CN106619588B

CN106619588B - It is a kind of containing Co-Q10 from micro-emulsion type alimentation composition, Preparation method and use

Info

Publication number: CN106619588B
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: 2019-08-16
Anticipated expiration: 2036-12-29
Also published as: CN106619588A

Abstract

The invention discloses a kind of containing Co-Q10 from micro-emulsion type alimentation composition, Preparation method and use.It is by 1~15 part of Co-Q10 of parts by weight, 1~15 part of curcumin, 10~50 parts of carrier oils, 15~75 parts of nonionic surface active agent, 1~5 part of cationic Gemini surfactants, 5~30 portions of cosurfactants, uniform, stable, clear solution that 0-2 parts of antioxidants are prepared.Its stability with height, significantly suppresses the crystallization of Co-Q10, extends shelf life.In application process, can simply and easily be added on demand in the systems such as water phase food, drug, safely, effectively.While whole preparation process is environmentally protective, low energy consumption, it is easy to accomplish industrialized production.

Description

It is a kind of containing Co-Q10 from micro-emulsion type alimentation composition, Preparation method and use

Technical field

The present invention relates to compositions field more particularly to it is a kind of containing Co-Q10 from micro-emulsion type alimentation composition, preparation side Method and purposes.

Background technique

Parkinson's disease (Parkinson disease, PD) is that one kind is mainly in the middle-aged and the old, the nervous system of chronic progression Degenerative disease, typical performance are static tremor, bradykinesia, myotonia and posture abnormal gait etc., at the same also with compared with Serious non-motor symptoms, such as cognitive disorder, sleep disturbance, depressive symptom and dysautonomia, this is not only The quality of life of patient seriously is reduced, and brings heavy burden to family and society.As China human mortality structure is old Yearization problem it is increasingly serious, the disease incidence of Parkinson's disease is also increasing considerably year by year, and it is old that Parkinson's disease has become influence The primary killers of year people's health.Therefore, active development safely and effectively prevents out or treats the drug and its preparation of Parkinson's disease Have become the arduous and urgent task of medical scientific research worker.

The pathogenesis of PD is extremely complex, and the cause of disease remains unknown so far.Inherent cause, oxidative stress, mitochondrial function barrier Hinder, immunologic dysfunction and environmental factor etc. all may induce PD.It is directed to the different clinical symptoms of PD at present, treatment method has medicine Object treatment, operative treatment, rehabilitation and psychotherapy etc..Drug therapy is still occupied an leading position, although drug can be obviously improved patient Symptom, but have the shortcomings that toxic side effects are big, bioavailability is low.Thus, select small toxicity, natural active matter pre- Anti- or treatment PD demand is increasing.

Co-Q10 (Coenzyme Q10, CoQ10) is the fat-soluble quinones being widely present in a kind of organism, Chemical name is 2,3- dimethoxy -5- methyl -6- last of the ten Heavenly stems isopentene group -1,4- benzoquinones.Co-Q10 is a kind of good biological medicament Object is the element for generating energy in human body, is present in each cells of organs film, can improve myocardial metabolism, reinforce 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 function and health-care effect of the Q10 in terms of biology are constantly revealed, along with its nontoxicity, 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, parkinsonism, and can prevention of arterial hardening, apoplexy and hypertension, have to heart, liver and kidney good Good health-care effect, the practical ranges of Co-Q10 are constantly expanded.Co-Q10 is widely used in eating in American-European countries Product, cosmetics, nutritional supplement etc. also have various relevant soft gel products on China's market today.

Largely studies have shown that Co-Q10 has important protective effect in the damage and reparation of nervous system.The U.S. The Q10 that the neurosurgeon Shults in University of California, branch school, San Diego imposes 3 kinds of dosage to PD patient's grouping has been carried out 16 months Clinical test, research find that in the experimental group of application maximum dose level Q10, the development process of Parkinson's disease is delayed 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 disturbance With.Mischley has found that PD patient Q10 content is significantly relatively low compared with normal population.The above fact illustrates Q10 in the prevention of PD or controls There is certain positive effect in treatment.

Co-Q10 is liposoluble substance, its water-insoluble makes it have difficulties in terms of the digestion and absorption of human body.And it is auxiliary There are quinonyls in enzyme Q10 structure, quite sensitive to light and oxygen, its life of conventional tablet, hard capsule and suspension type soft capsule is made Object utilization rate is extremely low.

Curcumin is a kind of yellow pigment extracted from the dry rhizome of Zingiber curcumin platymiscium, there is important warp Ji value and extensive pharmacological action (antitumor, anti-oxidant, anti-inflammatory, reducing blood lipid etc.).Since curcumin is highly-safe and malicious pair Act on small, in modern medicine, curcumin is because of its connection between nerve regneration (especially Parkinson's disease) and carcinogen It is and receives special attention.Recent studies indicate that curcumin can be used for controlling for neurodegenerative disease such as PD and AD It treats.But curcumin is practically insoluble in water as Q10, and oral administration biaavailability is very low.

