CN111973477A - Preparation method of idebenone and microcrystalline cellulose composite carrier and cosmetic - Google Patents
Preparation method of idebenone and microcrystalline cellulose composite carrier and cosmetic Download PDFInfo
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- CN111973477A CN111973477A CN202010921126.8A CN202010921126A CN111973477A CN 111973477 A CN111973477 A CN 111973477A CN 202010921126 A CN202010921126 A CN 202010921126A CN 111973477 A CN111973477 A CN 111973477A
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- microcrystalline cellulose
- idebenone
- oleic acid
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- 229920000168 Microcrystalline cellulose Polymers 0.000 title claims abstract description 114
- 229940016286 microcrystalline cellulose Drugs 0.000 title claims abstract description 114
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- 235000019813 microcrystalline cellulose Nutrition 0.000 title claims abstract description 113
- JGPMMRGNQUBGND-UHFFFAOYSA-N idebenone Chemical compound COC1=C(OC)C(=O)C(CCCCCCCCCCO)=C(C)C1=O JGPMMRGNQUBGND-UHFFFAOYSA-N 0.000 title claims abstract description 78
- 229960004135 idebenone Drugs 0.000 title claims abstract description 77
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- 238000002360 preparation method Methods 0.000 title claims abstract description 15
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- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 claims abstract description 43
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Images
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/35—Ketones, e.g. benzophenone
- A61K8/355—Quinones
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/36—Carboxylic acids; Salts or anhydrides thereof
- A61K8/361—Carboxylic acids having more than seven carbon atoms in an unbroken chain; Salts or anhydrides thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
- A61K8/73—Polysaccharides
- A61K8/731—Cellulose; Quaternized cellulose derivatives
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/08—Anti-ageing preparations
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
- A61K2800/41—Particular ingredients further characterized by their size
- A61K2800/412—Microsized, i.e. having sizes between 0.1 and 100 microns
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
- A61K2800/52—Stabilizers
- A61K2800/522—Antioxidants; Radical scavengers
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
- A61K2800/56—Compounds, absorbed onto or entrapped into a solid carrier, e.g. encapsulated perfumes, inclusion compounds, sustained release forms
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/80—Process related aspects concerning the preparation of the cosmetic composition or the storage or application thereof
- A61K2800/82—Preparation or application process involves sonication or ultrasonication
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Birds (AREA)
- Epidemiology (AREA)
- Emergency Medicine (AREA)
- Gerontology & Geriatric Medicine (AREA)
- Dermatology (AREA)
- Cosmetics (AREA)
Abstract
The invention discloses a preparation method of idebenone and microcrystalline cellulose composite carrier, comprising the following steps: taking microcrystalline cellulose powder, dispersing in an aqueous solution to form a suspension containing microcrystalline cellulose particles; dropwise adding an oleic acid ethanol solution into the suspension, stirring and mixing, carrying out surface oleic acid coating on the microcrystalline cellulose particles, and carrying out centrifugal washing to obtain oleic acid-coated microcrystalline cellulose particles; dispersing the obtained microcrystalline cellulose particles in an ethanol solution, introducing idebenone for compounding, and centrifugally drying to obtain the idebenone and microcrystalline cellulose composite carrier. The invention also provides a cosmetic. The invention has the following advantages: the sustained and slow release of idebenone is realized, so that the potential irritation is effectively reduced, meanwhile, the particle is simple in preparation process and good in biocompatibility, can be well used in skin external products, and is suitable for expanded production.
Description
[ technical field ] A method for producing a semiconductor device
The invention relates to the technical field of cosmetics, and particularly relates to a preparation method of an idebenone and microcrystalline cellulose composite carrier and a cosmetic.
[ background of the invention ]
Idebenone is chemically named 6- (10-hydroxydecyl) -2, 3-dimethoxy-5-methyl-1, 4-benzoquinone, has a structure similar to coenzyme Q10, is a CoQ10 short-chain branched structure analogue with a lower molecular weight, and has been clinically used for repairing photoaged skin. In the cosmetic field, the idebene has good antioxidant effect, and can scavenge free radicals, inhibit mitochondrial generation of lipid peroxide, inhibit inflammation, inhibit DNA damage, prevent photodamage, and relieve pigmentation. Researches show that the idebenone can improve fine lines and roughness of skin and improve elasticity, color and brightness of the skin, and is a very ideal cosmetic active substance.
