every liter
With 0.675 mole every liter, stir to get uniform suspension, be then 0.436 mole every liter of aqueous solution by phosphorous acid concentration
It is added dropwise, stops being added dropwise when the pH value of suspension is down to 10, the chlorine for being 4% with 50 milliliters of mass fractions after standing 18 hours
Change aqueous ammonium washing, the hydroxyapatite colloid being centrifugally separating to obtain is configured to 100 milliliters of aqueous solutions, 0.05 gram of Asia is added
It is stirred after methyl blue 2 hours and the hydroxyapatite colloid solution containing methylene blue is prepared；
(2) in 0.30 milliliter of the aqueous solution containing 40 milligrams of every milliliter of tannic acid, 10 milliliters is added and is made through step (1)
The standby obtained hydroxyapatite colloid solution containing methylene blue, is stirred to react after five minutes, and 0.30 milliliter of addition contains 10 milligrams
The aqueous solution of every milliliter of iron chloride is stirred to react 5 minutes；
(3) reaction solution for obtaining step (2) is centrifuged, and is washed with deionized twice, then with twice of ethanol washing
The hydroxyapatite containing methylene blue/tannic acid composite particles are obtained after drying 12 hours at 60oC afterwards.
The object phase (see figure 1) of X-ray diffraction method analysis particle.Wherein, the widthization diffraction maximum of hydroxyapatite appears in Fig. 1
In.
The pattern (see figure 2) of SEM scanning electron microscope detection particle.
For control for the sake of, through the step of embodiment 1 (1) prepare the hydroxyapatite colloid solution containing methylene blue pass through from
Gains in depth of comprehension do not clean sediment to sediment, obtain the hydroxy-apatite containing methylene blue after 12 hours dry at 60oC
Stone particle.
Visible spectrophotometry measures the hydroxyl in phosphorus buffer and the self-contained methylene blue of acetate buffer solution Methylene Blue
Discharged inside base apatite/tannic acid composite particles and hydroapatite particles containing methylene blue behavior (see respectively Fig. 3 and
Fig. 5), and the methylene blue monomer that is released 664 nanometers absorbance (A664) and dimer in 610 nanometers
Ratio (A664/A610) between absorbance (A610) changes with time situation (seeing Fig. 4 and Fig. 6 respectively).
It finds after tested, content of the methylene blue in the hydroxyapatite containing methylene blue/tannic acid composite particles is
5.51 milligrams every gram.In the solution of different pH value, compound of hydroxyapatite/tannic acid of the self-contained methylene blue of methylene blue
PH sensitive of the behavior to solution of intragranular portion release, initial stage quick release, to middle and later periods slow release, can conveniently regulating and controlling (see
Fig. 3 (a) and (b)).
Particularly, in phosphorus buffer, the hydroxy-apatite containing methylene blue that methylene blue is prepared from embodiment 1
A664/A610 value in stone/tannic acid composite particles when release will be much higher than in the hydroapatite particles of self-contained methylene blue
A664/A610 value when release (see Fig. 4 and Fig. 6).In acetate buffer solution, methylene blue contains from what embodiment 1 was prepared
A664/A610 value in the hydroxyapatite of methylene blue/tannic acid composite particles when release is higher than to be released in phosphorus buffer
The A664/A610 value for the methylene blue put (see Fig. 4 (a) and (b)).As it can be seen that the hydroxy-apatite of the self-contained methylene blue of methylene blue
It is mainly discharged in the form of monomer into solution in stone/tannin granulates.
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| CN107261381B (en) * | 2017-06-14 | 2020-08-11 | 山东理工大学 | Method for degrading methylene blue wrapped in particles by using titanium dioxide under sunlight |
| CN107158638B (en) * | 2017-06-20 | 2019-10-11 | 山东理工大学 | A method of using titanium dioxide to degrade methylene blue adsorbed in particles under sunlight |
| CN113755132B (en) * | 2021-09-17 | 2023-06-02 | 山东理工大学 | Preparation method of hydroxyapatite/carbon composite particles absorbing mid-infrared light intensity |
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