CN108079308B - Coenzyme Q10Nano-structure lipid carrier compounded with octacosanol and preparation method thereof - Google Patents
Coenzyme Q10Nano-structure lipid carrier compounded with octacosanol and preparation method thereof Download PDFInfo
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- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/12—Ketones
- A61K31/122—Ketones having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
Abstract
The invention discloses coenzyme Q10A nano-structure lipid carrier compounded with octacosanol and a preparation method thereof, belonging to the technical field of medicines and health care products. Coenzyme Q10The nano-structure lipid carrier compounded with octacosanol is mainly prepared from the following raw materials in parts by weight: coenzyme Q101-5 parts of octacosanol, 1-2 parts of octacosanol, 0.5-1 part of caprylic acid glyceride (ODO), 0.001-0.003 part of vitamin E and 2-5 parts of emulsifier. The invention adopts coenzyme Q10The lipid carrier with the nano structure is formed by compounding with octacosanol, has the effects of reducing blood fat, protecting heart and the like, and has the characteristics of higher release degree, bioavailability and sustained release.
Description
Technical Field
The invention relates to coenzyme Q10The nanostructured lipid carrier has the functions of enhancing immunity, relieving physical fatigue, protecting heart and the like, and belongs to the technical field of medicines and health-care products.
Background
Coenzyme Q10(Coenzyme Q10) Is a compound synthesized by human body, is named because the polymerization degree of the side chain-polyisoprene on the six-position of the mother nucleus is 10, and has a structure similar to vitamin K. Coenzyme Q10Divided into reduced coenzyme Q10(Co Q10H2Ubiquinol, panthenol) and oxidized coenzyme Q10(Co Q10Ubiquinone, Ubiquinone) two forms, Co Q10H2Is Co Q10The two-electron reduction of (1). In vivo, Co Q10H2And Co Q10The compound is used as a hydrogen/electron transfer body to jointly participate in transmembrane electron transport systems such as mitochondrial inner membrane respiratory chain and the like and the process of cell oxidative phosphorylation, and plays an important role in the synthesis of Adenosine Triphosphate (ATP). Coenzyme Q10Is an indispensable important physiological substance in human body, has many important physiological functions in human body due to the chemical structure characteristics, is an important energy transfer substance in life activities, is a key substance for the rate-limiting reaction of the mitochondrial respiratory chain, and plays an important role in cell energy generation and biological activity enhancement. Coenzyme Q10Has strong anti-oxidation stress effect, maintains the integrity of a mitochondrial membrane, can assist in reducing blood fat and reducing side effects when used with statins, and has good treatment and health care effects on cardiovascular diseases such as hyperlipidemia, tumors, diabetes, Parkinson and the like.
Octacosanol (1-Octacosanol), also known as montanol or policosanol, of formula C28H58O, a naturally occurring higher aliphatic alcohol, is extracted and refined mainly through sugar cane wax, rice bran and beeswax at present, is a world-recognized anti-fatigue substance, is used as a natural health food additive and a broad-spectrum natural good medicine in countries such as the United states, Japan and the like, and is widely used for sports drinks and natural health care productsAnd pharmaceuticals and cosmetics. Octacosanol has effects of improving body durability, reducing stress reaction of body, reducing blood lipid and cholesterol in body, and other physiological functions. Octacosanol also has effects of enhancing cardiac function, reducing cholesterol, resisting atherosclerosis, inhibiting gastric ulcer, resisting platelet aggregation, and protecting liver.
Coenzyme Q10The octacosanol and the octacosanol are fat-soluble substances, are insoluble in water, belong to the class II of pharmaceutics, are limited by dissolution and dissolution in oral administration and absorption, have low absolute bioavailability and coenzyme Q10Unstable in light and water properties, and in response to this situation, various methods for improving bioavailability of oral administration have been developed in recent years, such as inclusion techniques, self-emulsification techniques, liposomes, nanostructured lipid carriers, and the like. Among them, nano-drug delivery is a technology that improves bioavailability, and currently, nano-liposomes (NL), solid nano-structured lipid carriers (SLN), nano-emulsions (NPE), and the like have been developed. Nanostructured Lipid Carriers (NLC) are novel drug delivery systems developed on the basis of solid nanostructured lipid carriers (SLN), and the addition of solid lipids in a formulation is a necessary condition for forming solid lipid nanoparticles or nanostructured lipid carriers, and a common method is to add liquid lipids on the basis of solid lipids as carriers to disturb a perfect crystal form after solid lipids are solidified so as to increase drug loading rate and absorption. NLC drug delivery usually requires that the drug component can be dissolved in the melted lipid, the method is to dissolve the drug component after melting the solid lipid or to dissolve the lipid and the drug component with an organic solvent, usually a large amount of solid lipid is needed to be prepared after dissolving, the drug delivery rate of the drug component is limited by the solubility of the melted lipid, and the drug delivery rate is not high under normal conditions. Coenzyme Q10Octacosanol and octacosanol are both fat-soluble substances and are insoluble in water, the solubility of octacosanol and octacosanol in common solid lipid is relatively low, and a large amount of solid lipid is required to be dissolved and prepared according to a conventional preparation method of a nano-structure lipid carrier, so that a preparation with high drug loading rate is difficult to prepare.
The patent and literature published at present are searched, the related patent and literature research report of the lipid carrier with the nano structure compounded by the two or other nano preparations is not searched, and only coenzyme Q is searched10Literature or patents relating to the preparation of similar formulations with octacosanol alone, wherein associated with this patent are: chinese patent CN 105708799A nanostructured lipid carrier pharmaceutical composition and method for preparing nanostructured lipid carrier from poorly soluble drug10. Chinese patent CN101658468A coenzyme Q10A nano-structured lipid carrier and its preparing process are disclosed10Nanostructured lipid carriers and uses thereof. ② 2016,33(1):65-70 parts; 932-936 in China Hospital pharmaceutical journal 2012,32 (12); coenzyme Q is mentioned in the documents 2016,46(9):524-10The preparation and application of the nanostructured lipid carrier. European Journal of pharmaceuticals and biopharmaceuticals 67(2007) 141-148 by Rainer H.Muller entitled Cetyl-palmate-based NLC for topical delivery of Coenzyme Q10A Development, physicocheric chemical catalysis and in vitro release students article, which describes the preparation of 24% coenzyme Q using palmitate esters10The NLC method of (1). Coenzyme Q is described in the pharmaceutical Research, Vol.18, No.3,2001, published by Heike Bunjes of Incorporation of the Model drug urethane inner solid lipid Nanoparticles10And (3) preparing solid liquid nanoparticles. ③ Chinese patent CN100998438A discloses a preparation method of octacosanol emulsion, which relates to a method for preparing the emulsion with the highest content of 1.5% by adopting an emulsion method, the patent content does not disclose the particle size of the aqueous solution of octacosanol, and the process does not relate to the key links of the preparation of nano-structure lipid carrier, such as cooling, and the like. Chinese patent CN1316966C discloses a preparation method of a microcapsule of octacosanol extract and a preparation method thereof, and does not relate to the preparation content of octacosanol nano-structure lipid carriers. The above patents all relate to coenzyme Q10Or octacosanol alone to prepare a nanostructured lipid carrierAnd other related art, wherein the publication shows coenzyme Q10The drug loading rate of the nano-structured lipid carrier is generally low and is generally below 24%, and octacosanol does not relate to the technical content of the nano-structured lipid carrier. Coenzyme Q10The preparation of the nano-structure lipid carrier generally adopts a method of dissolving organic solvent and using the organic solvent as an oil phase. None of the above patent documents relate to the technical content of the present invention.