However, idebenone has a small molecular weight and a high permeation rate, and thus is irritating to the skin and eyes, and may cause irreversible damage to the skin. Meanwhile, the idebene is unstable in chemical property and easy to degrade and inactivate under the heating condition; in addition, since it is not easily dissolved in an aqueous solution and a part of oil and fat, the use thereof in a cosmetic formulation is limited. Therefore, in order to effectively utilize idebenone, the above-mentioned problems need to be solved.
Microcrystalline cellulose is a cellulose product which is partially depolymerized with dilute acid, and the structure of the microcrystalline cellulose is usually superfine short rod-shaped or powdery porous particles, and the main component of the microcrystalline cellulose is a linear chain polysaccharide substance combined by beta-1-4 glucoside bonds. Because of the special properties of low polymerization degree, large specific surface area and the like, the microcrystalline cellulose is widely applied to the industries of medicine, food, cosmetics and the like.
The microcrystalline cellulose has a certain physical adsorption capacity due to the porous structure, so that the microcrystalline cellulose has good potential for loading active substances. However, highly efficient loading and release of partially water insoluble actives is difficult to achieve by physical adsorption alone. Therefore, it is necessary to partially surface-modify microcrystalline cellulose to improve its application effect.
[ summary of the invention ]
The invention aims to provide a preparation method of idebenone and microcrystalline cellulose composite carrier and cosmetics, which are used for improving the stability of idebenone and providing controllable release.
In order to achieve the purpose, the technical scheme of the invention is as follows:
a preparation method of idebenone and microcrystalline cellulose composite carrier comprises the following steps:
taking microcrystalline cellulose powder, and dispersing the microcrystalline cellulose powder in an aqueous solution to form a suspension containing microcrystalline cellulose particles;
step two, dropwise adding an oleic acid ethanol solution into the suspension, stirring and mixing, then carrying out surface oleic acid coating on the microcrystalline cellulose particles, washing, and centrifuging to obtain microcrystalline cellulose particles coated with oleic acid;
dispersing the obtained oleic acid-coated microcrystalline cellulose particles in an ethanol solution, introducing 0.1-10mg/mL idebenone and oleic acid-coated microcrystalline cellulose particles for compounding, loading for 12-72 hours, and performing centrifugal drying to obtain the idebenone and microcrystalline cellulose composite carrier with the idebenone slow-release effect.
Preferably: in the first step, the microcrystalline cellulose powder is dispersed in the aqueous solution by ultrasonic, the mass concentration of the microcrystalline cellulose is 1-5%, and the microcrystalline cellulose is sheared and dispersed at 300-500 rpm to form uniform suspension.
Preferably: in the second step, after the suspension is heated to 60 ℃, 0.5 to 2 mass percent of oleic acid ethanol solution is added dropwise, and the mixture is stirred for 1 hour.
Preferably: the volume ratio of oleic acid to ethanol in the oleic acid ethanol solution is 1: 1.
Preferably: in step two, five washes with deionized water were performed.
Preferably: the microcrystalline cellulose particles have a particle size of 20 microns.
The invention also provides a cosmetic which comprises the idebenone and microcrystalline cellulose composite carrier, and the concentration of the microspheres in the cosmetic is less than or equal to 1000 mu g/mL.
