CN106619588A

CN106619588A - Self-microemulsion nutrient composition containing coenzyme Q10 and preparation method and application

Info

Publication number: CN106619588A
Application number: CN201611245883.8A
Authority: CN
Inventors: 王雪瑞; 朱林静; 陈中科; 陈芳芳
Original assignee: Xiamen Kingdomway Biotechnology Co Ltd; Xiamen Kingdomway Group Co
Current assignee: Xiamen Kingdomway Biotechnology Co Ltd; Xiamen Kingdomway Group Co
Priority date: 2016-12-29
Filing date: 2016-12-29
Publication date: 2017-05-10
Anticipated expiration: 2036-12-29
Also published as: CN106619588B

Abstract

The invention discloses a self-microemulsion nutrient composition containing coenzyme Q10 and a preparation method and application. The self-microemulsion nutrient composition comprises the following components in parts by weight: 1-15 parts of coenzyme Q10, 1-15 parts of curcumin, 10-50 parts of carrier oil, 15-75 parts of a nonionic surfactant, 1-5 parts of a cationic gemini surfactant, 5-30 parts of a cosurfactant and 0-2 parts of an antioxidant, wherein the components are prepared into a uniform, stable, clear and transparent solution. The self-microemulsion nutrient composition has good stability, crystallization of coenzyme Q10 is remarkably inhibited, and the product shelf life is prolonged. In the application process, the composition can be simply and conveniently added into systems of water-phase food, medicines and the like according to demand amounts, and is safe and effective. Meanwhile, the whole preparation process is green, environmental-friendly, low in energy consumption and easy in industrial production.

Description

A kind of self-microemulsion type alimentation composition, Preparation method and use containing Ubidecarenone

Technical field

The present invention relates to compositions field, more particularly to a kind of self-microemulsion type alimentation composition, preparation side containing Ubidecarenone Method and purposes.

Background technology

Parkinson disease (Parkinson disease, PD) are that one kind is mainly in middle-aged and elderly people, the nervous system of chronic progression Degenerative disease, typical performance is static tremor, bradykinesia, myotonia and posture abnormal gait etc., while also with compared with Serious non-motor symptoms, such as cognitive disorder, sleep disorder, depressive symptom and dysautonomia, this is not only The quality of life of patient is seriously reduced, and white elephant is brought to family and society.With China human mortality structure it is old Yearization problem it is increasingly serious, Parkinsonian sickness rate is also increasing considerably year by year, and it is old that parkinson disease have become impact The primary killers of year people health.Therefore, active development to go out safely and effectively prevent or treat Parkinsonian medicine and its preparation The arduous and urgent task of medical scientific research worker is become.

The pathogenesis of PD are extremely complex, and the cause of disease does not still understand so far.Inherited genetic factorss, oxidative stress, mitochondrial function barrier Hinder, immunologic dysfunction and environmental factorss etc. all may induction PD.Currently for the different clinical symptoms of PD, Therapeutic Method has medicine Thing treatment, operative treatment, rehabilitation and psychotherapy etc..Drug therapy is still occupied an leading position, although medicine can be obviously improved patient Symptom, but have the shortcomings that toxic side effects are big, bioavailability is low.Thus, it is pre- from small toxicity, natural active matter Demand that is anti-or treating PD is increasing.

Ubidecarenone (Coenzyme Q10, CoQ10) is the fat-soluble quinoness that a kind of biology is widely present in vivo, Chemical name is 2,3- dimethoxy -5- methyl -6- last of the ten Heavenly stems isopentene group -1,4- benzoquinone.Ubidecarenone is a kind of good biological medicament Thing, is the key element that energy is produced in human body, in being present in each cells of organs film, can improve myocardial metabolism, strengthen cardiac function； And its strong anti-oxidation function can protect body cell from the destruction of free radical, improve the immunity of body.With coenzyme Critical functions and health-care effect of the Q10 in terms of biology it is continuous revealed, along with its avirulence, without teratogenesis and nothing It is the characteristics of apparent side effect, interior at the international level in recent years, have been widely used for all kinds of heart diseases, diabetes, cancer, acute and chronic The treatment of the diseases such as hepatitis, Parkinson's disease, and can prevention of arterial hardening, apoplexy and hypertension, have good to heart, liver and kidney Good health-care effect, the practical ranges of Ubidecarenone are constantly expanded.Ubidecarenone is widely used in food in American-European countries Product, cosmetics, supplementary etc., the soft gel products for also having various correlations on China's market today.

Substantial amounts of research shows that Ubidecarenone has important protective effect in the damage and reparation of nervous system.The U.S. The neurosurgeon Shults in University of California San Diego branch school has carried out 16 months to the Q10 that PD patient's packet imposes 3 kinds of dosage Clinical trial, research finds that the development process of Parkinson's disease is delayed in the experimental group for applying maximum dose level Q10 44%.Liu Fei of Shandong University et al. has found that Q10 has improvement to make the cognitive function of PD patient, anxiety and sleep disorder With.Mischley has found that PD patient's Q10 contents are significantly low compared with normal population.The above is true to be illustrated Q10 in the prevention of PD or controls There is certain positive effect in treatment.

Ubidecarenone is liposoluble substance, and its water-insoluble makes it have difficulties at the aspect of digesting and assimilating of human body.And it is auxiliary There is quinonyl in enzyme Q10 structures, quite sensitive to light and oxygen, it is given birth to make conventional tablet, hard capsule and suspension type soft capsule Thing utilization rate is extremely low.

