KR100695244B1 - A method for preparing fluor fine capsule containing physiological activation material and fluor fine capsule containing physiological activation material prepared by the method - Google Patents

Abstract

A method for preparing a flour micro-capsule containing physiologically active materials is provided to efficiently produce the flour micro-capsule, which is adequate for human body without causing any harm, shows excellent physiological active materials encapsulating efficiency and has a uniform and fine particle size, within short period of time. The method for preparing a flour micro-capsule containing physiologically active materials comprises the steps of: (a) dissolving 1-10 wt.% of sodium bicarbonate in water; (b) dissolving 45-55 wt.% of flour in the aqueous solution obtained from the step(a); (c) dissolving 10-20 wt.% of propylene glycol in the aqueous solution obtained from the step(b); (d) dissolving physiologically active materials in the aqueous solution obtained from the step(c) or adding 0.1-100 wt.% of oil where physiologically active materials are suspended as a core material thereto; and (e) agitating the solution obtained from the step(d) to educe micro-capsule, where the steps(a) and (b) are performed at the same time or in sequence, and the steps(b) and (c) are performed at the same time or in sequence.

Description

Method for preparing flour-containing microcapsules containing bioactive substance and microcapsules containing bioactive substance produced from the same

1 is a 100-fold photograph of the flour microcapsules prepared by adding sodium bicarbonate according to the present invention (a) is 0% sodium bicarbonate, (b) is 1%, (c) is 5%, (d) Is a photograph at 10% addition.

Figure 2 is a 1000 times the photograph of the flour microcapsules prepared by adding sodium bicarbonate according to the present invention (a) is sodium bicarbonate 0%, (b) is 1%, (c) is 5%, (d) Is a photograph at 10% addition.

The present invention relates to a method for preparing wheat flour microcapsules containing a physiologically active substance in which the bioactive substance contained in administration can be released slowly over a long period of time in the body.

The delivery system of bioactive substance using microcapsules aims to maintain the concentration in the effective range and to release continuously for a certain time. Such a system is economical, sustainable and environmentally friendly. However, the delivery system using microcapsules requires the manufacture of capsules of appropriate size in consideration of the secretion ability according to the substance and target organ to be delivered. However, the encapsulation process is complicated, expensive, and requires a delivery device suitable for a physiological environment.

In order to prepare microcapsules, methods such as stirring, homogenization, spray drying, coating, and extrusion are used according to the manufacturing method, and the coating material and the emulsifier should be appropriately selected according to the chemical properties of various functional bioactive materials.

The coating material is edible, has high water solubility, affinity with dairy components, and should be inexpensive. The polysaccharides used mainly include gums such as arabian gum and guar gum, modified or hydrated starches such as maltodextrin and dextrin, cyclodextrin and The same new material polymer is used.

On the other hand, the bioactive substance mainly used for microencapsulation mainly consists of vitamins, unsaturated fatty acids, and fragrances used for the prevention and even treatment of health and disease. Alpha tocopherol is an antioxidant that can be used to treat and prevent infertility and to prevent aging. However, when oxidized due to instability of heat and oxygen, it becomes irreversibly a-tocopherol quinone and decreases antioxidant power. Therefore, microencapsulation can inhibit or delay oxidation and allow it to be secreted in the desired time and space. In addition, n-3 unsaturated fatty acid is effective in the prevention and treatment of hypertension, heart and vascular diseases, easily rancid by oxygen, heat, light, etc. Therefore, it is difficult to edible because of unpleasant taste and smell. Therefore, it is possible to increase the shelf life and consumption preference by encapsulating it. In addition, aromatic substances composed of organic compounds such as alcohols, aldehyde ketones, esters, ethers, etc. are very important factors for the quality and differentiation of food. In addition, it is possible to encapsulate bioactive substances extracted from farmers' products including herbal medicines. Bioactive substances extracted from by-products such as ginseng and red ginseng waste can be extracted and encapsulated.

As an example of a method for encapsulating a bioactive substance, Japanese Unexamined Patent Application Publication No. 1-57,087 discloses the formation of a W / O / W type emulsion to contain water-soluble drugs and drug-retaining substances when preparing microcapsules by an underwater drying method. Disclosed is a method for preparing a microcapsule which prepares a W / O type emulsion in which the inner layer is concentrated or solidified at a viscosity of about 5,000 cp or more, thereby efficiently injecting drugs into the microcapsules.