Disclosure of Invention
The present invention is to solve the above problems, and provides a coenzyme Q10The invention relates to a nano-structure lipid carrier compounded with octacosanol and a preparation method thereof, and coenzyme Q is adopted in the invention10The lipid carrier with the nano structure is formed by compounding with octacosanol, has the effects of reducing blood fat, protecting heart and the like, and has the characteristics of higher release degree, bioavailability and sustained release.
The preparation of the nanostructured lipid carrier generally requires that the encapsulated drug ingredients can be dissolved in the selected solid lipid for preparation, and the drug loading rate is generally not high. Coenzyme Q10Although octacosanol and octacosanol are fat-soluble substances, the solubility of octacosanol and octacosanol is not high in commonly used solid lipid, so that a large amount of solid lipid is needed for preparation according to a conventional method, and a nano carrier with high drug loading rate is difficult to prepare. Coenzyme Q10The melting point of 49 ℃ and the melting point of the octacosanol monomer of 83 ℃ are respectively, so that under the condition of water bath at 85 ℃, the two components are completely mixed and melted into a uniform lipid solid dispersion, the melting point peak of the solid dispersion melted by the two components is integrally moved downwards, and the solid dispersion is heated and mixed and melted at 40-70 ℃ according with the condition of preparing NLC (non-line NLC), so that the invention utilizes the physicochemical property characteristics of the two components, innovatively takes the main drug component as the solid lipid component, or adds a small amount of selected solid lipid and then heats and melts the solid lipid to form the high-content uniform solid dispersion lipid of the main drug, and then the preparation of the coenzyme Q with high drug loading rate can be realized by adopting an10With octacosanol nanostructured lipid carriers. To make this high drug loading rate coenzyme Q10The lipid carrier with the octacosanol nano structure is better applied to solid drug delivery preparations and forms NLC nano structureThe invention screens the kind of protective agent, and obtains the coenzyme Q which can be redissolved by adding the protective agent10And screening out the solid powder of the lipid carrier with the octacosanol nano structure, which is a drying method suitable for industrial production.
In order to solve the technical problems, the invention is realized by the following technical scheme:
coenzyme Q10The nano-structure lipid carrier compounded with octacosanol is mainly prepared from the following raw materials in parts by weight: coenzyme Q101-5 parts of octacosanol, 1-2 parts of octacosanol, 0.5-1 part of caprylic acid glyceride, 0.001-0.003 part of vitamin E and 2-5 parts of emulsifier.
Coenzyme Q10The nano-structure lipid carrier compounded with octacosanol is prepared from the following raw materials in parts by weight: coenzyme Q101-5 parts of octacosanol, 1-2 parts of octacosanol, 0.5-1.5 parts of solid lipid, 0.5-1 part of octyl, 0.001-0.003 part of capric glyceride, and 2-5 parts of emulsifier.
Coenzyme Q10The nano-structure lipid carrier compounded with octacosanol is prepared from the following raw materials in parts by weight: coenzyme Q101-5 parts of octacosanol, 1-2 parts of octacosanol, 0.5-1.5 parts of solid lipid, 0.5-1 part of octyl, 0.001-0.003 part of capric glyceride, 2-5 parts of emulsifier and 7-15 parts of protective agent.
The solid lipid is glyceryl monostearate or glyceryl behenate.
The emulsifier is at least one of lecithin, dodecaglycerol laurate, decaglycerol stearate, polyethylene glycol-12-hydroxystearate and tween-80.
The above-mentioned coenzyme Q10Is an oxidized coenzyme Q10Or reduced coenzyme Q10。
The octacosanol is octacosanol monomer component or C22-C36 higher fatty alkanol mixture containing octacosanol not less than 50%.
The protective agent is sodium starch octenyl succinate or mono-Arabic gum octenyl succinate.
Coenzyme Q10The preparation method of the nano-structure lipid carrier compounded with the octacosanol comprises the following process steps: weighing the coenzyme Q according with the weight part10Heating and melting octacosanol, octyl, tricaprin and vitamin E at 70-90 ℃, and uniformly stirring to form an oil phase; weighing the emulsifier according with the weight part, adding the emulsifier into water at 70-90 ℃, and uniformly stirring to form a water phase; adding the oil phase into the water phase, and shearing at 16000rpm for 1-2 min by using a shearing machine to form colostrum; then, introducing N into the mixture by using a high-pressure homogenizer under the pressure of 30-80 MP2And (4) protecting, forming an emulsion after 5-10 times of circulation, and cooling to room temperature to obtain the nano-structure lipid carrier aqueous solution.
The above-mentioned coenzyme Q10The preparation method of the nano-structure lipid carrier compounded with the octacosanol comprises the following process steps: weighing the coenzyme Q according with the weight part10Octacosanol, 0.5-1.5 parts of solid lipid, octyl, tricaprin and vitamin E are heated and melted at 70-90 ℃, and are stirred and mixed uniformly to form an oil phase; weighing the emulsifier according with the weight part, adding the emulsifier into water at 70-90 ℃, and uniformly stirring to form a water phase; adding the oil phase into the water phase, and shearing at 16000rpm for 1-2 min by using a shearing machine to form colostrum; then, introducing N into the mixture by using a high-pressure homogenizer under the pressure of 30-80 MP2And (3) protection, namely forming emulsion after 5-10 times of circulation, cooling to room temperature to prepare a nano-structured lipid carrier aqueous solution, adding 7-15 parts of a protective agent, uniformly stirring, and drying to prepare nano-structured lipid carrier solid powder.
The drying can be spray drying or freeze drying, and high pressure homogenization can be replaced by ultrasonic oscillation.
