CN107029249A - Carry the carboxymethyl beta cyclodextrin functionalization montmorillonite medicine-releasing system of jamaicin - Google Patents
Carry the carboxymethyl beta cyclodextrin functionalization montmorillonite medicine-releasing system of jamaicin Download PDFInfo
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- CN107029249A CN107029249A CN201710298972.7A CN201710298972A CN107029249A CN 107029249 A CN107029249 A CN 107029249A CN 201710298972 A CN201710298972 A CN 201710298972A CN 107029249 A CN107029249 A CN 107029249A
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4375—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
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- 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
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/40—Cyclodextrins; Derivatives thereof
Abstract
The present invention provides a kind of carboxymethyl beta cyclodextrin functionalization montmorillonite Supramolecular Network material, and the infrared spectrum that the material is produced is in 3421cm‑1,2934cm‑1,1637cm‑1,1414cm‑1,1159cm‑1,1087cm‑1,1039cm‑1,745cm‑1,613cm‑1,587cm‑1Left and right shows absworption peak.The medicine-releasing system prepared using CMCD APTES MMT Supramolecular Networks of the present invention as the carrier of Berberine hydrochloride, Berberine hydrochloride dispersiveness and dissolubility in water substantially increase, effectively increase the bioavilability of Berberine hydrochloride, relative to drug-loading system of the montmorillonite as carrier, drugloading rate is significantly improved, local delivery of drug amount is greatly improved, with stronger antibacterial effect.The present invention makes the medicine-releasing system that CMCD APTES MMT Supramolecular Networks are prepared as the carrier of Berberine hydrochloride, there is very strong capture ability to bacterium, CMCD APTES MMT Supramolecular Networks can be also wrapped up microorganism simultaneously, to strengthen being loaded into contact of the Berberine hydrochloride therein with bacterium, so as to lift the anti-microbial property of Berberine hydrochloride.
Description
Technical field
The present invention relates to active components of plants jamaicin, and in particular to the carboxymethyl-β-cyclodextrin functionalization for carrying jamaicin is covered
De- stone medicine-releasing system.
Background technology
The infection that bacterium is caused is to endanger one of key factor of human health.In the world, caused because sick within less than 5 years old
In dead children, it is that diarrhoea is lethal as caused by bacterium infection just to have 15%, follows closely and fatal rate the is in after pneumonia (18%)
Two.Since a nearly century, antibiotic medicine has been widely used in the prevention and treatment of clinical bacteria infection, but makes
The side effects such as diarrhoea, inflammation occur with the patient that in the bacterial infection patients of antibiotic therapy, there are about 5-25%.Except this it
Outside, abuse of antibiotics causes bacterial resistance problem to become increasingly serious, while also resulting in being greatly reduced for antibiotic curative effect.It is existing
Antibacterials can not fully meet the demand of clinical practice, therefore the new antibacterials of exploitation turn into trend of the times.
Under this overall background, the natural antibacterial compound of exploitation plant origin becomes the big plan for solving Problems Existing
Slightly.Obtained active components of plants is extracted from the Chinese herbal medicines such as the coptis, thorn bark of a cork tree, goldenseal, Echinacea, golden cypress, arcangelisia lourieiri small
Bark of a cork tree alkali, with stronger antibacterial activity, enjoys medicine scholar to pay close attention in recent years.Jamaicin belongs to isoquinoline alkaloid, in water
Middle indissoluble, while it is multidrug resistance pump (MDRs) substrate, therefore is easily discharged by MDRs, so that being difficult to enter thin
Born of the same parents, so directly being sterilized with jamaicin, bioavilability is relatively low.Jamaicin structural formula is as follows：
Montmorillonite (MMT), is the silicate with layer structure, and chemical formula is [(Na, Ca)0.33(Al,Mg)2(Si4O10)
(OH)2·nH2O], it is made up of an octahedra structure and two tetrahedron lamellas.Montmorillonite has larger surface area, more by force
Adsorption capacity, higher cation exchange capacity and bigger sheaf space are to accommodate organic drug molecule.Through looking into, at present not
There is montmorillonite to load the antibacterial research report of jamaicin.During research loaded Montmorillonite jamaicin medicine-releasing system, invention human hair
The easy aggregate and precipitate of hectorite microparticle in existing drug-loading system, so as to influence the release and absorption of active component jamaicin.
The content of the invention
In order to solve the problems of the prior art, according to the first aspect of the invention, it is an object of the invention to provide one
Plant carboxymethyl-β-cyclodextrin functionalization montmorillonite (CMCD-APTES-MMT) Supramolecular Network material.
Unless otherwise specified, number of the present invention is parts by weight, and the percentage is mass percent.
The object of the present invention is achieved like this：
A kind of carboxymethyl-β-cyclodextrin functionalization montmorillonite Supramolecular Network material, it is characterised in that：The infrared light of generation
Spectrum is in 3421cm-1,2934cm-1,1637cm-1,1414cm-1,1159cm-1,1087cm-1,1039cm-1,745cm-1,613cm-1,
587cm-1Left and right shows absworption peak.
Above-mentioned carboxymethyl-β-cyclodextrin functionalization montmorillonite Supramolecular Network material, it is characterised in that：In the θ of angle of diffraction 2
To have diffraction maximum at 5.39 ± 0.2 °, 8.72 ± 0.2 °.
Above-mentioned carboxymethyl-β-cyclodextrin functionalization montmorillonite Supramolecular Network material, it is characterised in that：In thermogravimetric analysis
Cheng Zhong, 90 ± 2 DEG C of sons that dry out, is thermally decomposed at 411 ± 2 DEG C.
According to the second aspect of the invention, cover de- it is an object of the invention to provide above-mentioned carboxymethyl-β-cyclodextrin functionalization
The preparation method of stone Supramolecular Network material.
The preparation method of carboxymethyl-β-cyclodextrin functionalization montmorillonite Supramolecular Network material of the present invention, it is characterised in that：
Using beta-schardinger dextrin, (such as sodium hydroxide) synthesizes carboxymethyl cyclodextrin with chloroacetic acid reaction in the basic conditions；Montmorillonite is entered
Row silanization, obtains the montmorillonite of three aminopropyl triethoxysilane silanizations；Pass through 1- (3- dimethylaminos at ambient temperature
Propyl group) -3- ethyl-carbodiimide hydrochlorides and n-hydroxysuccinimide catalysis, make carboxymethyl cyclodextrin and the second of three aminopropyl three
The montmorillonite reaction of TMOS silanization, obtains the montmorillonite material of carboxymethyl cyclodextrin functionalization.
Supermolecule refers to the class complexity being combined together by two or more molecule by intermolecular interaction
, organized aggregation, they show that clear and definite microstructures simultaneously keep its integrality, and with unique physicochemical characteristicses.
