CN110368373A - A kind of micro-capsule and the preparation method and application thereof - Google Patents
A kind of micro-capsule and the preparation method and application thereof Download PDFInfo
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Abstract
The invention discloses a kind of micro-capsule and the preparation method and application thereof, the raw material for preparing of the micro-capsule includes arborvitae volatile oil and capsule material.The preparation method, comprising the following steps: take morpankhi oil, be added in gumwater, stirring emulsifies obtained morpankhi oil colostrum, keeps the temperature spare；While agitating by gelatin solution, it is added in colostrum, obtains mixed liquor after mixing completely, control the pH value of mixed liquor between 3.8~4.0；It to mixed liquor plus water, stirs to after 32~35 DEG C, by mixed liquor rapid cooling to 10 DEG C hereinafter, the formaldehyde of addition volume for arborvitae oil volume (0.3~0.5) again, adjusts pH to 8~9, micro-capsule is precipitated after standing；Filtering is drained up to the micro-capsule.Arborvitae volatile oil is prepared into micro-capsule not only can improve it is inconvenient to the shortcomings that storing transport, additionally it is possible to improve bioavilability and maximizes drug effect and play, improve the bioavilability of arborvitae volatile oil, increase a kind of possibility for the healing of disease.
Description
Technical field
The present invention relates to pharmaceutical technology fields, and in particular to a kind of micro-capsule and the preparation method and application thereof.
Background technique
Arborvitae (Thuja sutchuenensis) is Cupressaceae Thuja-Arten aiphyllium, belongs to China's endemic species, is a kind of rise
Derived from " living fossil " of Age of Dinosaur.In recent years, in the influence of the factors such as geography, ecological environment, acid rain, global warming
Under, the quantity of wild arborvitae presents the trend being gradually reduced, and protects alliance (International Union by the world
For Conservation of Nature, IUCN) it is chosen as world-class pole danger species.
From arborvitae in 1999 by since rediscovering, research is concentrated mainly on arborvitae genecology, Community Ecology at present
The fields such as, genetic diversity and its biological property, relatively about the research of its pharmacological action, chemical component and quality evaluation
It is few.Arborvitae either timber or leaf or fruit can give out stronger fragrance, and this fragrance volatilizees from arborvitae
Oil, correlative study show there is antioxygen containing terpenoids such as thujopsene, australene, limonenes in arborvitae volatile oil
Change, antitumor, blood pressure lowering, anti-inflammatory, expelling parasite, eliminating the phlegm, diuresis, anti-malarial, keeps fit and healthy and other effects antibacterial.Since arborvitae is volatilized
Oily poorly water-soluble, direct use is not only inconvenient, and bioavilability is lower, and the mouthfeel of oil is bad, is easy when directly taking
Lead to the symptoms such as Nausea and vomiting, it is poor so as to cause the compliance of patient.Therefore, it is necessary to arborvitae volatile oil is prepared into it is suitable
In the dosage form of clinical application, to preferably play the medical value of Thuja extract.
Micro-capsule (microcapsules) technology be it is a kind of will using natural or synthesis macromolecule filming material (capsule material)
Liquid or solid drug (capsule core material, abbreviation core material) is wrapped to form 1~1000 μm of diameter (usually 5~250 μm) tiny capsules
Technology, can be made into various dosage forms.There is multiple superiority, such as: microcapsules can be effectively prevented extraneous ring after medicament microcapsule
Border factor (pH value, oxygen, humidity, heat, light and other substances etc.) generates the adverse effects such as destruction to core material；Can be reduced core material to
The diffusion or evaporation of environment inhibit the volatilization loss of effective active composition in core material, improve its stability, hold quality
Long；Able person is and efficiently controls the release of core material, plays the original efficiency of core material to the maximum extent；Core material can be covered
Peculiar smell, improve the mouthfeel and the sense of taste of core material；The physics and chemical property for changing core material are convenient for storing and transport, mentions
Stability, bioavilability and the bioequivalence etc. of high drug entirety.The method for preparing micro-capsule in the prior art includes phase point
From method, physicomechanical processes and chemical method three categories, phase separation method includes Simple coacervation, complex coacervation, solvent-nonsolvent method, changes
Temperature method and intra-liquid desiccation method；Physicomechanical processes include spray drying process, spray condensation method, air suspension, porous centrifugation
Method and pan coating method；Chemical method includes emulsion-crosslinking method and interface polycondensation.Different preparation methods is suitable for the different capsule hearts
Object and capsule material.