Curcumin is a kind of xanthein extracted from the dry rhizome of Zingiberaceae curcumin platymiscium, there is important Jing Ji value and extensive pharmacological action (antitumor, antioxidation, antiinflammatory, blood fat reducing etc.).Because curcumin is safe and malicious pair Effect is little, and in modern medicine, curcumin is because of itself and the connection between neuranagenesis (especially parkinson disease) and carcinogen It is and receives special attention.Recent studies indicate that, curcumin can be used for controlling for neurodegenerative diseases such as PD and AD Treat.But curcumin is as Q10, water is practically insoluble in, oral administration biaavailability is very low.

Therefore, Ubidecarenone and curcumin dissolubility in an aqueous medium and storage-stable how to be improved, become its Key technical problem during production and consumption.

Self-microemulsion drug-supplying system (self-microemulsifying drug delivery system, SMEDDS) be by Homogeneous, Thermodynamically stable, isotropic liquid oral that medicine, oil phase, surfactant and cosurfactant are constituted Dosage form or solid dosage formss.The basic feature of the drug-supplying system is, it is oral after spontaneously form particle diameter ＜ in the case where gastrointestinal is wriggled The oil in water emulsion of 100nm.SMEDDS can improve the dissolubility and bioavailability of poorly water-soluble or fat-soluble medicine, while can The pessimal stimulation of the degraded of labile drugs and medicine to gastrointestinal in avoid water.It promotes the mechanism and advantage of drug absorption It is mainly reflected in the following aspects：(1) free energy needed for emulsifying is very low, spontaneously forms in the case where gastrointestinal is slightly wriggled The emulsion droplet of particle diameter very little has larger surface area, increased the permeability of medicine chrotoplast on the gastrointestinal tract；(2) medicine is improved Dissolubility and improve the dissolution of medicine；(3) small microemulsion is dripped because of the parent with less surface tension and microemulsion surface Aqueouss so as to be easy to the hydrated sheath by gastrointestinal tract wall, increase penetrance, promote to absorb and improve bioavailability；(4) it is relative Emulsion, with higher physical stability；(5) preparation process is simple, is appropriate to industrialized production.

Correlational study shows that the gastrointestinal tract epithelial cell of body is electronegative.Thus sun can be introduced in microemulsion Ionic species so as to gastrointestinal tract epithelial cell because electrostatic attraction is acted on, so as to further promote the absorption of insoluble medicine, improve Bioavailability.Gemini is a kind of gemini surfactant, and it is in respective ion head by two monomcric surfactants The Ji Chu class surfactants that chemical bonding gets up by connection base.This special dimeric structure imparts Shuangzi surface It is the more superior performance of the more corresponding conventional single-ended base of activating agent, single alkane chain surfactant, such as high surface, low The water solublity that Krafft points are become reconciled, shows higher efficiency and ability, itself and monomer table in terms of the surface tension of water is reduced The compounding of face activating agent, especially nonionic surfactant can produce higher cooperative effect, to oil solubilising power more By force.

The content of the invention

It is an object of the invention to provide a kind of water solublity is good, excellent in stability, bioavailability are high containing Ubidecarenone Self-microemulsion type alimentation composition.

For achieving the above object, the present invention provides a kind of self-microemulsion type alimentation composition containing Ubidecarenone, and its feature exists In, it is prepared by each composition of following weight portion,

1～15 part of Ubidecarenone, 1～15 part of curcumin, 10～50 parts of carrier oils, 15～75 parts of non-ionic surfactants Agent, 1～5 portion of cationic Gemini surfactants, 5～30 portions of cosurfactants, 0-2 part antioxidants.

Further, it is prepared by each composition of following weight portion, 2～12 parts of Ubidecarenone, 2～12 parts of curcumins, 15 ～45 parts of carrier oils, 25～60 parts of nonionic surfactant, 1.5～4.5 parts of cationic Gemini surfactants, 10 ～25 portions of cosurfactants, 0-2 part antioxidants.

Further, it is prepared by each composition of following weight portion, 5～10 parts of Ubidecarenone, 5～10 parts of curcumins, 20 ～30 parts of carrier oils, 30～45 parts of nonionic surfactant, 2～3 parts of cationic Gemini surfactants, 12～20 Part cosurfactant, 0-1 part antioxidants；

Preferably, it is prepared by each composition of following weight portion, 8 parts of Ubidecarenone, 7 parts of curcumins, 28 parts of carriers Oil, 40 portions of nonionic surfactant, 2 portions of cationic Gemini surfactants, 15 portions of cosurfactants, 1 part resists Oxidant.