In addition, Japanese Patent Application Laid-Open No. 62-201,816 discloses the formation of a W / O / W type emulsion to adjust the viscosity of the W / O type emulsion to 150 to 10,000 cp when preparing microcapsules by an underwater drying method. Disclosed is a method for preparing a microcapsule for good injection of a drug into a microcapsule.

In addition, Japanese Laid-Open Patent Publication No. 2-124,814 discloses that a microcapsule having a low initial burst with good efficiency can be obtained by adding a basic drug retaining substance to an aqueous layer containing a water-soluble drug.

Furthermore, Japanese Unexamined Patent Application Publication No. 63-36,290 discloses a process for dissolving or dispersing an active agent such as a biologically active agent in a solvent in an external substance, and dispersing the resulting suspension or solution in a continuous phase generating medium such as high boiling water from the solvent. A process of producing O-type emulsion or O / W-type emulsion and a process of producing a microcapsule by increasing a part of the solvent from the dispersion obtained in the preliminary step, separating the microcapsules, and remaining from the obtained microcapsules Disclosed is a method for producing a microcapsule, which comprises a step of extracting a solvent, wherein the active agent content is high and a high quality microcapsules can be obtained.

However, the microcapsules obtained from the above methods have a problem that not only the particle size of the microcapsules is large, but also the particle size distribution is not uniform.

Therefore, the inventors of the present invention, in order to increase the efficiency of microencapsulation, the size of the capsule should be as small as possible and uniform, so that no layer separation may occur, thereby increasing the marketability, and in addition, it should be appropriate for use in consideration of the stability and hygiene of the capsule. As a result of the study, the present invention has been completed.

That is, an object of the present invention is to produce a biocapsule-containing flour microcapsules that are harmless and suitable for a living body, but have an excellent encapsulation efficiency of the bioactive material and are fine and uniform and do not cause layer separation in a short time.

Another object of the present invention is to provide good flour microcapsules regardless of the aqueous solution concentration, viscosity, etc. of the bioactive material to be included.

In order to achieve the above object, according to an aspect of the present invention,

Dissolving sodium bicarbonate in water; Simultaneously or sequentially

Dissolving flour; Simultaneously or sequentially

Dissolving propylene glycol;

Dissolving or suspending the bioactive substance together in the obtained aqueous solution as a main substance; And

There is provided a method of preparing a flour microcapsule containing a bioactive material comprising a; stirring the obtained bioactive material-containing solution to precipitate the microcapsules.

According to another aspect of the present invention,

It has a film material formed of the inclusion material containing the bioactive material and the polymer material having both biodegradability and suitability prepared by the above method, the particle size is in the range of 0.01-100㎛ Flour microcapsules containing are provided.

EMBODIMENT OF THE INVENTION Hereinafter, this invention is demonstrated in detail.

In the present invention, the biologically active substance that is the inclusion of the microcapsules is not particularly limited by pharmacological action or the like, and is a drug, herbal medicine, fertilizer that exhibits pharmacological action such as proteins, polypeptides and derivatives thereof, and antibiotics. , Feed, livestock additives, and many more. These bioactive substances differ depending on their type, properties, and the like, but are usually contained within the range of 0.01-100% by weight in microcapsules.

The core material used in the present invention is not limited thereto, but one or more of biocompatible oils such as soymilk, palm oil, and perilla oil may be used, and the content of the bioactive substance is usually included in the range of 0.1-100% by weight. do.

In addition, the outer material of the microcapsules used in the present invention may be any material as long as it is decomposed upon in vivo and has tissue compatibility. Particularly, wheat flour is preferably used, and the amount of gravity is used when gravity and strong powder are used. It is added within the range of 45-55% by weight, and in the case of using a force component, the addition within the range of 25-50% by weight is preferable in view of the rate of microcapsule formation.

Meanwhile, in the present invention, sodium bicarbonate may be used to achieve uniformity and stability of the final microcapsules that are suitable for living organisms, and the addition amount may be 1-10% by weight based on water, which is a solvent used in the present invention. It is preferable that it is and it is more preferable to use 1-5 weight%.