Due to the adoption of the technical scheme, the invention has the following characteristics and effects:
the present invention is different from the prior art in that coenzyme Q is adopted10The compound is compounded with octacosanol to form a preparation scheme, which aims to play a good synergistic effect because of the coenzyme Q10And octacosanol have good effect of strengthening heartFunctional and hypolipidemic actions, coenzyme Q10Is an antioxidant which is positioned in mitochondria in cells, has strong function of eliminating peroxidation free radicals in vivo, provides energy for cardiac muscle cells, treats and improves cardiovascular diseases, has the functions of resisting lipid peroxidation, protecting the integrity of the mitochondria of the cardiac muscle cells and regulating the energy metabolism of the cardiac muscle, inhibits the synthesis of cholesterol by regulating the activity of hydroxymethyl glutaryl coenzyme A (HMG-CoA) which is a key enzyme in the biosynthesis of the cholesterol, thereby reducing the total cholesterol of human bodies, and is also coenzyme Q in vivo10The synthetase of (2), it is therefore possible to treat coenzyme Q10The biological synthesis of the compound preparation has influence, the combination of the two compounds eliminates the influence, and simultaneously, because the two compounds have the functions of resisting oxidative stress and physiological activity based on different mechanisms, the combination of the two compounds has stronger physiological activity function through experimental verification, and particularly achieves better effect on the application of reducing blood fat.
Coenzyme Q prepared by the invention10The particle size of the nano-structure lipid carrier compounded with octacosanol is measured by a laser particle size analyzer, the particle size is 100-300nm, and the coenzyme Q is obtained10The drug loading rate can reach 20-50%, the octacosanol drug loading rate can reach 28%, the encapsulation rate is 90-99%, and the high drug loading rate exceeds that of the prior similar technology. After the protective agent is added, the solid powder can be dried, and the particle size of the redissolution can still be 200-400nm, so that the redissolution can be conveniently applied to solid preparations. The nano carrier of the invention is because of the coenzyme Q10The lipid carrier and the octacosanol have fat-soluble low-melting-point physicochemical properties, so that by utilizing the technical means adopted by the invention, the lipid dispersion mixed and melted with the octacosanol can be formed, the mixed and melted lipid dispersion with lower melting point can be generated without using or only using a small amount of solid lipid, conditions are created for further preparing the high-drug-loading-rate nano-structure lipid carrier, and an organic solvent is not used as an oil phase, so that the nano-structure lipid carrier prepared by the invention finally exceeds the prior technical effect.
Thermogram DSC shows coenzyme Q10Disappearance or shift of melting point peak with octacosanol, proving that it forms a homogeneous miscible lipid dispersion, coenzyme Q10With octacosanol in an amorphous state in a nanostructured lipid carrier, the crystalline state facilitating its absorption. Transmission electron microscope images show that the carrier particles of the invention are basically round, the particle size is 100-300nm, and the particle size of the redissolved aqueous solution of solid powder particles is 200-400 nm. Coenzyme Q prepared by the invention10Compared with the prototype drug, the nano-structure lipid carrier compounded with the octacosanol and the powder thereof have the advantages that the release degree is greatly improved, and the sustained release trend is presented. Coenzyme Q prepared by the invention10The in vitro antioxidant efficacy test of the nanostructured lipid carrier compounded with the octacosanol proves that the in vitro antioxidant property of the nanostructured lipid carrier, such as the scavenging capacity to DPPH free radicals, is obviously superior to that of coenzyme Q10The mixture of the nano-particle and the octacosanol prototype drug and the single nano-particle preparation thereof prove that the coenzyme Q is loaded simultaneously10The antioxidant effect of the nano-structure lipid carrier with octacosanol is obviously better than that of the nano-carrier prepared by the prior single raw material and the mixture of the two raw materials. The invention carries coenzyme Q10The nano-structure lipid carrier solid powder compounded with the octacosanol has better solid powder flowability, compressibility, redissolution and quick disintegration physical characteristics, so that the nano-structure lipid carrier solid powder is easier to prepare solid preparations such as tablets, capsules and the like.
The coenzyme Q of the invention10Coenzyme Q of nanostructured lipid carrier compounded with octacosanol10The content determination method mainly adopts high performance liquid chromatography, and is implemented by taking coenzyme Q10Heating and ultrasonically treating a proper amount of nano-structure lipid carrier sample compounded with octacosanol with ethanol, cooling to a constant volume to a specified concentration, filtering, taking a subsequent filtrate as a test solution, injecting a sample, and performing chromatographic conditions: coenzyme Q10: c18 column, mobile phase acetonitrile: tetrahydrofuran: water 55: 40: 5 (volume ratio), detecting the wavelength of 275nm, and quantifying by an external standard method to obtain the product.
The coenzyme Q of the invention10The content determination method of octacosanol of nano-structure lipid carrier compounded with octacosanol mainly adopts gas chromatography method, and is characterized by weighing coenzyme Q10An appropriate amount of the nanostructured lipid carrier sample compounded with the octacosanol is accurately placed in a 10mL test tube with a plugAdding 10mL of mixed extracting solution (chloroform: n-hexane volume ratio is 9:1), carrying out ultrasonic extraction for 15min, standing for layering, taking 1 mu L of supernatant, and carrying out chromatographic condition: the chromatographic column is PE-5MS (30m multiplied by 0.25mm multiplied by 0.25 mu m), the temperature is programmed to rise (180 ℃ is kept for 3min, 9 ℃/min is increased to 290 ℃, 35min is kept, 22 ℃/min is increased to 300 ℃, 5min is kept), the temperature of the sample inlet is 320 ℃, the temperature of the FID detector is 330 ℃, the split ratio is 60:1, the nitrogen flow rate is 50mL/min, the hydrogen flow rate is 35mL/min, and the air flow rate is 400 mL/min.
The coenzyme Q of the invention10The method for measuring the encapsulation rate of the nano-structure lipid carrier compounded with octacosanol comprises measuring the encapsulation rate and drug loading capacity by ultrafiltration centrifugation, diluting a proper amount of sample by 10 times, uniformly mixing by vortex for 1min, placing in an ultrafiltration centrifuge tube, centrifuging at 12000r/min for 10min, placing filtrate in a 10mL measuring flask, adding methanol for ultrasonic dissolution for 15min, fixing the volume to the scale, filtering with a 0.45 mu m microporous membrane, and measuring the amount of free drug (W) in the filtrateF) (ii) a Dissolving another appropriate amount of sample in 10mL volumetric flask with methanol under ultrasound for 15min, fixing volume to scale, filtering with 0.45 μm microporous membrane, and measuring total dose (W)T). Encapsulation ratio (%) - (W)T-WF)/WTX is 100%; drug loading (%) - (W)T-WF)/WLX is 100%; wherein, WL: mass of the nanostructured lipid carrier.
Drawings
Fig. 1 is a particle size distribution diagram of the aqueous NLC solution prepared in example 1.
FIG. 2 is a Zeta potential profile of the aqueous NLC solution prepared in example 1.
Fig. 3 is a particle size distribution diagram of the NLC solid powder prepared in example 14.
FIG. 4 shows NLC, blank NLC, coenzyme Q prepared in example 1410And DSC chart of octacosanol.
FIG. 5 shows coenzyme Q in NLC prepared in examples 1, 6 and 1410The release profile is accumulated.
FIG. 6 is a cumulative release profile of octacosanol in NLC prepared in examples 1, 6, 14.