Further, the Ubidecarenone is at least one in CoQ10, reduced coenzyme Q 10；Preferably, it is auxiliary At least one in Native Oxide type Ubidecarenone and reduced coenzyme Q 10 that enzyme Q10 is prepared for microbe fermentation method；

It is optional, the carrier oil be crude vegetal or it is strong to key component solvability, through structure of modification, water Vegetable oil or fatty acid ester after solution；Preferably, crude vegetal is soybean oil, Oleum Arachidis hypogaeae semen, olive oil, Oleum Ricini, safflower oil In one or more；Vegetable oil strong to key component solvability, after structure of modification, hydrolysis or fatty acid ester are Almond oil Oleic acid PEG-6 glyceride, isopropyl myristate, ethyl oleate, medium chain length fatty acid triglyceride, Oleic acid Polyethylene Glycol are sweet One or more in grease, Masine 35-1 and polypropylene glycol caprylate；

Optional, the nonionic surfactant is selected from the dihydroxy stearic acid ester of Polyethylene oxide ten, the poly- second of caprylic capric Glycol glyceride, Polyoxyl 40 Hydrogenated Castor Oil, the sucrose ester of HLB value 13～16, Pluronic F68, One or more in vitamin E polyethylene glycol succinic acid ester, tween 85, tween 80, Poloxamer 188, lecithin；

Optional, the cosurfactant is selected from glycerol, ethanol, ethylene glycol, PEG200-600, diethylene glycol mono-ethyl One or more in ether, propylene carbonate and Propylene Glycol；

Optional, the antioxidant is extracted selected from sodium ascorbate, natural Vitamin E and its ester derivant, Herba Rosmarini Officinalis One or more in thing.

Further, the self-microemulsion type alimentation composition containing Ubidecarenone of the present invention also contains antibacterial, stabilizer, helps One or more in stream agent and coloring agent.

Further, preparation method is,

Each component is weighed in proportion, by remaining each component mix homogeneously outside Ubidecarenone and curcumin, adds coenzyme Q10 and curcumin, are heated to 50-65 DEG C of stirring up to whole system transparent and homogeneous, then are incubated 15-60min, are cooled to room temperature i.e. Can.Insulated and stirred therein advantageously forms stable oil preparation, and Ubidecarenone is difficult crystallize.

Further, the preparation process and the preservation after preparing are in inert atmosphere or vacuum state；It is preferred that nitrogen or Helium atmosphere atmosphere.

Further, microcapsule, soft capsule, hard capsule, tablet, powder, pill, Emulsion or suspensoid can be prepared into.

The present invention also provides the self-microemulsion type alimentation composition containing Ubidecarenone for preparing prevention and/or treating handkerchief The purposes of the gloomy medicine of gold.

The present invention also provides the self-microemulsion type alimentation composition containing Ubidecarenone for preparing prevention and/or treating handkerchief The dietary supplement of the gloomy disease of gold or the purposes of health food.

The self-microemulsion type alimentation composition good stability containing Ubidecarenone that the present invention is prepared, it is existing without oil slick, aggregation As.When not in the amount ranges of the present invention, the self-microemulsion type alimentation composition oil preparation containing Ubidecarenone has oil slick, clustering phenomena.

Ubidecarenone of the present invention and curcumin have antioxidation, the function of eliminating free radical, repair injured nerve, send out A person of good sense has found that the two carries out by a certain percentage compatibility and can play the effect of Synergistic, and Ubidecarenone is stablized with the compatibility of curcumin, There is no chemical reaction, have no adverse reaction, it is safe and feasible.

The antioxidant does not have special restriction, can be sodium ascorbate, natural Vitamin E and its ester derivant, One or more in Herba Rosmarini Officinalis extract etc.；To the antibacterial, stabilizer, fluidizer, coloring agent etc., other adjuvants do not have It is special to limit, but should can be the composition for allowing to be added in food, medicine etc..

Self-microemulsion type alimentation composition containing Ubidecarenone of the present invention or its preparation, by oral administration after, in vivo by stomach The wriggling of intestinal spontaneously forms microemulsion of the oil droplet mean diameter less than 100nm.

Positively charged microemulsion is formed in the present invention by introducing the cationic Gemini surfactants of recipe quantity Drop, the effective absorption by electrostatic interaction with enhancing body to Ubidecarenone and curcumin.

The invention has the beneficial effects as follows：

1st, after the self-microemulsion type alimentation composition containing Ubidecarenone prepared by the present invention mixes with water, can form uniform, steady The fixed, solution of clear.In application process, simply and easily can on demand be added to the bodies such as water phase food, medicine In the middle of system.

2nd, the self-microemulsion type alimentation composition containing Ubidecarenone prepared by the present invention has the stability of height, significantly suppression The crystallize of Ubidecarenone has been made, shelf life has been extended.

2nd, the emulsion droplet size that the self-microemulsion type alimentation composition containing Ubidecarenone prepared by the present invention is formed is up to 10-100 Nanometer, belongs to nanometer formulation category, and body absorption effect is good.By the cationic Gemini surfactants for adding recipe quantity Drip to form positively charged microemulsion, the effective absorption by electrostatic interaction with enhancing body to Ubidecarenone and curcumin, Further improve the bioavailability of medicine.

3rd, after taking the self-microemulsion type alimentation composition containing Ubidecarenone of the present invention, Ubidecarenone is with curcumin in blood plasma The ratio of release is substantially constant, is not arbitrarily release, but slow, stable in blood plasma according to the ratio in formula Middle release, so as to ensure the safety and effectiveness taken.

4th, the Ubidecarenone and curcumin that have potential using value in prevention or treatment PD are carried out science by the present invention Compatibility, both at all-natural product, with obvious synergistic function.

5th, the present invention directly can add water solublity wall material solution on the basis of obtained self-emulsifying microemulsion oil preparation, stir Afterwards, it is spray-dried and the good self-emulsifying microemulsion microcapsule of water solublity is obtained, or is prepared into various desired dosage forms.

