CN108079308A - Ubiquinone10With the nano structured lipid carrier and preparation method of n-octacosanol compounding - Google Patents
Ubiquinone10With the nano structured lipid carrier and preparation method of n-octacosanol compounding Download PDFInfo
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- CN108079308A CN108079308A CN201810139968.0A CN201810139968A CN108079308A CN 108079308 A CN108079308 A CN 108079308A CN 201810139968 A CN201810139968 A CN 201810139968A CN 108079308 A CN108079308 A CN 108079308A
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
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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
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
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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
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Abstract
The invention discloses ubiquinones10With the nano structured lipid carrier and preparation method of n-octacosanol compounding, it belongs to drug, health product technology field.Ubiquinone10With the nano structured lipid carrier of n-octacosanol compounding, it is mainly prepared by following raw materials in parts by weight number：Ubiquinone1015 parts, 12 parts of n-octacosanol is pungent, 0.5 1 parts of glycerol decanoate (ODO), 0.001 0.003 parts of vitamin E, 25 parts of emulsifier.The present invention uses ubiquinone10It compounds to form nano structured lipid carrier with n-octacosanol, there is reducing blood lipid, cardioprotection, there is higher release and bioavilability, sustained release.
Description
Technical field
The present invention relates to a kind of ubiquinones10Nano structured lipid carrier and preparation method, the nanometer are compounded with n-octacosanol
Structured lipid carrier has the effects that strengthen immunity, alleviates physical fatigue, cardioprotection, it belongs to drug, health products technology
Field.
Background technology
Ubiquinone10(Coenzyme Q10) it is a kind of compound voluntarily synthesized by human body, because of the side on its parent nucleus six
The degree of polymerization of chain-polyisopreneyl is gained the name for 10, and structure is similar with vitamin K.Ubiquinone10It is divided into reduced coenzyme Q10
(Co Q10H2, Ubiquinol, panthenol) and oxidized coenzyme Q10(Co Q10, Ubiquinone, ubiquinone) and two kinds of forms, Co
Q10H2It is Co Q10Two-electron reduction product.In vivo, Co Q10H2With Co Q10Hydrogen/pass electron is passed as one kind to participate in jointly
The cross-films electronics transportation system such as mitochondrial inner membrane respiratory chain and cellular oxidation Phosphorylation events, in the conjunction of atriphos (ATP)
It plays an important role in.Ubiquinone10It is that indispensable important physiologically substance, chemical constitution feature determine it in human body
There are many important physiological functions in human body, it is energy transmission substance important in vital movement, is mitochondrial respiratory chain
The critical substances of rate-limiting reaction play a significant role in terms of cellular energy generation, enhancing biologos.Ubiquinone10With compared with
Strong anti-oxidative stress safeguards that mitochondrial membrane is complete, and reducing blood lipid can be aided in, reduce its pair work by being shared with statins
With it has the angiocardiopathies such as hyperlipidemia, tumour, diabetes, Parkinson etc. preferably treatment and health-care effect.
N-octacosanol (1-Octacosanol), also known as Montanylalcohol or policosanol, molecular formula C28H58O is natural
Existing higher aliphatic is universally acknowledged antifatigue substance at present mainly by sugarcane wax, rice bran, beeswax Hydrolysis kinetics,
In the U.S., Japan and other countries as natural health food additives, the natural good medicine of wide spectrum, sports drink, day are had been widely used for
The fields such as right health products, drug and cosmetics.N-octacosanol have improve body endurance, reduce body stress reaction,
Reduce internal blood fat and cholesterol and other physiological functions.N-octacosanol also has enhancing cardiac function, reduces cholesterol,
The effects that anti-body atherosclerosis, the gastric ulcer that inhibits, platelet aggregation-against, protection liver.
Ubiquinone10Be liposoluble substance with n-octacosanol, be insoluble in water, belong to II class substance of pharmacy, take orally to
Medicine absorption is limited to dissolve and dissolve out, and absolute bioavailability is relatively low, ubiquinone10It is unstable to light, aqueous nature, for this
Kind situation has developed a variety of methods for improving oral medication bioavilabilities, such as inclusion technique, self-emulsifying skill in recent years
Art, liposome, nano structured lipid carrier etc..Wherein nanometer administration is to improve the preferable technology of bioavilability, has been opened at present
It sends such as nano liposomes (nanoliposomes, NL), solid nanostructure lipid carrier (solid lipid nano-
Particles, SLN) and nanoemulsion (nano-particale emulsion, NPE) etc..Nano structured lipid carrier
(nanostructured lipid carriers, NLC) develops on the basis of solid nanostructure lipid carrier (SLN)
Novel Drug Delivery Systems, add in formula solid lipid be to be formed solid lipid nano granule or nano structured lipid carrier it is necessary
Condition, usual method are to add in liquid fatty on the basis of solid lipid is carrier, upset the perfection after Solid lipid cures
Crystal form, to increase drug delivery rate and absorption.It is that drug ingedient can be dissolved in the lipid of thawing that NLC, which carries medicine usual conditions,
Method is that drug ingedient is dissolved after solid lipid is melted or is dissolved lipid and drug ingedient using organic solvent, it usually needs
It is prepared after larger amount of solid lipid dissolving, drug ingedient carrying drug ratio is limited to it and is melting the solubility of lipid, ordinary circumstance
Its lower carrying drug ratio is not high.Ubiquinone10It is liposoluble substance with n-octacosanol, is insoluble in water, the two is in general solid lipid
Middle solubility is also smaller, usually needs larger amount of solid lipid molten according to conventional nano structured lipid carrier preparation method
It is prepared after solution, is so difficult the preparation for preparing high carrying drug ratio.
The current disclosed patent delivered and document are retrieved, do not retrieve the two compounding nano structured lipid carrier
Or related patents and the literature research report of other nanometer formulations, only retrieve ubiquinone10It is prepared separately with n-octacosanol similar
The document or patent of preparation, wherein with this patent is associated has：1. a kind of 105708799 nanostructured lipids of Chinese patent CN
The method that insoluble drug is prepared into nano structured lipid carrier is mentioned in carrier medicament composition and preparation method thereof, wherein difficult
Soluble drug includes ubiquinone10.Chinese patent CN101658468A ubiquinones10Nano structured lipid carrier and preparation method thereof public affairs
Ubiquinone is opened10Nano structured lipid carrier and its application.②《Fine chemistry industry》2016,33(1):65-70；《Chinese Hospitals pharmacy
Magazine》2012,32(12):932-936；《Daily chemical industry》2016,46(9):Coenzyme is mentioned in the above-mentioned document such as 524-529
Q10Nano structured lipid carrier preparation and application.Document European Journal of Pharmaceutics and
Author Rainer H.Muller deliver entitled Cetyl palmitate- in Biopharmaceutics 67 (2007) 141-148
based NLC for topical deliveryof Coenzyme Q10-Development,physicochemical
Characterizationand in vitro release studies articles, article is described to be prepared using palmitate
The ubiquinone of 24% content10NLC methods.Document pharmaceutical Research, Vol.18, No.3,2001, Heike
Bunjes delivers Incorporation of the Model DrugUbidecarenone into SolidLipid
Mono- texts of Nanoparticles describe ubiquinone10It is prepared by solid-liquid nanoparticle.3. Chinese patent CN100998438A 28
Alkanol emulsion and preparation method thereof describes emulsion of tadenan preparation method, is related to n-octacosanol using emulsification
The method that method prepares 1.5% emulsion of highest content, patent content do not announce its aqueous solution grain size, nano junction are not directed in technique
Prepared by structure lipid carrier such as cools down key link.A kind of Otacosane alcohol extract micro-encapsulation powder of Chinese patent CN1316966C
End and preparation method thereof discloses the preparation method of its micro-capsule, is not directed in the preparation of n-octacosanol nano structured lipid carrier
Hold.Above-mentioned patent is all on ubiquinone10Or nano structured lipid carrier and other correlation techniques are prepared separately in n-octacosanol
Content, wherein open source literature shows ubiquinone10Nano structured lipid carrier carrying drug ratio is usually relatively low, and carrying drug ratio is generally 24%
Hereinafter, n-octacosanol is not directed to nano structured lipid carrier technology contents.Ubiquinone10Nano structured lipid carrier prepares one
As all employ the method that organic solvent dissolves and is used as oil phase.Patent documents above is not directed to the technology of the present invention content.
