CN104688553A - Emulsion containing lipoic acid and preparation method of emulsion - Google Patents

Abstract

The invention relates to an emulsion containing lipoic acid and a preparation method of the emulsion. The emulation comprises the following components in parts by weight: 0.01-10 parts of lipoic acid, 5-15 parts of oil, 1-20 parts of phospholipid, 0.5-20 parts of a non-ionic surface active agent and 60-90 parts of a dispersion medium. The phospholipid is soya bean lecithin or egg yolk lecithin. According to the emulsion, lipoic acid is wrapped in lipid microspheres, so that the water solubility of lipoic acid and the stability are effectively improved, the problems of odor and water solubility are solved, and the external application of lipoic acid to skin is enhanced. The emulsion containing lipoic acid, provided by the invention, can be stored in a sealing way for 3 months at 37DEG C, and is stable in oxidation resistance and hard to decompose and deteriorate.

Description

A kind of Emulsion containing thioctic acid and preparation method thereof

Technical field

The present invention relates to the preparation of thioctic acid, be specifically related to a kind of Emulsion containing thioctic acid and preparation method thereof.

Background technology

Thioctic acid (alpha lipoic acid) is sulfur-bearing eight carbon fat acid, that one is present in mitochondrial enzyme, similar vitamin, accelerated ageing and the free radical caused a disease can be eliminated, 6,8 have disulfide bond be connected (hydrogen atom on C6 and C8 is replaced by disulfide bond), have oxidation, reduce two types, it is the Natural antioxidant, its chemical name is ALPHA-lipoic acid, distributes to some extent in the plant such as liver organization and Herba Spinaciae Fructus Lycopersici esculenti of animal.After thioctic acid is absorbed by the body, dihydrolipoic acid (DHLA) can be changed into rapidly in cell, and discharge extracellular.The synergy of thioctic acid and dihydrolipoic acid can be nearly all in purged body oxyradical.

Thioctic acid obtains investigation and application widely in fields such as medicine, food, cosmetics because of its strong anti-oxidation ability.Research shows, thioctic acid can suppress the development of cardiovascular and cerebrovascular disease effectively, can also alleviate the diseases such as the body tissue damage caused due to the increase of oxyradical in obese patient's body.In field of health care food, antioxidant health care of food product are mainly used in removing interior free yl, preventing lipid peroxidation.Cosmetic field, thioctic acid is used for whitening anti-wrinkling, the care of special sensitive part, repairs the impaired skin of light to reach the object of slow down aging.

Because thioctic acid has strong non-oxidizability, this just causes exposing aerial thioctic acid very easily by the oxidation in air, form the oxyradical of thioctic acid, cause the effective content of the thioctic acid that really can arrive in human body significantly to reduce, the thioctic acid after simultaneous oxidation can send a kind of pungent abnormal smells from the patient.In addition, thioctic acid is a kind of fat-soluble active substance, is very easily dissolved in ethanol, the Organic substances such as ether, and water insoluble.The mode that Germany Alipure product line is wrapped up by cyclodextrin, solves abnormal smells from the patient and water miscible problem.

Nanoemulsions (Nanoemulsion) is also known as microemulsion (microemulsion), be be made up according to appropriate proportioning of aqueous phase, oil phase, surfactant and cosurfactant, there is the transparent or semitransparent system that low viscosity, isotropic thermodynamics and kinetics are stable.Its advantage is the dissolubility increasing insoluble drug, and raising medicine stability and bioavailability, many insoluble drugs have slow release and targeting after making nano-emulsion; Nano-emulsion good biocompatibility, biodegradable, therefore, it is used as fat-soluble medicine and the carrier to water sensitive medicine, can reduce zest and the toxic and side effects of medicine, Thermodynamically stable, be long placed in not stratified, not breakdown of emulsion.

In general, nano-emulsion is divided into three types, i.e. oil-in-water type nano-emulsion (O/W), water-in-oil type nanoemulsion (W/O and bicontinuous nano-emulsion (B.C).

