CN109464423A - Ah-ACMS microballoon and preparation method carry medicine Ah-ACMS and preparation method - Google Patents

Ah-ACMS microballoon and preparation method carry medicine Ah-ACMS and preparation method Download PDF

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Publication number
CN109464423A
CN109464423A CN201811428339.6A CN201811428339A CN109464423A CN 109464423 A CN109464423 A CN 109464423A CN 201811428339 A CN201811428339 A CN 201811428339A CN 109464423 A CN109464423 A CN 109464423A
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China
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acms
microballoon
chitosan
sodium alginate
mixed solution
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CN109464423B (en
Inventor
贾永堂
苟琼友
董凤春
侯杰
侯一杰
王普凯
谢娟
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Wuyi University
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Wuyi University
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/48Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5005Wall or coating material
    • A61K9/5021Organic macromolecular compounds
    • A61K9/5036Polysaccharides, e.g. gums, alginate; Cyclodextrin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/335Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. cannabinols, methantheline
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04Antibacterial agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/10Antimycotics

Abstract

The present invention provides a kind of Ah-ACMS microballoon and preparation methods, carry medicine Ah-ACMS and preparation method, it is related to pharmaceutical carrier technical field, the preparation method of the Ah-ACMS microballoon includes the following steps: by electrostatic spray to spray sodium alginate soln into the mixed solution of chitosan and calcium chloride, obtain Ah-ACMS microballoon, improve and the bad technical problem of controlled release properties is delayed using nanosphere medicine carrier prepared by the precipitation method and emulsion process, Ah-ACMS microballoon provided by the invention is prepared by electrostatic spraying processes, process is simple, it is easy to operate, and microspherulite diameter is uniform, particle diameter distribution is at 20-50 μm, make it after containing drug, the slow controlled release of drug is easier to be precisely controlled.

Description

Ah-ACMS microballoon and preparation method, carry medicine Ah-ACMS and Preparation method
Technical field
The present invention relates to pharmaceutical carrier technical fields, more particularly, to a kind of Ah-ACMS microballoon and preparation side Method carries medicine Ah-ACMS and preparation method.
Background technique
As people go deep into Drug Carrier Systems research, in recent years, the corpuscular properties controlled drug delivery systems such as micro-capsule/ball are obtained To rapid development, clinically also it is widely used.
The method for preparing nanosphere medicine carrier at present mainly has the precipitation method and emulsion process, and process is tedious for these methods, microballoon Particle diameter distribution is wider, and greater particle size microballoon easy to form influences the whole homogeneity of pharmaceutical carrier, causes in medicine sustained and controlled release rank It is not easy to be precisely controlled in section.
In view of this, the present invention is specifically proposed.
Summary of the invention
One of the objects of the present invention is to provide a kind of preparation methods of Ah-ACMS microballoon, to improve use The precipitation method and emulsion process prepare nanosphere medicine carrier process is tedious, microspherulite diameter wider distribution, greater particle size microballoon easy to form, The whole homogeneity for influencing pharmaceutical carrier, causes the medicine sustained and controlled release stage to be not easy the technical issues of being precisely controlled.
The preparation method of Ah-ACMS microballoon provided by the invention, includes the following steps: sodium alginate soln It is sprayed by electrostatic spray into the mixed solution of chitosan and calcium chloride, obtains Ah-ACMS microballoon.
Further, the mass concentration of the sodium alginate soln is 1.5-4%, preferably 2-3%.
Further, in the mixed solution of the chitosan and calcium chloride, the mass concentration of chitosan is 0.05-0.2%, Preferably 0.08-0.12%;
And/or the mass concentration of calcium chloride is 1-3%, preferably my 1.5-2.5%.
Further, the jet velocity of the sodium alginate soln is 3-7mL/h, preferably 4.5-5.5mL/h;
Preferably, sodium alginate soln is sprayed by electrostatic spray to chitosan and chlorination using high-voltage electrostatic sprayer In the mixed solution of calcium.
The second object of the present invention is to provide a kind of Ah-ACMS microballoon, the seaweed provided according to the present invention The preparation method of sour calcium-chitosan microball obtains;
Preferably, the partial size of Ah-ACMS microballoon is 20-50 μm.