Compared with the related art, the preparation method of the idebenone and microcrystalline cellulose composite carrier provided by the invention has the following advantages:
(1) the oleophylic microcrystalline cellulose particles are obtained by the low-temperature water washing treatment of oleic acid. The microcrystalline cellulose is easy to degrade under high temperature conditions, so that the structure and the characteristics of the particles are changed. Through low-temperature lipophilic treatment at 60 ℃, lipophilic molecular oleic acid can be adsorbed on microcrystalline cellulose, so that the dispersion of the microcrystalline cellulose in a nonpolar oil solution is improved, and the binding effect of the microcrystalline cellulose on idebenone is enhanced, thereby having a good loading effect;
(2) physicochemical representation and investigation are carried out on the microcrystalline cellulose with different grain diameters, and the microcrystalline cellulose with the grain diameter of 20 microns is determined to have the best physical adsorption characteristic through the grain diameter, the appearance and the specific surface area;
(3) the optimal idebenone concentration and the carrier loading time are determined through static and dynamic adsorption experiments, and the subsequent active matter loading is guided and optimized through the optimization of the adsorption experiments;
(4) the raw materials adopted by the preparation method of the invention, including the active substances and the carrier substances, are non-toxic and green, have excellent biological safety, and have no use risk in the use catalogue of cosmetic raw materials;
(5) the idebenone and microcrystalline cellulose composite carrier can be used for effectively loading idebenone and realizing the sustained and slow release of the idebenone, so that the potential irritation is effectively reduced, and meanwhile, the particle is simple in preparation process and good in biocompatibility, can be well used in skin external products, and is suitable for expanded production.
[ description of the drawings ]
In order to more clearly illustrate the technical solutions in the embodiments of the present invention, the drawings needed to be used in the description of the embodiments are briefly introduced below, it is obvious that the drawings in the following description are only some embodiments of the present invention, and other drawings can be obtained by those skilled in the art without inventive efforts, wherein:
FIG. 1 shows the dispersibility of microcrystalline cellulose in hydrophilic and lipophilic solvents before and after oleic acid coating;
FIG. 2 is a scanning electron micrograph of the micro-morphology of microcrystalline cellulose with three particle sizes;
FIG. 3 is a graph showing the surface potentials of microcrystalline cellulose having three particle sizes;
FIG. 4 is an optical photograph of MCC-20 cellulose particles before and after loading;
FIG. 5 shows the IDB visible light absorption spectrum of the centrifuged supernatant before and after MCC-20 cellulose particle loading;
FIG. 6 is a graph of the static adsorption curves for different active concentrations of MCC-20 cellulose particles;
FIG. 7 is a graph showing the dynamic adsorption curves of MCC-20 cellulose particles at different adsorption times;
FIG. 8 is a curve of the release of an active of MCC-20 cellulose particles;
figure 9 shows idebenone, microcrystalline cellulose composite carrier biocompatibility.
[ detailed description ] embodiments
The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
The invention provides a preparation method of idebenone and microcrystalline cellulose composite carrier, comprising the following steps:
taking microcrystalline cellulose powder, and dispersing the microcrystalline cellulose powder in an aqueous solution to form a suspension containing microcrystalline cellulose particles;
specifically, microcrystalline cellulose powder is dispersed in an aqueous solution by adopting ultrasonic, the mass concentration of the microcrystalline cellulose is 1-5%, and the microcrystalline cellulose is sheared and dispersed at 300-500 rpm to form uniform suspension.
Step two, dropwise adding an oleic acid ethanol solution into the suspension, stirring and mixing, then carrying out surface oleic acid coating on the microcrystalline cellulose particles, washing, and centrifuging to obtain microcrystalline cellulose particles coated with oleic acid;
specifically, after the suspension is heated to 60 ℃, 0.5-2% of oleic acid ethanol solution in percentage by mass is added dropwise, the mixture is stirred for 1 hour, and the volume ratio of oleic acid to ethanol in the oleic acid ethanol solution is 1: 1. Washed five times with deionized water, then centrifugally dried.
Dispersing the obtained oleic acid-coated microcrystalline cellulose particles in an ethanol solution, introducing 0.1-10mg/mL idebenone to compound with the oleic acid-coated microcrystalline cellulose particles, loading for 12-72 hours, and centrifugally drying to obtain the idebenone and microcrystalline cellulose composite carrier with the idebenone slow-release effect.
Specifically, the particle size of the microcrystalline cellulose particles is 20 microns.
The invention also provides a cosmetic which comprises the idebenone and microcrystalline cellulose composite carrier, and the concentration of the microspheres in the cosmetic is less than or equal to 1000 mu g/mL.