The content of the invention
The present invention be exactly in order to solve the above-mentioned technical problem, and provide a kind of ubiquinone10With receiving for n-octacosanol compounding
Rice structured lipid carrier and preparation method, the present invention use ubiquinone10It compounds to form nanostructured lipid load with n-octacosanol
Body has the effects that reducing blood lipid, cardioprotection, has the characteristics that higher release and bioavilability, sustained release.
Preparing nano structured lipid carrier generally requires packaging medicine ingredient that can be dissolved just in selected solid lipid
It can prepare, its carrying drug ratio is not high under normal circumstances.Ubiquinone10Although it is liposoluble substance with n-octacosanol, usual
Solubility is not high in the solid lipid used, therefore conventionally prepares the larger amount of solid lipid of needs, so very
Hardly possible prepares the nano-carrier of high carrying drug ratio.Ubiquinone10Fusing point is 49 DEG C, and octacosane alcohol monomer fusing point is 83 DEG C, therefore in water-bath
In the case of 85 DEG C, the complete mixing of the two be homogeneous lipid solid dispersions, both melting solid dispersions in fusing point peak it is whole
Body moves down, and at 40-70 DEG C, meets the solid lipid condition for preparing NLC, therefore the present invention is special using both ingredient physicochemical properties
Point is innovated using main ingredient ingredient and heats mixing as solid lipid ingredient or after adding in solid lipid selected on a small quantity in itself, formed
The uniform solid dispersions lipid of main ingredient high-content, is then being achieved that without using organic solvent using emulsion process
Prepare the ubiquinone of high carrying drug ratio10With n-octacosanol nano structured lipid carrier.To make the ubiquinone of this high carrying drug ratio10With
N-octacosanol nano structured lipid carrier is more preferably applied to solid dosage formulation, is carried to having formed NLC nanostructured lipids
Nanoparticle is protected in body aqueous solution, and the present invention has screened protective agent species, obtains to answer by adding in protection agent method
Molten ubiquinone10With n-octacosanol nano structured lipid carrier solid powder, the drying side of suitable industrialized production is filtered out
Method.
In order to solve the above-mentioned technical problem, the present invention is to be achieved through the following technical solutions：
Ubiquinone10With the nano structured lipid carrier of n-octacosanol compounding, it mainly presses the weight by following raw materials
Number is prepared：Ubiquinone101-5 parts, 1-2 parts of n-octacosanol is pungent, 0.5-1 parts of glycerol decanoate, vitamin E 0.001-
0.003 part, 2-5 parts of emulsifier.
Ubiquinone10With the nano structured lipid carrier of n-octacosanol compounding, it is by the parts by weight by following raw materials
It is prepared：Ubiquinone101-5 parts, 1-2 parts of n-octacosanol, 0.5-1.5 parts of solid lipid is pungent, 0.5-1 parts of glycerol decanoate,
0.001-0.003 parts of vitamin E, 2-5 parts of emulsifier.
Ubiquinone10With the nano structured lipid carrier of n-octacosanol compounding, it is by the parts by weight by following raw materials
It is prepared：Ubiquinone101-5 parts, 1-2 parts of n-octacosanol, 0.5-1.5 parts of solid lipid is pungent, 0.5-1 parts of glycerol decanoate,
0.001-0.003 parts of vitamin E, 2-5 parts of emulsifier, 7-15 parts of protective agent.
Above-mentioned solid lipid is glycerin monostearate or Compritol 888 ATO.
Above-mentioned emulsifier is lecithin, ten polyglyceryl laurates, ten polyglycerol stearates, polyethylene glycol -12- hydroxyls
At least one of base stearate, Tween-80.
Above-mentioned ubiquinone10It is oxidized coenzyme Q10Or reduced coenzyme Q10。
Above-mentioned n-octacosanol is n-octacosanol monomer component or 50% one group of C22 is no less than containing n-octacosanol
~C36 higher aliphatic alkanol mixtures.
Above-mentioned protective agent is starch Sodium Octenyl Succinate or ocentyl succinic list Arabic gum ester.
Ubiquinone10With the preparation method of the nano structured lipid carrier of n-octacosanol compounding, it is walked including following techniques
Suddenly：Weigh the ubiquinone for meeting the parts by weight10, it is n-octacosanol, pungent, glycerol decanoate, vitamin E are at 70~90 DEG C
Heating melting, stirs and evenly mixs, and forms oil phase；It weighs and meets in emulsifier 70~90 DEG C of water of addition of the parts by weight, stirring
Mixing forms water phase；Above-mentioned oil phase is added in water phase, using cutter, after being sheared 1-2 minutes with 16000rpm, is formed just
Breast；Then using high pressure homogenizer, under the pressure of 30~80MP, N is led to2Protection by 5~10 Xun Huans, forms lotion, cold
But to room temperature, nano structured lipid carrier aqueous solution is made.
Above-mentioned ubiquinone10With the preparation method of the nano structured lipid carrier of n-octacosanol compounding, it includes following works
Skill step：Weigh the ubiquinone for meeting the parts by weight10, n-octacosanol, 0.5-1.5 parts of solid lipids, pungent, capric acid glycerine
Ester, vitamin E heat melting at 70~90 DEG C, stir and evenly mix, and form oil phase；Weigh the emulsifier for meeting the parts by weight
It adds in 70~90 DEG C of water, stirs and evenly mixs, form water phase；Above-mentioned oil phase is added in water phase, using cutter, with 16000rpm
After shearing 1-2 minutes, colostrum is formed；Then using high pressure homogenizer, under the pressure of 30~80MP, N is led to2Protection, by 5~
10 Xun Huans, form lotion, are cooled to room temperature, and nano structured lipid carrier aqueous solution is made, and add in 7-15 portions of protective agents, stirring
Uniformly, it is dry, nano structured lipid carrier solid powder is made.
Spray drying or freeze-drying may be employed in above-mentioned drying, high-pressure homogeneous to be substituted using ultrasonic oscillation.
Due to the adoption of the above technical scheme so that the present invention has following features and effect：
The present invention unlike previous technologies be using ubiquinone10It is shared with n-octacosanol compounding as a formulation protocol,
Purpose will play good synergistic effect, due to ubiquinone10There are good enhancing cardiac function and reducing blood lipid with n-octacosanol
Effect, ubiquinone10It is the intracellular antioxidant in mitochondria, has and remove internal peroxylradicals effect more by force,
Cardiac muscle cell provides energy, treatment and improvement angiocardiopathy, and n-octacosanol has anti peroxidation of lipid, protection cardiac muscle cell
Mitochondrial integrity and adjusting energy metabolism of myocardial effect, n-octacosanol is mainly by adjusting in Biosynthesis of cholesterol
The activity of key enzyme --- HMG CoA (HMG-CoA) inhibits the synthesis of cholesterol, so as to reducing the total courage of human body
Sterol, since the enzyme is also internal ubiquinone10Synzyme, it is therefore possible to ubiquinone10Biosynthesis form influence, two
Person, which shares, eliminates this influence, simultaneously because effect of the two based on different mechanism anti-oxidation stress and physiological activity,
Experiment proves that the two is shared with stronger physiological activity, especially in the application of reducing blood lipid, better effect is reached
Fruit.