Detailed Description
The present invention will be further described with reference to the following examples. The following examples are only a few specific examples of the present invention, but the design concept of the present invention is not limited thereto, and any insubstantial modifications made by the design concept should fall within the scope of infringing on the protection scope of the present invention.
The methods in the following examples are conventional methods unless otherwise specified, and the percentages are by mass.
Example 1
Oxidized coenzyme Q 102 parts, 1 part of octacosanol, 1 part of octyl, 1 part of tricaprin (ODO), 0.001 part of vitamin E, 1 part of decaglycerol laurate and 1 part of decaglycerol stearate.
Weighing 4g of oxidized coenzyme Q10Heating and melting 2g octacosanol, tricaprin (ODO) and 0.002g vitamin E at 90 ℃, and stirring and mixing uniformly to form an oil phase; weighing 2g of decaglycerol laurate and 2g of decaglycerol stearate, adding the decaglycerol laurate and the decaglycerol stearate into 200mL of water with the temperature of 90 ℃, and uniformly stirring to form a water phase; slowly adding the oil phase into the water phase, and shearing at 16000rpm for 1min by using a shearing machine to form colostrum; then introducing N under the pressure of 60MP by using a high-pressure homogenizer2And (4) protecting, forming emulsion after 5 times of circulation, and cooling to room temperature to obtain the nano-structure lipid carrier aqueous solution. The determination shows that the average particle diameter is 112.9nm, the potential is (-27.5 +/-4.99) mV, and the coenzyme Q10The drug loading rate and the encapsulation rate of the carrier are respectively 32.5 percent and 97.4 percent, and the drug loading rate and the encapsulation rate of the octacosanol are respectively 15.9 percent and 95.3 percent.
Example 2
Oxidized coenzyme Q 101 part, 2 parts of octacosanol, 1 part of octyl, 1 part of tricaprin (ODO), 0.002 part of vitamin E, 801.5 parts of tween-and 1.5 parts of soybean lecithin.
Weighing 2g of oxidized coenzyme Q10Heating and melting 4g octacosanol, 2g octacosanol, tricaprin (ODO) and 0.004g vitamin E at 85 ℃, and stirring and mixing uniformly to form an oil phase; weighing 3g of tween-80 and 3g of soybean phospholipid, adding into 250mL of water at 85 ℃, and uniformly stirring to form a water phase; slowly adding the oil phase into the water phase, and shearingShearing at 16000rpm for 1.5 min to obtain colostrum; then introducing N under the pressure of 70MP by using a high-pressure homogenizer2And (4) protecting, forming emulsion after 7 times of circulation, and quickly cooling to room temperature to prepare the nano-structured lipid carrier aqueous solution. The average grain diameter is 210.6nm and the coenzyme Q is measured10The drug loading rate and the encapsulation rate of the carrier are respectively 13.6 percent and 95.5 percent, and the drug loading rate and the encapsulation rate of the octacosanol are respectively 26.6 percent and 93.2 percent.
Example 3
Oxidized coenzyme Q 101 part, 1 part of a C22-C36 higher fatty alkanol mixture containing 70% octacosanol, 0.5 part of caprylic acid triglyceride (ODO), 0.003 part of vitamin E, 0.2 part of soybean lecithin and 1.8 parts of polyethylene glycol-12-hydroxystearate (HS 15).
Weighing 2g of oxidized coenzyme Q102g of a C22-C36 higher fatty alkanol mixture containing 70% octacosanol, 1g of octyl, tricaprin (ODO) and 0.006g of vitamin E are heated and melted at 70 ℃, and are stirred and mixed uniformly to form an oil phase; weighing 0.4g of soybean lecithin and 3.6g of polyethylene glycol-12-hydroxystearate (HS15), adding into 150mL of water at 70 ℃, and uniformly stirring to form a water phase; slowly adding the oil phase into the water phase, and shearing at 16000rpm for 2 min by using a shearing machine to form colostrum; then, using a high-pressure homogenizer, under a pressure of 30MP, introducing N2And (4) protecting, forming emulsion after 10 times of circulation, and quickly cooling to room temperature to prepare the nano-structured lipid carrier aqueous solution. The average grain diameter is 195.2nm and the coenzyme Q is measured10The drug loading rate and the encapsulation rate of the carrier are respectively 22.9 percent and 96.1 percent, and the drug loading rate and the encapsulation rate of the octacosanol are respectively 15.6 percent and 93.6 percent.
Example 4
Reduced coenzyme Q 105 parts, 2 parts of octacosanol, 0.5 part of caprylic acid triglyceride (ODO), 0.002 part of vitamin E, 0.2 part of egg yolk lecithin and 4.8 parts of polyethylene glycol-12-hydroxystearate (HS 15).
Weighing 5g of reduced coenzyme Q102g octacosanol, 0.5g octyl, tricaprin (ODO) and 0.002g vitamin E are heated and melted at 80 ℃, and are stirred and mixed uniformly to form an oil phase; weighing 0.2g egg yolk lecithin, 4.8Adding polyethylene glycol-12-hydroxystearate (HS15) into 210mL of water at 80 ℃, and uniformly stirring to form a water phase; slowly adding the oil phase into the water phase, and shearing at 16000rpm for 2 min by using a shearing machine to form colostrum; then introducing N under the pressure of 80MP by using a high-pressure homogenizer2And (4) protecting, forming an emulsion after 5 times of circulation, and quickly cooling to room temperature to prepare the nano-structured lipid carrier aqueous solution. The average grain diameter is 180.7nm through measurement, and the coenzyme Q10The drug loading rate and the encapsulation rate of the carrier are respectively 38.6 percent and 96.5 percent, and the drug loading rate and the encapsulation rate of the octacosanol are respectively 15.0 percent and 93.8 percent.
Example 5
Oxidized coenzyme Q 105 parts of octacosanol, 1 part of glyceryl monostearate, 1 part of octyl, 0.5 part of glyceryl decanoate (ODO), 0.003 part of vitamin E and 3 parts of polyethylene glycol-12-hydroxystearate (HS 15).
Weighing 5g of oxidized coenzyme Q10Heating and melting 1g octacosanol, 1g glyceryl monostearate, 0.5g octyl, glyceryl decanoate (ODO) and 0.003g vitamin E at 85 ℃, and uniformly stirring to form an oil phase; weighing 3g of polyethylene glycol-12-hydroxystearate (HS15) and adding into 180mL of water at 85 ℃, and uniformly stirring to form a water phase; slowly adding the oil phase into the water phase, and shearing at 16000rpm for 1min by using a shearing machine to form colostrum; then, using a high-pressure homogenizer, under a pressure of 30MP, introducing N2And (4) protecting, forming an emulsion after 5 times of circulation, and quickly cooling to room temperature to prepare the nano-structured lipid carrier aqueous solution. The average grain diameter is 222.6nm and the coenzyme Q is measured10The drug loading rate and the encapsulation rate are respectively 45.2 percent and 94.9 percent, and the drug loading rate and the encapsulation rate of the octacosanol are respectively 8.9 percent and 93.0 percent.