The efficacy of idebenone and microcrystalline cellulose composite carriers provided by the invention is verified by a specific experiment.
EXAMPLE 1 oleic acid-modified microcrystalline cellulose microparticles
1) Three solid microcrystalline cellulose powders (MCC-20, MCC-90, MCC-250) with different particle sizes were weighed, dispersed in an aqueous solution to a final mass concentration of 5%, and dispersed by shearing at 300-500 rpm after ultrasonic dispersion to form a uniform suspension.
2) The suspension was heated to 60 ℃, and a 2% by mass ethanol solution of oleic acid (volume ratio 1: 1) and dropwise adding the mixture into the suspension, stirring for 1 hour, after adsorption equilibrium, washing the obtained oleic acid modified microcrystalline cellulose particles with deionized water, repeating the steps for 5 times, centrifugally collecting and drying.
Microcrystalline cellulose itself has a certain adsorption capacity. By introducing oleic acid, the oleic acid can be adsorbed and combined with the surface of the microcrystalline cellulose, so that the microcrystalline cellulose coated by the oleic acid is formed. The introduction of oleic acid can increase the dispersion of the particles in a hydrophobic environment. In FIG. 1, an aqueous solution and a cyclohexane solution are used, respectively, and microcrystalline cellulose particles before and after modification are dispersed therein. As shown in fig. 1, before unmodified, the particles were dispersed in an aqueous solution; after being coated with oleic acid, the particles were dispersed in cyclohexane solution, thus confirming that the surface was modified to increase hydrophobicity.
And (3) performing apparent morphology observation of a scanning electron microscope on the prepared oleic acid modified microcrystalline cellulose particles: and (3) taking a proper amount of product particles, adding the product particles into absolute ethyl alcohol, carrying out ultrasonic dispersion, dropping 1-2 drops of particle suspension on a copper mesh, and pasting the sample on a conductive adhesive after the sample is dried. The surface morphology and size of the particles were observed using a field emission scanning electron microscope (FE-SEM, S-3400, Hitachi, Japan).
As can be seen from the scanning electron microscope image in fig. 2, the apparent morphology of the three microcrystalline cellulose powders with different particle sizes is different. In MCC-20, the particle size is small, the basic unit is a short rod, and the surface is rough. After stacking, slightly larger aggregates are formed, which in the form of stacking bring about a pore structure in the surface and thus have a larger specific surface area. In MCC-90 and MCC-250, the surface roughness decreases after the particle size increases gradually. The packing structure is no longer evident due to the increase in particle size, and therefore the specific surface area is also reduced.
After heat treatment to remove water, the specific surface area of the different particles was determined by BET adsorption. As can be seen from the adsorption data in Table 1, the specific surface area decreases significantly with increasing microcrystalline cellulose particle size, from 33.84m2The/g is reduced to 11.96m2/g。
TABLE 1
BET adsorption
And detecting the surface potential of the oleic acid modified microcrystalline cellulose particles by using a Malvern laser particle size potentiometer. Taking trace powder, and carrying out ultrasonic dispersion for 10min to obtain a uniform and turbid suspension. The solution was immediately placed in a potentiometric vessel and the surface potential of the particles was measured.
As can be seen from fig. 3, after undergoing the oleic acid modification, the surface charge of the particles is negative, originating from the carboxyl groups of the oleic acid. Wherein the MCC-20 is about-17 mV, the MCC-90 is about-13 mV, and the MCC-250 is about-22 mV. The surface has certain negative charges, which is beneficial to increasing the electrostatic interaction with partial positive charge nuclear active matters, thereby enhancing the physical adsorption capacity.