Ubiquinone prepared by the present invention10Laser particle is used with the nano structured lipid carrier grain size of n-octacosanol compounding
Instrument measures, and grain size is in 100~300nm, ubiquinone10Carrying drug ratio reaches as high as 20%~50%, and n-octacosanol carrying drug ratio can
Up to 28%, envelop rate is 90%~99%, and high carrying drug ratio is more than previous similar technique.It can be dried to admittedly after adding in protective agent
Body powder, redissolve solution grain size still can be applied to solid pharmaceutical preparation in 200~400nm so that it can facilitate.Nanometer of the present invention
Carrier is due to its ubiquinone10There is the physicochemical property of fat-soluble low melting point, therefore the skill used using the present invention with n-octacosanol
Art means both can form the lipid dispersions of mixing, can without using or only use a small amount of solid lipid and can just generate more
Low melting point mixing lipid dispersions create condition further to prepare high carrying drug ratio nano structured lipid carrier, and do not make
By the use of organic solvent as oil phase, therefore nano structured lipid carrier prepared by the last present invention has been more than previous technique effect.
Heat analysis collection of illustrative plates DSC shows ubiquinone10It disappears or deviates with n-octacosanol fusing point peak, it was demonstrated which form uniform
Mixing lipid dispersions, ubiquinone10Unformed state, the crystal are in nano structured lipid carrier with n-octacosanol
State contributes to its absorption.Images of transmissive electron microscope show carrier particle of the present invention be it is substantially circular, grain size in 100-300nm,
Solid powder particles redissolve aqueous solution grain size in 200-400nm.Ubiquinone prepared by the present invention10With receiving for n-octacosanol compounding
Rice structured lipid carrier and its powder and prototype medicine phases ratio, release have a more substantial increase, and sustained release trend is presented.
Ubiquinone prepared by the present invention10It is demonstrate,proved with the nano structured lipid carrier of n-octacosanol compounding by the antioxidation in vitro test of pesticide effectiveness
Bright, in vitro anti-oxidation is such as to DPPH radical scavenging activities significantly beyond ubiquinone10With n-octacosanol prototype medicine mixture
And their independent nano particle preparations, it was demonstrated that while loaded ubiquinone10Resist with the nano structured lipid carrier of n-octacosanol
Oxidation effectiveness is significantly better than nano-carrier and the two raw mixture prepared by previous single raw material.Present invention load ubiquinone10
With the nano structured lipid carrier solid powder of n-octacosanol compounding, there is preferable solid powder mobility, compressibility, answer
Dissolubility, fater disintegration physical characteristic make it be easier to prepare such as tablet, capsule solid pharmaceutical preparation.
Ubiquinone of the present invention10With the ubiquinone of the nano structured lipid carrier of n-octacosanol compounding10Content assaying method master
High performance liquid chromatography is used, method is to take ubiquinone10It is fitted with the nano structured lipid carrier sample of n-octacosanol compounding
Amount heats ultrasound with ethyl alcohol, lets cool after being settled to normal concentration, filters, take subsequent filtrate as test solution, sample introduction, chromatography
Condition：Ubiquinone10：C18 columns, mobile phase are acetonitrile：Tetrahydrofuran：Water=55：40：5 (volume ratios), Detection wavelength 275nm, outside
Mark standard measure to get.
Ubiquinone of the present invention10With the n-octacosanol assay side of the nano structured lipid carrier of n-octacosanol compounding
For method mainly using gas chromatography, method is to weigh ubiquinone10With the nano structured lipid carrier sample of n-octacosanol compounding
In right amount, it is accurate to add in 10mL mixed extract (chloroforms in 10mL tool plug test tubes：N-hexane volume ratio 9:1), ultrasound carries
It takes 15min, after stratification, takes 1 μ L of supernatant sample introduction, chromatographic condition：Chromatographic column is the PE-5MS (μ of 30m × 0.25mm × 0.25
M), (180 DEG C of holdings 3min, 9 DEG C/min rise to 290 DEG C, and 35min, 22 DEG C/min is kept to rise to 300 DEG C, is kept for temperature programming
5min), injector temperature is 320 DEG C, and fid detector temperature is 330 DEG C, split ratio 60:1, nitrogen flow rate 50mL/min,
Hydrogen flow rate is 35mL/min, air velocity 400mL/min.
Ubiquinone of the present invention10The entrapment efficiency determination method of the nano structured lipid carrier compounded with n-octacosanol, using super
Filter centrifugal process surveys its envelop rate and drugloading rate, and vortex 1min is uniformly mixed after taking 10 times of appropriate amount of sample dilution, is placed in ultrafiltration centrifugation
Guan Zhong, 12000r/min centrifuge 10min, and filtrate is taken to be placed in 10mL measuring bottles, quarter is settled to after adding methanol ultrasonic dissolution 15min
Degree with 0.45 μm of filtering with microporous membrane, measures the medication amount (W that dissociates in filtrateF)；Separately appropriate amount of sample is taken in 10mL volumetric flasks,
Scale is settled to after adding methanol ultrasonic dissolution 15min, with 0.45 μm of filtering with microporous membrane, measures total dose (WT).Envelop rate
(%)=(WT-WF)/WT× 100%；Drugloading rate (%)=(WT-WF)/WL× 100%；Wherein, WL：Nano structured lipid carrier
Quality.
Description of the drawings
Fig. 1 is the grain size distribution of NLC aqueous solutions prepared by embodiment 1.
Fig. 2 is the Zeta potential distribution map of NLC aqueous solutions prepared by embodiment 1.
Fig. 3 is the grain size distribution of NLC solid powders prepared by embodiment 14.
Fig. 4 is NLC, blank NLC, ubiquinone prepared by embodiment 1410, n-octacosanol DSC figure.
Fig. 5 is ubiquinone in NLC prepared by embodiment 1,6,1410Cumulative release curve.
Fig. 6 is n-octacosanol cumulative release curve in NLC prepared by embodiment 1,6,14.
Specific embodiment
With reference to embodiment, the present invention is described further.Following embodiment is only several specific realities of the present invention
Example is applied, but the design concept of the present invention is not limited thereto, all changes for carrying out unsubstantiality to the present invention using this design,
The behavior for invading the scope of the present invention should be belonged to.
Method in following embodiments is conventional method unless otherwise instructed, and the percentage composition is quality hundred
Divide content.
Embodiment 1
Oxidized coenzyme Q102 parts, 1 part of n-octacosanol is pungent, 1 part of glycerol decanoate (ODO), 0.001 part of vitamin E, and ten
1 part of polyglyceryl laurate, 11 part of polyglycerol stearates.
