KR101763947B1 - Method of microcapsulating phosphatidylserine - Google Patents

Abstract

(A) dissolving phosphatidylserine in an edible oil to prepare a phosphatidylserine liquid composition; (b) preparing a starch aqueous solution by mixing processed starch modified to have lipophilic and hydrophilic properties with water before, after or simultaneously with step (a); (c) mixing and homogenizing the aqueous starch solution with a phosphatidylserine liquid composition to emulsify; And (d) drying the resulting emulsion. The present invention also provides a microencapsulation method of phosphatidylserine.

Description

METHOD OF MICROCAPSULATING PHOSPHATIDYLSERINE < RTI ID = 0.0 >

The present invention relates to a method for producing phosphatidylserine (PS), which is well known as a material for improving brain function, using a microcapsule-type preparation. More specifically, the present invention relates to a method for producing phosphatidylserine Lt; RTI ID = 0.0 > microencapsulation < / RTI >

Microencapsulation technology is a method for protecting a core material from the external environment or releasing it at a desired rate under certain conditions by forming a film using a coating material on a solid, liquid, or gaseous phase core material. It can be widely applied in medicine, foods, cosmetics field, etc. It can protect the unstable central substance from external factors to reduce the loss, isolate the highly reactive central substance, and conceal or solidify the toxic, odorous, And to control the dissolution rate of the contents.

In the field of food, microencapsulation of highly reactive physiologically active ingredients and food materials has advantages such as prevention of oxidation and preservation, blocking of unwanted flavor, control of release, improvement of bioavailability, improvement of handling and workability by changing physical properties. Capsule covering materials used in foods must be edible, have good solubility, high emulsifiability, and should be easy to manipulate during microencapsulation. In addition, there is little reactivity with the central substance during processing and storage, and the central substance must be protected from the external environment. As a coating material, carbohydrates, gelatin, cellulose, oil, protein, gum and the like are used, and in order to overcome the disadvantages of materials with high reactivity, microencapsulation methods of coating with various coating materials have been studied.

Phosphatidylserine (PS) is a kind of phospholipid present in the natural world. It is composed of serine (hydrophilic part), phosphoric acid, glycerol and two fatty acid groups (hydrophobic part).

The human brain accounts for almost half of the lecithin in dry weight, and most of the lecithin is contained in the membranes of nerve cells. In this way, lysitin, an important component of the cell membrane, contains phosphatidylserine, which is particularly abundant in the brain and constitutes a nerve cell membrane, which is capable of releasing energy for lifesaving activities, releasing neurotransmitters, And is known to be deeply involved in the expression of neuronal functions such as signal transduction. For these reasons, phosphatidylserine is also called "brain nutrient."

Phosphatidylserine was first isolated by Jordi Folch in 1942, and has since become a dozen clinical trials, and as a result it is known to be effective in improving Alzheimer's dementia and improving brain function by aging have. In addition to improving brain function, it has been reported that it also exhibits the improvement effects of epilepsy, stress tolerance, and restoration of hormone secretion rhythm.

Although phosphatidylserine has been reported to be effective by ingesting 100 to 300 mg / day (day), there is a limit to the supply through food, and supply through various manufacturing processes is actively under investigation (Korean Patent Publication No. 2002-0085756 See also

Phosphatidylserine differs depending on the processing of the final product, but powder and granular forms are common. These powdery and granular forms are poorly soluble in fat and water, making them difficult to use in products. For maintenance As a method for increasing the solubility, Korean Patent Laid-Open Publication No. 2003-0058839 discloses a liquid composition in which a heavy chain fat is further added to a composition containing phosphatidylserine and fat. Such a liquid composition is disclosed that when the phosphatidylserine is dissolved in an unsaturated fatty acid-containing oil, the viscosity can be prevented from becoming high or hardened, and further, it can be used in health food and medicine in the form of a soft capsule. However, for the application of beverages, milk and the like, phosphatidylserine has poor water dispersibility and even if it is dispersed in an aqueous solution, the ester bond of phosphatidylserine is gradually hydrolyzed naturally and the oxidation stability is relatively low.