The accessory package that nano-emulsion is conventional contains four kinds of compositions such as oil phase, aqueous phase, surfactant, cosurfactant, wherein oil phase often selects the medicinal one-level vegetable oil of short chain and middle long-chain as oil phase, and also useful ethyl oleate, isopropyl myristate etc. are as oil phase; Aqueous phase commonly uses ultra-pure water or deionized water, also can replace with distilled water; Surfactant commonly uses polyoxyethylene groups non-ionic surface active agent as tween 80, poloxamer; Cosurfactant multiselect short chain alcohol and medium chain alcohol, as ethanol, 1,2-PD, glycerol etc.

But nano-emulsion itself is a thermodynamic instability system, change prescription or condition of storage for specific unstable mechanism, the stability of nano-emulsion could be improved and promote its application in practice.

About the nanometer formulation of zinc sulfate, there is following report:

CN200810107302.3 (CN101385713A) discloses a kind of preparation method of lipoic acid lipid nano-particles, comprise the following steps: step one: weigh matrix material and thioctic acid respectively, heat in thermostatic water bath, after melting, obtain the yellow clarification system of having dissolved thioctic acid; Step 2: take emulsifying agent and water respectively, heat in thermostatic water bath; Step 3: add in aqueous phase by the oil phase under design temperature T, after magnetic agitation mix homogeneously, obtains clarification system; Step 4: be down to room temperature, obtains lipoic acid lipid nano-particles dispersion liquid; Step 5: the dispersion liquid in step 4 is carried out lyophilization process and namely obtains lipoic acid lipid nano-particles.

Whether, although there is relevant report thioctic acid being made lipid nanometer preparation, the document is not write exactly after thioctic acid is prepared into lipid nanometer preparation yet, stabilizability, and finds through overtesting, and lipid nanometer preparation stability prepared by the document is poor.

Therefore, the lipoic acid lipid nanometer formulation that a kind of stable in properties is provided is needed.

Summary of the invention

The object of the invention is to relate to a kind of Emulsion containing thioctic acid.

A kind of Emulsion containing thioctic acid provided by the invention, it consists of the following composition: thioctic acid, phospholipid, oil, non-ionic surface active agent and disperse medium.

Concrete, described Emulsion is grouped into by the one-tenth of following weight fraction: thioctic acid 0.01-10 part, oily 5-15 part, phosphatidase 1-20 parts, non-ionic surface active agent 0.5-20 part and disperse medium 60-90 part.

In above-mentioned Emulsion:

Described non-ionic surface active agent is two or more in sorbester p18, sorbester p17, polyglycerol monooleate, Tween 80, polyoxyethylene castor oil or Polyethylene Glycol caprylic/capric glyceride;

Described phospholipid is soybean lecithin or Ovum Gallus domesticus Flavus lecithin, preferably soya lecithin;

Described oil is one or both of soybean oil, caprylic/capric glyceride, safflower oil or olive oil, is preferably caprylic/capric glyceride;

Described disperse medium is one or both in water, glycerol or propylene glycol.

As preferred version of the present invention, described Emulsion is grouped into by the one-tenth of following weight portion: thioctic acid 0.2-5 part, caprylic/capric glyceride 5-15 part, phosphatidase 1 .5-5 part, sorbester p17 0-1.5 part, polyglycerol monooleate 0-2 part, Tween 80 0.5-2 part, polyoxyethylene castor oil 0-2 part, Polyethylene Glycol caprylic/capric glyceride 0-2 part, glycerol 40-80 part and water 5-10 part.

Further preferably, described Emulsion (antioxidant effect is better) is grouped into by the one-tenth of following weight portion: thioctic acid 2-4 part, caprylic/capric glyceride 10-15 part, phosphatidase 1 .5-3 part, polyglycerol monooleate 0.3-1.0 part, Tween 80 0.8-1.5 part, Polyethylene Glycol caprylic/capric glyceride 0.5-1.5 part, glycerol 60-75 part and water 5-15 part.