Therefore, Co-Q10 and curcumin dissolubility in an aqueous medium and storage-stable how to be improved, become its Key technical problem during production and consumption.

From micro emulsion drug delivery system (self-microemulsifying drug delivery system, SMEDDS) be by Uniform, Thermodynamically stable, isotropic liquid oral composed by drug, oily phase, surfactant and cosurfactant Dosage form or solid dosage forms.The essential characteristic of the drug delivery system is, spontaneously formed under the wriggling of gastrointestinal tract after oral partial size < The oil in water emulsion of 100nm.The solubility and bioavilability of poorly water-soluble or fat-soluble medicine can be improved in SMEDDS, while can To avoid the pessimal stimulation to stomach and intestine of degradation and drug of labile drugs in water.It promotes the mechanism and advantage of drug absorption Be mainly reflected in the following aspects: (1) free energy needed for emulsification is very low, spontaneously forms under the slight wriggling of gastrointestinal tract The emulsion droplet of partial size very little has biggish surface area, increases the permeability of drug chrotoplast on the gastrointestinal tract；(2) drug is improved Solubility and improve the dissolution rate of drug；(3) small micro emulsion drop is because of the parent with lesser surface tension and micro emulsion surface It is aqueous, the hydrated sheath by gastrointestinal tract wall is made it easier to, penetrability is increased, promotes to absorb and improve bioavilability；(4) opposite Emulsion has higher physical stability；(5) preparation process is simple, is appropriate for industrialized production.

Correlative study shows that the gastrointestinal tract epithelial cell of body is electronegative.Sun can be thus introduced in microemulsion Ionic species make it with gastrointestinal tract epithelial cell because electrostatic attraction acts on, to further promote the absorption of insoluble medicine, improve Bioavilability.Gemini is a kind of gemini surfactant, it is by two monomcric surfactants in respective ion head A kind of surfactant that Ji Chu is chemically bonded by coupling base.This special dimeric structure imparts Shuangzi surface The more corresponding conventional single-ended base of activating agent, single more superior performance of alkane chain surfactant, such as high surface, low Krafft point and good water solubility show higher efficiency and ability, and monomer table in terms of the surface tension for reducing water The compounding of face activating agent, especially nonionic surface active agent can generate stronger synergistic effect, to oil solubilising power more By force.

Summary of the invention

The purpose of the present invention is to provide a kind of water-soluble good, excellent in stability, bioavilability it is high contain Co-Q10 From micro-emulsion type alimentation composition.

To achieve the above object, the present invention provide it is a kind of containing Co-Q10 from micro-emulsion type alimentation composition, feature exists In, it is prepared by each ingredient of following parts by weight,

1~15 part of Co-Q10,1~15 part of curcumin, 10~50 parts of carrier oils, 15~75 parts of non-ionic surfactants Agent, 1~5 part of cationic Gemini surfactants, 5~30 portions of cosurfactants, 0-2 parts of antioxidants.

Further, it is prepared by each ingredient of following parts by weight, 2~12 parts of Co-Q10s, 2~12 parts of curcumins, 15 ~45 parts of carrier oils, 25~60 parts of nonionic surface active agent, 1.5~4.5 parts of cationic Gemini surfactants, 10 ~25 portions of cosurfactants, 0-2 parts of antioxidants.

Further, it is prepared by each ingredient of following parts by weight, 5~10 parts of Co-Q10s, 5~10 parts of curcumins, 20 ~30 parts of carrier oils, 30~45 parts of nonionic surface active agent, 2~3 parts of cationic Gemini surfactants, 12~20 Part cosurfactant, 0-1 parts of antioxidants；

Preferably, it is prepared by each ingredient of following parts by weight, 8 parts of Co-Q10s, 7 parts of curcumins, 28 parts of carriers Oil, 40 parts of nonionic surface active agent, 2 parts of cationic Gemini surfactants, 15 portions of cosurfactants, 1 part anti- Oxidant.

Further, the Co-Q10 is at least one of CoQ10, reduced coenzyme Q 10；Preferably, auxiliary Enzyme Q10 is at least one of the Native Oxide type Co-Q10 that microbe fermentation method is prepared and reduced coenzyme Q 10；

It is optional, the carrier oil be crude vegetal or it is strong to main component solvability, by structure of modification, water Vegetable oil or aliphatic ester after solution；Preferably, crude vegetal is soybean oil, peanut oil, olive oil, castor oil, safflower oil One of or it is a variety of；Vegetable oil strong to main component solvability, after structure of modification, hydrolysis or aliphatic ester are Apricot kernel oil oleic acid PEG-6 glyceride, isopropyl myristate, ethyl oleate, medium-chain fatty glyceride, oleic acid polyethylene glycol are sweet One of grease, Masine 35-1 and polypropylene glycol caprylate are a variety of；

Optional, the nonionic surface active agent is selected from ten dihydroxy stearic acid ester of polyoxyethylene, the poly- second of caprylic capric Glycol glyceride, polyoxyl 40 hydrogenated castor oil, the sucrose ester of HLB value 13~16, Pluronic F68, One of vitamin E polyethylene glycol succinic acid ester, Tween-85, Tween-80, PLURONICS F87, lecithin are a variety of；

Optional, the cosurfactant is selected from glycerol, ethyl alcohol, ethylene glycol, PEG200-600, diethylene glycol mono-ethyl One of ether, propylene carbonate and propylene glycol are a variety of；

Optional, the antioxidant is selected from sodium ascorbate, natural VE and its ester derivant, rosemary extracts One of object is a variety of.