Weigh 4g oxidized coenzymes Q10, 2g n-octacosanols, 2g it is pungent, glycerol decanoate (ODO), 0.002g vitamin Es exist
Melting is heated at 90 DEG C, is stirred and evenly mixed, forms oil phase；Weigh ten polyglyceryl laurates of 2g, ten polyglycerol stearates of 2g add
Enter in 90 DEG C of 200mL water, stir and evenly mix, form water phase；Above-mentioned oil phase is slowly added in water phase, using cutter, with
After 16000rpm is sheared 1 minute, colostrum is formed；Then using high pressure homogenizer, under the pressure of 60MP, N is led to2Protection, by 5
Secondary cycling forms lotion, is cooled to room temperature, and nano structured lipid carrier aqueous solution is made.After measured, average grain diameter 112.9nm,
Current potential be (- 27.5 ± 4.99) mV, ubiquinone10Carrying drug ratio and envelop rate be respectively 32.5% and 97.4%, n-octacosanol
Drugloading rate and envelop rate are respectively 15.9% and 95.3%.
Embodiment 2
Oxidized coenzyme Q101 part, 2 parts of n-octacosanol is pungent, 1 part of glycerol decanoate (ODO), and 0.002 part of vitamin E is spat
- 80 1.5 parts of temperature, 1.5 parts of soybean lecithin.
Weigh 2g oxidized coenzymes Q10, 4g n-octacosanols, 2g it is pungent, glycerol decanoate (ODO), 0.004g vitamin Es exist
Melting is heated at 85 DEG C, is stirred and evenly mixed, forms oil phase；It weighs in 3g Tween-80s, 3g soybean lecithins 85 DEG C of 250mL water of addition, stirs
Mixing is mixed, forms water phase；Above-mentioned oil phase is slowly added in water phase, using cutter, after being sheared 1.5 minutes with 16000rpm,
Form colostrum；Then using high pressure homogenizer, under the pressure of 70MP, N is led to2Protection by 7 Xun Huans, forms lotion, rapidly
It is cooled to room temperature, nano structured lipid carrier aqueous solution is made.After measured, average grain diameter 210.6nm, ubiquinone10Carrying drug ratio and
Envelop rate is respectively 13.6% and 95.5%, and the drugloading rate and envelop rate of n-octacosanol are respectively 26.6% and 93.2%.
Embodiment 3
Oxidized coenzyme Q101 part, 1 part of C22~C36 higher aliphatics alkanol mixture containing n-octacosanol 70%, pungent, the last of the ten Heavenly stems
0.5 part of acid glyceride (ODO), 0.003 part of vitamin E, 0.2 part of soybean lecithin, polyethylene glycol-12-hydroxystearate
(HS15) 1.8 parts.
Weigh 2g oxidized coenzymes Q10, C22~C36 higher aliphatic alkanol mixture, 1g of the 2g containing n-octacosanol 70%
Pungent, glycerol decanoate (ODO), 0.006g vitamin Es heat melting at 70 DEG C, stir and evenly mix, and form oil phase；It is big to weigh 0.4g
Beans lecithin, 3.6g polyethylene glycol-12-hydroxystearate (HS15) are added in 70 DEG C of 150mL water, stirred and evenly mixed, and form water
Phase；Above-mentioned oil phase is slowly added in water phase, using cutter, after being sheared 2 minutes with 16000rpm, forms colostrum；Then make
With high pressure homogenizer, under the pressure of 30MP, lead to N2Protection by 10 Xun Huans, forms lotion, is rapidly cooled to room temperature, makes
Obtain nano structured lipid carrier aqueous solution.After measured, average grain diameter 195.2nm, ubiquinone10Carrying drug ratio and envelop rate be respectively
22.9% and 96.1%, the drugloading rate and envelop rate of n-octacosanol are respectively 15.6% and 93.6%.
Embodiment 4
Reduced coenzyme Q105 parts, 2 parts of n-octacosanol is pungent, 0.5 part of glycerol decanoate (ODO), 0.002 part of vitamin E,
0.2 part of egg yolk lecithin, 4.8 parts of polyethylene glycol-12-hydroxystearate (HS15).
Weigh 5g reduced coenzyme Qs10, 2g n-octacosanols, 0.5g it is pungent, glycerol decanoate (ODO), 0.002g vitamin Es
Melting is heated at 80 DEG C, is stirred and evenly mixed, forms oil phase；0.2g egg yolk lecithins are weighed, 4.8g polyethylene glycol -12- hydroxyls are hard
Resin acid ester (HS15) is added in 80 DEG C of 210mL water, is stirred and evenly mixed, and forms water phase；Above-mentioned oil phase is slowly added in water phase, is used
Cutter after being sheared 2 minutes with 16000rpm, forms colostrum；Then using high pressure homogenizer, under the pressure of 80MP, N is led to2
Protection by 5 Xun Huans, forms lotion, is rapidly cooled to room temperature, nano structured lipid carrier aqueous solution is made.After measured, put down
Equal grain size 180.7nm, ubiquinone10Carrying drug ratio and envelop rate be respectively 38.6% and 96.5%, the drugloading rate of n-octacosanol and
Envelop rate is respectively 15.0% and 93.8%.
Embodiment 5
Oxidized coenzyme Q105 parts, 1 part of n-octacosanol, 1 part of glycerin monostearate is pungent, glycerol decanoate (ODO) 0.5
Part, 0.003 part of vitamin E, 3 parts of polyethylene glycol-12-hydroxystearate (HS15).
Weigh 5g oxidized coenzymes Q10, 1g n-octacosanols, 1g glycerin monostearates, 0.5g it is pungent, glycerol decanoate
(ODO), 0.003g vitamin Es heat melting at 85 DEG C, stir and evenly mix, and form oil phase；Weigh 3g polyethylene glycol -12- hydroxyls
Stearate (HS15) is added in 85 DEG C of 180mL water, is stirred and evenly mixed, and forms water phase；Above-mentioned oil phase is slowly added in water phase, is made
With cutter, after being sheared 1 minute with 16000rpm, colostrum is formed；Then using high pressure homogenizer, under the pressure of 30MP, lead to
N2Protection by 5 Xun Huans, forms lotion, is rapidly cooled to room temperature, nano structured lipid carrier aqueous solution is made.After measured,
Average grain diameter 222.6nm, ubiquinone10Carrying drug ratio and envelop rate be respectively 45.2% and 94.9%, the drugloading rate of n-octacosanol
It is respectively 8.9% and 93.0% with envelop rate.
Embodiment 6
Oxidized coenzyme Q105 parts, 1 part of n-octacosanol, 1.5 parts of glycerin monostearate is pungent, glycerol decanoate (ODO)
0.75 part, 0.002 part of vitamin E, ten 2.67 parts of polyglyceryl laurates, ten 1.33 parts of polyglycerol stearates.
Weigh 5g oxidized coenzymes Q10, 1g n-octacosanols, 1.5g glycerin monostearates, 0.75g it is pungent, glycerol decanoate
(ODO), 0.002g vitamin Es heat melting at 75 DEG C, stir and evenly mix, and form oil phase；Weigh ten polyglycereol lauric acid of 2.67g
Ester, ten polyglycerol stearates of 1.33g are added in 75 DEG C of 220mL water, are stirred and evenly mixed, and form water phase；Above-mentioned oil phase is slowly added
Enter in water phase, using cutter, after being sheared 1 minute with 16000rpm, form colostrum；Then using high pressure homogenizer, in 40MP
Pressure under, lead to N2Protection by 6 Xun Huans, forms lotion, is rapidly cooled to room temperature, nano structured lipid carrier water is made
Solution.After measured, average grain diameter 120.5nm, ubiquinone10Carrying drug ratio and envelop rate be respectively 40.1% and 98.2%, 28
The drugloading rate and envelop rate of alkanol are respectively 7.9% and 96.8%.