Example 2 determination of adsorption Capacity of oleic acid-modified microcrystalline cellulose microparticles
1) Selecting microcrystalline cellulose MCC-20 with the diameter of 20 microns as a carrier, dispersing the carrier in an aqueous solution to enable the final mass concentration to be 5%, and after ultrasonic dispersion, shearing and dispersing at 300-500 rpm to form a uniform suspension;
2) the suspension was heated to 60 ℃, and a 2% by mass ethanol solution of oleic acid (volume ratio 1: 1) and added dropwise to the microcrystalline cellulose suspension, and stirred for 1 hour. After adsorption balance, washing the obtained oleic acid modified microcrystalline cellulose particles with deionized water, repeating the steps for 5 times, centrifuging, collecting and drying;
3) dispersing the particles modified by the oleic acid in an ethanol solution, introducing 10mg/mL idebenone, loading for 72 hours, centrifugally drying to obtain an idebenone/microcrystalline cellulose composite carrier, collecting the centrifuged supernatant, and determining the concentration of the residual idebenone solution;
4) dispersing unmodified MCC-20 serving as a carrier in an ethanol solution, introducing 10mg/mL idebenone, loading for 72 hours, carrying out centrifugal drying to obtain a control group carrier, collecting a centrifuged supernatant, and determining the concentration of the remaining idebenone solution.
After loading, drug-loaded particles and supernatant were obtained separately, and the loading performance was evaluated. FIG. 4 shows MCC-20/IDB composite particles and unloaded MCC-20 particles after centrifugal drying. As can be seen in FIG. 4, the MCC-20/IDB composite particles appeared as a distinct yellow powder after loading, confirming that idebenone was able to adsorb onto the cellulose particles.
FIG. 5 the centrifugation supernatant after active loading was collected and its adsorption capacity was determined by measuring the light absorption of idebenone in the supernatant. The lower the OD value of idebenone in the supernatant, the more idebenone adsorbed onto the particles. As can be seen from the experimental results, idebenone produces an absorption peak at about 280 nm. For the group of non-oleic acid coated microcrystalline cellulose particles (MCC-20), the free idebenone absorption peak in the centrate was significantly reduced, demonstrating that the particles are able to adsorb idebenone to form an active load. The oleic acid-coated microcrystalline cellulose particles (OA + MCC-20) showed a significant decrease in the absorbance peak of free idebenone in the centrifugate, and the OD value was lower than that of the unmodified group. This difference indicates that the hydrophobic oleic acid modified particles have a better adsorption effect on idebenone.
Example 3 measurement of static adsorption Capacity of microcrystalline cellulose Fine particles and idebenone
Dispersing 20mg of the obtained oleic acid modified microcrystalline cellulose particles in 5mL of ethanol solution, and introducing idebenone active substances with different concentrations to ensure that the final concentration is 0.1-10 mg/mL. Sonicate for 10min and magnetically stir at 400rpm for 24 hours at room temperature. After equilibrium of adsorption was reached, centrifugation was carried out at 6000rpm for 10min, and the resulting supernatant was measured for absorbance at λ -280 nm and the concentration of released drug was determined by comparison with a standard curve.
Wherein the adsorption efficiency is (total mass of idebenone-mass of idebenone in supernatant)/total mass of idebenone.
The adsorption amount is (total mass of idebenone-mass of idebenone in supernatant)/mass of non-drug-loaded particles.
As can be seen from the results of fig. 6, the total loading amount gradually increased as the concentration of the active substance added increased from the viewpoint of the adsorption amount, and the loading amount was in a dose-dependent relationship. When the concentration of idebenone reaches 10mg/mL, the adsorption amount of idebenone is obviously increased to 1.90g/g particles, and the adsorption amount is further increased along with the increase of the concentration. From the aspect of adsorption efficiency, when the addition concentration of idebenone is within 10mg/mL, the adsorption efficiency gradually increases with the concentration, and reaches 76.12% at 10 mg/mL. When the concentration exceeds 10mg/mL, the adsorption efficiency is rather reduced to 50% or less. Therefore, by integrating the adsorption amount and the adsorption efficiency, the final concentration of idebenone is 10mg/mL, and the idebenone has better adsorption amount and high adsorption efficiency.
Example 4 measurement of dynamic adsorption Capacity of microcrystalline cellulose Fine particles and idebenone
20mg of the obtained oleic acid-modified microcrystalline cellulose particles were dispersed in 5mL of an ethanol solution, and an idebenone active substance was introduced to a final concentration of 10 mg/mL. Sonicate for 10min and magnetically stir at 400rpm at room temperature for 12, 24, 72 hours. After equilibrium of adsorption was reached, centrifugation was carried out at 6000rpm for 10min, and the resulting supernatant was measured for absorbance at λ -280 nm and the concentration of released drug was determined by comparison with a standard curve.