Further, also containing bacteriostatic agent from micro-emulsion type alimentation composition, stabilizer, helping containing Co-Q10 of the present invention Flow one of agent and colorant or a variety of.

Further, preparation method is,

Each component is weighed in proportion, remaining each component outside Co-Q10 and curcumin is uniformly mixed, coenzyme is added Q10 and curcumin are heated to 50-65 DEG C of stirring up to whole system transparent and homogeneous, then keep the temperature 15-60min, are cooled to room temperature i.e. It can.Insulated and stirred therein advantageously forms stable finish, and Co-Q10 is not easy crystallization.

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

Further, microcapsules, soft capsule, hard capsule, tablet, powder, pill, emulsion or suspension be can be prepared into.

The present invention also provides described to be used to prepare prevention and/or treatment pa from micro-emulsion type alimentation composition containing Co-Q10 The purposes of the gloomy medicine of gold.

The purposes that health food is used for from micro-emulsion type alimentation composition containing Co-Q10 that the present invention also provides described.It is described Health food for example can be dietary supplements.

The present invention is prepared good from micro-emulsion type alimentation composition stability containing Co-Q10, existing without oil slick, aggregation As.Not in amount ranges of the invention, there are oil slick, clustering phenomena from micro-emulsion type alimentation composition finish containing Co-Q10.

Co-Q10 and curcumin of the present invention have function that is anti-oxidant, eliminating free radical, repair injured nerve, hair Bright people, which both has found to carry out compatibility by a certain percentage, can play synergistic effect, and the compatibility of Co-Q10 and curcumin is stablized, It does not chemically react, has no adverse reaction, it is safe and feasible.

The antioxidant does not have special limitation, can be sodium ascorbate, natural VE and its ester derivant, One of Rosmarinus officinalis extract etc. is a variety of；To the bacteriostatic agent, stabilizer, glidant, colorant etc., other auxiliary materials do not have Special limitation, but should can permit the ingredient being added in food, drug etc..

It is of the present invention containing Co-Q10 from micro-emulsion type alimentation composition or its preparation, by oral administration after, pass through stomach in vivo The wriggling of enteron aisle spontaneously forms the microemulsion that oil droplet average grain diameter is less than 100nm.

Positively charged micro emulsion is formed by introducing the cationic Gemini surfactants of recipe quantity in the present invention Drop, by electrostatic interaction to enhance effective absorption of the body to Co-Q10 and curcumin.

The beneficial effects of the present invention are:

1, it after the mix with water from micro-emulsion type alimentation composition containing Co-Q10 prepared by the present invention, can be formed uniform, surely Fixed, clear solution.In application process, the bodies such as water phase food, drug can be simply and easily added on demand In system.

2, the stability from micro-emulsion type alimentation composition with height containing Co-Q10 prepared by the present invention is significant to press down The crystallization for having made Co-Q10, extends shelf life.

2, the emulsion droplet size formed from micro-emulsion type alimentation composition containing Co-Q10 prepared by the present invention is up to 10-100 Nanometer, belongs to nanometer formulation scope, body absorption effect is good.By the cationic Gemini surfactants for adding recipe quantity It is dripped to form positively charged micro emulsion, by electrostatic interaction to enhance effective absorption of the body to Co-Q10 and curcumin, Further increase the bioavilability of drug.

3, take it is of the invention containing Co-Q10 from after micro-emulsion type alimentation composition, Co-Q10 and curcumin are in blood plasma The ratio of release be substantially it is constant, do not discharge arbitrarily, but according in formula ratio slowly, smoothly in blood plasma Middle release, to ensure the safety and validity taken.

4, the present invention will prevent or treating the Co-Q10 having potential application on PD and curcumin progress science Compatibility has obvious synergistic function both for all-natural product.

5, water-soluble wall material solution can be directly added in the present invention on the basis of self-emulsifying microemulsion finish obtained, stir evenly Afterwards, water-soluble good self-emulsifying microemulsion microcapsules are made in spray drying, or are prepared into various desired dosage forms.

6, the preparation process from micro-emulsion type alimentation composition of the present invention containing Co-Q10 is simple, and chemical change does not occur Change, do not change Co-Q10 and curcumin chemical structure, whole preparation process is environmentally protective, low energy consumption, it is easy to accomplish industrial metaplasia It produces.