6th, there is no chemical change in the preparation process is simple of the self-microemulsion type alimentation composition containing Ubidecarenone of the present invention Change, do not change Ubidecarenone and curcumin chemical constitution, whole preparation process environmental protection, low energy consumption, it is easy to accomplish industrial metaplasia Produce.

Specific embodiment

Embodiments of the invention are described below in detail, the example of the embodiment is being intended to for explaining the present invention, and not It is understood that as limitation of the present invention.Unreceipted particular technique or condition person in embodiment, are retouched according to document in the art The technology stated or condition are carried out according to product description.Agents useful for same or the unreceipted production firm person of instrument, being can be with By city available from conventional products.

Embodiment 1：

The each Ingredient Amount table of embodiment 1-6 of table 1

The each Ingredient Amount table of embodiment 7-13 of table 2

Preparation method：Each composition is weighed by listed mass fraction in table 1, by remaining each group outside Ubidecarenone and curcumin Divide mix homogeneously, add Ubidecarenone and curcumin, be heated to 55 DEG C of stirrings up to whole system transparent and homogeneous, then be incubated 30min, is down to after room temperature and obtains orange-yellow transparent homogeneous self-emulsifying microemulsion oil preparation.

Take gained self-emulsifying microemulsion oil preparation about 1g to be added in 100ml deionized waters, slightly shake, obtain orange-yellow transparent water Emulsion, it is therefore seen that this product water dispersible is good.

(1) gained self-emulsifying microemulsion oil preparation is obtained into Ubidecarenone-Rhizoma-curcumae-longae element-soft cap sule by soft capsule production equipment.

(2) water of 200 mass parts, stirring is added to be formed and put into after uniform solution 56 mass in gained self-emulsifying microemulsion oil preparation Part starch sodium octenyl succinate, 35 mass parts maltodextrins, 9 mass parts white sugars, stirring and dissolving, the homogenizing under 30Mpa, most Microemulsion is spray-dried afterwards, at 170 DEG C, air outlet temperature is controlled at 80 DEG C the control of spray tower intake air temperature, atomization Device rotating speed 1200r/min, is spray-dried to obtain self-emulsifying microemulsion microcapsule.

Embodiment 2

Raw material：It is shown in Table 1.

Preparation method：Each composition is weighed by listed mass fraction in table 1, by remaining each group outside Ubidecarenone and curcumin Divide mix homogeneously, add Ubidecarenone and curcumin, be heated to 50 DEG C of stirrings up to whole system transparent and homogeneous, then be incubated 40min, is down to after room temperature and obtains orange-yellow transparent homogeneous self-emulsifying microemulsion oil preparation.

(1) Ubidecarenone-Rhizoma-curcumae-longae element-soft cap sule is obtained by soft capsule production equipment.

(2) self-emulsifying microemulsion microcapsule is prepared by the microcapsule preparation process of embodiment 1.

Embodiment 3

Raw material：It is shown in Table 1.

Preparation method：Each composition is weighed by listed mass fraction in table 1, by remaining each group outside Ubidecarenone and curcumin Divide mix homogeneously, add Ubidecarenone and curcumin, be heated to 60 DEG C of stirrings up to whole system transparent and homogeneous, then be incubated 50min, is down to after room temperature and obtains orange-yellow transparent homogeneous self-emulsifying microemulsion oil preparation.

Embodiment 4

Raw material：It is shown in Table 1.

Preparation method：Each composition is weighed by listed mass fraction in table 1, by remaining each group outside Ubidecarenone and curcumin Divide mix homogeneously, add Ubidecarenone and curcumin, be heated to 65 DEG C of stirrings up to whole system transparent and homogeneous, then be incubated 60min, is down to after room temperature and obtains orange-yellow transparent homogeneous self-emulsifying microemulsion oil preparation.

Embodiment 5：

Raw material：It is shown in Table 1.

Preparation method：Each composition is weighed by listed mass fraction in table 1, by remaining each group outside Ubidecarenone and curcumin Divide mix homogeneously, add Ubidecarenone and curcumin, be heated to 52 DEG C of stirrings up to whole system transparent and homogeneous, then be incubated 35min, is down to after room temperature and obtains orange-yellow transparent homogeneous self-emulsifying microemulsion oil preparation.

Embodiment 6：

Raw material：It is shown in Table 1.

Preparation method：Each composition is weighed by listed mass fraction in table 1, by remaining each group outside Ubidecarenone and curcumin Divide mix homogeneously, add Ubidecarenone and curcumin, be heated to 62 DEG C of stirrings up to whole system transparent and homogeneous, then be incubated 45min, is down to after room temperature and obtains orange-yellow transparent homogeneous self-emulsifying microemulsion oil preparation.

Embodiment 7：

Raw material：It is shown in Table 2.

Preparation method：Each composition is weighed by listed mass fraction in table 1, by remaining each group outside Ubidecarenone and curcumin Divide mix homogeneously, add Ubidecarenone and curcumin, be heated to 54 DEG C of stirrings up to whole system transparent and homogeneous, then be incubated 55min, is down to after room temperature and obtains orange-yellow transparent homogeneous self-emulsifying microemulsion oil preparation.

Embodiment 8：

Raw material：It is shown in Table 2.