Intermolecular force generally includes hydrogen bond, coordinate bond, electrostatic interaction, hydrophobic bond etc..Present invention synthesis CMCD-APTES-MMT makees
For self assembly unit.The formation of CMCD-APTES-MMT supramolecular network self-assemblies, depends on two kinds of intermolecular hydrogen bondings：
A kind of is the oxygen atom and another module units cyclodextrin in a molecule module units in the silicon-oxy tetrahedron of montmorillonite surface
The hydrogen bond formed between hydroxyl；It is another be ketonic oxygen in a molecule module units with amido link in another module units
The hydrogen bond of hydrogen formation.The synergy of two kinds of hydrogen bonds promotes CMCD-APTES-MMT to be self-assembly of supramolecular network knot
Structure, and in this, as the novel carriers material for loading medicine.Compared with montmorillonite or cyclodextrin, the material is host more than one
The characteristic of system, montmorillonite and cyclodextrin haves both at the same time, therefore the advantage with hybrid inorganic-organic materials.
According to the third aspect of the invention we, it is an object of the invention to provide a kind of carboxymethyl-β-cyclodextrin for carrying jamaicin
The preparation method of functionalization montmorillonite medicine-releasing system, this method uses above-mentioned carboxymethyl-β-cyclodextrin functionalization montmorillonite supermolecule
Network material loads medicine-releasing system prepared by jamaicin, to the inhibitory action of gram-negative bacteria and gram positive bacteria far above free
Medicine.
The present invention carries the preparation method of the carboxymethyl-β-cyclodextrin functionalization montmorillonite medicine-releasing system of jamaicin, and its feature exists
In using following steps：
Berberine hydrochloride ultra-pure water is dissolved to the barberry aqueous alkali for obtaining concentration for the μ g/mL of 50 μ g/mL~350, pressed
It is 5~35 according to jamaicin and carboxymethyl-β-cyclodextrin functionalization montmorillonite Supramolecular Network quality of materials ratio：100 add carboxymethyl
Beta-schardinger dextrin functionalization montmorillonite Supramolecular Network material, is 30-80 DEG C, under conditions of pH is 2-11 in temperature, reacts 0.5-6
Hour, by the centrifugation of obtained suspension, filtering with microporous membrane, supernatant is collected, with ultraviolet specrophotometer at 345nm wavelength
Determine the content for the free hydrochloric acid jamaicin not being loaded；Then drugloading rate is calculated as follows
It is preferred that, the concentration of above-mentioned barberry aqueous alkali is the μ g/mL of 250 μ g/mL~350.
It is preferred that, the above-mentioned reaction time is 3-6 hours.
It is preferred that, above-mentioned reaction pH is 9-11.
It is preferred that, above-mentioned reaction temperature is 50-80 DEG C.
The present invention carries the preparation method of the carboxymethyl-β-cyclodextrin functionalization montmorillonite medicine-releasing system of jamaicin, and its feature exists
In using following steps：
(1), the preparation of carboxymethyl-β-cyclodextrin functionalization montmorillonite Supramolecular Network material；
Using beta-schardinger dextrin, (such as sodium hydroxide) synthesizes carboxymethyl cyclodextrin with chloroacetic acid reaction in the basic conditions；It is right
Montmorillonite carries out silanization, obtains the montmorillonite of three aminopropyl triethoxysilane silanizations；Pass through 1- (3- at ambient temperature
Dimethylamino-propyl) -3- ethyl-carbodiimide hydrochlorides and n-hydroxysuccinimide catalysis, make carboxymethyl cyclodextrin and three ammonia
The montmorillonite reaction of propyl-triethoxysilicane silanization, obtains the montmorillonite material of carboxymethyl cyclodextrin functionalization；
(2) preparation of the carboxymethyl-β-cyclodextrin functionalization montmorillonite medicine-releasing system of jamaicin, is carried
Berberine hydrochloride ultra-pure water is dissolved to the barberry aqueous alkali for obtaining concentration for the μ g/mL of 250 μ g/mL~350, pressed
It is 25~35 according to jamaicin and carboxymethyl-β-cyclodextrin functionalization montmorillonite Supramolecular Network quality of materials ratio：100 add carboxylic first
Base beta-schardinger dextrin functionalization montmorillonite Supramolecular Network material, is 50-80 DEG C, under conditions of pH is 9-11 in temperature, reacts 3-6
Hour, by the centrifugation of obtained suspension, with 0.45 μm of filtering with microporous membrane, collect supernatant, with ultraviolet specrophotometer in
The content for the free hydrochloric acid jamaicin not being loaded is determined at 345nm wavelength；Then drugloading rate is calculated as follows
Beneficial effect：
The present invention provides a kind of carboxymethyl-β-cyclodextrin functionalization montmorillonite (CMCD-APTES-MMT) Supramolecular Network material
Material, the infrared spectrum that the material is produced is in 3421cm-1,2934cm-1,1637cm-1,1414cm-1,1159cm-1,1087cm-1,
1039cm-1,745cm-1,613cm-1,587cm-1Left and right shows absworption peak；Compare montmorillonite (MMT) and silanization montmorillonite
(APTES-MMT), CMCD-APTES-MMT of the present invention is in 2934cm-1Nearby occur in that new absworption peak, the peak be belong to-
CH2Stretching vibration peak, this explanation APTES successfully graft in MMT.Thermal gravimetric analysis curve shows, CMCD-APTES- of the present invention
There is twice substantially weightlessness at 90 DEG C and 411 DEG C respectively in MMT Supramolecular Networks material, and the weightlessness occurred at 90 DEG C is due to remaining
The evaporation of moisture on material, and weightlessness at 411 DEG C is then the thermal decomposition of the APTES and CMCD groups by grafting thereon
It is caused.Powder diffraction shows that new diffraction occurs at 2 θ=8.67 ° in CMCD-APTES-MMT Supramolecular Networks material of the present invention
Peak, and the diffraction maximum at 27.57 °, 28.43 ° (2 θ) places disappears, and illustrates to compare MMT and APTES-MMT, CMCD-APTES- of the present invention
The crystal structure of MMT Supramolecular Network materials is changed；Also, MMT d0012 θ=6.97 ° of characteristic peak, d=
1.26nm, APTES-MMT d001θ=6.11 ° of peak 2, d=1.47nm, and CMCD-APTES-MMT d001θ=5.39 ° of peak 2, d
=1.64nm, d001Peak move to left and sheaf space expansion, all illustrate that CMCD groups not only graft in MMT surface, also simultaneously layer
Insert in MMT interlayer.The scanned Electronic Speculum of CMCD-APTES-MMT Supramolecular Networks material of the present invention shows that material presents irregular
It is network-like, network density is incremented by with material concentration, when material concentration reaches 1.2mg/mL, at the beginning of the loose network of individual layer is presented
Beginning form；When material concentration reaches 1.8mg/mL, fine and close network structure is formed, and its average pore size is less than 1 μm.