For different capsule core materials select different capsule material and preparation process for can encystation and micro-capsule obtained shape
State, partial size, particle diameter distribution, medicine assay, drug release and drugloading rate etc. all have great influence.Currently, there has been no needles
The relevant report of micro-capsule is prepared as capsule core material to arborvitae volatile oil.
Summary of the invention
The first technical problem to be solved by the present invention is: providing, one kind is easy to carry and high bioavilability to be contained
The micro-capsule of arborvitae volatile oil.
Second technical problem to be solved by this invention is: providing a kind of easy to carry and high bioavilability contain
The preparation method of the micro-capsule of arborvitae volatile oil.
Third technical problem to be solved by this invention is: providing a kind of application of above-mentioned micro-capsule.
In order to solve above-mentioned first technical problem, the technical solution adopted by the present invention are as follows: a kind of micro-capsule, the micro-capsule
Preparing raw material includes arborvitae volatile oil and capsule material.
Further, the capsule material includes Arabic gum and gelatin.
Further, the volume mass ratio of the arborvitae volatile oil and the Arabic gum is (3~4) ml:(3~4) g；
Preferably, the volume mass ratio of the arborvitae volatile oil and the Arabic gum is 3ml:4g.
Further, the mass ratio of the Arabic gum and gelatin is (3~5): 3；Preferably, the Arabic gum with it is bright
The mass ratio of glue is 4:3.
The beneficial effects of the present invention are: the present invention program has been put forward for the first time arborvitae volatile oil and has been prepared into micro-capsule, micro-capsule energy
The bad smell for enough covering drug increases compliance, and liquid drug solid state improves the stability of drug, improves drug
Bioavilability, while the advantages that micro-capsule also has both targeting, slow release long-acting and embolic；Therefore, it prepared by arborvitae volatile oil
It can not only be improved at micro-capsule is inconvenient to the shortcomings that storing transport, additionally it is possible to improve bioavilability for drug effect and maximize hair
It waves, improves the bioavilability of arborvitae volatile oil, increase a kind of possibility for the healing of disease.
In order to solve above-mentioned second technical problem, the technical solution adopted by the present invention are as follows: a kind of preparation method of micro-capsule,
The following steps are included:
The preparation of S1, gelatin solution: taking gelatin to soak in water, and dissolves by heating at 35~55 DEG C after swelling, stirs evenly and protects
It is spare that gelatin solution is made in temperature；
The preparation of S2, gumwater: taking Arabic gum to soak in water, and dissolves by heating at 35~55 DEG C after swelling,
It stirs evenly and keeps the temperature, it is spare that gumwater is made；
The preparation of S3, morpankhi oil colostrum: taking morpankhi oil, is added in gumwater, and morpankhi oil is made in stirring, emulsification
Colostrum is kept the temperature spare；
S4, mixing: while agitating by gelatin solution made from step S1, being added in colostrum made from step S3,
Mixed liquor is obtained after mixing completely, controls the pH value of mixed liquor between 3.8~4.0；
S5, solidification: to step S4 treated mixed liquor adds water, stirring is to after 32~35 DEG C, by mixed liquor rapid cooling
To 10 DEG C hereinafter, it is the formaldehyde of arborvitae oil volume (0.3~0.5) again that volume, which is added, (15~30) min is stirred, pH to 8 is adjusted
~9, continue to stir (20~40) min, micro-capsule is precipitated after standing；
S6, post-processing: filtering is drained up to the micro-capsule.
Further, the rapid cooling in the step S5 refers to completes cooling operation in 3~5min.
Further, operation is drained in the filtering specifically: after micro-capsule sedimentation completely, incline supernatant, and filtering is used in combination
It is drained after water washing to formaldehydeless taste to get the micro-capsule.
Further, the mass percentage concentration of gelatin is 3~5% in the gelatin emulsion prepared in the step S2.
Further, in the gumwater prepared in the step S3 the mass percentage concentration of Arabic gum be 3~
5%.
Further, in the step S3, the revolving speed of the Emulsification Procedure is that (8000~12000) turn/min；It is excellent
Selection of land, in the step S3, the revolving speed in the Emulsification Procedure is 12000 revs/min.
Further, in the step S3, the time of the emulsification procedure is 20s~70s；Preferably 30s~60s.
Preferably, it is 4.0 that pH value is controlled in the step S4, and control pH value is 8.0 in the step S5.