Specific embodiment

The embodiment of the present invention is described below in detail, the examples of the embodiments are being intended to be used to explain the present invention, without It can be interpreted as limitation of the present invention.In the examples where no specific technique or condition is specified, it is retouched according to the literature in the art The technology or conditions stated are carried out according to product description.Reagents or instruments used without specified manufacturer, being can be with Conventional products that are commercially available.

Embodiment 1:

Each Ingredient Amount table of 1 embodiment 1-6 of table

Each Ingredient Amount table of 2 embodiment 7-13 of table

Preparation method: weighing each ingredient by listed mass fraction in table 1, by remaining each group outside Co-Q10 and curcumin Divide and be uniformly mixed, add Co-Q10 and curcumin, is heated to 55 DEG C of stirrings up to whole system transparent and homogeneous, then keep the temperature 30min is down to after room temperature and obtains orange-yellow transparent uniform self-emulsifying microemulsion finish.

It takes gained self-emulsifying microemulsion finish about 1g to be added in 100ml deionized water, slightly shakes, obtain orange-yellow transparent water Lotion, it is therefore seen that this product water dispersible is good.

(1) gained self-emulsifying microemulsion finish is obtained into Co-Q10-Rhizoma-curcumae-longae element-soft cap sule by soft capsule production equipment.

(2) water of 200 mass parts is added in gained self-emulsifying microemulsion finish, stirring puts into 56 mass after forming uniform solution Part starch Sodium Octenyl Succinate, 35 mass parts maltodextrins, 9 mass parts white granulated sugars, stirring and dissolving, the homogeneous at 30Mpa, most Microemulsion is spray-dried afterwards, for the control of spray tower intake air temperature at 170 DEG C, air outlet temperature controls the atomization at 80 DEG C Device revolving speed 1200r/min, spray drying derive from micro emulsion microcapsules.

Embodiment 2

Raw material: it is shown in Table 1.

Preparation method: weighing each ingredient by listed mass fraction in table 1, by remaining each group outside Co-Q10 and curcumin Divide and be uniformly mixed, add Co-Q10 and curcumin, is heated to 50 DEG C of stirrings up to whole system transparent and homogeneous, then keep the temperature 40min is down to after room temperature and obtains orange-yellow transparent uniform self-emulsifying microemulsion finish.

(1) Co-Q10-Rhizoma-curcumae-longae element-soft cap sule is obtained by soft capsule production equipment.

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

Embodiment 3

Raw material: it is shown in Table 1.

Preparation method: weighing each ingredient by listed mass fraction in table 1, by remaining each group outside Co-Q10 and curcumin Divide and be uniformly mixed, add Co-Q10 and curcumin, is heated to 60 DEG C of stirrings up to whole system transparent and homogeneous, then keep the temperature 50min is down to after room temperature and obtains orange-yellow transparent uniform self-emulsifying microemulsion finish.

Embodiment 4

Raw material: it is shown in Table 1.

Preparation method: weighing each ingredient by listed mass fraction in table 1, by remaining each group outside Co-Q10 and curcumin Divide and be uniformly mixed, add Co-Q10 and curcumin, is heated to 65 DEG C of stirrings up to whole system transparent and homogeneous, then keep the temperature 60min is down to after room temperature and obtains orange-yellow transparent uniform self-emulsifying microemulsion finish.

Embodiment 5:

Raw material: it is shown in Table 1.

Preparation method: weighing each ingredient by listed mass fraction in table 1, by remaining each group outside Co-Q10 and curcumin Divide and be uniformly mixed, add Co-Q10 and curcumin, is heated to 52 DEG C of stirrings up to whole system transparent and homogeneous, then keep the temperature 35min is down to after room temperature and obtains orange-yellow transparent uniform self-emulsifying microemulsion finish.

Embodiment 6:

Raw material: it is shown in Table 1.

Preparation method: weighing each ingredient by listed mass fraction in table 1, by remaining each group outside Co-Q10 and curcumin Divide and be uniformly mixed, add Co-Q10 and curcumin, is heated to 62 DEG C of stirrings up to whole system transparent and homogeneous, then keep the temperature 45min is down to after room temperature and obtains orange-yellow transparent uniform self-emulsifying microemulsion finish.

Embodiment 7:

Raw material: 2 are shown in Table.

Preparation method: weighing each ingredient by listed mass fraction in table 1, by remaining each group outside Co-Q10 and curcumin Divide and be uniformly mixed, add Co-Q10 and curcumin, is heated to 54 DEG C of stirrings up to whole system transparent and homogeneous, then keep the temperature 55min is down to after room temperature and obtains orange-yellow transparent uniform self-emulsifying microemulsion finish.

Embodiment 8:

Raw material: 2 are shown in Table.

Preparation method: weighing each ingredient by listed mass fraction in table 1, by remaining each group outside Co-Q10 and curcumin Divide and be uniformly mixed, add Co-Q10 and curcumin, is heated to 56 DEG C of stirrings up to whole system transparent and homogeneous, then keep the temperature 32min is down to after room temperature and obtains orange-yellow transparent uniform self-emulsifying microemulsion finish.

Embodiment 9:

Raw material: 2 are shown in Table.