Further preferred, described Emulsion (antioxidant effect is best) is grouped into by the one-tenth of following weight portion: thioctic acid 3 parts, caprylic/capric glyceride 15 parts, phosphatidase 1 .5 part, polyglycerol monooleate 0.5 part, Tween 80 1 part, Polyethylene Glycol caprylic/capric glyceride 1 part, glycerol 73 parts and 5 parts, water.

Another object of the present invention is to provide the preparation method of the described Emulsion containing thioctic acid, and the method comprises the steps:

1) thioctic acid, phospholipid, oil, non-ionic surface active agent mixing, high speed shear under 8000-12000rpm condition, without the visible solid content of naked eyes to system;

2) disperse medium is added step 1) product, high speed shear under 8000-12000rpm condition, obtains colostrum, and colostrum is through high pressure homogenizer process, and pressure 800-2000bar used, cycle-index 5-10 time, obtains transparent or semitransparent Emulsion.

Present invention also offers above-mentioned Emulsion and prepare the application in antioxidative cosmetics.

Emulsion containing thioctic acid provided by the invention has the following advantages:

1, the Emulsion containing thioctic acid provided by the invention, by thioctic acid and phospholipid, oil, non-ionic surface active agent, disperse medium are carried out suitable proportioning, reasonable mixture ratio, especially multiple non-ionic surface active agent is selected, avoid the shortcoming that single surfactant can not merge thioctic acid completely, the nano-emulsion good stability of final combination.

2, thioctic acid is wrapped in lipid microsphere by the present invention, can effectively increase thioctic acid water solublity, effectively can increase stability, solves abnormal smells from the patient and water miscible problem, thus enhances the application of thioctic acid in external preparation for skin field.

3, the Emulsion containing thioctic acid provided by the invention airtight preservation 3 months under 37 DEG C of conditions, its antioxygenic property is stablized, it is rotten to be not easy to decompose.

Detailed description of the invention

Following examples for illustration of the present invention, but are not used for limiting the scope of the invention.

Embodiment 1: the Emulsion containing thioctic acid

1, form:

2, preparation method:

1) by recipe quantity, thioctic acid, phospholipid, caprylic/capric glyceride, Tween 80, polyoxyethylene castor oil mix, and high speed shear under 12000rpm condition, without the visible solid content of naked eyes to system;

2) glycerol, water are added step 1) product, high speed shear under 8000rpm condition, after obtaining colostrum, high pressure homogenizer process, pressure 800bar used, circulates 5 times, obtains Emulsion.

Embodiment 2: the Emulsion containing thioctic acid

1, form:

2, preparation method:

1) by recipe quantity, thioctic acid, phospholipid, caprylic/capric glyceride, sorbester p17, polyglycerol monooleate, Tween 80, polyoxyethylene castor oil mix, and high speed shear under 10000rpm condition, without the visible solid content of naked eyes to system;

2) glycerol, water are added step 1) product, high speed shear under 12000rpm condition, after obtaining colostrum, high pressure homogenizer process, pressure 1000bar used, circulates 7 times, obtains Emulsion.

Embodiment 3: the Emulsion containing thioctic acid

1, form:

2, preparation method:

1) by recipe quantity, thioctic acid, phospholipid, caprylic/capric glyceride, polyglycerol monooleate, Tween 80, Polyethylene Glycol caprylic/capric glyceride mix, and high speed shear under 8000rpm condition, without the visible solid content of naked eyes to system;

2) glycerol, water are added step 1) product, high speed shear under 10000rpm condition, after obtaining colostrum, high pressure homogenizer process, pressure 2000bar used, circulates 10 times, obtains Emulsion.

Embodiment 4: the Emulsion containing thioctic acid

1, form:

2, preparation method:

1) by recipe quantity, thioctic acid, phospholipid, caprylic/capric glyceride, polyglycerol monooleate, Tween 80, Polyethylene Glycol caprylic/capric glyceride mix, and high speed shear under 12000rpm condition, without the visible solid content of naked eyes to system;

2) glycerol, water are added step 1) product, high speed shear under 8000rpm condition, after obtaining colostrum, high pressure homogenizer process, pressure 1500bar used, circulates 5 times, obtains Emulsion.