Preparation method：Each composition is weighed by listed mass fraction in table 1, by remaining each group outside Ubidecarenone and curcumin Divide mix homogeneously, add Ubidecarenone and curcumin, be heated to 56 DEG C of stirrings up to whole system transparent and homogeneous, then be incubated 32min, is down to after room temperature and obtains orange-yellow transparent homogeneous self-emulsifying microemulsion oil preparation.

Embodiment 9：

Raw material：It is shown in Table 2.

Preparation method：Each composition is weighed by listed mass fraction in table 1, by remaining each group outside Ubidecarenone and curcumin Divide mix homogeneously, add Ubidecarenone and curcumin, be heated to 58 DEG C of stirrings up to whole system transparent and homogeneous, then be incubated 15min, is down to after room temperature and obtains orange-yellow transparent homogeneous self-emulsifying microemulsion oil preparation.

Embodiment 10：

Raw material：It is shown in Table 2.

Preparation method：Each composition is weighed by listed mass fraction in table 1, by remaining each group outside Ubidecarenone and curcumin Divide mix homogeneously, add Ubidecarenone and curcumin, be heated to 59 DEG C of stirrings up to whole system transparent and homogeneous, then be incubated 20min, is down to after room temperature and obtains orange-yellow transparent homogeneous self-emulsifying microemulsion oil preparation.

Embodiment 11：

Raw material：It is shown in Table 2.

Preparation method：Each composition is weighed by listed mass fraction in table 1, by remaining each group outside Ubidecarenone and curcumin Divide mix homogeneously, add Ubidecarenone and curcumin, be heated to 61 DEG C of stirrings up to whole system transparent and homogeneous, then be incubated 25min, is down to after room temperature and obtains orange-yellow transparent homogeneous self-emulsifying microemulsion oil preparation.

Embodiment 12：

Raw material：It is shown in Table 2.

Preparation method：Each composition is weighed by listed mass fraction in table 1, by remaining each group outside Ubidecarenone and curcumin Divide mix homogeneously, add Ubidecarenone and curcumin, be heated to 63 DEG C of stirrings up to whole system transparent and homogeneous, then be incubated 52min, is down to after room temperature and obtains orange-yellow transparent homogeneous self-emulsifying microemulsion oil preparation.

Embodiment 13：

Raw material：It is shown in Table 2.

Preparation method：Each composition is weighed by listed mass fraction in table 1, by remaining each group outside Ubidecarenone and curcumin Divide mix homogeneously, add Ubidecarenone and curcumin, be heated to 64 DEG C of stirrings up to whole system transparent and homogeneous, then be incubated 57min, is down to after room temperature and obtains orange-yellow transparent homogeneous self-emulsifying microemulsion oil preparation.

Embodiment 14：Droplet measurement, the experiment of self-emulsifying microemulsion time

Droplet measurement：

Self-emulsifying microemulsion oil preparation prepared by case study on implementation and self-emulsifying microemulsion microcapsule sample distilled water are with 1:20 ratio Dilute, gently shake up, that is, form the microemulsion of clarification.Then emulsion is determined with laser fineness gage (Malvern companies of Britain) Particle diameter distribution, temperature of the measurement be 25 DEG C.

Self-microemulsion speed：

According to《Pharmacopoeia of People's Republic of China》(2005 editions) annex leaching slurry processes are measured, Example 1-4's Self-emulsifying microemulsion oil preparation and self-emulsifying microemulsion microcapsule (each 100mg) are dissolved in 37 DEG C of simulated gastric fluids, record each case study on implementation self-microemulsion The change time.

The particle diameter of the self-micro emulsion formulation of table 1, self emulsifying time data table

Experimental result shows that emulsion mean diameter is respectively less than 100nm, and solution clear illustrates to define stable uniform Microemulsion；The emulsion dispersion uniform time completely is respectively less than 3 minutes, with self-emulsifying microemulsion speed faster, i.e., by slight Stirring, it becomes possible to form the homogeneous Emulsion of appearance transparent.

The result of embodiment 5-13 is herewith.

Embodiment 15：Stability experiment：

Self-emulsifying microemulsion oil preparation, self-emulsifying microemulsion microcapsule and the Ubidecarenone raw material that Example 1 is prepared is respectively placed in The irradiation of 4500Lx intensities of illumination, oxygenation fill (25 DEG C), 60 DEG C (calorstat) place 15 days, respectively at 0 day, 5 days, 10 days, 15 Its sampling and measuring, with HPLC methods Ubidecarenone content is determined, and investigates illumination, oxygen, temperature conditionss to Ubidecarenone sign content (%) impact.As a result it is as shown in table 2：

Impact table of the illumination of table 2 to stability

Impact of the oxygen of table 3 to stability

Impact table of the temperature of table 4 to stability

Influence factor test result indicate that, the self-emulsifying microemulsion oil preparation and the self-emulsifying microemulsion that further prepares of the present invention is micro- Under illumination, oxygenation, hot conditionss, Ubidecarenone sign content and face shaping are not changed in capsule.Face shaping aspect, Self-emulsifying microemulsion oil preparation is in yellow clear solution, does not crystallize precipitation；Self-emulsifying microemulsion microcapsule is yellow powder, not bright in color It is aobvious to change.Ubidecarenone sign content aspect, As time goes on (5 days, 10 days, 15 days), its Ubidecarenone sign contains quantitative change Change less, it is more more stable than the Ubidecarenone sign content in Ubidecarenone raw material.Illustrate the self-emulsifying microemulsion oil preparation of the present invention and enter one The self-emulsifying microemulsion microcapsule that step is prepared has preferable stability, reduces the shadow of illumination, oxygen, temperature to its property Ring, extend product storage life.