Preparation method: weighing each ingredient by listed mass fraction in table 1, by remaining each group outside Co-Q10 and curcumin Divide and be uniformly mixed, add Co-Q10 and curcumin, is heated to 58 DEG C of stirrings up to whole system transparent and homogeneous, then keep the temperature 15min is down to after room temperature and obtains orange-yellow transparent uniform self-emulsifying microemulsion finish.

Embodiment 10:

Raw material: 2 are shown in Table.

Preparation method: weighing each ingredient by listed mass fraction in table 1, by remaining each group outside Co-Q10 and curcumin Divide and be uniformly mixed, add Co-Q10 and curcumin, is heated to 59 DEG C of stirrings up to whole system transparent and homogeneous, then keep the temperature 20min is down to after room temperature and obtains orange-yellow transparent uniform self-emulsifying microemulsion finish.

Embodiment 11:

Raw material: 2 are shown in Table.

Preparation method: weighing each ingredient by listed mass fraction in table 1, by remaining each group outside Co-Q10 and curcumin Divide and be uniformly mixed, add Co-Q10 and curcumin, is heated to 61 DEG C of stirrings up to whole system transparent and homogeneous, then keep the temperature 25min is down to after room temperature and obtains orange-yellow transparent uniform self-emulsifying microemulsion finish.

Embodiment 12:

Raw material: 2 are shown in Table.

Preparation method: weighing each ingredient by listed mass fraction in table 1, by remaining each group outside Co-Q10 and curcumin Divide and be uniformly mixed, add Co-Q10 and curcumin, is heated to 63 DEG C of stirrings up to whole system transparent and homogeneous, then keep the temperature 52min is down to after room temperature and obtains orange-yellow transparent uniform self-emulsifying microemulsion finish.

Embodiment 13:

Raw material: 2 are shown in Table.

Preparation method: weighing each ingredient by listed mass fraction in table 1, by remaining each group outside Co-Q10 and curcumin Divide and be uniformly mixed, add Co-Q10 and curcumin, is heated to 64 DEG C of stirrings up to whole system transparent and homogeneous, then keep the temperature 57min is down to after room temperature and obtains orange-yellow transparent uniform self-emulsifying microemulsion finish.

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

Droplet measurement:

By the self-emulsifying microemulsion finish of case study on implementation preparation and self-emulsifying microemulsion microcapsules sample distilled water with the ratio of 1:20 Dilution gently shakes up, that is, forms clear micro emulsion.Then lotion is measured with laser fineness gage (Malvern company, Britain) Particle diameter distribution, measuring temperature be 25 DEG C.

From micro emulsion rate:

It is measured according to the Pharmacopoeia of the People's Republic of China (2005 editions) annex leaching slurry processes, Example 1-4's Self-emulsifying microemulsion finish and self-emulsifying microemulsion microcapsules (each 100mg) are dissolved in 37 DEG C of simulated gastric fluids, record each case study on implementation from micro emulsion Change the time.

The partial size of 1 self-micro emulsion formulation of table, self-emulsifying time tables of data

Experimental result shows that lotion average grain diameter is respectively less than 100nm, and solution clear illustrates to form stable uniform Microemulsion；The complete emulsion dispersion uniform time is respectively less than 3 minutes, has faster self-emulsifying microemulsion speed, i.e., by slight Stirring, it will be able to form the uniform emulsion of appearance transparent.

The result of embodiment 5-13 is herewith.

Embodiment 15: stability experiment:

Self-emulsifying microemulsion finish, self-emulsifying microemulsion microcapsules and the Co-Q10 raw material that Example 1 is prepared are respectively placed in 4500Lx intensity of illumination irradiation, be oxygenated filling (25 DEG C), 60 DEG C (insulating box) place 15 days, respectively at 0 day, 5 days, 10 days, 15 It is measured by sampling, and measures Co-Q10 content with HPLC method, investigates illumination, oxygen, temperature condition and indicates content to Co-Q10 The influence of (%).The results are shown in Table 2:

Influence table of 2 illumination of table to stability

Influence of 3 oxygen of table to stability

Influence table of 4 temperature of table to stability

Influence factor the experimental results showed that, self-emulsifying microemulsion finish of the invention and the self-emulsifying microemulsion being further prepared are micro- Under illumination, oxygenation, hot conditions, Co-Q10 mark content and face shaping do not change capsule.In terms of face shaping, Self-emulsifying microemulsion finish is in yellow clear solution, does not crystallize precipitation；Self-emulsifying microemulsion microcapsules are yellow powder, not bright in color It is aobvious to change.In terms of Co-Q10 indicates content, over time (5 days, 10 days, 15 days), Co-Q10 mark contains quantitative change Change less, it is more more stable than the Co-Q10 mark content in Co-Q10 raw material.Illustrate self-emulsifying microemulsion finish of the invention and into one Walking the self-emulsifying microemulsion microcapsules that are prepared has preferable stability, reduces illumination, oxygen, temperature to the shadow of its property It rings, extends product storage life.