The weak main cause of free hydrochloric acid jamaicin antibacterial activity is its poorly water-soluble and multidrug resistance pump to it
Outer row effect, make its be difficult to enter bacterial cell in play antibacterial action.The present invention uses CMCD-APTES-MMT supermolecules
The medicine-releasing system that network is prepared as the carrier of Berberine hydrochloride, Berberine hydrochloride dispersiveness and dissolubility in water substantially increase
Plus, effectively increase the bioavilability of Berberine hydrochloride；Relative to drug-loading system of the montmorillonite as carrier, drugloading rate is obvious
Improve, local delivery of drug amount is greatly improved, with stronger antibacterial effect.The present invention makees CMCD-APTES-MMT Supramolecular Networks
The medicine-releasing system prepared for the carrier of Berberine hydrochloride, has very strong capture ability to bacterium, while CMCD-APTES-MMT
Supramolecular Network can be also wrapped up microorganism, to strengthen being loaded into contact of the Berberine hydrochloride therein with bacterium, from
And lift the anti-microbial property of Berberine hydrochloride.Extracorporeal bacteria inhibitor test result shows that the present invention uses CMCD-APTES-MMT oversubscription
The medicine-releasing system that sub-network is prepared as the carrier of Berberine hydrochloride is to Escherichia coli (Gram-negative bacteria) and golden yellow grape
The inhibitory action of coccus (gram-positive bacteria) be far above free drug jamaicin, and bacteriostasis property present concentration dependent and
Long-term effect, the present invention uses the drug release system that CMCD-APTES-MMT Supramolecular Networks material is prepared as the carrier of Berberine hydrochloride
Unite and 98.45% and 97.81% are respectively reached to the inhibiting rate of Escherichia coli and staphylococcus aureus.
Brief description of the drawings
Fig. 1 is CMCD-APTES-MMT Supramolecular Network material infrared analysis collection of illustrative plates figures prepared by embodiment 1；
Fig. 2 is CMCD-APTES-MMT Supramolecular Network material thermogravimetric analysis figures prepared by embodiment 1；
Fig. 3 is CMCD-APTES-MMT Supramolecular Network material X-ray powder diffraction patterns prepared by embodiment 1；
Fig. 4 is CMCD-APTES-MMT Supramolecular Network material Flied emission scanning electron microscope (SEM) photographs prepared by embodiment 1, wherein A
For the CMCD-APTES-MMT Supramolecular Network materials of the sparse form of low concentration, B is the partial enlargement of A figures, and C is that high concentration is fine and close
CMCD-APTES-MMT Supramolecular Network the materials of form, D is the partial enlargement of C figures；
Fig. 5 is influence figure of the reaction time to CMCD-APTES-MMT Supramolecular Network material drug carrier rates in embodiment 3；
Fig. 6 is influence of the BBH initial concentrations to CMCD-APTES-MMT Supramolecular Network material drug carrier rates in embodiment 3
Figure；
Fig. 7 is influence figure of the temperature to CMCD-APTES-MMT Supramolecular Network material drug carrier rates in embodiment 3；
Fig. 8 is influence figures of the pH to CMCD-APTES-MMT Supramolecular Network material drug carrier rates in embodiment 3；
Fig. 9 is the releasing curve diagram of Berberine hydrochloride under simulation physiological condition (7.4,37 DEG C of pH) in embodiment 3；
Figure 10 is swelling behavior figure of the embodiment 3CMCD-APTES-MMT Supramolecular Network materials in water-soluble medium,
Wherein a is the 1st day, and b is the 3rd day, and c is the 5th day；
Figure 11 is the field emission scanning electron microscope figure of embodiment 4, wherein (a) S. aureus L-forms opportunistic pathogen, (b) Escherichia coli opportunistic pathogen, (c) is carried
Medicine CMCD-APTES-MMT Supramolecular Networks material is contacted 12 hours with S. aureus L-forms, and (d) carries medicine CMCD-APTES-MMT supermolecules
Network material is contacted 12 hours (e) with Escherichia coli, is carried medicine CMCD-APTES-MMT Supramolecular Network materials and is contacted with S. aureus L-forms
24 hours, (f) carried medicine
CMCD-APTES-MMT Supramolecular Networks material is contacted 24 hours with Escherichia coli.
Embodiment
The present invention is specifically described below by specific embodiment, it is pointed out here that following examples are served only for this hair
It is bright to be further described, it is impossible to be interpreted as limiting the scope of the invention, the person skilled in the art of this area can root
Some nonessential modifications and adaptations are made to the present invention according to foregoing invention content.
Raw material and reagent
All raw materials and reagent of the invention are commercially available prod.Wherein Berberine hydrochloride standard items (Aladdin reagent)；Sodium
Base montmorillonite (Zhejiang Fenghong New Material Co., Ltd., model CEC 80mmol/100g)；Beta-schardinger dextrin (Chinese medicines group
Chemical reagent Co., Ltd)；Three aminopropyl triethoxysilanes (Sigma)；EDC (the limited public affairs of Shanghai Mike's woods biochemical technology
Department)；Monochloroacetic acid (Shanghai Mike's woods biochemical technology Co., Ltd)；N-Hydroxysuccinimide (on
Hai Maikelin biochemical technologies Co., Ltd)；Cetyl ammonium bromide (Sigma)；Escherichia coli freeze bacterium powder, and (Su Zhoubei, which receives, creates connection
Bioisystech Co., Ltd, numbering CMCC (B) 44102)；Staphylococcus aureus freezes bacterium powder, and (Su Zhoubei, which receives, creates the biological skill of connection
Art Co., Ltd, numbering CMCC (B) 26003)；LB broth bouillons (Qingdao Rishui Biotechnology Co., Ltd.)；LB agar is trained
Support base (Qingdao Rishui Biotechnology Co., Ltd.).
The preparation of the carboxymethyl-β-cyclodextrin functionalization montmorillonite material of embodiment 1
The preparation of carboxymethyl cyclodextrin (CMCD)
9.3g sodium hydroxides are weighed in round-bottomed flask, addition 37mL deionized waters, which are placed in ice-water bath, to be stirred to completely molten
Solution.Add 10g beta-schardinger dextrin stirring and dissolvings.The 27mL 16.3% chloroacetic acid aqueous solution is prepared, it is standby.By above-mentioned round bottom
Flask is placed in 60 DEG C of thermostat water bath, and the chloroacetic acid aqueous solution (being added in 20 minutes), question response 5 hours is slowly added dropwise
Afterwards, reaction solution is poured into large beaker, is added dropwise to concentrated hydrochloric acid to ph test paper after cooling while stirring and is detected as neutrality.Add
A large amount of absolute methanols are in beaker, quick stirring, it is seen that white precipitate is separated out.Suction filtration, collects white precipitate in beaker, adds
A small amount of deionized water (about 5mL) makes precipitation be dissolved completely in water, is added with into absolute methanol (about 800mL), makes white heavy
Shallow lake is separated out again, and suction filtration is washed 5 times with methanol, collects white precipitate, this white precipitate is carboxymethyl cyclodextrin.