Embodiment 7
Oxidized coenzyme Q104 parts, 2 parts of n-octacosanol, 1 part of Compritol 888 ATO is pungent, glycerol decanoate (ODO) 0.5
Part, 0.001 part of vitamin E, ten 1.67 parts of polyglyceryl laurates, ten 3.33 parts of polyglycerol stearates.
Weigh 4g oxidized coenzymes Q10, 2g n-octacosanols, 1g Compritol 888 ATOs, 0.5g it is pungent, glycerol decanoate
(ODO), 0.001g vitamin Es heat melting at 60 DEG C, stir and evenly mix, and form oil phase；Weigh ten polyglycereol lauric acid of 1.67g
Ester, ten polyglycerol stearates of 3.33g are added in 70 DEG C of 140mL water, are stirred and evenly mixed, and form water phase；Above-mentioned oil phase is slowly added
Enter in water phase, using cutter, after being sheared 2 minutes with 16000rpm, form colostrum；Then using high pressure homogenizer, in 50MP
Pressure under, lead to N2Protection by 6 Xun Huans, forms lotion, is rapidly cooled to room temperature, nano structured lipid carrier water is made
Solution.After measured, average grain diameter 178.4nm, ubiquinone10Carrying drug ratio and envelop rate be respectively 30.8% and 96.4%, 28
The drugloading rate and envelop rate of alkanol are respectively 15.0% and 93.5%.
Embodiment 8
Oxidized coenzyme Q105 parts, 1 part of n-octacosanol, 1.5 parts of Compritol 888 ATO is pungent, glycerol decanoate (ODO) 0.6
Part, 0.002 part of vitamin E, 1 part of Tween-80,2 parts of soybean lecithin.
Weigh 5g oxidized coenzymes Q10, 1g n-octacosanols, 1.5g Compritol 888 ATOs, 0.6g it is pungent, glycerol decanoate
(ODO), 0.002g vitamin Es heat melting at 80 DEG C, stir and evenly mix, and form oil phase；Weigh 1g Tween-80s, 2g soybean phosphorus
Fat is added in 80 DEG C of 170mL water, is stirred and evenly mixed, and forms water phase；Above-mentioned oil phase is slowly added in water phase, using cutter, with
After 16000rpm is sheared 1 minute, colostrum is formed；Then using high pressure homogenizer, under the pressure of 60MP, N is led to2Protection, by 8
Secondary cycling forms lotion, is rapidly cooled to room temperature, and nano structured lipid carrier aqueous solution is made.After measured, average grain diameter
178.8nm, ubiquinone10Carrying drug ratio and envelop rate be respectively 43.3% and 96.2%, the drugloading rate and envelop rate of n-octacosanol
Respectively 8.4% and 93.3%.
Embodiment 9
Reduced coenzyme Q101 part, 2 parts of n-octacosanol, 0.5 part of Compritol 888 ATO is pungent, glycerol decanoate (ODO)
0.75 part, 0.003 part of vitamin E, 4 parts of polyethylene glycol-12-hydroxystearate.
Weigh 2g reduced coenzyme Qs10, 4g n-octacosanols, 1g Compritol 888 ATOs, 1.5g it is pungent, glycerol decanoate
(ODO), 0.006g vitamin Es heat melting at 65 DEG C, stir and evenly mix, and form oil phase；Weigh 8g polyethylene glycol -12- hydroxyls
Stearate is added in 75 DEG C of 160mL water, is stirred and evenly mixed, and forms water phase；Above-mentioned oil phase is slowly added in water phase, uses shearing
Machine after being sheared 2 minutes with 16000rpm, forms colostrum；Then using high pressure homogenizer, under the pressure of 40MP, N is led to2Protection,
By 5 Xun Huans, lotion is formed, is rapidly cooled to room temperature, nano structured lipid carrier aqueous solution is made.After measured, average grain
Footpath 168.1nm, ubiquinone10Carrying drug ratio and envelop rate be respectively 11.9% and 97.8%, the drugloading rate of n-octacosanol and encapsulating
Rate is respectively 23.3% and 96.2%.
Embodiment 10
Oxidized coenzyme Q103 parts, 1 part of n-octacosanol, 1 part of glycerin monostearate is pungent, glycerol decanoate (ODO) 1
Part, 0.003 part of vitamin E, 1.33 parts of Tween-80,0.67 part of soybean lecithin.
Weigh 6g oxidized coenzymes Q10, 2g n-octacosanols, 2g glycerin monostearates, 2g it is pungent, glycerol decanoate
(ODO), 0.006g vitamin Es heat melting at 85 DEG C, stir and evenly mix, and form oil phase；Weigh 2.66g Tween-80s, 1.34g
Soybean lecithin is added in 85 DEG C of 150mL water, is stirred and evenly mixed, and forms water phase；Above-mentioned oil phase is slowly added in water phase, uses shearing
Machine after being sheared 1.5 minutes with 16000rpm, forms colostrum；Then using high pressure homogenizer, under the pressure of 30MP, N is led to2It protects
Shield by 5 Xun Huans, forms lotion, is rapidly cooled to room temperature, nano structured lipid carrier aqueous solution is made.After measured, it is average
Grain size 238.2nm, ubiquinone10Carrying drug ratio and envelop rate be respectively 36.0% and 96.1%, the drugloading rate and bag of n-octacosanol
Envelope rate is respectively 11.6% and 93.2%.
Embodiment 11
Reduced coenzyme Q105 parts, 2 parts of n-octacosanol, 1.5 parts of Compritol 888 ATO is pungent, glycerol decanoate (ODO)
0.75 part, 0.002 part of vitamin E, ten 3.75 parts of polyglyceryl laurates, ten 1.25 parts of polyglycerol stearates, octenyl amber
Single 7 parts of the Arabic gum ester of amber acid.
Weigh 5g reduced coenzyme Qs10, 2g n-octacosanols, 1.5g Compritol 888 ATOs, 0.75g it is pungent, glycerol decanoate
(ODO), 0.002g vitamin Es heat melting at 65 DEG C, stir and evenly mix, and form oil phase；Weigh ten polyglycereol lauric acid of 3.75g
Ester, ten polyglycerol stearates of 1.25g are added in 75 DEG C of 300mL water, are stirred and evenly mixed, and form water phase；Above-mentioned oil phase is slowly added
Enter in water phase, using cutter, after being sheared 1.5 minutes with 16000rpm, form colostrum；Then high pressure homogenizer is used,
Under the pressure of 40MP, lead to N2Protection by 5 Xun Huans, forms lotion, is rapidly cooled to room temperature, adds in 7g ocentyl succinics
Single Arabic gum ester, stirs evenly, spray-dried, and nano structured lipid carrier solid powder is made.After measured, average grain diameter
280.4nm, ubiquinone10Carrying drug ratio and envelop rate be respectively 22.3% and 94.8%, the drugloading rate and envelop rate of n-octacosanol
Respectively 8.8% and 93.4%.
Embodiment 12
Oxidized coenzyme Q105 parts, 1 part of n-octacosanol, 0.5 part of glycerin monostearate is pungent, glycerol decanoate (ODO)
0.5 part, 0.001 part of vitamin E, 11 part of polyglyceryl laurates, 13 parts of polyglycerol stearates, octenyl succinic acid starch
11 parts of sodium.