Example 6
Oxidized coenzyme Q 105 parts, 1 part of octacosanol, 1.5 parts of glycerin monostearate, 0.75 part of caprylic acid glyceride (ODO), 0.002 part of vitamin E, 2.67 parts of decaglycerol laurate and 1.33 parts of decaglycerol stearate.
Weighing 5g of oxidized coenzyme Q101g octacosanol, 1.5g glyceryl monostearate, 0.75g octyl and decyl glyceride ()ODO) and 0.002g of vitamin E are heated and melted at 75 ℃, and are stirred and mixed uniformly to form an oil phase; weighing 2.67g of decaglycerol laurate and 1.33g of decaglycerol stearate, adding the decaglycerol laurate and the decaglycerol stearate into 220mL of water at 75 ℃, and uniformly stirring to form a water phase; slowly adding the oil phase into the water phase, and shearing at 16000rpm for 1min by using a shearing machine to form colostrum; then introducing N under the pressure of 40MP by using a high-pressure homogenizer2And (4) protecting, forming emulsion after 6 times of circulation, and quickly cooling to room temperature to prepare the nano-structure lipid carrier aqueous solution. The average grain diameter is 120.5nm through measurement, and the coenzyme Q10The drug loading rate and the encapsulation rate are respectively 40.1 percent and 98.2 percent, and the drug loading rate and the encapsulation rate of the octacosanol are respectively 7.9 percent and 96.8 percent.
Example 7
Oxidized coenzyme Q 104 parts of octacosanol, 2 parts of glyceryl behenate, 1 part of octyl, 0.5 part of glyceryl caprate (ODO), 0.001 part of vitamin E, 1.67 parts of decaglycerol laurate and 3.33 parts of decaglycerol stearate.
Weighing 4g of oxidized coenzyme Q10Heating and melting 2g octacosanol, 1g glyceryl behenate, 0.5g octyl, glyceryl decanoate (ODO) and 0.001g vitamin E at 60 ℃, and stirring and mixing uniformly to form an oil phase; weighing 1.67g of decaglycerol laurate and 3.33g of decaglycerol stearate, adding the decaglycerol laurate and the decaglycerol stearate into 140mL of water with the temperature of 70 ℃, and uniformly stirring to form a water phase; slowly adding the oil phase into the water phase, and shearing at 16000rpm for 2 min by using a shearing machine to form colostrum; then introducing N under the pressure of 50MP by using a high-pressure homogenizer2And (4) protecting, forming emulsion after 6 times of circulation, and quickly cooling to room temperature to prepare the nano-structure lipid carrier aqueous solution. The average grain diameter is 178.4nm through measurement, and the coenzyme Q10The drug loading rate and the encapsulation rate of the carrier are respectively 30.8 percent and 96.4 percent, and the drug loading rate and the encapsulation rate of the octacosanol are respectively 15.0 percent and 93.5 percent.
Example 8
Oxidized coenzyme Q 105 parts, 1 part of octacosanol, 1.5 parts of glyceryl behenate, 0.6 part of caprylic acid glyceride (ODO), 0.002 part of vitamin E, 801 parts of tween-801 and 2 parts of soybean lecithin.
5g of an oxide are weighedCoenzyme Q101g octacosanol, 1.5g glyceryl behenate, 0.6g octyl, glyceryl caprate (ODO) and 0.002g vitamin E are heated and melted at 80 ℃, and are stirred and mixed uniformly to form an oil phase; weighing 1g of tween-80 and 2g of soybean lecithin, adding into 170mL of water at 80 ℃, and uniformly stirring to form a water phase; slowly adding the oil phase into the water phase, and shearing at 16000rpm for 1min by using a shearing machine to form colostrum; then introducing N under the pressure of 60MP by using a high-pressure homogenizer2And (4) protecting, forming emulsion after 8 times of circulation, and quickly cooling to room temperature to prepare the nano-structure lipid carrier aqueous solution. The average grain diameter is 178.8nm through measurement, and the coenzyme Q10The drug loading rate and the encapsulation rate of the carrier are respectively 43.3 percent and 96.2 percent, and the drug loading rate and the encapsulation rate of the octacosanol are respectively 8.4 percent and 93.3 percent.
Example 9
Reduced coenzyme Q 101 part, 2 parts of octacosanol, 0.5 part of glyceryl behenate, 0.75 part of caprylic acid, 0.003 part of tricaprin (ODO), and 4 parts of polyethylene glycol-12-hydroxystearate.
Weighing 2g of reduced coenzyme Q10Heating and melting 4g octacosanol, 1g glyceryl behenate, 1.5g octyl, glyceryl decanoate (ODO) and 0.006g vitamin E at 65 ℃, and stirring uniformly to form an oil phase; weighing 8g of polyethylene glycol-12-hydroxystearate, adding into 160mL of water with the temperature of 75 ℃, and uniformly stirring to form a water phase; slowly adding the oil phase into the water phase, and shearing at 16000rpm for 2 min by using a shearing machine to form colostrum; then introducing N under the pressure of 40MP by using a high-pressure homogenizer2And (4) protecting, forming an emulsion after 5 times of circulation, and quickly cooling to room temperature to prepare the nano-structured lipid carrier aqueous solution. The average particle diameter is 168.1nm and the coenzyme Q is measured10The drug loading rate and the encapsulation rate of the carrier are respectively 11.9 percent and 97.8 percent, and the drug loading rate and the encapsulation rate of the octacosanol are respectively 23.3 percent and 96.2 percent.
Example 10
Oxidized coenzyme Q103 parts, 1 part of octacosanol, 1 part of glyceryl monostearate, octyl, 1 part of glyceryl decanoate (ODO), 0.003 part of vitamin E, 801.33 parts of tween-and 0.67 part of soybean phospholipid.
Weighing 6g of oxidized coenzyme Q10Heating and melting 2g octacosanol, 2g glyceryl monostearate, 2g octyl, glyceryl decanoate (ODO) and 0.006g vitamin E at 85 ℃, and uniformly stirring to form an oil phase; weighing 2.66g of tween-80 and 1.34g of soybean lecithin, adding into 150mL of water at 85 ℃, and uniformly stirring to form a water phase; slowly adding the oil phase into the water phase, and shearing at 16000rpm for 1.5 minutes by using a shearing machine to form colostrum; then, using a high-pressure homogenizer, under a pressure of 30MP, introducing N2And (4) protecting, forming an emulsion after 5 times of circulation, and quickly cooling to room temperature to prepare the nano-structured lipid carrier aqueous solution. The average grain diameter is 238.2nm and the coenzyme Q is measured10The drug loading rate and the encapsulation rate of the carrier are respectively 36.0 percent and 96.1 percent, and the drug loading rate and the encapsulation rate of the octacosanol are respectively 11.6 percent and 93.2 percent.