The third object of the present invention is to provide a kind of load medicine Ah-ACMS microballoon, including drug and the present invention The Ah-ACMS microballoon of offer, drug are coated in Ah-ACMS microballoon;
Preferably, the partial size for carrying medicine Ah-ACMS microballoon is 20-50 μm.
The fourth object of the present invention is to provide the preparation method of above-mentioned load medicine Ah-ACMS microballoon, including such as Lower step: the mixed solution of drug and sodium alginate is sprayed by electrostatic spray to the mixed solution to chitosan and calcium chloride In, it obtains carrying medicine Ah-ACMS microballoon.
Further, in the mixed solution of the drug and sodium alginate, the mass concentration of sodium alginate is 1.5-4%, Preferably 2-3%;
And/or in the mixed solution of the drug and sodium alginate, the mass concentration of drug is 0.5-1.5%, preferably 0.8-1.2%.
Further, in the mixed solution of the chitosan and calcium chloride, the mass concentration of chitosan is 0.05-0.2%, Preferably 0.08-0.12%;
And/or the mass concentration of calcium chloride is 1-3%, preferably 1.5-2.5%.
Further, the jet velocity of the mixed solution of the drug and sodium alginate is 3-7mL/h, preferably 4.5- 5.5mL/h;
Preferably, sodium alginate soln is sprayed to the mixed solution to chitosan and calcium chloride using high-voltage electrostatic sprayer In.
Ah-ACMS microballoon provided by the invention is prepared by electrostatic spraying processes, and process is simple, operation side Just, and microspherulite diameter is uniform, and particle diameter distribution makes it after containing drug at 20-50 μm, and the slow controlled release of drug is easier to precisely control System.
Ah-ACMS microspherulite diameter provided by the invention is uniform, and particle diameter distribution contains cladding at 20-50 μm Afterwards, the slow controlled release of drug is easier to be precisely controlled.
Load medicine Ah-ACMS microballoon provided by the invention, uniform particle diameter, particle diameter distribution is at 20-50 μm, drug packet Envelope rate is high, and slow controlled-release effect is good, can effectively improve the therapeutic effect of drug.
Detailed description of the invention
Fig. 1 is the optical microscope for the Ah-ACMS microballoon that embodiment 5 provides;
Fig. 2 is the optical microscopy map for the load medicine Ah-ACMS microballoon that embodiment 14 provides;
Fig. 3 is the SEM figure for the Ah-ACMS microballoon that embodiment 5 provides;
Fig. 4 is the SEM figure for the load medicine Ah-ACMS microballoon that embodiment 14 provides;
Fig. 5 is drug Cumulative release amount and the pass of release time for the load medicine Ah-ACMS that embodiment 14 provides It is curve;
Fig. 6 is absorbance and the pass of resting period for carrying medicine Ah-ACMS and naringenin that embodiment 14 provides It is curve.
Specific embodiment
Technical solution of the present invention will be clearly and completely described below, it is clear that described embodiment is this hair Bright a part of the embodiment, instead of all the embodiments.Based on the embodiments of the present invention, those of ordinary skill in the art are not having Every other embodiment obtained under the premise of creative work is made, shall fall within the protection scope of the present invention.
According to an aspect of the present invention, the present invention provides a kind of preparation method of Ah-ACMS microballoon, packets Include following steps: by sodium alginate soln by obtaining alginic acid in electrostatic spray to the mixed solution of chitosan and calcium chloride Calcium-chitosan microball.
The preparation method of Ah-ACMS microballoon provided by the invention, sodium alginate soln are sprayed by electrostatic spray It being incident upon in the mixed solution of chitosan and calcium chloride, microballoon can be prepared, process is simple, and it is easy to operate, and microspherulite diameter Uniform, particle diameter distribution makes it after containing drug at 20-50 μm, and the slow controlled release of drug is easier to be precisely controlled.
In the preferred embodiment of the present invention, the mass concentration of sodium alginate soln is 1.5-4%.
It is micro- to obtain the high Ah-ACMS of entrapment efficiency by controlling the mass concentration of sodium alginate soln Ball pharmaceutical carrier if the quality solubility of sodium alginate soln is lower than 1.5% is difficult that the microballoon of uniform particle diameter is prepared, if The mass concentration of sodium alginate soln is higher than 4%, then the microspherulite diameter being prepared is excessive, and being not suitable as pharmaceutical carrier makes With.