Weigh 5g oxidized coenzymes Q10, 1g n-octacosanols, 0.5g glycerin monostearates, 0.5g it is pungent, glycerol decanoate
(ODO), 0.001g vitamin Es heat melting at 75 DEG C, stir and evenly mix, and form oil phase；Weigh ten polyglyceryl laurates of 1g,
Ten polyglycerol stearates of 3g are added in 75 DEG C of 260mL water, are stirred and evenly mixed, and form water phase；Above-mentioned oil phase is slowly added to water phase
In, using cutter, after being sheared 1 minute with 16000rpm, form colostrum；Then using high pressure homogenizer, in the pressure of 50MP
Under, lead to N2Protection by 5 Xun Huans, forms lotion, is rapidly cooled to room temperature, adds in 11g starch Sodium Octenyl Succinates, stir
It mixes uniformly, it is spray-dried, nano structured lipid carrier solid powder is made.After measured, average grain diameter 380.4nm, ubiquinone10
Carrying drug ratio and envelop rate be respectively 21.9% and 96.5%, the drugloading rate and envelop rate of n-octacosanol are respectively 4.3% He
94.6%.
Embodiment 13
Reduced coenzyme Q105 parts, 1.5 parts of n-octacosanol, 0.75 part of Compritol 888 ATO is pungent, glycerol decanoate (ODO)
1 part, 0.002 part of vitamin E, 5 parts of soybean lecithin, 7 parts of starch Sodium Octenyl Succinate.
Weigh 5g reduced coenzyme Qs10, 1.5g n-octacosanols, 0.75g Compritol 888 ATOs, 1g it is pungent, glycerol decanoate
(ODO), 0.002g vitamin Es heat melting at 80 DEG C, stir and evenly mix, and form oil phase；It weighs 5g soybean lecithins and adds in 80 DEG C
It in 270mL water, stirs and evenly mixs, forms water phase；Above-mentioned oil phase is slowly added in water phase, using cutter, is cut with 16000rpm
After cutting 2 minutes, colostrum is formed；Then using high pressure homogenizer, under the pressure of 70MP, N is led to2Protection, by 10 Xun Huans, shape
Into lotion, room temperature is rapidly cooled to, 7g starch Sodium Octenyl Succinates is added in, stirs evenly, it is freeze-dried, nano junction is made
Structure lipid carrier solid powder.After measured, average grain diameter 314.2nm, ubiquinone10Carrying drug ratio and envelop rate be respectively 24.3%
With 98.3%, the drugloading rate and envelop rate of n-octacosanol are respectively 7.0% and 95.1%.
Embodiment 14
Oxidized coenzyme Q101 part, 2 parts of n-octacosanol, 0.6 part of glycerin monostearate is pungent, glycerol decanoate (ODO)
0.5 part, 0.002 part of vitamin E, 1 part of Tween-80,1 part of soybean lecithin, 13 parts of ocentyl succinic list Arabic gum ester.
Weigh 1g oxidized coenzymes Q10, 2g n-octacosanols, 0.6g glycerin monostearates, 0.5g it is pungent, glycerol decanoate
(ODO), 0.002g vitamin Es heat melting at 85 DEG C, stir and evenly mix, and form oil phase；Weigh 1g Tween-80s, 1g soybean ovum
Phosphatide is added in 85 DEG C of 200mL water, is stirred and evenly mixed, and forms water phase；Above-mentioned oil phase is slowly added in water phase, using cutter,
After being sheared 1 minute with 16000rpm, colostrum is formed；Then using high pressure homogenizer, under the pressure of 50MP, N is led to2Protection, warp
5 Xun Huans are crossed, form lotion, are rapidly cooled to room temperature, 13g ocentyl succinic list Arabic gum esters is added in, stirs evenly, are passed through
Nano structured lipid carrier solid powder is made in spray drying.After measured, average grain diameter 284.0nm, ubiquinone10Carrying drug ratio and
Envelop rate is respectively 4.9% and 93.5%, and the drugloading rate and envelop rate of n-octacosanol are respectively 9.6% and 91.6%.
Embodiment 15
Oxidized coenzyme Q102 parts, 2 parts of n-octacosanol, 1.5 parts of glycerin monostearate is pungent, glycerol decanoate (ODO)
0.75 part, 0.003 part of vitamin E, 12 parts of polyglyceryl laurates, 11 part of polyglycerol stearates, ocentyl succinic list
15 parts of Arabic gum ester.
Weigh 2g oxidized coenzymes Q10, 2g n-octacosanols, 1.5g glycerin monostearates, 0.75g it is pungent, glycerol decanoate
(ODO), 0.003g vitamin Es heat melting at 90 DEG C, stir and evenly mix, and form oil phase；Weigh ten polyglyceryl laurates of 2g,
Ten polyglycerol stearates of 1g are added in 90 DEG C of 280mL water, are stirred and evenly mixed, and form water phase；Above-mentioned oil phase is slowly added to water phase
In, using cutter, after being sheared 2 minutes with 16000rpm, form colostrum；Then using high pressure homogenizer, in the pressure of 60MP
Under, lead to N2Protection by 8 Xun Huans, forms lotion, is rapidly cooled to room temperature, adds in 15g ocentyl succinic list Arabic gums
Ester stirs evenly, spray-dried, and nano structured lipid carrier solid powder is made.After measured, average grain diameter 294.5nm, it is auxiliary
Enzyme Q10Carrying drug ratio and envelop rate be respectively 8.2% and 98.9%, the drugloading rate and envelop rate of n-octacosanol are respectively 8.0%
With 97.1%.
Embodiment 16
Oxidized coenzyme Q104 parts, 1 part of C22~C36 higher aliphatics alkanol mixture containing n-octacosanol 50%, behenyl
0.5 part of acid glyceride, pungent, 0.8 part of glycerol decanoate (ODO), 0.001 part of vitamin E, polyethylene glycol-12-hydroxystearate
(HS15) 4 parts, 7 parts of starch Sodium Octenyl Succinate.
Weigh 4g oxidized coenzymes Q10, C22~C36 higher aliphatic alkanol mixtures of the 1g containing n-octacosanol 50%,
0.5g Compritol 888 ATOs, 0.8g are pungent, and glycerol decanoate (ODO), 0.001g vitamin Es heat melting at 90 DEG C, and stirring is mixed
It is even, form oil phase；It weighs 4g polyethylene glycol-12-hydroxystearate (HS15) to add in 90 DEG C of 290mL water, stir and evenly mix, shape
Cheng Shuixiang；Above-mentioned oil phase is slowly added in water phase, using cutter, after being sheared 1.5 minutes with 16000rpm, forms colostrum；
Then using high pressure homogenizer, under the pressure of 50MP, N is led to2Protection by 5 Xun Huans, forms lotion, is rapidly cooled to room
Temperature adds in 7g starch Sodium Octenyl Succinates, freeze-dried, stirs evenly, nano structured lipid carrier solid powder is made.
After measured, average grain diameter 284.9nm, ubiquinone10Carrying drug ratio and envelop rate be respectively 23.1% and 97.1%, n-octacosanol
Drugloading rate and envelop rate be respectively 2.8% and 94.1%.
Embodiment 17
Oxidized coenzyme Q101 part, 2 parts of n-octacosanol, 1.5 parts of glycerin monostearate is pungent, glycerol decanoate (ODO)
0.75 part, 0.002 part of vitamin E, 12 parts of polyglyceryl laurates, 11 part of polyglycerol stearates, ocentyl succinic list
15 parts of Arabic gum ester.