The result of embodiment 2-13 is herewith.

Embodiment 16: internal pharmacokinetic studies:

16.1 sample:

Co-Q10-Rhizoma-curcumae-longae element-soft cap sule (code name are as follows: sample 1, sample 2, sample 3, sample 4) of Examples 1 to 4 preparation；

Co-Q10-curcumin raw material medicine solution agent configuration: precision weighs 50g Co-Q10,10g curcumin (the two weight Amount ratio 5:1, consistent with 1 ratio of sample), it is dissolved in (v/v, 1:1) (code name are as follows: raw material in 800ml ethyl alcohol-PEG400 solution Sample).

A total of five sample carries out animality experiment.

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

16.3 experimental animals and grouping: by Changsha Kaifu District Dong Chuan Animal Science service department, (experimental animal is used The SPF grade Kunming kind female mice that credit number provides for SYXK (Hunan) 2010-0010), age of mouse 3 months, 18~22g of weight. Animal is operated according to International Laboratory Animal experiment criterion, to reduce the pain of experimental animal during the experiment.Using Completely randomized design is divided into one group for the mouse of fasting 12h random every 10, and totally five groups.

16.4 oral administrations and sample acquisition, processing: intragastric administration on mice same dose (35mg/kg: Co-Q10 is given respectively With curcumin total content) from micro emulsion drug delivery system sample (i.e. sample 1-4) and bulk pharmaceutical chemicals (i.e. raw material sample), after administration respectively at 5,15,30min and 1,2,4,6,12h acquisition blood plasma mix, 3000r/min centrifugal treating into the anticoagulant centrifuge tube containing heparin After 10min, separated plasma detects plasma drug level with HPLC method after processing.

16.5 pharmacokinetic studies

According to blood concentration as a result, applied statistics, which analyzes software, carries out statistics Fitting Analysis to experimental result, blood is calculated As a result concentration data indicate (table 5) with means standard deviation.

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

The result shows that after oral administration, from micro-emulsion type preparation (i.e. Co-Q10-Rhizoma-curcumae-longae element-soft cap sule of embodiment 1-4) Cmax cmax value is significantly higher than the cmax value (P < 0.05) of bulk pharmaceutical chemicals, AUC value also greater than bulk pharmaceutical chemicals AUC value, Co-Q10 with Curcumin is accelerated in mouse body absorption after self-emulsifying microemulsion and can reach higher plasma concentration, the bioavilability of body It dramatically increases.Self-micro emulsion formulation belongs to nanometer formulation scope, is conducive to the uniformity for improving drug absorption, shown self-micro emulsion formulation The fluctuation of Cmax is less than bulk pharmaceutical chemicals, to improve the safety of medication.

The ratio table of 6 mouse oral of table clothes administration Co-Q10 and curcumin under each detection time in plasma concentration

From table 6 according to comparison each sample, the raw material sample concentration of Co-Q10 and curcumin ratio in different test period blood plasma Value, it can be seen that the ratio that self-micro emulsion formulation Co-Q10 and curcumin prepared by the present invention discharge in blood plasma is substantially perseverance Fixed, it is slowly, smoothly to be discharged according to the ratio in formula.

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

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

The F value of sample 1 is 206.9% (72.88/35.22), the i.e. bioavilability of self microemulsifying preparation as known from Table 7 It is 2.07 times of bulk pharmaceutical chemicals, sample 2 is 217.9%, and sample 3 is 226.8%, and sample 4 is 202.5%.Illustrate to change dosage form pair Absorption process substantially improves drug in vivo.Illustrate that the present invention is prepared containing Co-Q10 from micro-emulsion type alimentation composition Different dosage forms substantially improve the body absorption process of drug.

The biological half-life t of self-micro emulsion formulation_1/2It is not significantly different with bulk pharmaceutical chemicals, illustrates that self microemulsifying preparation does not influence The elimination of drug in vivo.

The result of embodiment 5-13 is herewith.

Embodiment 17: animal behavioral study and test:

17.1 sample:

Sample 1: self-emulsifying microemulsion finish prepared by embodiment 1.

Reference substance 1: the curcumin in the formula of embodiment 1 is substituted for the MCT of equal quality number, remaining component and preparation side Method and embodiment 1 are consistent, and self-emulsifying microemulsion finish reference substance 1 is prepared.

Reference substance 2: the Co-Q10 in the formula of embodiment 1 is substituted for the MCT of equal quality number, remaining component and preparation Method and embodiment 1 are consistent, and self-emulsifying microemulsion finish reference substance 2 is prepared.

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

17.3 experimental animals and grouping: by Changsha Kaifu District Dong Chuan Animal Science service department, (experimental animal is used The SPF grade Kunming kind female mice that credit number provides for SYXK (Hunan) 2010-0010), age of mouse 3 months, 18~22g of weight. Animal is operated according to International Laboratory Animal experiment criterion, to reduce the pain of experimental animal during the experiment.Using Completely randomized design is divided into one group for mouse random every 10, and totally 6 groups.Each control group intraperitoneal injection volume is consistent, injects daily Time point is similar.