Example 11
Reduced coenzyme Q 105 parts, 2 parts of octacosanol, 1.5 parts of glyceryl behenate, 0.75 part of caprylic acid glyceride (ODO), 0.002 part of vitamin E, 3.75 parts of decaglycerol laurate, 1.25 parts of decaglycerol stearate and 7 parts of octenyl succinic acid mono-arabic-gum.
Weighing 5g of reduced coenzyme Q10Heating and melting 2g octacosanol, 1.5g glyceryl behenate, 0.75g octyl, glyceryl caprate (ODO) and 0.002g vitamin E at 65 ℃, and stirring and mixing uniformly to form an oil phase; weighing 3.75g of decaglycerol laurate and 1.25g of decaglycerol stearate, adding the decaglycerol laurate and the decaglycerol stearate into 300mL of water at the temperature of 75 ℃, and uniformly stirring to form a water phase; slowly adding the oil phase into the water phase, and shearing at 16000rpm for 1.5 minutes by using a shearing machine to form colostrum; then introducing N under the pressure of 40MP by using a high-pressure homogenizer2Protecting, circulating for 5 times to form emulsion, rapidly cooling to room temperature, adding 7g of octenyl succinic acid mono-arabic gum, stirring, and spray drying to obtain nanostructured lipid carrier solid powder. The average grain diameter is 280.4nm and the coenzyme Q is measured10The drug loading rate and the encapsulation rate of the carrier are respectively 22.3 percent and 94.8 percent, and the drug loading rate and the encapsulation rate of the octacosanol are respectively 8.8 percent and 93.4 percent.
Example 12
Oxidized coenzyme Q 105 parts of octacosanol, 1 part of glyceryl monostearate, 0.5 part of octyl, 0.5 part of glyceryl decanoate (ODO), 0.001 part of vitamin E, 1 part of decaglycerol laurate, 3 parts of decaglycerol stearate and 11 parts of starch sodium octenyl succinate.
Weighing 5g of oxidized coenzyme Q10Heating and melting 1g octacosanol, 0.5g glyceryl monostearate, 0.5g octyl, glyceryl decanoate (ODO) and 0.001g vitamin E at 75 ℃, and stirring and uniformly mixing to form an oil phase; weighing 1g of decaglycerol laurate and 3g of decaglycerol stearate, adding the materials into 260mL of water with the temperature of 75 ℃, and uniformly stirring to form a water phase; slowly adding the oil phase into the water phase, and shearing at 16000rpm for 1min by using a shearing machine to form colostrum; then introducing N under the pressure of 50MP by using a high-pressure homogenizer2Protecting, circulating for 5 times to form emulsion, rapidly cooling to room temperature, adding 11g sodium starch octenyl succinate, stirring, and spray drying to obtain solid powder of nano-structured lipid carrier. The average grain diameter is 380.4nm and the coenzyme Q is measured10The drug loading rate and the encapsulation rate of the carrier are respectively 21.9 percent and 96.5 percent, and the drug loading rate and the encapsulation rate of the octacosanol are respectively 4.3 percent and 94.6 percent.
Example 13
Reduced coenzyme Q 105 parts, 1.5 parts of octacosanol, 0.75 part of glyceryl behenate, 1 part of caprylic acid, 1 part of glyceryl caprate (ODO), 0.002 part of vitamin E, 5 parts of soybean phospholipid and 7 parts of starch sodium octenyl succinate.
Weighing 5g of reduced coenzyme Q10Heating and melting 1.5g octacosanol, 0.75g glyceryl behenate, 1g octyl, glyceryl caprate (ODO) and 0.002g vitamin E at 80 ℃, and stirring and mixing uniformly to form an oil phase; weighing 5g of soybean phospholipid, adding into 270mL of water at 80 ℃, and uniformly stirring to form a water phase; slowly adding the oil phase into the water phase, and shearing at 16000rpm for 2 min by using a shearing machine to form colostrum; then introducing N under the pressure of 70MP by using a high-pressure homogenizer2Protecting, forming emulsion after 10 times of circulation, rapidly cooling to room temperature, adding 7g sodium starch octenyl succinate, stirring uniformly, and freeze-drying to obtain the solid powder of the nano-structured lipid carrier.The average grain diameter is 314.2nm and the coenzyme Q is measured10The drug loading rate and the encapsulation rate are respectively 24.3 percent and 98.3 percent, and the drug loading rate and the encapsulation rate of the octacosanol are respectively 7.0 percent and 95.1 percent.
Example 14
Oxidized coenzyme Q 101 part, 2 parts of octacosanol, 0.6 part of glycerin monostearate, 0.5 part of octyl, 0.002 part of tricaprin (ODO), 0.801 part of vitamin E, 1 part of tween-801, and 13 parts of octenyl succinic acid mono-arabic-gum.
Weighing 1g of oxidized coenzyme Q10Heating and melting 2g octacosanol, 0.6g glyceryl monostearate, 0.5g octyl, glyceryl decanoate (ODO) and 0.002g vitamin E at 85 ℃, and stirring and uniformly mixing to form an oil phase; weighing 1g of tween-80 and 1g of soybean lecithin, adding into 200mL of water at 85 ℃, and uniformly stirring to form a water phase; slowly adding the oil phase into the water phase, and shearing at 16000rpm for 1min by using a shearing machine to form colostrum; then introducing N under the pressure of 50MP by using a high-pressure homogenizer2Protecting, circulating for 5 times to form emulsion, rapidly cooling to room temperature, adding 13g of octenyl succinic acid mono-arabic gum, stirring, and spray drying to obtain nanostructured lipid carrier solid powder. The average grain diameter is 284.0nm and the coenzyme Q is measured10The drug loading rate and the encapsulation rate are respectively 4.9 percent and 93.5 percent, and the drug loading rate and the encapsulation rate of the octacosanol are respectively 9.6 percent and 91.6 percent.
Example 15
Oxidized coenzyme Q 102 parts of octacosanol, 1.5 parts of glycerin monostearate, octyl, 0.75 part of tricaprin (ODO), 0.003 part of vitamin E, 2 parts of decaglycerol laurate, 1 part of decaglycerol stearate and 15 parts of octenyl succinic acid mono-arabic-gum.
Weighing 2g of oxidized coenzyme Q10Heating and melting 2g octacosanol, 1.5g glyceryl monostearate, 0.75g octyl, glyceryl decanoate (ODO) and 0.003g vitamin E at 90 ℃, and uniformly stirring to form an oil phase; weighing 2g of decaglycerol laurate and 1g of decaglycerol stearate, adding the decaglycerol laurate and the decaglycerol stearate into 280mL of water with the temperature of 90 ℃, and uniformly stirring to form a water phase; slowly adding water into the oil phaseIn phase, colostrum was formed after 2 minutes of shearing at 16000rpm using a shear; then introducing N under the pressure of 60MP by using a high-pressure homogenizer2Protecting, circulating for 8 times to form emulsion, rapidly cooling to room temperature, adding 15g of octenyl succinic acid mono-arabic gum, stirring, and spray drying to obtain nanostructured lipid carrier solid powder. The average particle diameter is 294.5nm through measurement, and the coenzyme Q10The drug loading rate and the encapsulation rate are respectively 8.2 percent and 98.9 percent, and the drug loading rate and the encapsulation rate of the octacosanol are respectively 8.0 percent and 97.1 percent.