Weigh 1g oxidized coenzymes Q10, 2g n-octacosanols, 1.5g glycerin monostearates, 0.75g it is pungent, glycerol decanoate
(ODO), 0.002g vitamin Es heat melting at 90 DEG C, stir and evenly mix, and form oil phase；Weigh ten polyglyceryl laurates of 2g,
Ten polyglycerol stearates of 1g are added in 85 DEG C of 260mL water, are stirred and evenly mixed, and form water phase；Above-mentioned oil phase is slowly added to water phase
In, using cutter, after being sheared 2 minutes with 16000rpm, form colostrum；Then using high pressure homogenizer, in the pressure of 60MP
Under, lead to N2Protection by 7 Xun Huans, forms lotion, is rapidly cooled to room temperature, adds in 15g ocentyl succinic list Arabic gums
Ester stirs evenly, spray-dried, and nano structured lipid carrier solid powder is made.After measured, average grain diameter 306.5nm, it is auxiliary
Enzyme Q10Carrying drug ratio and envelop rate be respectively 4.2% and 96.9%, the drugloading rate and envelop rate of n-octacosanol are respectively 8.3%
With 96.1%
Embodiment 18
The present invention is further described below by way of experiment：
1. grain size and Zeta potential measure：
The ubiquinone of Example 1-1010It is diluted, surveys in right amount with n-octacosanol nano structured lipid carrier aqueous solution
It is 25 DEG C to try temperature, and testing time is 3 times, and grain size and Zeta potential are measured using dynamic laser light scattering particle size determination instrument.
The ubiquinone of Example 11-1710Grain is measured after being dissolved in right amount with n-octacosanol nano structured lipid carrier solid powder
Footpath.Fig. 1 is 1 nano-carrier dynamic laser light scattering grain size collection of illustrative plates of embodiment, and Fig. 2 is 1 nano-carrier Zeta potential of embodiment, is schemed
3 be 14 nano-carrier powder dynamic laser light scattering grain size collection of illustrative plates of embodiment.
2.DSC is measured：
Blank nano structured lipid carrier is done according to the preparation method of embodiment 14 and (ubiquinone is free of in raw material10With 28
Alkanol), blank nano structured lipid carrier, the ubiquinone of embodiment 14 are weighed respectively10It is carried with n-octacosanol nanostructured lipid
Body solid powder, ubiquinone10With each 3-5mg of n-octacosanol in sealed aluminum crucible, 25-200 DEG C of temperature range, heating rate
For 20 DEG C/min, tabletting carries out heat analysis (DSC) measure, and the result is shown in Fig. 4.The result shows that load ubiquinone10With n-octacosanol
The fusing point of double medicament-carried nano structured lipid support powders is less than ubiquinone10With the fusing point of n-octacosanol, ubiquinone10With 28
Alkanol fusing point peak disappears substantially, it was demonstrated which form uniform mixing lipid dispersions, ubiquinones10With n-octacosanol in nanometer
Contribute to its absorption in unformed state, the state in structured lipid carrier.
3. morphology is investigated：
The ubiquinone of Example 110It is appropriate with n-octacosanol nano structured lipid carrier, it uniformly spreads on copper mesh, drips
Add 2% phosphotungstic acid aqueous solution negative staining 15min, after natural drying, take out copper mesh, the surface shape of sample is observed under transmission electron microscope
State and structure, nano structured lipid carrier are circular or similar round entity bead, and size is well dispersed than more uniform, substantially without
It is adhered.
4. centrifugal stability：
The ubiquinone of Example 110With n-octacosanol nano structured lipid carrier aqueous solution 50mL, used at 4 DEG C
10000rpm centrifuges 10min, sees whether to form precipitation and surveys supernatant grain size.Precipitation, after measured, grain size are not formed after centrifugation
For 116.2nm, PDI0.177, illustrate ubiquinone10With the centrifugal stability of n-octacosanol nano structured lipid carrier aqueous solution compared with
It is good.
Embodiment 19
Drug release determination：The ubiquinone of the preparation of the embodiment of the present invention 1,6,14 is measured using Bag filter method10With n-octacosanol
Nano structured lipid carrier, ubiquinone10It is tested with the vitro release of n-octacosanol physical mixture.Select cellulose acetate
Semi-permeable membrane (molecular cut off 10000) is permeable membrane, and half an hour is boiled in ultra-pure water before using.Drug release medium is
5%Labrasol-20% ethyl alcohol-PBS solution.Take a certain amount of ubiquinone10With n-octacosanol nano structured lipid carrier powder
End, ubiquinone10It is added in n-octacosanol physical mixture in bag filter, tightens both ends with rope, bag filter is placed in and is equipped with
In the conical flask of the 250mL-PBS dissolution mediums of ethyl alcohol containing 5%labarsol-20%, (37 ± 0.5) DEG C shaking table shakes, and speed is
200r/min in 1h, 2h, 3h, 5h, 7h, 9h, 12h, samples 10mL, then the blank release that rapid supplement 10mL phases are synthermal for 24 hours
Medium, sample measure Q respectively with HPLC methods and GC methods10With the burst size of n-octacosanol, obtain cumulative release curve such as Fig. 5 with
Fig. 6.
Embodiment 20
It removes DPPH free radical methods and surveys oxidation resistance test：The ubiquinone that respectively prepared by Example 1~1710With 28
Alkanol nano structured lipid carrier and blank sample (are free of CoQ10With the NLC of n-octacosanol) 150 μ l add in 2.85mL surpass
In pure water, that is, dilute 20 times.It is dissolved with absolute ethyl alcohol and prepares DPPH solution (5 × 10-5Mol/L it is) for use.Test tube is taken to number, by table
1 is loaded, and is uniformly mixed, and after reacting 60min at 37 DEG C of water-bath, sample to be tested reaction solution extinction is measured at 517nm wavelength
The absorbance of angle value and blank sample.(zeroing reference mixes for 1mL blank samples with 2mL ultra-pure waters) table 1 removes DPPH
Free radical tests each ingredient aequum
| Group | Sample to be tested/mL | Blank sample/mL | DPPH/mL | Ultra-pure water/mL |
| ATreat test sample .DPPH | 2.0 | 0 | 4.0 | 0 |
| ATreat test sample water | 2.0 | 0 | 0 | 4.0 |
| ABlank sample .DPPH | 0 | 2.0 | 4.0 | 0 |
Inhibiting rate is calculated using following formula：Inhibiting rate E (%)=(1- (ATreat test sample .DPPH-ATreat test sample water)/ABlank sample .DPPH)×
100%
To loading ubiquinone10With the nano structured lipid carrier (being prepared according to embodiment 1~16) and coenzyme of n-octacosanol
Q10With n-octacosanol bulk pharmaceutical chemicals mixture, ubiquinone10NLC, n-octacosanol NLC, which are compared, removes DPPH free radical energy
Power, as a result such as table 2：Table 2 removes DPPH free radical method experimental results
Embodiment 21
The carrier solids powder 125g of Example 11~16 respectively adds in 100g microcrystalline celluloses, 105g povidone
K30,106g maltodextrin, 50g crospovidone, 9g citric acids, 5g magnesium stearates, with pressure 30-50N compressed tabletses 1000
Piece, specification 0.5g/ pieces.Its powder angle of repose is tested, disintegration time limited, solubility the results are shown in Table 3.3 embodiment 11,14,16 of table is made
The evaluation index of standby NLC tablets
Claims (10)
1. ubiquinone10With the nano structured lipid carrier of n-octacosanol compounding, it is characterised in that it is mainly pressed by following raw materials
The parts by weight are prepared：Ubiquinone101-5 parts, 1-2 parts of n-octacosanol is pungent, 0.5-1 parts of glycerol decanoate, vitamin
E0.001-0.003 parts, 2-5 parts of emulsifier.