Wherein the adsorption amount is (total mass of idebenone-mass of idebenone in supernatant)/mass of non-drug-loaded particles.
From the results of fig. 7, it is understood that the adsorption amount of the active material gradually increases as the load time increases. At a loading time of 12 hours, the active adsorption capacity is about 1.0 g/g; after the loading time is prolonged to 24 hours, the adsorption capacity is increased to about 1.9 g/g; and the adsorption time is further prolonged to 72 hours, and the adsorption quantity is not obviously changed. Therefore, at 24 hours, the active reached saturation adsorption. A treatment time of 24 hours was finally selected as the time to reach maximum adsorption of the active.
EXAMPLE 5 microcrystalline cellulose microparticles, idebenone active Release Curve determination
10mg of drug-loaded particles are weighed, dispersed in 10mL of ethanol solution, and placed in a constant temperature shaking box at 37 ℃ with the shaking speed of 80rpm and the amplitude of 20 mm. At different time nodes (1, 2, 4, 8, 12, 24 hours), the suspension was removed and centrifuged at 6000rpm for 10 min. The resulting supernatant was measured for absorbance at λ 280nm and the concentration of idebenone released was determined by comparison with a standard curve. At the same time, 10ml of fresh ethanol solution was supplemented, keeping the volume constant. And calculating the accumulated drug release amount to obtain the in-vitro drug release curve of the drug-loaded particles.
As can be seen from the release profile of fig. 8, the cumulative amount of idebenone released gradually increased with the increase of the release time, showing a distinct controlled release profile. Within the initial 1 hour, about 13% of the active is released; while the cumulative release increased gradually to 80% over 24 hours. Compared with free idebenone, the microcrystalline cellulose can realize a slow release effect after being loaded, thereby being beneficial to reducing irritation.
Example 6 biocompatibility
The biocompatibility of the zinc oxide/calcium alginate core-shell structure microsphere is detected by adopting an MTT method.
(a) Using vascular endothelial cell HuVEC as model, HuVEC cells were inoculated into 96-well culture plates at 3000-2Culturing in an incubator overnight;
(b) placing the zinc oxide/calcium alginate core-shell structure microspheres in a high-temperature high-pressure sterilization pot, and performing high-pressure sterilization at 121 ℃ for 30min to ensure sterility;
(c) after the cells are completely attached to the wall, replacing the culture solution in each hole with particles with different concentrations of 0-1000 mug/mL, keeping the temperature at 37 ℃ and 5% CO2Culturing in an incubator for 24 to 72 hours;
(d) after the culture is finished, adding 30 mu L of MTT reagent into each hole, and continuously incubating for 4 hours at 37 ℃;
(e) and removing the upper liquid layer, adding 200 mu L of DMSO (dimethyl sulfoxide) into each hole, shaking at 37 ℃ for 10min to fully dissolve purple crystalline formazan, taking out 150 mu L of each hole, putting the 150 mu L of each hole into a new 96-hole enzyme label plate, detecting the absorbance value of each hole at the wavelength of 570nm to remove the influence of cells and particles deposited at the bottom on the absorbance value, and taking the ratio of the microcrystalline cellulose microparticle drug-loaded particles to the control group data as the toxicity of the microcrystalline cellulose microparticle drug-loaded particles to the cells under the action condition.
From the MTT results in FIG. 9, it can be seen that the cell activities measured after co-culturing the cells and the particles for 24 hours to 72 hours were all above 90% in the tested concentration range of 0 to 1000. mu.g/mL, indicating that the supported strain has good biocompatibility.