The beneficial effects of the present invention are: the present invention program, which provides one kind, (has phase using two kinds by complex coacervation
The high molecular material of counter charges by capsule core material dispersion, is suspended or is emulsified in the aqueous solution of capsule material, certain as compound capsule material
Under the conditions of be crosslinked and agglomerate encystation with capsule core material) preparation arborvitae volatile oil micro-capsule, by the method for the invention being capable of partial size obtained
Micro-capsule uniform, size distribution dispersion is small and appearance roundness is good；By complex coacervation using Arabic gum and gelatin as capsule material,
Carry out arborvitae volatile oil package, reduce the factors such as pH value in external environment, oxygen, temperature and humidity and illumination to volatile oil at
The destruction divided, reduces the volatilization loss of active constituent in volatile oil, improves the stability of drug effect, while can also cover arborvitae
The peculiar smell and sense of discomfort of volatile oil, increase the compliance of user；This method is easy to operate, each technological parameter is easily controllable and raw
It produces high-efficient.
In order to solve above-mentioned third technical problem, the technical solution adopted by the present invention are as follows: a kind of above-mentioned micro-capsule is in drug
Application in the preparation of injection, tablet or capsule.
The beneficial effects of the present invention are: micro-capsule, which is made, in the present invention program has good medical value, can be widely applied
In being prepared into the finished dosage forms such as injection, tablet or capsule, also can be used directly.
Detailed description of the invention
Fig. 1 is the pattern observed under 40 power microscopes after colostrum made from the embodiment of the present invention 1~3 dyes；
Fig. 2 is the state after micro-capsule made from the embodiment of the present invention 1~3 is stood；
Fig. 3 is pattern of the micro-capsule under 40 power microscopes made from the embodiment of the present invention 1；
Fig. 4 is pattern of the micro-capsule under 40 power microscopes made from the embodiment of the present invention 2；
Fig. 5 is pattern of the micro-capsule under 40 power microscopes made from the embodiment of the present invention 3；
Fig. 6 is the particle size distribution figure of micro-capsule made from the embodiment of the present invention 1~3 randomly selected.
Specific embodiment
To explain the technical content, the achieved purpose and the effect of the present invention in detail, below in conjunction with embodiment and cooperate attached
Figure is explained.
The embodiment of the present invention one are as follows: a kind of micro-capsule, preparation process the following steps are included:
1, take gelatin 3g be added 20ml distilled water after in beaker impregnate swelling after stirred in 50 DEG C of thermostat water baths it is molten
Xie Hou is added distilled water and stirs evenly to 100ml, gelatin emulsion is made, keeps the temperature at 50 DEG C spare；
2, take Arabic gum 3g that 20ml distilled water immersion, stirring and dissolving in Yu Hengwen (50 DEG C) water-bath after swelling is added
Afterwards, distilled water is added to stir evenly to 100ml, and is kept the temperature at 50 DEG C, it is spare that gumwater is made；
3, arborvitae volatile oil 3ml is taken, addition 100ml gumwater is placed on emulsification 1min in tissue refiner and (turns
12000 revs/min of speed), it is transferred in beaker and is prepared into colostrum, heat preservation (50 DEG C) is spare；
4, gelatin emulsion is added in colostrum under stiring, it is to be mixed completely after, measure mixed liquor pH be 5.0；
5, pH value is adjusted while stirring with acetum (mass percent 10%) to after 3.9, and distilled water is added
400ml, after being placed in a beaker stirring to room temperature (35 DEG C), with ice cube rapid cooling to 10 DEG C hereinafter, 37% formaldehyde is added
2.5ml after stirring 15min, after being adjusted to 8.0 with sodium hydroxide solution (mass percent 20%) adjusting pH, continues to stir
It is stood after 20min；
6, after micro-capsule settles down completely, supernatant is filtered off, is filtered with Vacuum filtration device, and be washed with distilled water to
Do not have until formaldehyde to get micro-capsule sterling.