It is an object of the present invention to provide a method of microencapsulating phosphatidylserine using starch as a coating material and to improve the dispersibility, solubility and stability of phosphatidylserine in an aqueous solution and to prevent oxidation by light or oxygen in air And it is possible to improve the long-term preservation and transportation characteristics while maintaining the inherent function of phosphatidylserine.

Another object of the present invention is to provide a microcapsule preparation which can be prepared by the above method.

In order to accomplish the above object, the present invention provides a process for preparing a phosphatidylserine liquid composition, comprising the steps of: (a) dissolving phosphatidylserine in edible oil to prepare a phosphatidylserine liquid composition; (b) preparing a starch aqueous solution by mixing processed starch modified to have lipophilic and hydrophilic properties with water before, after or simultaneously with step (a); (c) mixing and homogenizing the starch aqueous solution and the phosphatidylserine liquid composition to emulsify; And (d) drying the resulting emulsion. The present invention also provides a microencapsulation method of phosphatidylserine.

To achieve the above objects, the present invention provides a microcapsule preparation comprising phosphatidylserine suitable for food or pharmaceutical use, which can be prepared by the above-described method.

The microencapsulation method of phosphatidylserine according to the present invention can prevent phosphatidylserine from being oxidized by oxygen in light or air, improve dispersibility, solubility and stability to water, and improve storage and transportation characteristics. In addition, phosphatidylserine can be effectively formulated into capsule formulations such as health functional foods (especially beverages) and medicines while retaining the inherent functions of phosphatidylserine, such as prevention of cognitive decline and stress relief.

The present invention relates to a method for microencapsulating phosphatidylserine having a function of improving brain function such as memory, improvement of dementia, improvement of epilepsy, resistance to stress, and recovery of hormone secretion by using starch which is a biodegradable polymer material as a coating material , In particular microencapsulated in powder form.

Hereinafter, the microencapsulation process of the phosphatidylserine of the present invention will be described in detail.

(1) a step of dissolving phosphatidylserine in edible oil to prepare a phosphatidylserine liquid composition

The phosphatidylserine liquid composition according to the present invention is prepared by dissolving phosphatidylserine in the form of powder or granules in an edible oil. The powdered phosphatidylserine is difficult to incorporate into lipophilic modified starches because the powder particles are not well soluble in water and also because of the nature of the phospholipids, they have a hydrophilic part and a hydrophobic part together. Therefore, it is important to make phosphatidylserine dissolve using edible oil to make the holding type closer to lipophilic.

The phosphatidylserine may be natural phosphatidylserine derived from animal tissue; Natural phosphatidylserine from plant tissue; Phosphatidylserine obtained by reacting lecithin selected from the group consisting of soybean lecithin, vegetable lecithin, fish-derived lecithin, molluscic animal-derived lecithin and egg yolk lecithin with serine in the presence of phospholipase D, wherein the phosphatidylserine is a saturated fatty acid having 6 to 30 carbon atoms, Unsaturated fatty acid or polyhydric-unsaturated fatty acid, or a sodium salt, potassium salt, magnesium salt, ammonium salt, phosphate salt, hydrochloride salt or sulfate thereof.

The edible oil may be at least one selected from heavy-chain fat, soybean oil, sunflower oil, grape seed oil, vegetable oil, olive oil, corn oil, pumpkin seed oil, safflower seed oil, palm oil,

As used herein, the term "heavy chain fat" refers to a fat consisting of fatty acids having 6 to 10 carbon atoms. The heavy chain fat can be absorbed without pancreatic lipase and bile, and its absorption rate is 4 times faster than the long chain fat, and it does not accumulate fat. In addition, it is more suitable for solubilizing phosphatidylserine because of its higher polarity than long chain fatty acids.

The phosphatidylserine liquid composition may further contain at least one functional ingredient such as fish oil containing DHA or EPA, Saw palmetto fruit extract, vitamin, flavor and the like.