In a preferred embodiment of the invention, the typical but non-limiting mass concentration of sodium alginate soln is for example 1.5%, 1.8%, 2%, 2.2%, 2.5%, 2.8%, 3%, 3.2%, 3.5%, 3.8% or 4%.
In the preferred embodiment of the present invention, in the mixed solution of chitosan and calcium chloride, the quality of chitosan Concentration is 0.05-0.2%,
In a preferred embodiment of the invention, in the mixed solution by controlling chitosan and calcium chloride, chitosan Concentration, with the partial size and particle diameter distribution of the Ah-ACMS microballoon being prepared.
In the preferred embodiment of the present invention, in chitosan and calcium chloride mixed solution, the typical case of chitosan but Unrestricted mass concentration for example 0.05%, 0.08%, 0.1%, 0.12%, 0.15%, 0.18% or 0.2%.
In the preferred embodiment of the present invention, in the mixed solution of chitosan and calcium chloride, the quality of calcium chloride Concentration is 1-3%.
In the present invention, calcium chloride is used to carry out calcium ion-exchanged with sodium alginate, obtains gelatinous calcium alginate.
In a preferred embodiment of the invention, in the mixed solution of chitosan and calcium chloride, calcium chloride it is typical but non- Restrictive mass concentration for example 1%, 1.2%, 1.5%, 1.8%, 2%, 2.2%, 2.5%, 2.8% or 3%.
In the preferred embodiment of the present invention, the jet velocity of sodium alginate soln is 3-7mL/h.
In a preferred embodiment of the invention, the typical but non-limiting jet velocity for example 3 of sodium alginate soln, 3.5,4,4.5,5,5.5,6,6.5 or 7mL/h.
By controlling the jet velocity of sodium alginate soln, so that the partial size of manufactured Ah-ACMS microballoon More uniform, entrapment efficiency is higher.
In the preferred embodiment of the present invention, sodium alginate soln is passed through by electrostatic using high-voltage electrostatic sprayer It is sprayed onto the mixed solution of chitosan and calcium chloride by spraying.
In present invention further optimization embodiment, the voltage of high-voltage electrostatic sprayer is 12-20kV, preferably 14-18kV。
In a preferred embodiment of the invention, the typical but non-limiting voltage for example 12 of high-voltage electrostatic sprayer, 12.5,13,13.5,14,14.5,15,15.5,16,16.5,17,17.5 or 18kV.
Voltage by controlling high-voltage electrostatic sprayer is 12-20kV, and uniform particle diameter is prepared, and partial size is 15- 60 μm of microballoon.
According to the second aspect of the invention, the present invention provides a kind of Ah-ACMS microballoons, according to the present invention The preparation method that first aspect provides obtains.
Ah-ACMS microspherulite diameter provided by the invention is uniform, and particle diameter distribution contains cladding at 20-50 μm Afterwards, the slow controlled release of drug is easier to be precisely controlled.
In the preferred embodiment of the present invention, the partial size of Ah-ACMS microballoon is 20-50 μm.
In a preferred embodiment of the invention, the typical but non-limiting partial size of Ah-ACMS microballoon is such as It is 20,22,25,28,30,35,40,45 or 50 μm.
According to the third aspect of the present invention, the present invention provides a kind of load medicine Ah-ACMS microballoons, including medicine Object and Ah-ACMS microballoon provided by the invention, wherein drug is coated in Ah-ACMS microballoon.
Load medicine Ah-ACMS microballoon provided by the invention, uniform particle diameter, particle diameter distribution is at 20-50 μm, drug packet Envelope rate is high, and slow controlled-release effect is good, can effectively improve the therapeutic effect of drug.
In the preferred embodiment of the present invention, the partial size for carrying medicine Ah-ACMS microballoon is 20-50 μm.
In a preferred embodiment of the invention, the typical but non-limiting grain of medicine Ah-ACMS microballoon is carried For example 20,22,25,28,30,35,40,45 or 50 μm of diameter.
According to the fourth aspect of the present invention, the present invention provides a kind of preparations for carrying medicine Ah-ACMS microballoon Method includes the following steps: by electrostatic spray to spray the mixed solution of drug and sodium alginate to chitosan and calcium chloride Mixed solution in, obtain carry medicine-chitosan microball.