The result of embodiment 2-13 is herewith.

Embodiment 16：Internal pharmacokinetic studies：

16.1 samples：

(code name is Ubidecarenone-Rhizoma-curcumae-longae element-soft cap sule prepared by embodiment 1～4：Sample 1, sample 2, sample 3, sample 4)；

The configuration of Ubidecarenone-curcumin raw material medicine solution agent：Precision weighs 50g Ubidecarenone, 10g curcumins (the two weight Amount ratio 5:1, consistent with the ratio of sample 1), be dissolved in 800ml ethanol-PEG400 solution (v/v, 1:1) (code name is：Raw material Sample).

Total of five sample carries out animality experiment.

16.2 experiment conditions：25 ± 3 DEG C of laboratory rearing ambient temperature, relative humidity 55%～70% is freely drunk daily Water is ingested (deionized water and standard feed), its fasting 12h before experiment, free water.

16.3 laboratory animals and packet：By Changsha Kaifu District Dong Chuan Animal Sciences service department, (laboratory animal is used Credit number be SYXK (Hunan) 2010-0010) provide SPF levels Kunming kind female mice, 3 months Mus ages, 18～22g of body weight. Animal is operated according to International Laboratory Animal experiment criterion, to reduce pain of the laboratory animal in experimentation.Using The mice of fasting 12h is divided into one group by completely randomized design per 10 at random, totally five groups.

16.4 oral administrations and sample collecting, process：Mouse stomach same dose (35mg/kg is given respectively：Ubidecarenone With curcumin total content) self-microemulsion drug-supplying system sample (i.e. sample 1-4) and crude drug (i.e. raw material sample), after administration respectively at 5th, 15,30min and 1,2,4,6,12h collections blood plasma extremely contain in the anticoagulant centrifuge tube of heparin, mix, 3000r/min centrifugal treating After 10min, separated plasma detects plasma drug level after process with HPLC methods.

16.5 pharmacokinetic studies

According to blood drug level result, applied statistics analysis software carries out statistics Fitting Analysis to experimental result, calculates blood Concentration data, are as a result represented (table 5) with means standard deviation.

Its mouse oral of table 5 clothes are administered sample average blood concentration-time (mean ± SD, n=10) (mg/L) table

As a result show after oral administration, self-microemulsion type preparation (i.e. Ubidecarenone-the Rhizoma-curcumae-longae element-soft cap sule of embodiment 1-4) Peak concentration cmax value is significantly higher than the cmax value (P ＜ 0.05) of crude drug, AUC also greater than crude drug AUC, Ubidecarenone Accelerate and can reach higher plasma concentration, the bioavailability of body in mice body absorption Jing after self-emulsifying microemulsion with curcumin Also dramatically increase.Self-micro emulsion formulation belongs to nanometer formulation category, is conducive to improving the uniformity of drug absorption, shown self-microemulsion system The fluctuation of agent peak concentration is less than crude drug, so as to improve the safety of medication.

Its mouse oral of table 6 clothes administration Ubidecarenone and ratio table of the curcumin in plasma concentration under each detection time

From table 6 according to contrast each sample, the concentration ratio of raw material sample Ubidecarenone and curcumin in different test period blood plasma Value, it can be seen that the ratio that self-micro emulsion formulation Ubidecarenone and curcumin prepared by the present invention discharges in blood plasma is substantially perseverance Fixed, it is slowly, smoothly to discharge according to the ratio in formula.

Relative bioavailability F is to weigh bioavailability of a certain medicine compared to other prescriptions of same medicine, That is the ratio of the lower area of blood concentration-time curve AUC of test agent and reference reagent, with regard to the important of drug absorption performance Parameter.The results are shown in Table 7.

Its mouse oral of table 7 clothes administration sample medicine kinetic parameter table

As known from Table 7 the F values of sample 1 are 206.9% (72.88/35.22), the i.e. bioavailability of self microemulsifying preparation It it is 2.07 times of crude drug, sample 2 is 217.9%, sample 3 is 226.8%, sample 4 is 202.5%.Illustrate to change dosage form pair In vivo absorption process is substantially improved medicine.Illustrate the self-microemulsion type alimentation composition containing Ubidecarenone that the present invention is prepared Different dosage form substantially improve the body absorption process of medicine.

The biological half-life t of self-micro emulsion formulation_1/2It is not significantly different from crude drug, illustrates that self microemulsifying preparation does not affect Medicine elimination in vivo.

The result of embodiment 5-13 is herewith.

Embodiment 17：Animal behavioral study and test：

17.1 samples：

Sample 1：Self-emulsifying microemulsion oil preparation prepared by embodiment 1.

Reference substance 1：Curcumin in the formula of embodiment 1 is substituted for the MCT of equal quality number, remaining component and preparation side Method is consistent with embodiment 1, prepares self-emulsifying microemulsion oil preparation reference substance 1.

Reference substance 2：Ubidecarenone in the formula of embodiment 1 is substituted for the MCT of equal quality number, remaining component and preparation Method is consistent with embodiment 1, prepares self-emulsifying microemulsion oil preparation reference substance 2.