The powder or granular phosphatidylserine and edible oil used in the present invention may be dissolved in an organic solvent and then concentrated under reduced pressure to remove all the organic solvent. As the organic solvent, common organic solvents such as ethanol, propanol, hexane, and cyclohexane can be used singly or in combination of two or more kinds.

The phosphatidylserine may be included in the composition in an amount of 10 to 50% by weight based on the total weight of the composition, but is not limited thereto.

(2) preparing a starch aqueous solution by mixing processed starch modified to have lipophilic and hydrophilic properties with water

Starch is used as the outer wall material of the phosphatidylserine powder capsule of the present invention. When the starch is used, the film constituting the surface is roughened, but has a rigid and flexible elasticity and impact resistance, and a formulation excellent in the property of protecting internal substances from oxidation is obtained.

The processed starches used as coating materials can be prepared by heating unmodified starches to form enzymes such as hydrolytic enzymes, isotonizing enzymes, oxidizing enzymes, branching enzymes, acids (eg succinic acid, succinic acid, acetic acid , Hydrochloric acid, etc.), unlike ordinary starch, has processed starch (modified starch), which has both hydrophilic and lipophilic properties, and has stable emulsion formation and excellent film forming ability. It is the starch used for the purpose.

The starch may be used by being gelled at 50 to 90 DEG C, preferably at 80 DEG C, in water of about 5 to 30 times (w / w), preferably 5 to 15 times (w / w)

The preparation of the aqueous starch solution may be carried out before, after or simultaneously with the step of preparing the phosphatidylserine liquid composition described above.

Optionally, the aqueous starch solution may contain at least one selected from the group consisting of maltodextrin, arabic gum, guar gum, xanthan gum, casein sodium, gelatin, lecithin, sodium alginate, and the like to inhibit the dissolution of phosphatidylserine incorporated into the starch, One or more excipients may be further included.

(3) a step of mixing and homogenizing the starch aqueous solution and the phosphatidylserine liquid composition to emulsify

In this step, the above-prepared starch aqueous solution and phosphatidylserine liquid composition are mixed and homogenized at 1,000 to 10,000 rpm for 5 to 10 minutes to obtain a primary emulsion. Then, a high-pressure homogenizer, an ultrasonic emulsifier or the like is added And further homogenizing the primary emulsion at a pressure of 200 to 300 bar for 10 to 30 minutes to obtain a secondary emulsion.

Here, the phosphatidylserine may be mixed in an amount of 20 to 50 parts by weight based on 100 parts by weight of the starch.

The phosphatidylserine may be from 1 to 30% by weight, preferably from 3 to 20% by weight, based on the total weight of the mixture. If the content of phosphatidylserine is less than 1% by weight, it is difficult to maintain the concentration at which the physiologically active function is exerted in the final product. If the content exceeds 30% by weight, emulsion stability may be deteriorated.

The secondary emulsification may be performed one or more times to further stabilize the composition.

Heat may be generated in the primary and secondary emulsification processes, and the homogenization temperature may generally be 30 to 60 ° C, preferably 50 ° C. If the homogenization temperature exceeds 60 DEG C, acid phosphatidylserine rust can be promoted. If the homogenization temperature is less than 30 DEG C, the coating material may harden and the stability of the capsule may be deteriorated. When the temperature is approximately 50 ° C, the degree of gelation of the internal material and the coating material can be maintained uniformly, and particularly, it is effective in suppressing the rancidity of phosphatidylserine.

At least one of the primary emulsion and the secondary emulsion may contain at least one of maltodextrin, arabic gum, guar gum, xanthan gum, casein sodium, gelatin, lecithin and the like to inhibit the elution of phosphatidylserine incorporated into the starch, , Sodium alginate, and the like.

After primary encapsulation of phosphatidylserine with starch, secondary encapsulation can be performed with another covering material to improve the acid resistance, shelf life, transportability, and ability to protect the internal material from oxidation. The coating material used for the secondary encapsulation includes, but is not limited to, whey protein, cyclodextrin, maltodextrin, casein sodium, gelatin, starch, and the like.