The preparation of silanization montmorillonite (APTES-MMT)
Prepare 200mL ethanol-water solution (volume ratios：75/25) in round-bottomed flask, 2.5g montmorillonites is weighed, are scattered in
In 200mL ethanol-water solutions, magnetic agitation 30 minutes is to being uniformly dispersed.It is eventually adding the aminopropyl triethoxysilanes of 2.1mL tri-
(APTES), heating water bath is to 80 DEG C, back flow reaction 8 hours.After reaction terminates, room temperature is cooled to, is filtered, mixes molten with water alcohol
Liquid washing and filtering 5 times, removes the complete APTES of unreacted, and (ninhydrin can be with primary amine groups untill the detection of filtrate ninhydrin does not develop the color
The aobvious pink colour of reaction).
The preparation of CMCD-APTES-MMT Supramolecular Network materials
0.7g APTES-MMT are weighed to be scattered in 10mL pH5.8 PBS (phosphate buffer), it is standby.Weigh 1.193g
CMCD and 0.115g NHS (n-hydroxysuccinimide) are in 40mL PBS (pH=5.8), and magnetic agitation 30 minutes is added
0.192g EDC (1- (3- dimethylamino-propyls) -3- ethyl-carbodiimide hydrochlorides) activated carboxyl, activation continues 30 minutes.It is living
After change is finished, 10mL APTES-MMT suspensions are then added.At room temperature, magnetic agitation 24 hours.After having reacted, deionization is used
Water washing, suction filtration, collect product, are placed in vacuum drying chamber 50 DEG C and are dried overnight, produce.
Infrared spectrum analysis
Appropriate MMT, CMCD, APTES-MMT, CMCD-APTES-MMT sample and spectroscopic pure KBr are taken, 80 DEG C of baking ovens are placed in
Middle drying 24 hours, it is standby.Testing sample is prepared using sufficient KBr tablettings are dried, in wave number 4000-400cm-1In the range of enter
Row infrared scan.Infrared spectrum is as shown in figure 1, CMCD-APTES-MMT Supramolecular Networks material of the present invention, the infrared light of generation
Spectrum is in 3421cm-1,2934cm-1,1637cm-1,1414cm-1,1159cm-1,1087cm-1,1039cm-1,745cm-1,613cm-1,
587cm-1Left and right shows absworption peak.MMT, APTES-MMT and CMCD-APTES-MMT are compared in 2934cm-1Nearby occur
New absworption peak, the peak is to belong to-CH2Stretching vibration peak, this explanation APTES successfully graft in MMT.Meanwhile, the present invention
CMCD-APTES-MMT is 587,613,745cm–1Place occurs in that the vibration absorption peak of typical beta-schardinger dextrin ring structure, Yi Ji
1159cm–1There is C-O-C stretching vibrations and O-H flexural vibrations peaks；1039 and 1037cm–1Absworption peak be to be stretched by C-O, C-C
Caused by contracting vibration and O-H flexural vibrations；1414cm–1Absworption peak be C-H and O-H flexural vibrations peak；3421cm-1Come
From in the stretching vibration peak of-OH on MMT surfaces and cyclodextrin；And 1637cm–1Amido link stretching vibration peak then confirm
The generation of condensation reaction between CMCD and APTES-MMT, CMCD is successfully grafted on APTE-MMT by amido link.
Thermogravimetric analysis
Weigh about 8mg MMT, CMCD, APTES-MMT, CMCD-APTES-MMT samples respectively, under ar gas environment, with
15 DEG C/min the rate of heat addition, 800 DEG C are warming up to by 30 DEG C.Thermal gravimetric analysis curve as shown in Fig. 2 in the range of 30-800 DEG C,
MMT occurs substantially weightless twice, is the weightlessness 4.5% at 89 DEG C for the first time, during this part of weight loss is due to sample
The evaporation of residual moisture.Second in 622 DEG C of weightlessness 3.4%.It is due to then the dissociation of MMT in itself.And APTES-MMT then distinguishes
111,494 DEG C of weightlessness substantially, 111 DEG C of weightlessness is equally the evaporation because residual moisture, and 494 DEG C weightless is then derived from
The decomposition of APTES group of the grafting on MMT, weightless ratio is about 6.3%.CMCD-APTES-MMT Supramolecular Networks of the present invention
The TGA curves of material show that it substantially weightlessness occurs twice at 90 DEG C and 411 DEG C respectively, and the weightlessness occurred at 90 DEG C is due to
The evaporation of the moisture remained on material, and weightlessness at 411 DEG C is then the heat of the APTES and CMCD groups by grafting thereon
Caused by decomposing；It is up to 16.6% mass loss at 128-411 DEG C.From data above it can be calculated that CMCD-APTES-
The quality accounting of CMCD groups is about 6.9% in MMT.
X-ray powder diffraction is analyzed
Using Cu KαRadiationPower 40kV × 200mA, respectively determine MMT, APTES-MMT and
The crystal structure of CMCD-APTES-MMT samples.As shown in figure 3, comparing the diffracting spectrum of three samples, CMCD-APTES-MMT
Occur new diffraction maximum at 2 θ=8.67 °, and the diffraction maximum at 27.57 °, 28.43 ° (2 θ) places disappears, and illustrates CMCD-APTES-
MMT crystal structure is changed compared to MMT and APTES-MMT.Also, MMT d0012 θ=6.97 ° of characteristic peak, d=
1.26nm, APTES-MMT d001θ=6.11 ° of peak 2, d=1.47nm, and CMCD-APTES-MMT d001θ=5.39 ° of peak 2, d
=1.64nm, d001Peak move to left and sheaf space expansion, all illustrate that CMCD groups not only graft in MMT surface, also simultaneously layer
Insert in MMT interlayer.
Field emission scanning electron microscope is analyzed
18mg CMCD-APTES-MMT are weighed in round-bottomed flask, 10mL deionized waters are added, magnetic agitation is obtained for 30 minutes
To homogeneous CMCD-APTES-MMT suspensions.A drop suspension sample is taken with dropper, is placed on monocrystalline silicon piece, good seal rear chamber
Temperature is dried 24 hours, and metal spraying is carried out to sample after drying, standby observation.Field emission scanning electron microscope is analyzed as shown in figure 4, A is low
The loosely organized network material of concentration (1.2mg/mL) CMCD-APTES-MMT formation, can from the partial enlargement (figure B) of A figures
Go out, before fine and close Supramolecular Network is formed, self-assembly has just initially formed the initial form of network, with CMCD-APTES-
MMT concentration improves (1.8mg/mL), and CMCD-APTES-MMT Supramolecular Networks are ultimately formed (figure C, D).Scanned according to Flied emission
Electron microscopic observation learns that CMCD-APTES-MMT supramolecular materials of the present invention are presented irregular network-like, and network density is with material
Increasing concen-trations, when material concentration reaches 1.2mg/mL, are presented the loose network initial configuration of individual layer；When material concentration reaches
Fine and close network structure is formed during 1.8mg/mL, and its average pore size is less than 1 μm.