Load medicine Ah-ACMS microballoon provided by the invention is prepared by electrostatic spraying method, and process is simple, It is easy to operate, and microspherulite diameter is uniform, entrapment efficiency is high, is easy to be precisely controlled the slow controlled release behavior of drug.
In the preferred embodiment of the present invention, in the mixed solution of drug and sodium alginate, the matter of sodium alginate Amount concentration is 1.5-4%.
In mixed solution by controlling drug and sodium alginate, the mass concentration of sodium alginate, to obtain drug encapsulation The high load medicine Ah-ACMS microballoon of rate if sodium alginate quality solubility is lower than 1.5% is difficult that partial size is prepared Uniform microballoon, and entrapment efficiency is low, if the mass concentration of sodium alginate is higher than 4%, the microspherulite diameter mistake being prepared Greatly, it is unable to satisfy drug delivery system requirement.
In a preferred embodiment of the invention, in the mixed solution of drug and sodium alginate, the typical case of sodium alginate but Unrestricted mass concentration for example 1.5%, 1.8%, 2%, 2.2%, 2.5%, 2.8%, 3%, 3.2%, 3.5%, 3.8% Or 4%.
In the preferred embodiment of the present invention, in the mixed solution of drug and sodium alginate, the quality of drug is dense Degree is 0.5-1.5%.
In a preferred embodiment of the invention, in the mixed solution of drug and sodium alginate, the typical but non-limit of drug The mass concentration for example 0.5,0.6,0.7,0.8,0.9,1,1.1,1.2,1.3,1.4 or 1.5% of property processed.
In the preferred embodiment of the present invention, in the mixed solution of chitosan and calcium chloride, the quality of chitosan Concentration is 0.05-0.2%,
In a preferred embodiment of the invention, in the mixed solution by controlling chitosan and calcium chloride, chitosan Concentration, carrying medicine calcium alginate-chitosan microball partial size with the sea being prepared is that 20-50 μm and particle diameter distribution are uniform.
In the preferred embodiment of the present invention, in chitosan and calcium chloride mixed solution, the typical case of chitosan but Unrestricted mass concentration for example 0.05%, 0.08%, 0.1%, 0.12%, 0.15%, 0.18% or 0.2%.
In the preferred embodiment of the present invention, in the mixed solution of chitosan and calcium chloride, the quality of calcium chloride Concentration is 1-3%.
In the present invention, calcium chloride is used to carry out calcium ion-exchanged with sodium alginate, obtains gelatinous calcium alginate.
In a preferred embodiment of the invention, in the mixed solution of chitosan and calcium chloride, calcium chloride it is typical but non- Restrictive mass concentration for example 1%, 1.2%, 1.5%, 1.8%, 2%, 2.2%, 2.5%, 2.8% or 3%.
In the preferred embodiment of the present invention, the mixed solution of drug and sodium alginate is typical but non-limiting For example 3,3.5,4,4.5,5,5.5,6,6.5 or 7mL/h of jet velocity.
By controlling the jet velocity of drug and sodium alginate soln, so that manufactured drug Ah-ACMS The partial size of microballoon is more uniform, and entrapment efficiency is higher.
In the preferred embodiment of the present invention, using high-voltage electrostatic sprayer by the mixing of drug and sodium alginate Solution is sprayed onto the mixed solution of chitosan and calcium chloride by electrostatic spray.
In present invention further optimization embodiment, the voltage of high-voltage electrostatic sprayer is 12-20kV, preferably 14-18kV。
In a preferred embodiment of the invention, the typical but non-limiting voltage for example 12 of high-voltage electrostatic sprayer, 12.5,13,13.5,14,14.5,15,15.5,16,16.5,17,17.5 or 18kV.
Voltage by controlling high-voltage electrostatic sprayer is 12-20kV, and uniform particle diameter is prepared, and partial size is 15- 60 μm of drug bearing microsphere.
In the preferred embodiment of the present invention, medicine Ah-ACMS is carried to be prepared in accordance with the following steps:
(a) mixed solution of drug and sodium alginate is sprayed by electrostatic atomizer mixed to chitosan and calcium chloride It closes in solution;
(b) the resulting solution of step (a) is centrifuged, removes supernatant, and be washed with deionized for several times, it is dry, it obtains Ah-ACMS microballoon.