Example 16
Oxidized coenzyme Q 104 parts, 1 part of a C22-C36 higher fatty alkanol mixture containing octacosanol 50%, 0.5 part of glyceryl behenate, 0.8 part of octyl, 0.001 part of glyceryl decanoate (ODO), 4 parts of polyethylene glycol-12-hydroxystearate (HS15) and 7 parts of starch sodium octenyl succinate.
Weighing 4g of oxidized coenzyme Q101g of C22-C36 higher fatty alkanol mixture containing octacosanol 50%, 0.5g of glyceryl behenate, 0.8g of octyl, glyceryl decanoate (ODO) and 0.001g of vitamin E are heated and melted at 90 ℃, and are stirred and mixed uniformly to form an oil phase; weighing 4g of polyethylene glycol-12-hydroxystearate (HS15) and adding into 290mL of water with the temperature of 90 ℃, and uniformly stirring to form a water phase; slowly adding the oil phase into the water phase, and shearing at 16000rpm for 1.5 minutes by using a shearing machine to form colostrum; then introducing N under the pressure of 50MP by using a high-pressure homogenizer2Protecting, forming emulsion after 5 times of circulation, rapidly cooling to room temperature, adding 7g sodium starch octenyl succinate, freeze drying, and stirring to obtain solid powder of the lipid carrier with the nano structure. The average grain diameter is 284.9nm and the coenzyme Q is measured10The drug loading rate and the encapsulation rate are respectively 23.1 percent and 97.1 percent, and the drug loading rate and the encapsulation rate of the octacosanol are respectively 2.8 percent and 94.1 percent.
Example 17
Oxidized coenzyme Q 101 part, 2 parts of octacosanol, 1.5 parts of glycerin monostearate, octyl, 0.75 part of tricaprin (ODO), 0.002 part of vitamin E, 2 parts of decaglycerol laurate, 1 part of decaglycerol stearate,15 parts of octenyl succinic acid Arabic gum ester.
Weighing 1g of oxidized coenzyme Q10Heating and melting 2g octacosanol, 1.5g glyceryl monostearate, 0.75g octyl, glyceryl decanoate (ODO) and 0.002g vitamin E at 90 ℃, and stirring and uniformly mixing to form an oil phase; weighing 2g of decaglycerol laurate and 1g of decaglycerol stearate, adding the decaglycerol laurate and the decaglycerol stearate into 260mL of water with the temperature of 85 ℃, and uniformly stirring to form a water phase; slowly adding the oil phase into the water phase, and shearing at 16000rpm for 2 min by using a shearing machine to form colostrum; then introducing N under the pressure of 60MP by using a high-pressure homogenizer2Protecting, circulating for 7 times to form emulsion, rapidly cooling to room temperature, adding 15g of octenyl succinic acid mono-arabic gum, stirring, and spray drying to obtain nanostructured lipid carrier solid powder. The average grain diameter is 306.5nm and the coenzyme Q is measured10The drug loading rate and the encapsulation rate are respectively 4.2 percent and 96.9 percent, and the drug loading rate and the encapsulation rate of the octacosanol are respectively 8.3 percent and 96.1 percent
Example 18
The invention is further illustrated by the following experiments:
1. particle size and Zeta potential measurements:
taking the coenzyme Q of examples 1-1010Diluting with octacosanol nanostructured lipid carrier water solution at 25 deg.C for 3 times, and measuring particle diameter and Zeta potential with dynamic laser light scattering particle diameter measuring instrument. Taking the coenzyme Q of examples 11 to 1710Dissolving the solid powder with octacosanol nano-structure lipid carrier solid powder in a proper amount, and then determining the particle size. FIG. 1 is a dynamic laser light scattering particle size spectrum of a nano-carrier of example 1, FIG. 2 is a Zeta potential of the nano-carrier of example 1, and FIG. 3 is a dynamic laser light scattering particle size spectrum of nano-carrier powder of example 14.
DSC measurement:
a blank nanostructured lipid carrier (coenzyme Q was not contained in the starting material) was prepared according to the preparation method of example 1410And octacosanol), the blank nanostructure lipid carrier, coenzyme Q of example 14 were weighed separately10With octacosanol nano-structure lipid carrier solid powder and auxiliaryEnzyme Q10Placing 3-5mg of octacosanol in sealed aluminum crucible at 25-200 deg.C, heating rate of 20 deg.C/min, tabletting, and performing thermal analysis (DSC) measurement, the results are shown in FIG. 4. The results show that the coenzyme Q is loaded10The melting point of the lipid carrier powder with the octacosanol double-drug-loading nano structure is lower than that of coenzyme Q10Melting Point with octacosanol, coenzyme Q10Substantially disappeared with the melting point peak of octacosanol, proving that it forms a homogeneous miscible lipid dispersion, coenzyme Q10With octacosanol in an amorphous state in a nanostructured lipid carrier, which facilitates its absorption.
3. Morphological investigation:
the coenzyme Q of example 1 was taken10Uniformly spreading the carrier and a proper amount of octacosanol nanostructure lipid carrier on a copper mesh, dropwise adding 2% phosphotungstic acid aqueous solution for negative dyeing for 15min, naturally drying, taking out the copper mesh, and observing the surface morphology and structure of a sample under a transmission electron microscope, wherein the nanostructure lipid carrier is a round or quasi-round solid sphere, has uniform size and good dispersion and basically has no adhesion.
4. Centrifugal stability:
the coenzyme Q of example 1 was taken10And 50mL of octacosanol nano-structured lipid carrier aqueous solution is centrifuged at 10000rpm for 10min at 4 ℃, whether a precipitate is formed or not is observed, and the particle size of the supernatant is measured. No precipitate was formed after centrifugation, and the particle size was determined to be 116.2nm, PDI0.177, indicating coenzyme Q10The centrifugal stability of the nano octacosanol lipid carrier aqueous solution is better.
Example 19
And (3) measuring the release degree: coenzyme Q determination by dialysis bag method for the preparations of examples 1, 6 and 14 of the present invention10With octacosanol nanostructure lipid carrier and coenzyme Q10In vitro release assay with physical mixture of octacosanol. A cellulose acetate semipermeable membrane (with a molecular weight cutoff of 10000) is selected as a permeable membrane, and is boiled in ultrapure water for half an hour before use. The drug release medium is 5% Labrasol-20% ethanol-PBS solution. Taking a certain amount of coenzyme Q10With octacosanol nanostructure lipid carrier powder and coenzyme Q10Adding the physical mixture with octacosanol into dialysis bag, fastening two ends with rope, placing the dialysis bag into 250mL conical flask containing 5% labarsol-20% ethanol-PBS release medium, shaking at 37 + -0.5 deg.C with shaking table at 200r/min, sampling 10mL at 1h, 2h, 3h, 5h, 7h, 9h, 12h and 24h, rapidly supplementing 10mL blank release medium at the same temperature, and respectively determining Q by HPLC method and GC method10And the amount of octacosanol released, the cumulative release profiles were obtained as shown in fig. 5 and 6.