2. ubiquinone according to claim 110With the nano structured lipid carrier of n-octacosanol compounding, it is characterised in that
It is to be prepared by following raw materials by the parts by weight：Ubiquinone101-5 parts, 1-2 parts of n-octacosanol, solid lipid 0.5-
It is 1.5 parts, pungent, 0.5-1 parts of glycerol decanoate, 0.001-0.003 parts of vitamin E, 2-5 parts of emulsifier.
3. ubiquinone according to claim 110With the nano structured lipid carrier of n-octacosanol compounding, it is characterised in that
It is to be prepared by following raw materials by the parts by weight：Ubiquinone101-5 parts, 1-2 parts of n-octacosanol, solid lipid 0.5-
It is 1.5 parts, pungent, 0.5-1 parts of glycerol decanoate, 0.001-0.003 parts of vitamin E, 2-5 parts of emulsifier, 7-15 parts of protective agent.
4. the ubiquinone according to Claims 2 or 310With the nano structured lipid carrier of n-octacosanol compounding, feature exists
In the solid lipid be glycerin monostearate or Compritol 888 ATO.
5. according to the ubiquinone described in claim 1,2 or 310With the nano structured lipid carrier of n-octacosanol compounding, feature
It is that lecithin, ten polyglyceryl laurates, ten polyglycerol stearates, polyethylene glycol -12- hydroxyls are hard to be the emulsifier
At least one of resin acid ester, Tween-80.
6. according to the ubiquinone described in claim 1,2 or 310With the nano structured lipid carrier of n-octacosanol compounding, feature
It is the ubiquinone10It is oxidized coenzyme Q10Or reduced coenzyme Q10。
7. according to the ubiquinone described in claim 1,2 or 310With the nano structured lipid carrier of n-octacosanol compounding, feature
It is that the n-octacosanol is n-octacosanol monomer component or 50% C22~C36 high is no less than containing n-octacosanol
Grade fatty alkyl alcohol mixture.
8. ubiquinone according to claim 310With the nano structured lipid carrier of n-octacosanol compounding, it is characterised in that
The protective agent is starch Sodium Octenyl Succinate or ocentyl succinic list Arabic gum ester.
9. ubiquinone described in claim 110It is special with the preparation method of the nano structured lipid carrier of n-octacosanol compounding
Sign is that it includes following processing steps：Weigh the ubiquinone for meeting the parts by weight10, it is n-octacosanol, pungent, glycerol decanoate,
Vitamin E heats melting at 70~90 DEG C, stirs and evenly mixs, and forms oil phase；It weighs and meets the emulsifiers of the parts by weight and add
Enter in 70~90 DEG C of water, stir and evenly mix, form water phase；Above-mentioned oil phase is added in water phase, using cutter, is cut with 16000rpm
After cutting 1-2 minutes, colostrum is formed；Then using high pressure homogenizer, under the pressure of 30~80MP, N is led to2Protection, by 5~10
Secondary cycling forms lotion, is cooled to room temperature, and nano structured lipid carrier aqueous solution is made.
10. according to the ubiquinone described in right 910It is special with the preparation method of the nano structured lipid carrier of n-octacosanol compounding
Sign is that it includes following processing steps：Weigh the ubiquinone for meeting the parts by weight10, n-octacosanol, 0.5-1.5 parts it is solid
Body fat matter, pungent, glycerol decanoate, vitamin E heat melting at 70~90 DEG C, stir and evenly mix, and form oil phase；It weighs and meets institute
The emulsifier for stating parts by weight is added in 70~90 DEG C of water, is stirred and evenly mixed, and forms water phase；Above-mentioned oil phase is added in water phase, is made
With cutter, after being sheared 1-2 minutes with 16000rpm, colostrum is formed；Then using high pressure homogenizer, in the pressure of 30~80MP
Under, lead to N2Protection by 5~10 Xun Huans, forms lotion, is cooled to room temperature, nano structured lipid carrier aqueous solution is made, adds
Enter 7-15 portions of protective agents, stir evenly, it is dry, nano structured lipid carrier solid powder is made.
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| CN109077943A (en) * | 2018-09-11 | 2018-12-25 | 南通大学 | A kind of preparation method and application of the liposome containing n-octacosanol |
| CN110742912A (en) * | 2019-11-05 | 2020-02-04 | 深圳市芬多精纳米生物科技有限公司 | Method for preparing nano fendorin |
| CN111000811A (en) * | 2019-12-31 | 2020-04-14 | 济南大学 | Orally rapidly disintegrating tablet containing policosanol |
| CN111513326A (en) * | 2020-05-26 | 2020-08-11 | 宿迁医美科技有限公司 | Coenzyme Q10Microemulsion and preparation method thereof |
| CN112999158A (en) * | 2021-03-03 | 2021-06-22 | 江西省科学院生物资源研究所 | Preparation method and application of policosanol nano-liposome |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101766590A (en) * | 2010-02-01 | 2010-07-07 | 北京康比特体育科技股份有限公司 | Combination for protecting peroxide injury of myocardium |
| CN104337851A (en) * | 2014-10-28 | 2015-02-11 | 华东理工大学 | Preparation method of oleum fructus bruceae nano structure lipid carrier and freeze-dried powder thereof |
-
2018
- 2018-02-11 CN CN201810139968.0A patent/CN108079308B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101766590A (en) * | 2010-02-01 | 2010-07-07 | 北京康比特体育科技股份有限公司 | Combination for protecting peroxide injury of myocardium |
| CN104337851A (en) * | 2014-10-28 | 2015-02-11 | 华东理工大学 | Preparation method of oleum fructus bruceae nano structure lipid carrier and freeze-dried powder thereof |
Non-Patent Citations (2)
| Title |
|---|
| QIANG XIA ET AL.: ""Preparation and Characterization of Coenzyme Q10-loaded Nanostructured Lipid Carriers"", 《MATERIALS SCIENCE FORUM》 * |
| YANG YUE ET AL.: ""The advantages of a novel CoQ10 delivery system in skin photo-protection"", 《INTERNATIONAL JOURNAL OF PHARMACEUTICS》 * |
Cited By (7)
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| CN109077943A (en) * | 2018-09-11 | 2018-12-25 | 南通大学 | A kind of preparation method and application of the liposome containing n-octacosanol |
| CN109077943B (en) * | 2018-09-11 | 2021-06-22 | 南通大学 | Preparation method and application of octacosanol-containing liposome |
| CN110742912A (en) * | 2019-11-05 | 2020-02-04 | 深圳市芬多精纳米生物科技有限公司 | Method for preparing nano fendorin |
| CN111000811A (en) * | 2019-12-31 | 2020-04-14 | 济南大学 | Orally rapidly disintegrating tablet containing policosanol |
| CN111513326A (en) * | 2020-05-26 | 2020-08-11 | 宿迁医美科技有限公司 | Coenzyme Q10Microemulsion and preparation method thereof |
| CN112999158A (en) * | 2021-03-03 | 2021-06-22 | 江西省科学院生物资源研究所 | Preparation method and application of policosanol nano-liposome |
| CN112999158B (en) * | 2021-03-03 | 2022-04-01 | 江西省科学院生物资源研究所 | Preparation method and application of policosanol nano-liposome |
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