(4) Drying step of emulsion

The emulsion obtained in the above is somewhat lacking in stability in the slurry and there is a possibility that the internal material may escape to the outside. When the emulsion is dried, the phosphatidylserine can be microencapsulated and pulverized simultaneously with drying.

Continuous spray drying or fluidized bed drying may be used to pulverize the final product form.

For example, spray drying can be carried out by spraying an emulsion using a nozzle having a size of 1 to 5 mm at a temperature of 150 to 200 ° C in a hot air temperature, a temperature of 100 to 150 ° C in a nozzle part, and a temperature of 40 to 100 ° C in a cyclone part Spraying.

The average particle size of the microcapsules obtained after drying may range from approximately 400 to 700 nm.

The microcapsules prepared by the above method can improve the dispersibility, solubility and stability of phosphatidylserine in an aqueous solution, prevent oxidation by light or oxygen in the air, And the phosphatidylserine can be contained at a high concentration, thereby enhancing the ability to use phosphatidylserine as a main ingredient in pharmaceuticals and foods (health functional foods).

Accordingly, the present invention also provides a microcapsule preparation comprising phosphatidylserine suitable for food or pharmaceutical use, which can be prepared by the above-described method. The content of phosphatidylserine may vary from 1 to 25% by weight, based on the total weight of the microcapsules, depending on the effectiveness of the final application.

Hereinafter, the present invention will be described in detail with reference to examples. However, the following examples are for illustrative purposes only and are not intended to limit the scope of the present invention.

Manufacturing example : Phosphatidylserine  Preparation of liquid composition

≪ Preparation Example 1 &

500 ml of a hexane: ethanol = 95: 5 solution was added to 100 g of phosphatidylserine powder (DS-PS60SW, Doosan Corporation), and the mixture was stirred at 35 캜 until the mixture became transparent. Subsequently, 66.7 g of medium chain triglycerides (MCTs, Welgah Co.) was added thereto, and the mixture was stirred until the mixture became completely transparent and dried under reduced pressure to prepare a liquid composition containing 30% by weight of phosphatidylserine.

≪ Preparation Example 2 &

To 100 g of phosphatidylserine powder (PS40SW, Doosan Corporation), 500 ml of a hexane: ethanol = 100: 3 solution was added, and the mixture was stirred at 35 캜 until it became transparent. Then, 60 g of soybean oil (Welga Co., Ltd.) was added and stirred until the mixture became completely transparent and dried under reduced pressure to prepare a liquid composition containing 25% by weight of phosphatidylserine.

≪ Preparation Example 3 &

500 ml of a hexane: ethanol = 100: 3 solution was added to 100 g of phosphatidylserine powder (PS60SW, Doosan Corporation), and the mixture was mixed at 35 캜 until the mixture became transparent. After adding a mixture of 90 g of heavy chain fat (MCTs, Welga) and 10 g of tuna-derived fish oil (containing 27% by weight of DHA) (Croda Co.) in a ratio of 10: 1 (w / w) And dried under reduced pressure to prepare a liquid composition containing 25 wt% of phosphatidylserine.

Example : Phosphatidylserine  Microencapsulation

≪ Example 1 >

40 g of processed starch substituted with succinic acid was mixed with 540 g of sterilized water, and the mixture was gelled at 80 캜 and then cooled to 50 캜. 20 g of the phosphatidylserine liquid composition prepared in Preparation Example 1 was mixed (starch: phosphatidylserine = 2: 1 (w / w)) and homogenized at 9000 rpm for 9 minutes using a homogenizer to obtain primary An emulsion was prepared.

To enhance the stability of the composition, the primary emulsion was further homogenized by passing twice through a 250 bar high pressure homogenizer. Thereafter, And spray-dried and pulverized for 2 hours to prepare microcapsules (containing 10% by weight of phosphatidylserine) having an average particle size of 527 nm. Here, the average particle size of the microcapsules was measured by diluting the capsule aqueous solution with sterilized tertiary distilled water using Zeta PALS.