17.2 experiment conditions：25 ± 3 DEG C of laboratory rearing ambient temperature, relative humidity 55%～70% is freely drunk daily Water is ingested (deionized water and standard feed), its fasting 12h before experiment, free water.

17.3 laboratory animals and packet：By Changsha Kaifu District Dong Chuan Animal Sciences service department, (laboratory animal is used Credit number be SYXK (Hunan) 2010-0010) provide SPF levels Kunming kind female mice, 3 months Mus ages, 18～22g of body weight. Animal is operated according to International Laboratory Animal experiment criterion, to reduce pain of the laboratory animal in experimentation.Using Mice is divided into one group by completely randomized design per 10 at random, totally 6 groups.Each matched group lumbar injection volume is consistent, daily injection Time point is similar.

Normal group：Continuous intraperitoneal injection of saline 24 days；

Solvent control group：Continuous 5 days lumbar injections 30mg/kg MPTP (1- methyl 4-phenyl -1,2,3,6- tetrahydrochysene pyrroles Pyridine), subsequent continuous 19 days lumbar injection DMSO (dimethyl sulfoxide)；

Treat 1 group：Sample 1+MPTP groups, i.e., continuous 5 days lumbar injections 30mg/kg MPTP, then use 30mg/kg samples 1 instead Continuous injection 19 days；

Treat 2 groups：Reference substance 1+MPTP groups, i.e., continuous 5 days lumbar injections 30mg/kg MPTP, then use 30mg/kg pair instead Continuously inject 19 days according to product 1；

Treat 3 groups：Reference substance 2+MPTP groups, i.e., continuous 5 days lumbar injections 30mg/kg MPTP, then use 30mg/kg pair instead Continuously inject 19 days according to product 2；

Prevention group：Inject 30mg/kg samples 1 within continuous 7 days before MPTP models treated is carried out, then continuous 5 days abdominal cavities note 30mg/kg MPTP are penetrated, subsequently continuous 19 days lumbar injection DMSO；

17.4 apomorphines induce rotation test：In each point observing time in mouse subcutaneous injection dosage for 0.3mg/kg's Apomorphine, induces the circling behavior of mice, it is stipulated that be rotated by 360 ° as one turn, records the rotation revolution in mice 30min.If receiving Examination thing group rotation revolution is significantly less than solvent control group rotation revolution, and difference has significance (P<0.05), can determine that this is tested Thing has prevention or alleviates Parkinsonian effect.Result of the test is shown in Table 8.

The apomorphine of table 8 induces rotation test revolution (X ± S, n=10) table

As can be seen from Table 8, the apomorphine induction rotation test revolution for the treatment of group 1-3 groups and prevention group is significantly lower than molten Agent matched group, and difference has significance (P<0.05), illustrate that the self-emulsifying microemulsion oil preparation of the present invention has and prevent or alleviate parkinson The effect of disease.Simultaneously visible, Ubidecarenone has obvious synergistic function (the test effect of 1 group for the treatment of with the compatibility of curcumin Fruit is significantly better than 3 groups of 2 groups for the treatment of and treatment).

The asymmetrically placed experiment of 17.5 triggerings：Hold mice trunk and leave ground, by its side antenna touching table angle.When Placement action of the homonymy forelimb to table angle can be induced during the antenna touching table angle of mice side, impaired forelimb can not be by forelimb into power amplifier It is placed in table angle.During scoring, both sides forelimb is tested respectively 10 times, calculates the asymmetrically placed experiment score of triggering.The data obtained is meter Amount data, if the asymmetrically placed experiment score of tested material group triggering is significantly lower than solvent control group, and difference has significance (P< 0.05), can determine that the tested material has prevention or alleviates Parkinsonian effect.Result of the test is shown in Table 9.

Table 9 triggers asymmetrically placed experiment score (X ± S, n=10) table

As can be seen from Table 9,1-3 groups are treated and the asymmetrically placed experiment score of prevention group triggering is significantly lower than solvent control Group, and difference has significance (P<0.05) the self-emulsifying microemulsion oil preparation for, illustrating the present invention has prevention or alleviates Parkinsonian work With.Simultaneously visible, Ubidecarenone has obvious synergistic function with the compatibility of curcumin, and (test effect of 1 group for the treatment of is notable Better than 3 groups of 2 groups for the treatment of and treatment).

17.6 immunohistochemical analysis：

After the detection of each group mice behavior, under urethane deep anaesthesia, with the fixed brain of (4 DEG C) perfusions of 4% paraformaldehyde Tissue, takes Mus brain midbrain sections, 24 hours in immersion fixative.Select midbrain black after Mus brain midbrain sections after fixation is processed Matter, striatum position, carry out immunohistochemical staining process, are placed in after mounting under laser confocal microscope and are observed, will be each The black substance TH Positive Cell Counts of group mice, it is as a result as shown in table 10 below：

The black substance TH Positive Cell Counts and P value tables of the mice of table 10

As can be seen from Table 10, treat 1-3 groups, the TH positive cell numbers of prevention group substantially increases (P ＜ compared with solvent control group 0.05), it can be seen that, Ubidecarenone and curcumin can promote the expression of TH, reduce neurotoxin Dui -matter TH damage, enter And preventing or to treat have on PD potential using value.Simultaneously visible, Ubidecarenone has obvious with the compatibility of curcumin Synergistic function (1 group of test effect for the treatment of is significantly better than 3 groups of 2 groups for the treatment of and treatment), and have no adverse reaction, safety High, good stability.