In the present invention, drug includes but is not limited to naringenin and barbaloin.
Technical solution provided by the invention is further described below with reference to embodiment and comparative example.
Embodiment 1
A kind of Ah-ACMS microballoon is present embodiments provided, preparation method includes the following steps:
(1) configuration sodium alginate soln is taken water as a solvent, the mass concentration of sodium alginate is 1.5%;
(2) mixed solution of chitosan and calcium chloride is configured using acetic acid as solvent, wherein the concentration of chitosan is 0.2%, The concentration of calcium chloride is 1%;
(3) by the mixed solution of naringenin and sodium alginate with the jet velocity of 4.5mL/h by electrostatic spray spray to In the mixed solution of chitosan and calcium chloride;
(4) solution in step (3) is centrifuged with the speed of 5000 turns/min, removes supernatant, then uses deionization again It water washing 3 times, obtains carrying medicine Ah-ACMS microsphere suspension liquid, freeze-drying obtains carrying medicine Ah-ACMS microballoon.
Embodiment 2
A kind of Ah-ACMS microballoon is present embodiments provided, preparation method and the difference of embodiment 1 exist In in step (1), the mass concentration of sodium alginate soln is 4%;In step (2), the mixing of chitosan and calcium chloride is molten In liquid, the mass concentration of chitosan is 0.05%, and the mass concentration of calcium chloride is 3%.
Embodiment 3
A kind of Ah-ACMS microballoon is present embodiments provided, preparation method and the difference of embodiment 1 exist In in step (1), the mass concentration of sodium alginate soln is 2%;In step (2), the mixing of chitosan and calcium chloride is molten In liquid, the mass concentration of chitosan is 0.1%, and the mass concentration of calcium chloride is 1.5%.
Embodiment 4
A kind of Ah-ACMS microballoon is present embodiments provided, preparation method and the difference of embodiment 1 exist In in step (1), the mass concentration of sodium alginate soln is 3%;In step (2), the mixing of chitosan and calcium chloride is molten In liquid, the mass concentration of chitosan is 0.1%, and the mass concentration of calcium chloride is 2.5%.
Embodiment 5
A kind of Ah-ACMS microballoon is present embodiments provided, preparation method and the difference of embodiment 1 exist In in step (1), in the mixed solution of sodium alginate soln, the mass concentration of sodium alginate is 2.5%;In step (2) In, in the mixed solution of chitosan and calcium chloride, the mass concentration of chitosan is 0.1%, and the mass concentration of calcium chloride is 2%.
Embodiment 6
A kind of Ah-ACMS microballoon is present embodiments provided, preparation method and the difference of embodiment 5 exist In in step (1), the mass concentration of sodium alginate soln is 0.5%.
Embodiment 7
A kind of Ah-ACMS microballoon is present embodiments provided, preparation method and the difference of embodiment 5 exist In in step (1), the mass concentration of sodium alginate soln is 10%.
Embodiment 8
A kind of Ah-ACMS microballoon is present embodiments provided, preparation method and the difference of embodiment 5 exist In in step (2), in the mixed solution of chitosan and calcium chloride, the mass concentration of chitosan is 0.01%.
Embodiment 9
A kind of Ah-ACMS microballoon is present embodiments provided, preparation method and the difference of embodiment 5 exist In in step (2), in the mixed solution of chitosan and calcium chloride, the mass concentration of chitosan is 0.5%.
Embodiment 10
Embodiment 10 provides a kind of load medicine Ah-ACMS microballoon comprising what naringenin and embodiment 1 provided Ah-ACMS nanosphere medicine carrier, preparation method difference from example 1 is that, in step (1), will Naringenin is dissolved in sodium alginate soln, and the mass concentration of naringenin is 1%.
Embodiment 11-18
Embodiment 11-18 each provides a kind of load medicine Ah-ACMS microballoon, is mentioned respectively by embodiment 2-9 Naringenin is coated in Ah-ACMS microballoon by the Ah-ACMS microballoon of confession as pharmaceutical carrier, system Preparation Method is with embodiment 10, and details are not described herein.
Comparative example 1
This comparative example provides a kind of load medicine calcium alginate microsphere, preparation method include the following steps: naringenin and The mixed solution of sodium alginate is sprayed by electrostatic spray to be prepared into calcium chloride solution, wherein naringenin and sodium alginate Mixed solution in, the mass concentration of naringenin is 1%, and the mass concentration of sodium alginate is 2.5%, in calcium chloride solution, chlorine The mass concentration for changing calcium is 2%, and details are not described herein.