Embodiment 5: the Emulsion containing thioctic acid

1, form:

2, preparation method:

1) by recipe quantity, thioctic acid, phospholipid, caprylic/capric glyceride, polyglycerol monooleate, Tween 80, Polyethylene Glycol caprylic/capric glyceride mix, and high speed shear under 10000rpm condition, without the visible solid content of naked eyes to system;

2) glycerol, water are added step 1) product, high speed shear under 8000rpm condition, after obtaining colostrum, high pressure homogenizer process, pressure 800bar used, circulates 8 times, obtains Emulsion.

Comparative example 1:

With reference to the embodiment 1 of CN200810107302.3 (CN101385713A), particular content refers to this patent.

Experimental example 1: particle size determination

1, test specimen:

Sample 1-5: the embodiment 1-3 Emulsion prepared;

Reference substance: the lipid nanometer preparation that comparative example 1 provides.

2, particle size determination:

Adopt Malvern Zetasizer 3000HSA Particle Size Analyzer to detect particle diameter, before mensuration, sample 1-3 and reference substance Millipore ultra-pure water are diluted 30 times.

3, result of the test: in table 1

Table 1: different sample particle diameter size

Title

Sample 1

Sample 2

Sample 3

Sample 4

Sample 5

Reference substance

Mean diameter

134nm

171nm

84nm

97nm

92nm

253nm

Table 1 result shows: the mean diameter after sample 1-5 emulsifying is less than reference substance, especially sample 3-5, and particle diameter is significantly less than reference substance.

Result shows: the Emulsion particle diameter containing thioctic acid provided by the invention is less than 180nm.

Experimental example 2: stability test

1, test specimen:

Sample 1-5: the Emulsion prepared by embodiment 1-5.

Reference substance 1,2: the method preparation that reference substance 1 provides with reference to comparative example 1, reference substance 2 is independent thioctic acid.

2, test method: by sample 1-5 and reference substance 1,2, under being placed in 37 DEG C of conditions respectively, airtight placement 3 months, is tested and sensory test by free radical scavenging, investigates the shelf-stability of different sample.

2.1 free radical scavenging tests:

2.1.1 test principle: DPPH is a kind of stable free radical in organic solvent, and its lone pair electrons have strong absorption (aobvious darkviolet) near 517nm.When organic scavenger exists, lone pair electrons are paired, and absorb and disappear or weaken, and by measuring the degree absorbing and weaken, can evaluate the activity of free radical scavenger.

2.1.2 test method: extracting sample solution 2mL and concentration are that the DPPH solution 2mL of 100 μm of oL/L successively adds in same tool plug test tube, shake up; Left at room temperature 30min, working sample absorbance under 517nm wavelength.

Suppression ratio: K%=[1-(Ai-Aj)/Ac] × 100%, in formula:

The absorbance of Ai:2mLDPPH solution+2mL product to be tested solution

The absorbance of Aj:2mL product to be tested solution+2mL solvent

The absorbance of Ac:2mLDPPH solution+2mL solvent

During test, product to be tested being unified diluted concentration is 0.1% (w/v)

2.1.3 experimental result: in table 2.

Table 2: different sample is to the clearance rate (%) of DPPH

Title

Sample 1

Sample 2

Sample 3

Sample 4

Sample 5

Reference substance 1

Reference substance 2

Clearance rate

80.3％

84.5％

95.1％

93.6％

91.5％

58.2％

35.8％

Table 2 result shows: respectively compared with reference substance 1,2, under same placement condition, sample 1-5 can improve the stability of thioctic acid significantly, especially sample 3-5 more remarkable effect.

2.2 abnormal smells from the patient sensory tests

2.2.1 test method:

Blind cross matching, in process of the test, 12 olfactory sensation healthy premenopausal volunteers, respectively to the sample of numbering in advance, with the taste of the different sample of olfactory sensation, and experience separately with the five-grade marking system record, average, 0 point of expression does not have uncomfortable taste, and 5 points represent that abnormal smells from the patient is difficult to accept, between remaining fraction medium.Before each news sample, experimenter treats more than 30min in outdoor fresh air.