Normal group: continuous intraperitoneal injection of saline 24 days；

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

Treat 1 group: sample 1+MPTP group, i.e. continuous 5 days intraperitoneal injection 30mg/kg MPTP, then use 30mg/kg sample 1 instead Continuous injection 19 days；

Treat 2 groups: reference substance 1+MPTP group, i.e. continuous 5 days intraperitoneal injection 30mg/kg MPTP, then use 30mg/kg pairs instead It is continuously injected 19 days according to product 1；

Treat 3 groups: reference substance 2+MPTP group, i.e. continuous 5 days intraperitoneal injection 30mg/kg MPTP, then use 30mg/kg pairs instead It is continuously injected 19 days according to product 2；

Prevention group: the continuous 7 days injection 30mg/kg samples 1 before carrying out MPTP model treatment, then continuous 5 days abdominal cavities are infused 30mg/kg MPTP is penetrated, subsequent continuous 19 days intraperitoneal injection DMSO；

17.4 apomorphines induce rotation test: in mouse subcutaneous injection dosage being 0.3mg/kg in each observing time point Apomorphine induces the circling behavior of mouse, it is specified that being rotated by 360 ° is one turn, records the rotation revolution in mouse 30min.If by Examination object group rotation revolution is significantly less than solvent control group rotation revolution, and difference has conspicuousness (P < 0.05), can determine that this is tested Object plays the role of prevention or alleviates Parkinson's disease.Test result is shown in Table 8.

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

As can be seen from Table 8, the apomorphine for the treatment of group 1-3 group and prevention group induction rotation test revolution is significantly lower than molten Agent control group, and difference has conspicuousness (P < 0.05), illustrates that self-emulsifying microemulsion finish of the invention has and prevents or alleviate Parkinson The effect of disease.Simultaneously as it can be seen that the compatibility of Co-Q10 and curcumin has obvious synergistic function (the test effect of 1 group for the treatment of Fruit is significantly better than 3 groups of 2 groups for the treatment of and treatment).

17.5 triggerings are asymmetrically placed experiment: holding mouse trunk and leave ground, one side antenna is touched table angle.When Mouse side antenna can induce ipsilateral forelimb and act to the placement at table angle when touching table angle, impaired forelimb cannot be by forelimb at power amplifier It is placed in table angle.When scoring, two sides forelimb is tested 10 times respectively, is calculated triggering and is asymmetrically placed experiment score.The data obtained is meter Amount data, if the triggering of tested material group is asymmetrically placed experiment score significantly lower than solvent control group, and difference have conspicuousness (P < 0.05) it, can determine that the tested material plays the role of prevention or alleviates Parkinson's disease.Test result is shown in Table 9.

The triggering of table 9 is asymmetrically placed experiment score (X ± S, n=10) table

As can be seen from Table 9, it treats 1-3 group and prevention group triggering is asymmetrically placed experiment score significantly lower than solvent control Group, and difference has conspicuousness (P < 0.05), illustrates that self-emulsifying microemulsion finish of the invention has the work for preventing or alleviating Parkinson's disease With.As it can be seen that the compatibility of Co-Q10 and curcumin has obvious synergistic function, (test effect of 1 group for the treatment of is significant simultaneously 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 mouse brain midbrain segment, immerses in fixer 24 hours.Selection midbrain after mouse brain midbrain segment processing after fixation is black Matter, corpus straitum position carry out immunohistochemical staining processing, and mounting is placed under laser confocal microscope and is observed, will be each The black substance TH Positive Cell Counts of group mouse, as a result as shown in the following table 10:

The black substance TH Positive Cell Counts and P value table of 10 mouse of table

As can be seen from Table 10, the TH positive cell number for treating 1-3 group, prevention group obviously increase compared with solvent control group (P < 0.05), it can be seen that, Co-Q10 and curcumin can promote the expression of TH, reduce neurotoxin Dui ?matter TH damage, into And preventing or treating to have potential application on PD.Simultaneously as it can be seen that the compatibility of Co-Q10 and curcumin has significantly Synergistic function (test effect of 1 group 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 Height, stability are good.

The result of embodiment 2-13 is herewith.

Although the embodiments of the present invention has been shown and described above, it is to be understood that above-described embodiment is example Property, it is not considered as limiting the invention, those skilled in the art are not departing from the principle of the present invention and objective In the case where can make changes, modifications, alterations, and variations to the above described embodiments within the scope of the invention.

Claims

1. it is a kind of containing Co-Q10 from micro-emulsion type alimentation composition, which is characterized in that it is prepared by each ingredient of following parts by weight It obtains,

1~15 part of Co-Q10,1~15 part of curcumin, 10~50 parts of carrier oils, 15~75 parts of nonionic surface active agent, 1 ~5 parts of cationic Gemini surfactants, 5~30 portions of cosurfactants, 0-2 parts of antioxidants.