≪ Example 2 >

60 g of processed starch substituted with succinic acid was mixed with 520 g of sterilized water, and the mixture was gelled at 80 캜 and then cooled to 50 캜. 20 g of the phosphatidylserine liquid composition prepared in Preparation Example 2 was mixed (starch: phosphatidylserine = 3: 1 (w / w)) and homogenized at 9,000 rpm for 9 minutes using a homogenizer to prepare a primary emulsion Respectively.

To enhance the stability of the composition, the primary emulsion was further homogenized by passing twice through a 250 bar high pressure homogenizer. Thereafter, the mixture was spray-dried at 180 DEG C for 2 hours and powdered to prepare microcapsules (containing 6 wt% of phosphatidylserine) having an average particle size of 542 nm.

≪ Example 3 >

60 g of processed starch substituted with succinic acid was mixed with 520 g of an aqueous solution containing 3 wt% arabic gum, and the mixture was gelled at 80 캜 and then cooled to 50 캜. 20 g of the phosphatidylserine liquid composition prepared in Preparation Example 2 was mixed (starch: phosphatidylserine = 3: 1 (w / w)) and homogenized at 9000 rpm for 9 minutes using a homogenizer to prepare a first emulsion .

To enhance the stability of the composition, the primary emulsion was further homogenized by passing twice through a 250 bar high pressure homogenizer. Thereafter, the mixture was spray-dried at 180 ° C for 2 hours to be pulverized to prepare microcapsules (containing 6% by weight of phosphatidylserine) having an average particle size of 487 nm.

<Example 4>

60 g of the processed starch substituted with succinic acid was mixed with 520 g of an aqueous solution containing 1 wt% xanthan gum, and the mixture was gelled at 80 DEG C and then cooled to 50 DEG C. [ 20 g of the phosphatidylserine liquid composition prepared in Preparation Example 2 was mixed (starch: phosphatidylserine = 3: 1 (w / w)) and homogenized at 9000 rpm for 9 minutes using a homogenizer to prepare a first emulsion.

To enhance the stability of the composition, the primary emulsion was further homogenized by passing twice through a 250 bar high pressure homogenizer. Thereafter, the mixture was spray-dried at 180 DEG C for 2 hours to be powdered to prepare microcapsules (containing 6 wt% of phosphatidylserine) having an average particle size of 475 nm.

&Lt; Example 5 >

40 g of processed starch substituted with succinic acid was mixed with 520 g of sterilized water, and the mixture was gelled at 80 캜 and then cooled to 50 캜. 20 g of the phosphatidylserine liquid composition prepared in Preparation Example 1 was mixed (starch: phosphatidylserine = 2: 1 (w / w)) and homogenized at 9000 rpm for 9 minutes using a homogenizer to prepare a primary emulsion.

After 15 g of maltodextrin was added to the primary emulsion and stirred, the primary emulsion was further homogenized by passing it through a 250 bar high pressure homogenizer twice to increase the stability of the composition. Thereafter, the mixture was spray-dried at 180 DEG C for 2 hours and powdered to prepare microcapsules (containing 6 wt% of phosphatidylserine) having an average particle size of 463 nm.

< Test Example  1> Water dispersibility and storage stability test

A phosphatidylserine-containing microcapsule prepared in Example 1-5, a phosphatidylserine powder (DS-PS60SW, Doosan Corporation) as Comparative Example 1, and a liquid composition containing 30 wt% of phosphatidylserine prepared in Preparation Example 1 as Comparative Example 2 of, Phosphatidylserine was dissolved in distilled water to a concentration of 300 mg / 100 ml, and then stored for 3 months at 4 ° C in a refrigerated condition. The dispersibility and emulsification stability were visually observed. The results are shown in Table 1 below.

◎: Stable without sedimentation ○: Very fine sedimentation

△: little precipitation phenomenon X: severe precipitation phenomenon

Example 1 Example 2 Example 3 Example 4 Example 5 Comparative Example 1 Comparative Example 2 0 days ◎ ◎ ◎ ◎ ◎ ○ X 30 days ◎ ◎ ◎ ◎ ◎ X X 60 days ◎ ◎ ◎ ◎ ◎ X X 90 days ◎ ◎ ◎ ◎ ◎ X X

As shown in Table 1, the phosphatidylserine-containing microcapsules prepared according to the method of the present invention were stable at 4 ° C for 3 months or longer without precipitation and layer separation, and thus water dispersibility and stability were very good . It can also be seen that a microcapsule formulation of a very stable form can be obtained in the case of formulations using excipients or additional coating materials other than starch.