The embodiment of the present invention two are as follows: a kind of micro-capsule, preparation process the following steps are included:
1, take gelatin 3g be added 20ml distilled water after in beaker impregnate swelling after stirred in 50 DEG C of thermostat water baths it is molten
Xie Hou is added distilled water and stirs evenly to 100ml, gelatin emulsion is made, keeps the temperature at 50 DEG C spare；
2, take Arabic gum 3g that 20ml distilled water immersion, stirring and dissolving in Yu Hengwen (50 DEG C) water-bath after swelling is added
Afterwards, distilled water is added to stir evenly to 100ml, and is kept the temperature at 50 DEG C, it is spare that gumwater is made；
3, arborvitae volatile oil 3ml is taken, 100ml gumwater is added and is placed in emulsification 1min (revolving speed in tissue refiner
12000 revs/min), it is transferred in beaker and is prepared into colostrum, heat preservation (50 DEG C) is spare；
4, gelatin emulsion is added in colostrum under stiring, it is to be mixed completely after, measure mixed liquor pH be 5.0；
5, pH value is adjusted while stirring with acetum (mass percent 10%) to after 3.9, and distilled water is added
400ml, is placed in a beaker stirring to after room temperature (25 DEG C), with ice cube rapid cooling to 10 DEG C hereinafter, 37% formaldehyde 3ml is added,
After stirring 15min, after being adjusted to 9.0 with sodium hydroxide solution (mass percent 20%) adjusting pH, continue after stirring 30min
It stands；
6, after micro-capsule settles down completely, supernatant is filtered off, is filtered with Vacuum filtration device, and be washed with distilled water to
Do not have until formaldehyde to get micro-capsule sterling.
The embodiment of the present invention three are as follows: a kind of micro-capsule, preparation process the following steps are included:
1, take gelatin 3g be added 20ml distilled water after in beaker impregnate swelling after stirred in 50 DEG C of thermostat water baths it is molten
Xie Hou is added distilled water and stirs evenly to 100ml, gelatin emulsion is made, keeps the temperature at 50 DEG C spare；
2, take Arabic gum 3g that 20ml distilled water immersion, stirring and dissolving in Yu Hengwen (50 DEG C) water-bath after swelling is added
Afterwards, distilled water is added to stir evenly to 100ml, and is kept the temperature at 50 DEG C, it is spare that gumwater is made；
3, arborvitae volatile oil 3ml is taken, 100ml gumwater is added and is placed in emulsification 1min (revolving speed in tissue refiner
12000 revs/min), it is transferred in beaker and is prepared into colostrum, heat preservation (50 DEG C) is spare；
4, gelatin emulsion is added in colostrum under stiring, it is to be mixed completely after, measure mixed liquor pH be 5.0；
5, pH value is adjusted while stirring with acetum (mass percent 10%) to after 4.0, and distilled water is added
400ml, is placed in a beaker stirring to after room temperature (25 DEG C), with ice cube rapid cooling to 10 DEG C hereinafter, 37% formaldehyde 4ml is added,
After stirring 15min, after being adjusted to 8.0 with sodium hydroxide solution (mass percent 5%) adjusting pH, continue after stirring 30min
It stands；
6, after micro-capsule settles down completely, supernatant is filtered off, is filtered with Vacuum filtration device, and be washed with distilled water to
Do not have until formaldehyde to get micro-capsule sterling.
After colostrum made from step 2 is dyed with the film in Example 1~3, staining conditions are observed under 40 power microscopes,
To analyze emulsion type, as a result as shown in Figure 1, A, B and C are corresponding in turn to the colostrum obtained in embodiment 1,2 and 3 in Fig. 1, from
As can be seen that emulsifier obtained is multiple emulsion in example scheme in figure.
Step 4 treated micro-capsule product is as shown in Fig. 2, A, B and C correspond respectively to implement in Fig. 2 in Examples 1 to 3
Example 1,2 and 3, it can be seen from the figure that micro-capsule obtained is milky, graininess, band oiliness and is deposited in beaker bottom.
Observe step 5 treated micro-capsule product in Examples 1 to 3, as a result, it has been found that micro-capsule obtained filter after in slightly
The gelatin object of oiliness.
The partial size that micro-capsule sterling obtained observes micro-capsule under 40 power microscopes after step 5 processing of Example 1~3 is big
Small, encystation situation and particle diameter distribution situation, the micro-capsule that microscopically observation arrives are successively as shown in Figures 4 and 5.
A and B is respectively the MIcrosope image in the micro-capsule difference visual field made from embodiment 1 in Fig. 3, can from figure
Out, micro-capsule difference in size made from the embodiment is larger, and for particle diameter distribution between 10~500 μm, the average grain diameter of particle is 249
μm, the roundness of part micro-capsule is bad, and whole preferable, resulting micro-capsule is compound micro-capsule.