Furthermore, in the present invention, propylene glycol may be added, the amount of which is preferably 20% by weight or less based on water, considering the size and uniformity of the manufactured capsule including the manufacturing cost, and stably maintaining the environment of the capsule. It is sufficient to use about 10-20% by weight from the viewpoint of maintaining and inhibiting the growth of microorganisms to increase the shelf life of the capsule solution.

Biocapsule-containing microcapsules of the present invention is prepared by the following method.

First, 1-10% by weight of sodium bicarbonate is dissolved in water. At the same time or sequentially dissolve the flour further. The amount of flour used depends on the amount of the core used. If the amount of the core used is less than 5%, the microcapsules can be produced even with 1% flour. When 50% of the core material is used, 45-55 It is added in the range of weight%, and in the case of using a force component, the content is added in the range of 25-50% by weight.

At the same time or sequentially, propylene glycol is further added and dissolved within the range of 20% by weight or less.

The aqueous solution containing the bioactive substance is prepared by dissolving or suspending the bioactive substance together in the aqueous solution thus obtained as a central substance. The content of the bioactive substance is 0.1-100% by weight is sufficient.

In addition, in the present invention, an HLB value of 10 or more may be used as an emulsifier, but preferably HLB15 or more, and one or more selected from these may be contained in 0.1-1.0%, preferably 0.4-0.5%, in the microcapsules. have. The added emulsifier acts as a bridge between the core material and the wall material, and further divides the core material into small pieces, thereby reducing the size of the capsule and also increasing the durability of the capsule.

The obtained bioactive substance-containing solution is stirred to precipitate microcapsules. At this time, as the stirring conditions, the physiologically active substance-containing polymer solution was slowly added while stirring at a speed of 200 to 20,000 rpm at a temperature of 10 to 80 ° C., preferably 20 to 60 ° C., followed by stirring for 1 to 60 minutes to form capsules. Can be derived. As the stirring device, a homogenizer, an ultrasonic emulsifier, or the like may also be used.

The microcapsules prepared by the present invention have a uniform particle size of 0.01 to 100 μm, preferably 0.1 to 10 μm, and may contain up to 100 wt% of bioactive material. In this case, the particle size may be determined by the rotational speed, viscosity, and composition ratio of the solution.

The microcapsules produced by the method of the present invention are useful as feed additives, or as encapsulations of pesticides, fertilizers, etc., as well as various pharmacological resources, including herbal medicines, to be used as drug delivery agents that slowly release and degrade drugs. Can be used.

That is, this technology enables the production of high-quality meat and functional meat when it is produced as a feed additive in the animal husbandry field, and can be practical for encapsulation of fertilizers or pesticides, and this technology, which mainly uses food materials, is applied to the food industry and is functional. It can be used in the production of supplements. Furthermore, by extracting and encapsulating pharmacological components from herbal medicines and various resources, it is possible to promote convenience and efficiency of use.

Hereinafter, the present invention will be described in more detail based on the following examples. However, the following examples are intended to illustrate the invention and are not intended to limit the invention thereto.

Example 1 Effect of Propylene Glycol on Microcapsule Formation

Dissolve 5 g of NaHCO _{3 in} 100 ml of water, dissolve 50 g of flour (WP), add propylene glycol of the concentration shown in Table 1, and add 0.5% emulsifier (HLB 15; Tween 80). 50 ml of soy milk added) was added and stirred at 10,000 rpm with a homogenizer at room temperature to induce encapsulation.

After stirring, the sample was examined at 400 × magnification, and the capsule ratio was calculated. The results obtained are shown in Table 1 together.

Capsule size (㎛) Propylene Glycol Concentration (%) 0 15 6-10 0.5 0.1 1-5 50.8 46.0 <1 48.7 53.9

As shown in the above table, when 15% of propylene glycol was added, the size of the microcapsules decreased and showed a uniform phenomenon. In particular, the number of microcapsules of 1 μm or less increased. In conclusion, the addition of propylene glycol is suitable for the preparation of microcapsules in consideration of the efficiency of encapsulation and the increase of shelf life due to propylene glycol.