Test example 1
By the Ah-ACMS microballoon that embodiment 5 provides and the load medicine Ah-ACMS that embodiment 15 provides Microballoon carries out optical microscopy test and sem test respectively, and as a result as shown in Figs 1-4, wherein Fig. 1 is that embodiment 5 provides Ah-ACMS microballoon optical microscope;Fig. 2 is that the load medicine Ah-ACMS that embodiment 14 provides is micro- The optical microscope of ball;Fig. 3 is the SEM figure for the Ah-ACMS microballoon that embodiment 5 provides, and Fig. 4 is that embodiment 14 mentions The SEM figure of the load medicine Ah-ACMS microballoon of confession.From Fig. 1 and Fig. 2 as can be seen that Ah-ACMS microballoon and The uniform particle diameter of medicine Ah-ACMS microballoon is carried, and Ah-ACMS microballoon is hollow structure, and carries medicine seaweed It is coated with substance in sour calcium-chitosan microball, this illustrates that the load medicine Ah-ACMS microballoon that embodiment 14 provides can be at Naringenin is coated in Ah-ACMS microballoon by function.
As can be seen from Figure 3, the Ah-ACMS microspherulite diameter that embodiment 5 provides is uniform, is 20-50 μm, can from Fig. 4 To find out, the load medicine Ah-ACMS microballoon that embodiment 14 provides has apparent core-shell structure, this also illustrates embodiment Naringenin can be successfully coated in Ah-ACMS microballoon by the 14 load medicine Ah-ACMS microballoons provided.
Test example 2
The load medicine Ah-ACMS microballoon for taking 0.2g embodiment 14 to provide is dissolved in 20mLPBS solution, is placed in perseverance Warm shaking table (37 DEG C, 70r/min) takes 2ml in specific time, supplements the fresh PBS solution of 2ml after surveying absorbance, passes through extinction Degree calculates the burst size of naringenin, and curve, curve are drawn by abscissa of the time by ordinate of naringenin Cumulative release amount As shown in figure 5, from fig. 5, it can be seen that the Cumulative release amount of naringenin continues to increase with the extension of time, until when 12h, shaddock ped Plain basic release finishes, this illustrates the pharmaceutical release time energy for the load medicine Ah-ACMS that the embodiment of the present invention 14 provides Enough reach 12h.
Test example 3
The drug bearing microsphere for taking 12mg embodiment 10-18 and comparative example 1 to provide respectively carries out entrapment efficiency test, as a result such as Shown in table 1.
1 drug bearing microsphere naringenin encapsulation rate tables of data of table
Embodiment 11-18 and the comparison of comparative example 1 are found out from table 1, the load medicine calcium alginate-that embodiment 11-18 is provided The entrapment efficiency of chitosan microball is significantly higher than comparative example 1, this illustrates that load medicine Ah-ACMS provided by the invention is micro- Ball is mutually cooperateed with by calcium alginate and chitosan, entrapment efficiency is significantly improved, so as to effectively improve drug bearing microsphere Therapeutic effect.
It can be seen that the drug bearing microsphere that embodiment 11-14 is provided from the comparison of embodiment 11-14 and embodiment 15-18 Entrapment efficiency is significantly higher than embodiment 15-18, this explanation is when preparing drug bearing microsphere, when the mixing of naringenin and sodium alginate In solution, the mass concentration of sodium alginate is 1.5-4%, and in the mixed solution of chitosan and calcium chloride, the quality of chitosan is dense Degree is 0.05-0.2%, when the mass concentration of calcium chloride is 1-3%, the load medicine Ah-ACMS microballoon that is prepared Entrapment efficiency is higher.
Test example 4
Load medicine Ah-ACMS microballoon and naringenin that embodiment 14 provides are respectively placed in refrigerator (- 20 DEG C) Middle preservation, weighs 0.01g naringenin respectively at regular intervals, and 0.02g carries medicine Ah-ACMS microballoon, is dissolved in 10mPBS solution surveys its absorbance, draws naringenin respectively and carries the suction of medicine Ah-ACMS microballoon changed over time Luminosity curve, as a result as shown in Figure 6.