2.2.2 experimental result: in table 3.

Table 3 different sample abnormal smells from the patient degree

Title	Sample 1	Sample 2	Sample 3	Sample 4	Sample 5	Reference substance 1	Reference substance
								Score value	1.23	1.31	0.17	0.23	0.21	3.04	3.81

Table 3 result shows, and respectively compared with reference substance 1,2, under same placement condition, the odour value of sample 1-5 is starkly lower than reference substance, and wherein the odour value of sample 3-5 is significantly lower than reference substance.

Result shows: the Emulsion containing thioctic acid provided by the invention airtight preservation 3 months under 37 DEG C of conditions, and its antioxygenic property is stablized, it is rotten to be not easy to decompose.

Although above with general explanation, detailed description of the invention and test, the present invention is described in detail, and on basis of the present invention, can make some modifications or improvements it, this will be apparent to those skilled in the art.Therefore, these modifications or improvements without departing from theon the basis of the spirit of the present invention, all belong to the scope of protection of present invention.

Claims (10)

1. the Emulsion containing thioctic acid, it consists of the following composition: thioctic acid 0.01-10 part, oily 5-15 part, phosphatidase 1-20 parts, non-ionic surface active agent 0.5-20 part and disperse medium 60-90 part.

2. Emulsion according to claim 1, is characterized in that, described non-ionic surface active agent is two or more in Tween 80, sorbester p17, polyglycerol monooleate, polyoxyethylene castor oil or Polyethylene Glycol caprylic/capric glyceride.

3. Emulsion according to claim 1, is characterized in that, described phospholipid is soybean lecithin or Ovum Gallus domesticus Flavus lecithin.

4. Emulsion according to claim 1, is characterized in that, described oil is one or both of soybean oil, caprylic/capric glyceride, safflower oil or olive oil.

5. Emulsion according to claim 1, is characterized in that, described disperse medium is one or both in water, glycerol or propylene glycol.

6. the Emulsion according to any one of claim 1-5, it is characterized in that, described Emulsion is grouped into by the one-tenth of following weight portion: thioctic acid 0.2-5 part, caprylic/capric glyceride 5-15 part, phosphatidase 1 .5-5 part, sorbester p17 0-1.5 part, polyglycerol monooleate 0-2 part, Tween 80 0.5-2 part, polyoxyethylene castor oil 0-2 part, Polyethylene Glycol caprylic/capric glyceride 0-2 part, glycerol 40-80 part and water 5-10 part.

7. the Emulsion according to any one of claim 1-5, it is characterized in that, described Emulsion is grouped into by the one-tenth of following weight portion: thioctic acid 2-4 part, caprylic/capric glyceride 10-15 part, phosphatidase 1 .5-3 part, polyglycerol monooleate 0.3-1.0 part, Tween 80 0.8-1.5 part, Polyethylene Glycol caprylic/capric glyceride 0.5-1.5 part, glycerol 60-75 part and water 5-15 part.

8. Emulsion according to claim 7, it is characterized in that, described Emulsion is grouped into by the one-tenth of following weight portion: thioctic acid 3 parts, caprylic/capric glyceride 15 parts, phosphatidase 1 .5 part, polyglycerol monooleate 0.5 part, Tween 80 1 part, Polyethylene Glycol caprylic/capric glyceride 1 part, glycerol 73 parts and 5 parts, water.

9. prepare a method for the Emulsion described in any one of claim 1-8, it is characterized in that, the method comprises the following steps:

1) thioctic acid, phospholipid, oil, non-ionic surface active agent mixing, high speed shear under 8000-12000rpm condition, without the visible solid content of naked eyes to system;

2) disperse medium is added step 1) product, high speed shear under 8000-12000rpm condition, obtains colostrum, and colostrum is through high pressure homogenizer process, and pressure 800-2000bar used, cycle-index 5-10 time, obtains transparent or semitransparent Emulsion.

10. the application in antioxidative cosmetics prepared by the Emulsion described in any one of claim 1-8.