The foundation of the Berberine hydrochloride ultraviolet spectrophotometry content assaying method of embodiment 2
The determination of Berberine hydrochloride (BBH) UV absorption wavelength
Precision weighs 105 DEG C of dryings to the Berberine hydrochloride standard items 18mg of constant weight, after being completely dissolved with ultra-pure water, constant volume
In 25mL volumetric flasks, Berberine hydrochloride storing solution is obtained.It is fixed in 25mL volumetric flasks that precision draws 1mL Berberine hydrochlorides storing solution
Hold, the Berberine hydrochloride solution that final obtained concentration is 29 μ g/mL.With ultraviolet-visible spectrophotometer in 200-600nm scopes
Interior sweep measuring absorbance.As a result show, Berberine hydrochloride has absorption maximum at 228,263, tri- wavelength of 345nm, is
Impurity interference that may be present near the low wavelength of 200nm is avoided, therefore 345nm is used as Detection wavelength at selection upper wavelength.
The drafting of standard curve
7mg BBH standard items are weighed, adds after appropriate ultra-pure water, heating for dissolving, is placed in 100mL volumetric flasks, ultra-pure water
Constant volume.The BBH storing solutions that concentration is 70 μ g/mL are made.The accurate BBH for measuring 1,1.5,2,2.5,3,3.5,4mL is laid in respectively
Liquid uses ultra-pure water constant volume in 25mL volumetric flasks,.Using ultra-pure water as blank control, using ultraviolet spectrophotometry in 345nm
Absorbance is determined at wavelength.As shown in Table 1, Berberine hydrochloride is in 2.8-11.2 μ g/mL concentration ranges, and concentration is in absorbance
Good linear relation, regression equation：A=0.0599C-0.0078, r=0.9995.
The Berberine hydrochloride standard curve determination result (n=7) of table 1
Precision test
Precision draws Berberine hydrochloride standard items storing solution, and the hydrochloric acid for being each configured to 3,7,11 tri- kinds of concentration of μ g/mL is small
Bark of a cork tree aqueous slkali.Three parts of samples are spaced same time period 5 absorbances of replication in 1 day, examine or check withinday precision；Three parts
Sample surveys an absorbance daily, and METHOD FOR CONTINUOUS DETERMINATION 5 days examines or check day to day precision.As shown in Table 2, concentration standard in high, normal, basic three
The in a few days and in the daytime RSD values of product solution are respectively less than 1%, illustrates that instrument precision well, can meet ultraviolet determination requirement.
The Precision test result of table 2 (n=5)
Embodiment 3CMCD-APTES-MMT Supramolecular Network material drug carriers performance check study is tested
CMCD-APTES-MMT carrying drug ratio is calculated according to following equation：
Carry influence of the medicine time to carrying drug ratio
50mg Berberine hydrochlorides are weighed in round-bottomed flask, 100mL ultra-pure waters is added and dissolves by heating, weigh 100mg
In the dispersed said medicine solution of CMCD-APTES-MMT, lasting stirring, and in seclected time point：0.5、1、2、3、4、5、6
It is hour accurate to draw suspension, centrifuged 5 minutes in 12,000rpm, collect supernatant, and with 0.45 μm of filtering with microporous membrane supernatant
Liquid removes suspended particles.Containing for the Berberine hydrochloride that dissociates in supernatant is determined at 345nm wavelength using ultraviolet spectrophotometry
Amount.All samples are triplicate, parallel test.As shown in Figure 5, it is 3.01% to carry 0.5 hour carrying drug ratio of medicine；Medicine is carried to carry within 1 hour
Medicine rate is 5.67%；It is 12.11% to carry 2 hours carrying drug ratios of medicine；It is 15.02% to carry 3 hours carrying drug ratios of medicine；Carry medicine and carry medicine in 4 hours
Rate is 15.56%；It is 17.23% to carry 5 hours carrying drug ratios of medicine.When CMCD-APTES-MMT carrying drug ratio is with medicine is carried in 5 hours
Between increase and improve, therefore the present invention is used as the optimal load medicine time to carry out follow-up test for selected 5 hours.
Influence of the initial drug concentrations to carrying drug ratio
Weigh 5 respectively, 10,15,20,25,30,35mg Berberine hydrochlorides are in round-bottomed flask, then be separately added into 100mL and surpass
Pure water is dissolved by heating.100mg CMCD-APTES-MMT are weighed to be separately added into the Berberine hydrochloride solution of above-mentioned 7 concentration, in
Room temperature is persistently stirred 5 hours.After reaction terminates, ibid method collects supernatant, and determines the Berberine hydrochloride that dissociates in supernatant
Content.It will be appreciated from fig. 6 that when the initial concentration of Berberine hydrochloride is 50 μ g/mL, CMCD-APTES-MMT carrying drug ratio is
5.69%；When initial concentration is 100 μ g/mL, carrying drug ratio is 7.33%；When initial concentration is 150 μ g/mL, carrying drug ratio is
10.68%；When initial concentration is 200 μ g/mL, carrying drug ratio is 13.23%；When initial concentration is 250 μ g/mL, carrying drug ratio is
16.41%；When initial concentration is 300 μ g/mL, carrying drug ratio is 18.73%.It can be seen that with the increase of initial concentration, CMCD-
APTES-MMT carrying drug ratio is also accordingly improved, and when initial concentration increases to 350 μ g/mL, carrying drug ratio is reduced to 18.10%, because
This selected μ g/mL of initial concentration 300 carries out follow-up test.
Influence of the temperature to carrying drug ratio
Weigh 30mg Berberine hydrochlorides to dissolve by heating in 100mL ultra-pure waters, add 100mg CMCD-APTES-MMT, point
Persistently stirred 5 hours not in 30, under the conditions of 40,50,60,70,80 DEG C, ibid method determines free BBH contents.As shown in Figure 7,
CMCD-APTES-MMT carrying drug ratio is improved as temperature increases, and 27.8% is reached during to 50 DEG C, continues to raise after this
Temperature, carrying drug ratio improves unobvious.Therefore from the aspect of energy-conservation, 50 DEG C of selection is used as optimal load medicine temperature.