Compared with the related art, the preparation method of the idebenone and microcrystalline cellulose composite carrier provided by the invention has the following advantages:
(1) the oleophylic microcrystalline cellulose particles are obtained by the low-temperature water washing treatment of oleic acid. The microcrystalline cellulose is easy to degrade under high temperature conditions, so that the structure and the characteristics of the particles are changed. Through low-temperature lipophilic treatment at 60 ℃, lipophilic molecular oleic acid can be adsorbed on microcrystalline cellulose, so that the dispersion of the microcrystalline cellulose in a nonpolar oil solution is improved, and the binding effect of the microcrystalline cellulose on idebenone is enhanced, thereby having a good loading effect;
(2) physicochemical representation and investigation are carried out on the microcrystalline cellulose with different grain diameters, and the microcrystalline cellulose with the grain diameter of 20 microns is determined to have the best physical adsorption characteristic through the grain diameter, the appearance and the specific surface area;
(3) the optimal idebenone concentration and the carrier loading time are determined through static and dynamic adsorption experiments, and the subsequent active matter loading is guided and optimized through the optimization of the adsorption experiments;
(4) the raw materials adopted by the preparation method of the invention, including the active substances and the carrier substances, are non-toxic and green, have excellent biological safety, and have no use risk in the use catalogue of cosmetic raw materials;
(5) the idebenone and microcrystalline cellulose composite carrier can be used for effectively loading idebenone and realizing the sustained and slow release of the idebenone, so that the potential irritation is effectively reduced, and meanwhile, the particle is simple in preparation process and good in biocompatibility, can be well used in skin external products, and is suitable for expanded production.
The technical features of the embodiments described above may be arbitrarily combined, and for the sake of brevity, all possible combinations of the technical features in the embodiments described above are not described, but should be considered as being within the scope of the present specification as long as there is no contradiction between the combinations of the technical features.
The above-mentioned embodiments only express several embodiments of the present invention, and the description thereof is more specific and detailed, but not construed as limiting the scope of the invention. It should be noted that, for a person skilled in the art, several variations and modifications can be made without departing from the inventive concept, which falls within the scope of the present invention. Therefore, the protection scope of the present patent shall be subject to the appended claims.
Claims (7)
1. A preparation method of idebenone and microcrystalline cellulose composite carrier is characterized by comprising the following steps: the method comprises the following steps:
taking microcrystalline cellulose powder, and dispersing the microcrystalline cellulose powder in an aqueous solution to form a suspension containing microcrystalline cellulose particles;
step two, dropwise adding an oleic acid ethanol solution into the suspension, stirring and mixing, then carrying out surface oleic acid coating on the microcrystalline cellulose particles, washing, and centrifuging to obtain microcrystalline cellulose particles coated with oleic acid;
dispersing the obtained oleic acid-coated microcrystalline cellulose particles in an ethanol solution, introducing 0.1-10mg/mL idebenone and oleic acid-coated microcrystalline cellulose particles for compounding, loading for 12-72 hours, and performing centrifugal drying to obtain the idebenone and microcrystalline cellulose composite carrier with the idebenone slow-release effect.
2. The method for preparing idebenone and microcrystalline cellulose composite carrier according to claim 1, characterized in that: in the first step, the microcrystalline cellulose powder is dispersed in the aqueous solution by ultrasonic, the mass concentration of the microcrystalline cellulose is 1-5%, and the microcrystalline cellulose is sheared and dispersed at 300-500 rpm to form uniform suspension.
3. The method for preparing idebenone and microcrystalline cellulose composite carrier according to claim 1, characterized in that: in the second step, after the suspension is heated to 60 ℃, 0.5 to 2 mass percent of oleic acid ethanol solution is added dropwise, and the mixture is stirred for 1 hour.
4. The method for preparing idebenone-microcrystalline cellulose composite carrier according to claim 3, characterized in that: the volume ratio of oleic acid to ethanol in the oleic acid ethanol solution is 1: 1.
5. The method for preparing idebenone and microcrystalline cellulose composite carrier according to claim 1, characterized in that: in step two, five washes with deionized water were performed.
6. The method for preparing idebenone and microcrystalline cellulose composite carrier according to claim 1, characterized in that: the microcrystalline cellulose particles have a particle size of 20 microns.
7. A cosmetic characterized by: comprising the idebenone, microcrystalline cellulose composite carrier according to any one of claims 1-6, wherein the concentration of microspheres in the cosmetic is less than or equal to 1000 μ g/mL.
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