On the other hand, in the case of phosphatidylserine of Comparative Example 2 in which phosphatidylserine was not solubilized in edible oils and was not coated with the processed starch, the phosphatidylserine of Comparative Example 1, which did not coat with processed starch immediately after one day, Precipitation and layer separation occurred.

Claims (10)

(a) dissolving phosphatidylserine in an edible oil to prepare a phosphatidylserine liquid composition;
(b) preparing a starch aqueous solution by mixing processed starch modified to have lipophilic and hydrophilic properties with water before, after or simultaneously with step (a);
(c) mixing and homogenizing the starch aqueous solution and the phosphatidylserine liquid composition to emulsify; And
(d) drying the obtained emulsion
Lt; RTI ID = 0.0 &gt; of &lt; / RTI &gt; phosphatidylserine. The method according to claim 1,
The phosphatidylserine may be natural phosphatidylserine derived from animal tissue; Natural phosphatidylserine from plant tissue; Or a phosphatidylserine obtained by reacting lecithin selected from the group consisting of soybean lecithin, vegetable lecithin, fish-derived lecithin, molluscic animal-derived lecithin and egg yolk lecithin in the presence of phospholipase D with serine, wherein the phosphatidylserine is a saturated fatty acid having 6 to 30 carbon atoms, Wherein the phosphatidylserine is a phosphatidylserine comprising an unsaturated fatty acid or polyhydric-unsaturated fatty acid, or a sodium salt, potassium salt, magnesium salt, ammonium salt, phosphate salt, hydrochloride salt or sulfate thereof. The method according to claim 1,
In the step (a), the edible oil may be at least one selected from the group consisting of fatty acids having 6 to 10 carbon atoms, soybean oil, sunflower oil, grape seed oil, vegetable oil, olive oil, corn oil, pumpkin seed oil, safflower seed oil, and palm oil &Lt; / RTI &gt; wherein the phosphatidylserine is microencapsulated. The method of claim 1, wherein
In the step (a), the phosphatidylserine liquid composition further comprises at least one selected from the group consisting of fish oil containing DHA or EPA, Saw palmetto fruit extract, vitamins and flavorings. Lt; / RTI &gt; The method of claim 1, wherein
In the step (b), the processed starch is treated with at least one selected from the group consisting of heat, enzyme and acid &Lt; / RTI &gt; wherein said protein is a starch. The method of claim 1, wherein
Characterized in that in step (b), the processed starch is gelatinized at a temperature of 50 to 90 占 폚 in 5 to 30 times (w / w) of water. The method of claim 1, wherein
Wherein at least one of the aqueous starch solution of step (b) and the emulsion of step (c) is at least one selected from maltodextrin, arabic gum, guar gum, xanthan gum, sodium caseinate, gelatin, lecithin and sodium alginate Lt; RTI ID = 0.0 &gt; 1, &lt; / RTI &gt; further comprising one or more excipients selected from the group consisting of phosphatidylserine. The method of claim 1, wherein
The step (c)
(c1) homogenizing the mixture of the starch aqueous solution and the phosphatidylserine liquid composition at 30 to 60 DEG C at 1,000 to 10,000 rpm to obtain a first emulsion; And
(c2) homogenizing the primary emulsion at 30 to 60 DEG C under a pressure of 200 to 300 bar to obtain a secondary emulsion
Lt; RTI ID = 0.0 &gt; of &lt; / RTI &gt; phosphatidylserine. The method of claim 1, wherein
Wherein in step (d), the drying is spray drying or fluidized bed drying. 9. A microcapsule preparation comprising phosphatidylserine suitable for food or pharmaceutical use, which can be prepared by the method of any one of claims 1 to 9.