2. described in claim 1 containing Co-Q10 from micro-emulsion type alimentation composition, which is characterized in that it is by following parts by weight Each ingredient is prepared, 2~12 parts of Co-Q10s, 2~12 parts of curcumins, 15~45 parts of carrier oils, 25~60 parts of non-ionic tables Face activating agent, 1.5~4.5 parts of cationic Gemini surfactants, 10~25 portions of cosurfactants, 0-2 parts anti-oxidant Agent.

3. described in claim 2 containing Co-Q10 from micro-emulsion type alimentation composition, which is characterized in that it is by following parts by weight Each ingredient is prepared, 5~10 parts of Co-Q10s, 5~10 parts of curcumins, 20~30 parts of carrier oils, 30~45 parts of non-ionic tables Face activating agent, 2~3 parts of cationic Gemini surfactants, 12~20 portions of cosurfactants, 0-1 parts of antioxidants.

4. described in claim 3 containing Co-Q10 from micro-emulsion type alimentation composition, which is characterized in that it is by following parts by weight Each ingredient is prepared, 8 parts of Co-Q10s, 7 parts of curcumins, 28 parts of carrier oils, 40 parts of nonionic surface active agent, 2 parts of sun from Subtype Gemini surface active, 15 portions of cosurfactants, 1 part of antioxidant.

5. described in claim any one of 1-4 containing Co-Q10 from micro-emulsion type alimentation composition, which is characterized in that the coenzyme Q10 is at least one of CoQ10, reduced coenzyme Q 10.

6. described in claim 5 containing Co-Q10 from micro-emulsion type alimentation composition, which is characterized in that Co-Q10 is microorganism hair At least one of Native Oxide type Co-Q10 and reduced coenzyme Q 10 obtained by the preparation of ferment method.

7. described in claim any one of 1-4 containing Co-Q10 from micro-emulsion type alimentation composition, which is characterized in that the carrier Oil is crude vegetal or vegetable oil or aliphatic ester strong to main component solvability, after structure of modification, hydrolysis； The vegetable oil strong to main component solvability, after structure of modification, hydrolysis or aliphatic ester are apricot kernel oil oleic acid PEG-6 glyceride, isopropyl myristate, ethyl oleate, medium-chain fatty glyceride, oleic acid LABRAFIL M 1944CS, Dan Ya One of olein and polypropylene glycol caprylate are a variety of.

8. described in claim 7 containing Co-Q10 from micro-emulsion type alimentation composition, which is characterized in that crude vegetal is soybean One of oil, peanut oil, olive oil, castor oil, safflower oil are a variety of.

9. described in claim any one of 1-4 containing Co-Q10 from micro-emulsion type alimentation composition, which is characterized in that it is described it is non-from Subtype surfactant is selected from ten dihydroxy stearic acid ester of polyoxyethylene, Labraso, 40 hydrogen of polyoxyethylene Change castor oil, the sucrose ester of HLB value 13~16, Pluronic F68, vitamin E polyethylene glycol succinic acid ester, One of Tween-85, Tween-80, PLURONICS F87, lecithin are a variety of.

10. described in claim any one of 1-4 containing Co-Q10 from micro-emulsion type alimentation composition, which is characterized in that it is described to help table Face activating agent is in glycerol, ethyl alcohol, ethylene glycol, PEG200-600, diethylene glycol monoethyl ether, propylene carbonate and propylene glycol It is one or more.

11. described in claim any one of 1-4 containing Co-Q10 from micro-emulsion type alimentation composition, which is characterized in that the antioxygen Agent is selected from one of sodium ascorbate, natural VE, Rosmarinus officinalis extract or a variety of.

12. described in claim any one of 1-4 containing Co-Q10 from micro-emulsion type alimentation composition, which is characterized in that also containing suppression One of microbial inoculum, stabilizer, glidant and colorant are a variety of.

13. described in claim any one of 1-4 containing Co-Q10 from micro-emulsion type alimentation composition, which is characterized in that preparation method For,

Weigh each component in proportion, remaining each component outside Co-Q10 and curcumin be uniformly mixed, add Co-Q10 and Curcumin is heated to 50-65 DEG C of stirring up to whole system transparent and homogeneous, then keeps the temperature 15-60min, is cooled to room temperature.

14. described in claim 13 containing Co-Q10 from micro-emulsion type alimentation composition, which is characterized in that the preparation process and Preservation after preparation is in inert atmosphere or vacuum state.

15. described in claim 14 containing Co-Q10 from micro-emulsion type alimentation composition, which is characterized in that the preparation process and Preservation after preparation is in nitrogen or helium atmosphere atmosphere.

16. described in claim any one of 1-4 containing Co-Q10 from micro-emulsion type alimentation composition, which is characterized in that can be prepared into Microcapsules, soft capsule, hard capsule, tablet, powder, pill, emulsion or suspension.

17. described in a kind of any one of claim 1-16 containing Co-Q10 from micro-emulsion type alimentation composition being used to prepare prevention and/ Or the purposes for the treatment of anti-parkinson drug.