From fig. 6, it can be seen that naringenin absorbance is in preceding 36h, absorbance is held essentially constant, and after 36h, absorbance It is decreased obviously, this illustrates that naringenin decomposes after retaining 36h, is decreased obviously absorbance;And carry medicine alginic acid Calcium-chitosan microball absorbance curve equal held stationary in 60h, this illustrates that load medicine Ah-ACMS microballoon can The stability for significantly improving naringenin reduces the decomposition of naringenin.
Test example 5
By the Ah-ACMS microballoon that embodiment 5 provides and the load medicine Ah-ACMS that embodiment 14 provides Microballoon dissolves in PBS solution respectively, is configured to the solution of identical mass concentration, then measures the antibiotic rate of the two microballoon respectively, The results are shown in Table 2.
2 microballoon anti-microbial property tables of data of table
From table 2 it can be seen that the load medicine sea that Ah-ACMS microballoon and embodiment 14 that embodiment 5 provides provide Calcium alginate-chitosan microball all has the load medicine Ah-ACMS that apparent bacteriostasis, especially embodiment 14 provide After micro-spheres have naringenin, anti-microbial property is more preferably.
Finally, it should be noted that the above embodiments are only used to illustrate the technical solution of the present invention., rather than its limitations;To the greatest extent Pipe present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that: its according to So be possible to modify the technical solutions described in the foregoing embodiments, or to some or all of the technical features into Row equivalent replacement;And these are modified or replaceed, various embodiments of the present invention technology that it does not separate the essence of the corresponding technical solution The range of scheme.

Claims (10)

1. a kind of preparation method of Ah-ACMS microballoon, which comprises the steps of: sodium alginate is molten Liquid is sprayed by electrostatic spray into the mixed solution of chitosan and calcium chloride, and Ah-ACMS microballoon is obtained.
2. preparation method according to claim 1, which is characterized in that the mass concentration of the sodium alginate soln is 1.5- 4%, preferably 2-3%.
3. preparation method according to claim 1, which is characterized in that in the mixed solution of the chitosan and calcium chloride, The mass concentration of chitosan is 0.05-0.2%, preferably 0.08-0.12%;
And/or the mass concentration of calcium chloride is 1-3%, preferably 1.5-2.5%.
4. preparation method according to claim 1, which is characterized in that the jet velocity of the sodium alginate soln is 3- 7mL/h, preferably 4.5-5.5mL/h;
Preferably, sodium alginate soln is sprayed into the mixed solution of chitosan and calcium chloride using high-voltage electrostatic sprayer.
5. a kind of Ah-ACMS microballoon, which is characterized in that preparation method according to claim 1-4 It obtains;
Preferably, the partial size of Ah-ACMS microballoon is 20-50 μm.
6. a kind of load medicine Ah-ACMS microballoon, which is characterized in that including alginic acid described in drug and claim 5 Calcium-chitosan microball, the drug are coated in the Ah-ACMS microballoon;
Preferably, the partial size for carrying medicine Ah-ACMS microballoon is 20-50 μm.
7. the preparation method according to claim 6 for carrying medicine Ah-ACMS microballoon, which is characterized in that including such as Lower step: the mixed solution of drug and sodium alginate is sprayed by electrostatic spray to the mixed solution to chitosan and calcium chloride In, it obtains carrying medicine Ah-ACMS microballoon.
8. preparation method according to claim 7, which is characterized in that in the mixed solution of the drug and sodium alginate, The mass concentration of sodium alginate is 1.5-4%, preferably 2-3%;
And/or in the mixed solution of the drug and sodium alginate, the mass concentration of drug is 0.5-1.5%, preferably 0.8- 1.2%.
9. preparation method according to claim 7, which is characterized in that in the mixed solution of the chitosan and calcium chloride, The mass concentration of chitosan is 0.05-0.2%, preferably 0.08-0.12%;
And/or the mass concentration of calcium chloride is 1-3%, preferably 1.5-2.5%.
10. preparation method according to claim 7, which is characterized in that the mixed solution of the drug and sodium alginate Jet velocity is 3-7mL/h, preferably 4.5-5.5mL/h;
Preferably, it is sprayed by high-voltage electrostatic sprayer into the mixed solution of chitosan and calcium chloride using syringe.
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