Example 2 Effect of Sodium Bicarbonate on Microcapsule Formation

Sodium bicarbonate (NaHCO ₃ ) of various concentrations shown in Table 2 was dissolved in 100 ml of water, then 50 g of strong flour was dissolved, 12 g of propylene glycol was dissolved, and 50 ml of soymilk added with 0.5% emulsifier (HLB 16.7; Tween 20) was added thereto. The mixture was strongly stirred with an ultrasonic emulsifier to induce capsule formation.

Samples after stirring were examined at 400x and 1000x magnification, respectively, and the obtained results are shown in Table 2 and FIGS. 1 and 2 together.

Capsule Size (㎛) NaHCO ₃ concentration (g / 100ml) 0 One 5 10 > 10 1.0 0 0 0.1 6-10 3.2 0.6 0.2 0 1-5 37.7 29.9 41.3 40.3 <1 58.1 69.5 58.4 59.6

Although as shown in the above table, microcapsules of less than 5㎛ size is increased to more than 99.4% from 95.8% when the addition of NaHCO _3, there was no difference between the level of addition of NaHCO _3. However, nanocapsule ratio of less than 1㎛ 1% NaHCO _{3 .} It was the highest when added, but relatively high incidence of polymer at 1% and 10% NaHCO ₃ addition level and inferior uniformity of capsule size (see FIG. 1). In addition, as shown in Figure 1, the polymer incidence was low at the 5% NaHCO ₃ addition level, as well as shown in Figure 2, the capsule was uniform.

Meanwhile, as shown in FIG. 2A, the microcapsule solution prepared without adding NaHCO ₃ is very large and nonuniform and forms a lump, and thus, layer separation is expected and the efficiency of encapsulation is considered to be extremely low.

Therefore, when the microcapsules were prepared using NaHCO ₃ , it was confirmed that the addition amount was about 1-5%, considering the formation rate and the polymer generation rate of the microcapsules.

Example 3 Effect of the Type and Addition of Flour (Wall Material) on the Formation of Microcapsules

Dissolve 5 g of sodium bicarbonate in 100 ml of water, divide the flour into gravity and strong ingredients, add 50, 25 and 12.5%, respectively, add 15% of propylene glycol, and add 0.5% emulsifier (HLB 16.7; Tween 20). 50 ml of the added soymilk was added thereto, followed by vigorous stirring using a stirrer to induce capsule formation.

After stirring, the sample was examined at 250 × magnification, and the ratio of capsules of 4 μm or less was calculated and the results obtained are shown in the following 3.

WP Type WP addition amount (%) 12.5 25 50 weak flour 60.3 80.3 83.3 Gravity 61.9 73.4 87.7 Strong 53.3 79.4 88.4

As shown in the table above, as the amount of flour was increased, the formation rate of microcapsules increased in all flours, and when the 50% flour was added, it was confirmed that the formation rate of microcapsules was higher in the strength component than in the force component and the gravity component. .

Appropriate amount is appropriate in general, but 50% is recommended for strong and gravity components, and 25-50% is recommended for powerful components.

Example 4 Effect of Type of Core Oil on Microcapsule Formation

Dissolve 5 g of sodium bicarbonate in 100 ml of water, add 50 g of strong flour, dissolve it, add 15% of propylene glycol, and add palm oil, soy milk, and perilla oil with 0.5% of emulsifier (HLB 16.7; Tween 20). As described in, 50ml each alone or mixed, and vigorously stirred with a homogenizer to induce capsule formation.

The sample was stirred at 250 × magnification and the capsule ratio of 4 μm or less is shown together in Table 4 below.

Core <4㎛ capsule (%) soy milk 85.3 palm oil 89.6 Perilla oil 97.7 Soy milk + palm oil (5: 5) 90.3 Soy milk + Perilla oil (9: 1) 91.1 Soy milk + palm oil + perilla oil (4.5: 5: 0.5) 87.6

As shown in the above table, the central oil containing the bioactive substance was included in the microcapsules up to 100% by weight, but microcapsules were formed in the range of 85-97%. Among core oils, the percentage of microcapsules was the highest when perilla oil was used alone, but the lowest was 85.3% when using soymilk. It was confirmed that there is no significant difference in the ratio of the microcapsules produced when the oil used as the remaining core material is used in combination.