A and B is respectively the MIcrosope image in the micro-capsule difference visual field made from embodiment 2 in Fig. 4, can from figure
Out, micro-capsule difference in size made from the embodiment is larger, and for particle diameter distribution between 10~500 μm, the average grain diameter of particle is 234
μm, the roundness of micro-capsule is preferable, and resulting micro-capsule is compound micro-capsule.
A and B is respectively the MIcrosope image in the micro-capsule difference visual field made from embodiment 3 in Fig. 5, can from figure
Out, micro-capsule difference in size made from the embodiment is smaller, and for particle diameter distribution between 10~270 μm, the average grain diameter of particle is 150
μm, the roundness of micro-capsule is good, and resulting micro-capsule is compound micro-capsule.
100 particles in micro-capsule made from each embodiment are randomly selected, observe under the microscope and count partial size point
Cloth situation, as a result as shown in Figure 6 (250 μm or less parts are illustrated only in figure), the as can be seen from Figure 6 system in embodiment 3
The microcapsule diameter distribution obtained is more concentrated.
The above description is only an embodiment of the present invention, is not intended to limit the scope of the invention, all to utilize this hair
Equivalents made by bright specification and accompanying drawing content are applied directly or indirectly in relevant technical field, similarly include
In scope of patent protection of the invention.
Claims (10)
1. a kind of micro-capsule, it is characterised in that: the raw material for preparing of the micro-capsule includes arborvitae volatile oil and capsule material.
2. micro-capsule according to claim 1, it is characterised in that: the capsule material includes Arabic gum and gelatin.
3. micro-capsule according to claim 2, it is characterised in that: the volume matter of the arborvitae volatile oil and the Arabic gum
Amount is than being (3~4) ml:(3~4) g；Preferably, the volume mass ratio of the arborvitae volatile oil and the Arabic gum is 3ml:
4g。
4. micro-capsule according to claim 2, it is characterised in that: the mass ratio of the Arabic gum and gelatin is (3~5):
3；Preferably, the mass ratio of the Arabic gum and gelatin is 4:3.
5. a kind of preparation method of micro-capsule, it is characterised in that: the following steps are included:
The preparation of S1, gelatin solution: taking gelatin to soak in water, and dissolves by heating at 35~55 DEG C after swelling, stirs evenly and keeps the temperature, system
It is spare to obtain gelatin solution；
The preparation of S2, gumwater: taking Arabic gum to soak in water, and dissolves by heating, stirs evenly at 35~55 DEG C after swelling
And keep the temperature, it is spare that gumwater is made；
The preparation of S3, morpankhi oil colostrum: taking morpankhi oil, is added in gumwater, and morpankhi oil colostrum is made in stirring, emulsification,
It keeps the temperature spare；
S4, mixing: while agitating by gelatin solution made from step S1, being added in colostrum made from step S3, mixing
Mixed liquor is obtained after completely, controls the pH value of mixed liquor between 3.8~4.0；
S5, solidification: to step S4 treated mixed liquor adds water, stirring is to after 32~35 DEG C, by mixed liquor rapid cooling to 10
DEG C hereinafter, formaldehyde that volume is arborvitae oil volume (0.3~0.5) times is added, (15~30) min is stirred, pH to 8~9 is adjusted,
Continue to stir (20~40) min, micro-capsule is precipitated after standing；
S6, post-processing: filtering is drained up to the micro-capsule.
6. the preparation method of micro-capsule according to claim 5, it is characterised in that: the rapid cooling in the step S5 refers to
Cooling operation is completed in 3~5min.
7. the preparation method of micro-capsule according to claim 5, it is characterised in that: the gelatin solution prepared in the step S1
The mass percentage concentration of middle gelatin is 3~5%.
8. the preparation method of micro-capsule according to claim 5, it is characterised in that: the Arabic gum prepared in the step S2
The mass percentage concentration of Arabic gum is 3~5% in solution.
9. the preparation method of micro-capsule according to claim 5, it is characterised in that: in the step S3, the emulsification procedure
Time be 20~70s；Preferably 30~60s.
10. a kind of such as the described in any item micro-capsules of Claims 1 to 4 answering in the preparation of drug injection, tablet or capsule
With.
Priority Applications (1)
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| CN114504564A (en) * | 2020-10-28 | 2022-05-17 | 北京远大九和药业有限公司 | Eucalyptus and pinene enteric-coated microcapsule and preparation method thereof |
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Application publication date: 20191025 |