Influences of the pH to carrying drug ratio
Weigh appropriate 0.1M KH2PO4It is dissolved in ultra-pure water, is separately added into different amounts of 0.1M HCL and 0.1M NaOH,
PH is adjusted using pH meter, pH2-11 series of buffer is made.30mg BBH heating for dissolving is separately added into, then is separately added into 100mg
CMCD-APTES-MMT, after 50 DEG C are persistently stirred 5 hours, determines free drug content, according to formula with ultraviolet specrophotometer
Calculate the carrying drug ratio of CMCD-APTES-MMT under condition of different pH.As shown in Figure 8, with the rise of pH value, carrying drug ratio is also presented
Ascendant trend, in pH=10, carrying drug ratio reaches maximum 27.8%.CMCD-APTES-MMT Supramolecular Network materials are released in vitro
Degree of putting is examined or check
Weigh 200mg and carry medicine CMCD-APTES-MMT (molecular cut off 8,000-12,000Da) in bag filter), add
Sack is tamping after 2mL of PBS (0.1M, pH 7.4).Bag filter is placed in the cone equipped with 100mL PBS (0.1M, pH 7.4)
In shape bottle, persistently shaken with 150rpm in the constant temperature oscillation case that conical flask is put in 37 ± 0.5 DEG C, and at seclected time interval
It is interior, 4mL is sampled in dissolution medium, and be added to the PBS solution of new equivalent.Using ultraviolet specrophotometer at 345nm, survey
Determine BBH contents in dissolution medium.The in-vitro simulated release test that load medicine Supramolecular Network material lasts 5 days can be seen that (Fig. 9), carry
The release of Berberine hydrochloride is main in two steps in body, in the releases of first 12 hours up to 49.3%, and release, which slows down, afterwards shows
Go out sustained releasing character, total release rate is 63.7% in 5 days.
The release behavior of Berberine hydrochloride is by many factors shadow in CMCD-APTES-MMT Supramolecular Networks carrier of the present invention
Ring, lead to field emission microscopy observation and understand that montmorillonite material is easily swelled (Figure 10) in water in itself, with what is be swelled
Occur, the Berberine hydrochloride molecule being loaded between montmorillonite layer is progressively discharged, therefore the degree being swelled can be to release behavior
Produce influence；The cation exchange attribute of montmorillonite, make the ion in dissolution medium can with the sun that is loaded between montmorillonite layer from
Sub- compound frees displacement, so as to influence release.
The present invention successfully synthesizes CMCD-APTES-MMT oversubscription first by gentle, environmentally friendly reaction condition and reagent
Sub-network material.Prove that CMCD-APTES-MMT Supramolecular Networks are to model drug hydrochloric acid barberry through the external medicine, release test of carrying
Alkali has higher charging ratio, under the conditions of simulation physiological environment, and carrying medicine CMCD-APTES-MMT Supramolecular Networks has long-acting delay
Release performance.
The in-vitro antibacterial performance test of the medicine-releasing system of the present invention of embodiment 4
The preparation of bacteria suspension
The preparation of LB culture mediums
1.25g LB broth bouillon powder is weighed in conical flask, 50mL PBS is added and dissolves by heating obtained LB broth cultivations
Support base standby.Weigh 4g LB agar mediums to add after 100mL PBS heating for dissolving, in uncolled preceding and broth bouillon one
Rise be put into high-pressure sterilizing pot in 121 DEG C sterilize 30 minutes.The agar culture for bacterium of having gone out is taken, one is quickly poured into before agar does not solidify
Secondary property sterile petri dish (about 15mL), after after agar solidification, is inverted standby.
The recovery and passage of strain
Take and freeze bacterium powder in right amount in broth bouillon, conical flask is placed in 37 DEG C of constant temperature oscillators, trained with 150rpm
Educate 24 hours, obtain 1 generation bacterium.The meat soup containing 1 generation bacterium is picked with oese, in streak inoculation on agar plate.By agar plate
Inversion is put in biochemical cultivation case 37 DEG C and cultivated 24 hours.Obtain 2nd generation bacterium.On agar plate, 2 bacterium colonies of picking are inoculated
In 50mL broth bouillons.Cultivated 24 hours through 37 DEG C of vibrations, it is about 10 to obtain concentration7The bacteria suspension of CFU/mL the 3rd generation bacterium,
For follow-up antibacterial tests.
Escherichia coli and the examination of staphylococcus aureus Surviving time
The present invention is first to Escherichia coli (E.coli) and staphylococcus aureus (S.aureus) in limited nutrition condition
Under the existence time limit tested.It is 10 to take concentration respectively7CFU/mL two kinds of bacterium bacteria suspension 0.1mL in conical flask, then
It is separately added into 4mL meat soups.Conical flask is placed in into 100rpm in 37 DEG C of constant temperature oscillators to cultivate 5 days, sampling 0.1mL is using flat daily
Plate dilution method observes viable count, survival condition of the 2 kinds of bacterium of examination in 5 days.Hanged respectively containing Escherichia coli and S. aureus L-forms bacterium
Broth bouillon, by the cultivation of 5 days, takes spread plate daily, in observing clump count after 24 hours.As a result show,
1-3 days, less, but after cultivating the 4th day, viable count started obvious reduction to the viable count difference of two kinds of bacterium in meat soup.Explanation
Under limited nutritional condition, the survival degree of Escherichia coli and S. aureus L-forms in 3 days is unaffected, but after 4 days bacterium due to
The discharge of nutrition supply and itself noxious material that cannot be sufficient, causes bacterial death.Therefore for exclusion condition factor
Interference, the reliability of true reflection medicine carrying material antibacterial activity data, the cultivation time of follow-up all antibacterial tests is all controlled 3
Within it.
Carry the examination of medicine CMCD-APTES-MMT Supramolecular Networks antibacterial activity
BBH 0.6mg and 2mg are weighed respectively；Medicine CMCD-APTES-MMT (containing 600 μ g BBH) 2mg and 7mg is carried, in ultra-clean
Ultraviolet irradiation is scattered in 1mL sterilizings PBS respectively after 30 minutes in platform.It is separately added into again equipped with 4mL bacteria suspensions (107CFU/
ML in conical flask), it is that BBH contents are in 150 μ g/mL, E.coli bacteria suspensions to make in final S.aureus bacteria suspensions BBH contents
400μg/mL.37 DEG C of shaken cultivations 24 hours.Respectively take 0.5mL cultivate after bacteria suspension, after appropriate dilution, then to draw 0.1mL dilute
The bacterium solution released is on agar plate, and even spread stands 10 minutes, and flat board is inverted after bacterium solution is fully absorbed by agar in 37 DEG C
Biochemical cultivation case, is cultivated 24 hours.Calculate clump count.By comparing the clump count on agar plate, it is evident that either
To Escherichia coli or staphylococcus aureus, medicine CMCD-APTES-MMT antibacterial activity is carried all apparently higher than free BBH.