The result of embodiment 2-13 is herewith.

Although embodiments of the invention have been shown and described above, it is to be understood that above-described embodiment is example Property, it is impossible to limitation of the present invention is interpreted as, one of ordinary skill in the art is in the principle and objective without departing from the present invention In the case of above-described embodiment can be changed within the scope of the invention, change, replace and modification.

Claims

1. a kind of self-microemulsion type alimentation composition containing Ubidecarenone, it is characterised in that it is prepared by each composition of following weight portion Obtain,

1～15 part of Ubidecarenone, 1～15 part of curcumin, 10～50 parts of carrier oils, 15～75 parts of nonionic surfactant, 1 ～5 portions of cationic Gemini surfactants, 5～30 portions of cosurfactants, 0-2 part antioxidants.

2. the self-microemulsion type alimentation composition of Ubidecarenone is contained described in claim 1, it is characterised in that it is by following weight portion Each composition is prepared, 2～12 parts of Ubidecarenone, 2～12 parts of curcumins, 15～45 parts of carrier oils, 25～60 parts of nonionic tables Face activating agent, 1.5～4.5 portions of cationic Gemini surfactants, 10～25 portions of cosurfactants, 0-2 part antioxidation Agent.

3. the self-microemulsion type alimentation composition of Ubidecarenone is contained described in claim 2, it is characterised in that it is by following weight portion Each composition is prepared, 5～10 parts of Ubidecarenone, 5～10 parts of curcumins, 20～30 parts of carrier oils, 30～45 parts of nonionic tables Face activating agent, 2～3 portions of cationic Gemini surfactants, 12～20 portions of cosurfactants, 0-1 part antioxidants；

Preferably, it is prepared by each composition of following weight portion, 8 parts of Ubidecarenone, 7 parts of curcumins, 28 parts of carrier oils, 40 Part nonionic surfactant, 2 portions of cationic Gemini surfactants, 15 portions of cosurfactants, 1 part of antioxidation Agent.

4. the self-microemulsion type alimentation composition of Ubidecarenone is contained described in any one of claim 1-3, it is characterised in that the coenzyme Q10 is at least one in CoQ10, reduced coenzyme Q 10；Preferably, Ubidecarenone is microbe fermentation method preparation Obtained by least one in Native Oxide type Ubidecarenone and reduced coenzyme Q 10；

It is optional, the carrier oil be crude vegetal or it is strong to key component solvability, after structure of modification, hydrolysis Vegetable oil or fatty acid ester；Preferably, crude vegetal is in soybean oil, Oleum Arachidis hypogaeae semen, olive oil, Oleum Ricini, safflower oil One or more；Vegetable oil strong to key component solvability, after structure of modification, hydrolysis or fatty acid ester are Semen Armeniacae Amarum Oleic acid PEG-6 glyceride, isopropyl myristate, ethyl oleate, medium chain length fatty acid triglyceride, Oleic acid polyethylene glycol glycerol One or more in ester, Masine 35-1 and polypropylene glycol caprylate；

Optional, the nonionic surfactant is selected from the dihydroxy stearic acid ester of Polyethylene oxide ten, caprylic capric Polyethylene Glycol Glyceride, Polyoxyl 40 Hydrogenated Castor Oil, the sucrose ester of HLB value 13～16, Pluronic F68, dimension life One or more in plain E polyethanediol succinates, tween 85, tween 80, Poloxamer 188, lecithin；

It is optional, the cosurfactant selected from glycerol, ethanol, ethylene glycol, PEG200-600, TC, One or more in propylene carbonate and Propylene Glycol；

Optional, the antioxidant is in sodium ascorbate, natural Vitamin E and its ester derivant, Herba Rosmarini Officinalis extract One or more.

5. the self-microemulsion type alimentation composition of Ubidecarenone is contained described in any one of claim 1-4, it is characterised in that also containing suppression One or more in microbial inoculum, stabilizer, fluidizer and coloring agent.

6. the self-microemulsion type alimentation composition of Ubidecarenone is contained described in any one of claim 1-4, it is characterised in that preparation method For,

Weigh each component in proportion, by remaining each component mix homogeneously outside Ubidecarenone and curcumin, add Ubidecarenone and Curcumin, is heated to 50-65 DEG C of stirring up to whole system transparent and homogeneous, then is incubated 15-60min, is cooled to room temperature.

7. the self-microemulsion type alimentation composition of Ubidecarenone is contained described in claim 6, it is characterised in that the preparation process and system Preservation after standby is in inert atmosphere or vacuum state；It is preferred that nitrogen or helium atmosphere atmosphere.

8. the self-microemulsion type alimentation composition of Ubidecarenone is contained described in any one of claim 1-4, it is characterised in that can be prepared into Microcapsule, soft capsule, hard capsule, tablet, powder, pill, Emulsion or suspensoid.

9. described in a kind of any one of claim 1-4 containing Ubidecarenone self-microemulsion type alimentation composition be used for prepare prevention and/or The purposes for the treatment of anti-parkinson drug.

10. described in a kind of any one of claim 1-4 containing Ubidecarenone self-microemulsion type alimentation composition be used for prepare prevention and/ Or the dietary supplement or the purposes of health food for the treatment of Parkinson's disease.