Example 5 Stability of Sodium Bicarbonate / Propylene Glycol Microcapsules

Dissolve 5 g of sodium bicarbonate in 100 ml of water, then dissolve 50 g of flour, add 15% propylene glycol, mix, add 100 ml of soymilk mixed with 0.5% emulsifier (HLB 16.7; Tween 20), and stir vigorously with a regular blender. Encapsulation was induced.

After stirring the sample in 24 hours in various cultures, the results obtained by assaying at 400x and 1000x magnification, respectively, are shown in Table 5 together.

Capsule Size (㎛) Medium (24 hours) water Saline solution pH2 PBS pH6 PBS pH8 PBS 6-10 0.5 0 1.5 0 2.7 1-5 39.7 33.6 39.7 37.1 47.1 <1 59.8 66.4 58.8 62.9 50.2

As shown in the table, the central oil containing the bioactive material contained up to 100% by weight in the microcapsules, but the microcapsules having a size of less than 1 μm were formed until around 60%. In other words, when producing the microcapsules with the present technology it can encapsulate the core material up to 200% by weight compared to the wall material in the microcapsules.

On the other hand, the level of nanocapsules before incubation was 59.8%, but after 24 hours of incubation, there was a slight difference in the stability of the capsules depending on the culture solution. That is, the ratio of nanocapsules in pH8 PBS decreased compared to other solutions. When the microcapsules are exposed to water, pH 6, pH 2 (stomach), pH 8 (small intestine) in order, it can be seen that the level of nanocapsules decreases sequentially to 59.8, 62.9, 58.8, and 50.2 levels.

Therefore, the microcapsules are gradually destabilized in consideration of the digestive absorption pathway of the living organs, and especially in the case where the digestive fluid is secreted in the small intestine, the contents may be released from the target organ in vivo.

As described above, the present invention was developed to increase the usability of microcapsules used as a delivery device of a bioactive substance, and in particular, by preparing a micro-level capsule, the stability and durability of the capsule were improved and the separation of the capsule solution was suppressed. In addition, it could be preserved at room temperature by maximizing shelf life.

First of all, considering the instability of the capsule, it has the advantage of being designed to release bioactive substances from the target organs in vivo.

Claims (9)

Dissolving sodium bicarbonate in water; Simultaneously or sequentially Dissolving wheat flour in the aqueous solution; Simultaneously or sequentially Dissolving propylene glycol in the aqueous solution; Dissolving or suspending the bioactive substance together in the obtained aqueous solution as a main substance; And A method of producing a flour microcapsule containing a bioactive substance comprising a; the step of precipitating the microcapsules by stirring the obtained bioactive substance-containing solution. The method of claim 1, wherein the sodium bicarbonate is a method for producing a flour microcapsule containing a bioactive material, characterized in that used in the range of 1-10% by weight. The method of claim 1, wherein the oil containing the bioactive material is a method of producing a flour microcapsule containing a bioactive material, characterized in that used in the range of 0.1-100% by weight. The method of claim 1, wherein the flour is a method for producing flour microcapsules containing bioactive material, characterized in that used in the range of 45-55% by weight of at least one selected from gravity and strong components. The method of claim 4, wherein the flour is a method of producing a microcapsule containing flour bioactive material, characterized in that the use of a force component within the range of 25-50% by weight. The method of claim 1, wherein the propylene glycol is a method of producing a flour microcapsule containing a bioactive material, characterized in that used in the range of 10-20% by weight. The flour microcapsules containing bioactive substances according to claim 1, wherein an emulsifier selected from Tween 80 having an HLB value of 15 or Tween 20 having an HLB value of 16.7 is added within a range of 0.1-1.0 wt%. Manufacturing method. The method of claim 1, wherein the agitation is a flour microcapsules containing bioactive material, characterized in that for 1-60 minutes at a speed of 200-20,000rpm in the temperature range of 10-80 ℃. Claims 1 to 8 prepared by the method of any one of claims 1 to 8, containing inclusions containing bioactive substances and the outer material having biodegradability and histocompatibility, and has flour, the particle diameter is in the range of 0.01-100μm, Flour microcapsules containing bioactive substance containing 85-97% by weight of active substance.

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