Experimental result is shown, carries medicine CMCD-APTES-MMT after S. aureus L-forms, Escherichia coli are cultivated 24 hours together, viable bacteria is dense
Spend from initial 107CFU/mL drops to 10 respectively1CFU/mL (S. aureus L-forms) and 102CFU/mL (Escherichia coli), and pass through free
Viable count in the bacteria suspension of BBH processing is then 104With 107.Therefore, made using CMCD-APTES-MMT Supramolecular Networks material
For BBH carriers, BBH antibacterial activity is greatly improved.
Carry influence of the medicine CMCD-APTES-MMT Supramolecular Networks concentration to antibacterial activity
Dilution plate counting method observes viable count
Weigh respectively after appropriate load medicine CMCD-APTES-MMT, ultraviolet radiation sterilization, be scattered in PBS, obtain 50-
The load medicine CMCD-APTES-MMT suspensions of 600 μ g/mL various concentrations, then be separately added into equipped with 107CFU/mL E.coli and
In the conical flask of S.aureus bacteria suspensions, cultivated 24 hours in 37 DEG C of shakings.Blank is used as using the PBS of not pastille.Cultivation is finished
Afterwards, 0.5mL is sampled in each conical flask, after appropriate dilution, takes 0.1mL spread plates, be inverted after cultivating 24 hours and calculate bacterium colony
Count and take pictures.As a result show, carry medicine CMCD-APTES-MMT and concentration is showed to the inhibitory action of S. aureus L-forms and Escherichia coli
The characteristic of dependence.When carrying medicine CMCD-APTES-MMT concentration and reaching 600 μ g/mL, its inhibiting rate to Escherichia coli reaches
91.57 ± 2.11%；When carrying medicine CMCD-APTES-MMT concentration and reaching 250 μ g/mL, its inhibiting rate to S. aureus L-forms then reaches
93.9 ± 1.35%.
Fluorescence microscopy bacterium intracellular Berberine hydrochloride concentration
It is 10 that the load medicine oversubscription subcarrier that concentration is 50-600 μ g/mL is separately added into bacteria concentration7CFU/mL LB meat soups
In, it is separately sampled after 24 hours cultivate by 37 DEG C, carrier meat soup suspension is centrifuged 10 minutes with 500rpm, carrier is removed
Material, collects supernatant, is centrifuged 20 minutes then at 4000rpm.Thalline is collected, is centrifuged again with PBS 3 times, then be suspended from again ultrapure
For Fluirescence observation in water.Fluorescence microscope selects excitation wavelength 355nm, launch wavelength 517nm.Because jamaicin itself has
Fluorescence, therefore absorption of the bacterium to Berberine hydrochloride can be observed using fluorescence microscope.As a result show, with load medicine
The raising of CMCD-APTES-MMT concentration, the amount that Berberine hydrochloride enters bacterium also gradually increases, therefore the fluorescence intensity of bacterium
Gradually strengthen.Fluorescence developing has intuitively confirmed the antibacterial activity for carrying medicine CMCD-APTES-MMT concentration dependants.
Carry medicine CMCD-APTES-MMT Supramolecular Network long-acting bacteriostatic performance check studies
Concentration is scattered in 1mL of PBS respectively for 50-600 μ g/mL load medicine oversubscription subcarrier, then by suspension
It is 10 to be separately added into 4mL bacterial concentrations7In CFU/mL meat soup.The soup containing bacterial context of blank group only adds PBS.Above-mentioned sample is whole
In 37 DEG C, 100rpm shakings are cultivated, respectively at 4, sampling in 8,12,18,24,36,48 and 72 hours, using ultraviolet spectrophotometry
OD value is determined at 600nm wavelength.As a result show, the period selected in 3 days is to through carrying at medicine CMCD-APTES-MMT
The optical density of the bacteria suspension of reason is detected that, with the increase for carrying medicine CMCD-APTES-MMT concentration, OD value substantially drops
It is low.After processing three days, concentration reaches for 600 μ g/mL load medicine CMCD-APTES-MMT to the inhibiting rate of Escherichia coli
98.45%；Concentration for 250 μ g/mL load medicine CMCD-APTES-MMT to the inhibiting rate of staphylococcus aureus up to 97.81%.
By field emission microscopy observation, carrying medicine CMCD-APTES-MMT Supramolecular Networks can wrap to microorganism
Wrap up in, so as to strengthen the contact between Berberine hydrochloride and bacterium.Such as Figure 11, medicine CMCD-APTES-MMT Supramolecular Networks are being carried
After being contacted respectively 24 hours with S. aureus L-forms and Escherichia coli, material realizes complete parcel to thalline, and makes thalline
Torsional deformation.The extracorporeal bacteria inhibitor test result of CMCD-APTES-MMT Supramolecular Networks for loading Berberine hydrochloride shows, its
To the inhibitory action of Escherichia coli (Gram-negative bacteria) and staphylococcus aureus (gram-positive bacteria) far above free
Medicine, and concentration dependent and long-term effect is presented in bacteriostasis property, and medicine CMCD-APTES-MMT oversubscription subnets are carried in the present invention
Network respectively reaches 98.45% and 97.81% to the inhibiting rate of Escherichia coli and staphylococcus aureus.
Material toxicity is examined or check
The CMCD-APTES-MMT carrier materials of the not pastille with loading 50-600 μ g/mL BBH equivalent are weighed respectively, point
Not Jia Ru bacterial concentration be 107In CFU/mL meat soup, very to be cultivated 24 hours in 37 DEG C.Calculated using dilution plate counting method
Viable count after cultivation.As a result show, by 37 DEG C, the cultivation of 72 hours, in 50-600 μ g/mL dosage ranges, blank material
Expect the growth to bacterium, almost without inhibitory action, therefore CMCD-APTES-MMT network materials are safe and reliable.
In the present invention, the Supramolecular Network as formed by CMCD-APTES-MMT self assemblies is synthesized and it is made first
Evaluating in vitro has been carried out for the properties of antibacterials carrier.In CMCD-APTES-MMT Supramolecular Networks, montmorillonite and ring
Dextrin can load model drug Berberine hydrochloride, therefore CMCD-APTES-MMT Supramolecular Network phases simultaneously as pharmaceutical carrier
Than single montmorillonite material, carrying drug ratio has obtained significant increase, in vitro under optimal conditions carrying drug ratio up to 27.8%.Carry medicine
The raising of rate causes during insoluble drug release, local drug concentration also relative increase, therefore act on the medicine of bacterium
Concentration improve, antibacterial action enhancing.By extracorporeal bacteria inhibitor test it is also seen that, free drug suppress Escherichia coli Growth
When, required drug concentration is much higher than medicine needed for suppression staphylococcus aureus, and this is mainly due to Gram-negative bacteria
Cellulosa have one layer of special outer membrane structure, hinder the entrance of medicine.Although carrying medicine CMCD-APTES-MMT supermolecules
Concentration carries medicine CMCD-APTES- also above staphylococcus aureus, but compared to free drug needed for network confrontation Escherichia coli
MMT Supramolecular Networks have obvious reduction to the minimal inhibitory concentration for suppressing Escherichia coli.