Example 20
The method for testing the oxidation resistance by removing DPPH free radical comprises the following steps: the coenzyme Q prepared in examples 1 to 17 were each taken10And octacosanol nanostructured lipid carrier, and blank sample (without CoQ)10And octacosanol NLC) 150. mu.l was added to 2.85mL of ultrapure water, i.e., diluted 20-fold. Dissolving with anhydrous ethanol to obtain DPPH solution (5 × 10)-5mol/L) for standby. The test tubes are numbered, the samples are added according to the table 1, the mixture is uniformly mixed, the reaction is carried out for 60min in a water bath at the temperature of 37 ℃, and then the absorbance value of the reaction liquid of the sample to be tested and the absorbance value of the blank sample are measured at the wavelength of 517 nm. (zero-setting reference is 1mL of blank sample mixed with 2mL of ultrapure water) Table 1 required amount for eliminating DPPH free radical experiment ingredients
| Group of | Sample to be tested/mL | Blank sample/mL | DPPH/mL | Ultrapure water/mL |
| ADPPH as sample to be measured | 2.0 | 0 | 4.0 | 0 |
| AWater as sample to be tested | 2.0 | 0 | 0 | 4.0 |
| ABlank DPPH | 0 | 2.0 | 4.0 | 0 |
The inhibition rate was calculated using the following formula: inhibition rate E (%) - (1- (a)DPPH as sample to be measured-AWater as sample to be tested)/ABlank DPPH)×100％
For loading coenzyme Q10Nanostructured lipid Carriers with octacosanol (prepared as in examples 1-16) and coenzyme Q10Mixed with octacosanol raw material medicine and coenzyme Q10The results of comparing the ability of NLC and octacosanol NLC to scavenge DPPH free radicals are shown in Table 2: TABLE 2 experimental results of DPPH radical scavenging method
Example 21
125g of the carrier solid powder of example 11-16 is taken, 100g of microcrystalline cellulose, 105g of povidone K30, 106g of maltodextrin, 50g of crospovidone, 9g of citric acid and 5g of magnesium stearate are added, and 1000 tablets with the specification of 0.5 g/tablet are pressed under the pressure of 30-50N. The powder was tested for angle of repose, disintegration time, redissolution and the results are shown in Table 3. TABLE 3 evaluation index of NLC tablets prepared in examples 11, 14 and 16
Claims (10)
1. Coenzyme Q10The nano-structured lipid carrier compounded with octacosanol is characterized by being mainly prepared from the following raw materials in parts by weight: coenzyme Q101-5 parts of octacosanol, 1-2 parts of octacosanol, 0.5-1 part of caprylic acid glyceride, 0.001-0.003 part of vitamin E and 2-5 parts of emulsifier.
2. The coenzyme Q according to claim 110The nano-structured lipid carrier compounded with octacosanol is characterized by being prepared from the following raw materials in parts by weight: coenzyme Q101-5 parts of octacosanol, 1-2 parts of octacosanol, 0.5-1.5 parts of solid lipid, 0.5-1 part of octyl, 0.001-0.003 part of capric glyceride, and 2-5 parts of emulsifier.
3. The coenzyme Q according to claim 110The nano-structured lipid carrier compounded with octacosanol is characterized by being prepared from the following raw materials in parts by weight: coenzyme Q101-5 parts of octacosanol, 1-2 parts of octacosanol, 0.5-1.5 parts of solid lipid, 0.5-1 part of octyl, 0.001-0.003 part of capric glyceride, 2-5 parts of emulsifier and 7-15 parts of protective agent.
4. The coenzyme Q according to claim 2 or 310The nano-structure lipid carrier compounded with octacosanol is characterized in thatThe solid lipid is glyceryl monostearate or glyceryl behenate.
5. The coenzyme Q according to claim 1, 2 or 310The nano-structured lipid carrier compounded with the octacosanol is characterized in that the emulsifier is at least one of lecithin, decaglycerol laurate, decaglycerol stearate, polyethylene glycol-12-hydroxystearate and tween-80.
6. The coenzyme Q according to claim 1, 2 or 310The nano-structured lipid carrier compounded with octacosanol is characterized in that the coenzyme Q10Is an oxidized coenzyme Q10Or reduced coenzyme Q10。
7. The coenzyme Q according to claim 1, 2 or 310The nano-structure lipid carrier compounded with the octacosanol is characterized in that the octacosanol is a octacosanol monomer component or a C22-C36 higher fatty alkanol mixture containing not less than 50% of the octacosanol.
8. The coenzyme Q according to claim 310The nanostructured lipid carrier compounded with octacosanol is characterized in that the protective agent is octenyl succinic acid starch sodium or octenyl succinic acid mono-Arabic gum ester.
9. The coenzyme Q according to claim 110The preparation method of the nano-structure lipid carrier compounded with octacosanol is characterized by comprising the following process steps: weighing the coenzyme Q according with the weight part10Heating and melting octacosanol, octyl, tricaprin and vitamin E at 70-90 ℃, and uniformly stirring to form an oil phase; weighing the emulsifier according with the weight part, adding the emulsifier into water at 70-90 ℃, and uniformly stirring to form a water phase; adding the oil phase into the water phase, and shearing at 16000rpm for 1-2 min by using a shearing machine to form colostrum; then introducing N into the mixture by using a high-pressure homogenizer under the pressure of 30-80 MPa2And (4) protecting, forming an emulsion after 5-10 times of circulation, and cooling to room temperature to obtain the nano-structure lipid carrier aqueous solution.
10. The coenzyme Q according to claim 910The preparation method of the nano-structure lipid carrier compounded with the octacosanol is characterized by comprising the following process steps: weighing the coenzyme Q according with the weight part10Octacosanol, 0.5-1.5 parts of solid lipid, octyl, tricaprin and vitamin E are heated and melted at 70-90 ℃, and are stirred and mixed uniformly to form an oil phase; weighing the emulsifier according with the weight part, adding the emulsifier into water at 70-90 ℃, and uniformly stirring to form a water phase; adding the oil phase into the water phase, and shearing at 16000rpm for 1-2 min by using a shearing machine to form colostrum; then introducing N into the mixture by using a high-pressure homogenizer under the pressure of 30-80 MPa2And (3) protection, namely forming emulsion after 5-10 times of circulation, cooling to room temperature to prepare a nano-structured lipid carrier aqueous solution, adding 7-15 parts of a protective agent, uniformly stirring, and drying to prepare nano-structured lipid carrier solid powder.
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