Claims (10)
1. a kind of carboxymethyl-β-cyclodextrin functionalization montmorillonite Supramolecular Network material, it is characterised in that：The infrared spectrum of generation
In 3421cm-1, 2934cm-1, 1637cm-1, 1414cm-1, 1159cm-1, 1087cm-1, 1039cm-1, 745cm-1,
613cm-1, 587cm-1Show absworption peak.
2. carboxymethyl-β-cyclodextrin functionalization montmorillonite Supramolecular Network material as claimed in claim 1, it is characterised in that：Spreading out
Firing angle degree 2θTo have diffraction maximum at 5.39 ± 0.2 °, 8.72 ± 0.2 °.
3. carboxymethyl-β-cyclodextrin functionalization montmorillonite Supramolecular Network material as claimed in claim 1 or 2, it is characterised in that：
During thermogravimetric analysis, 90 ± 2 DEG C of sons that dry out are thermally decomposed at 411 ± 2 DEG C.
4. the preparation side of carboxymethyl-β-cyclodextrin functionalization montmorillonite Supramolecular Network material as described in claim any one of 1-3
Method, it is characterised in that：Carboxymethyl cyclodextrin is synthesized with chloroacetic acid reaction using beta-schardinger dextrin in the basic conditions；To montmorillonite
Silanization is carried out, the montmorillonite of three aminopropyl triethoxysilane silanizations is obtained；Pass through 1- (3- diformazan ammonia at ambient temperature
Base propyl group) -3- ethyl-carbodiimide hydrochlorides and n-hydroxysuccinimide catalysis, make carboxymethyl cyclodextrin and three aminopropyls three
The montmorillonite reaction of Ethoxysilane silanization, obtains the montmorillonite material of carboxymethyl cyclodextrin functionalization.
5. carry the preparation method of the carboxymethyl-β-cyclodextrin functionalization montmorillonite medicine-releasing system of jamaicin, it is characterised in that use
Following steps：Berberine hydrochloride ultra-pure water is dissolved to the barberry aqueous alkali for obtaining concentration for the μ g/mL of 50 μ g/mL~350, pressed
It is 5~35 according to jamaicin and carboxymethyl-β-cyclodextrin functionalization montmorillonite Supramolecular Network quality of materials ratio：100 add carboxymethyl
Beta-schardinger dextrin functionalization montmorillonite Supramolecular Network material, is 30-80 DEG C, under conditions of pH is 2-11 in temperature, reacts 0.5-6
Hour, by the centrifugation of obtained suspension, filtering with microporous membrane, supernatant is collected, with ultraviolet specrophotometer at 345nm wavelength
Determine the content for the free hydrochloric acid jamaicin not being loaded；Then drugloading rate is calculated as follows
。
6. method as claimed in claim 5, it is characterised in that：The concentration of the barberry aqueous alkali is the μ of 250 μ g/mL~350
g/mL。
7. the method as described in claim 5 or 6, it is characterised in that：The reaction time is 3-6 hours.
8. the method as described in claim 5 or 6, it is characterised in that：The reaction pH is 9-11.
9. the method as described in claim 5 or 6, it is characterised in that：The reaction temperature is 50-80 DEG C.
10. carry the preparation method of the carboxymethyl-β-cyclodextrin functionalization montmorillonite medicine-releasing system of jamaicin, it is characterised in that use
Following steps：
（1）, carboxymethyl-β-cyclodextrin functionalization montmorillonite Supramolecular Network material preparation；
Beta-schardinger dextrin synthesizes carboxymethyl cyclodextrin under conditions of sodium hydroxide is catalyst with chloroacetic acid reaction；To montmorillonite
Silanization is carried out, the montmorillonite of three aminopropyl triethoxysilane silanizations is obtained；Pass through 1- (3- diformazan ammonia at ambient temperature
Base propyl group) -3- ethyl-carbodiimide hydrochlorides and n-hydroxysuccinimide catalysis, make carboxymethyl cyclodextrin and three aminopropyls three
The montmorillonite reaction of Ethoxysilane silanization, obtains the montmorillonite material of carboxymethyl cyclodextrin functionalization；
（2）, carry jamaicin carboxymethyl-β-cyclodextrin functionalization montmorillonite medicine-releasing system preparation
Berberine hydrochloride ultra-pure water is dissolved to the barberry aqueous alkali for obtaining concentration for the μ g/mL of 250 μ g/mL~350, according to small
Bark of a cork tree alkali is 25~35 with carboxymethyl-β-cyclodextrin functionalization montmorillonite Supramolecular Network quality of materials ratio：100 addition carboxymethyl β-
Cyclodextrin functionalization montmorillonite Supramolecular Network material, is 50-80 DEG C, under conditions of pH is 9-11 in temperature, reaction 3-6 is small
When, by the centrifugation of obtained suspension, with 0.45 μm of filtering with microporous membrane, collect supernatant, with ultraviolet specrophotometer in
The content for the free hydrochloric acid jamaicin not being loaded is determined at 345nm wavelength；Then drugloading rate is calculated as follows
。
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|---|---|---|---|---|
| CN117205334A (en) * | 2023-10-09 | 2023-12-12 | 青岛市中心医院 | Berberine-loaded montmorillonite composite material and preparation method and application thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS62191416A (en) * | 1986-02-14 | 1987-08-21 | Natl Inst For Res In Inorg Mater | Montmorillonite-methylated cyclodextrin-type crystalline composite and production thereof |
| CN104437414A (en) * | 2014-12-25 | 2015-03-25 | 江南大学 | Montmorillonite-reinforced polyethylene glycol/ cyclodextrin gel and preparation method thereof |
-
2017
- 2017-04-27 CN CN201710298972.7A patent/CN107029249A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS62191416A (en) * | 1986-02-14 | 1987-08-21 | Natl Inst For Res In Inorg Mater | Montmorillonite-methylated cyclodextrin-type crystalline composite and production thereof |
| CN104437414A (en) * | 2014-12-25 | 2015-03-25 | 江南大学 | Montmorillonite-reinforced polyethylene glycol/ cyclodextrin gel and preparation method thereof |
Non-Patent Citations (3)
| Title |
|---|
| TSUYOSHI KIJIMA等: "Complexes of Na-, Ca-, and Zn-Montmorillonties with an Aminaated Cyclodextrin", 《JOURNAL OF INCLUSION PHENOMENA》 * |
| 孙萌: "盐酸小檗碱/蒙脱石复合散的研究", 《中国优秀硕士学位论文全文数据库.医药卫生科技辑》 * |
| 梅涛锋等: "环糊精对粘土的修饰改性研究", 《功能材料》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN117205334A (en) * | 2023-10-09 | 2023-12-12 | 青岛市中心医院 | Berberine-loaded montmorillonite composite material and preparation method and application thereof |
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