KR100245773B1 - Alginic acid bead for sustained release drug delivery system and preparation method thereof - Google Patents

Abstract

Alginic acid beet for sustained-release pharmaceutical delivery system of the present invention is composed of alginic acid, a structural material, and a medicinal active material, by mixing a structural material in an alginate aqueous solution to prepare an aqueous solution slurry, the desired pharmaceutically active substance in the aqueous solution slurry And mixing the slurry solution drop by drop into the polyvalent cation solution to cure, wash the cured beads, and dry the washed beads. The alginic acid beads prepared above are coated with an aqueous alginate solution to improve properties such as sustained release effect of the alginic acid beads, adsorption effect of heavy metals, and the like. The alginic acid beads prepared above were immersed in an aqueous alginate solution to give an alginate coating having a thickness of about 0.5 mm, and the coated alginic acid beads were injected into a polyvalent cation solution to cure the coating film, wash the cured beads, and wash the beads Alginic acid coated alginic acid beads are prepared by drying. Depending on the degree of effect desired, this coating process is repeated to produce multi-layer coated alginic acid beads.

Description

Alginic acid beads for sustained release pharmaceutical delivery system using alginic acid and a method for producing the same.

: slow release) 의약 전달 시스템 (drug delivery system: DDS)용 알긴산 비드(beads)로부터 L-페닐알라닌이 방출되는 효과를 도시한 그래프이다.1 is a sustained release according to the present invention (

: slow release A graph showing the effect of L-phenylalanine release from alginic acid beads (dads) for drug delivery systems (DDS).

2 is a graph showing the adsorption effect of heavy metals (lead) by alginic acid beads for a sustained release pharmaceutical delivery system according to the present invention.

3 is a photograph showing the results of entrapment and dissolution of cholesterol by alginic acid beads for sustained-release drug delivery system according to the present invention.

[Field of Invention]

:slow release) 의약 전달 시스템 (drug delivery system: DDS)용 알긴산 비드(bead)에 관한 것이다. 보다 구체적으로, 본 발명은 의약 활성 물질의 지연 방출 효과를 위해서 알긴산염이 다가 양이온에 의해 경화된 상태의 비드에 구조성 전분이 혼합된 형태로 이루어지는 의약 전달 시스템용 알긴산 비드에 관한 것이다. 본 발명은 또한 구강으로 복용하는 경우 포만감을 제공하고 체내의 불순 노폐물인 콜레스테롤을 포집하고 체내의 중금속을 흡착할 수 있는 알긴산 비드에 관한 것이다.The present invention is a sustained release using alginic acid (

: slow release Alginate beads for a drug delivery system (DDS). More specifically, the present invention relates to alginic acid beads for medicament delivery systems, wherein the structural starch is mixed with beads in which alginate is cured by a polyvalent cation for delayed release of the pharmaceutically active substance. The present invention also relates to alginic acid beads which provide satiety when taken orally, which can trap cholesterol, which is an impurity waste in the body, and adsorb heavy metals in the body.

Background of the Invention and Prior Art

Alginic acid is a polysaccharide that is abundantly contained on the surface of seaweeds such as laver, blue seaweed, woodweed, seaweed and kelp. From the molecular point of view, alginic acid is randomly composed of β-D-mannuronic acid and gluronic acid (α-L-gluronic acid) without branch chain. It is a compound formed by binding. Since there is no alginate digestive enzyme in the body, there is no nutritional value, and it is mainly used for ice cream, fruit juice, pie contents, and candy for improving texture and stability of foods.

Alginic acid is also used as dental bonds, pharmaceuticals, water resistance enhancers in papers and inks, viscosity improvers in cosmetics and dyes, or flocculants in wastewater treatment.

Alginic acid beads are simple to manufacture in one step, and the manufacturing environment is a mild condition in which cells can live, thus immobilizing hybridoma cells to immobilize living cells or to prepare monogroup antibodies in the fermentation reactor. It has been widely used for the collection of animal cells for transplantation into (US Pat. Nos. 5,073,491, 5,070,019, and 4,927,761) and US Pat. No. 5,459,054. The capture of transgenic cells has been shown to have the effect of reducing immunity in transplantation.

In general, alginate beads are prepared by dissolving 0.5-5% (w / v) sodium alginate in distilled water to form an aqueous solution. Live cells, microorganisms, or animal cells are added to the polyhydric cation solution (CaCl ₂ , SrCl ₂ , BaCl ₂ , AlCl _3, etc.) at the concentration of 0.1-2.0 M, which is stirred, Drops drop at a height of 10-30cm and instantly harden to form beads. At this time, the curing time by polyvalent cation is about 5-30 minutes and then washed with distilled water.

U.S. Patent No. 5,472,648 discloses a method for producing alginate beads with a precise degree of spherical size by spouting alginic acid through a controlled vibrating nozzle and curing it with calcium ions. U.S. Patent No. 4,401,456 also discloses a process for preparing alginic acid beads containing herbicide components.

U.S. Patent No. 5,385,741 discloses that when a microorganism such as yeast is collected in an alginate gel and subjected to a fermentation reaction, the content of a calcium hardener is slightly insufficient, so that calcium or potassium can be adsorbed during fermentation. It can be used for the adsorption of metal ions that regulate the activity of enzymes.

U.S. Patent 5,368,862 discloses the preparation of tablets (5-50 wt% containing alginic acid) containing alginic acid and bioalgin (a polysaccharide in the form of alginic acid produced by microorganisms) for sustained release. U.S. Patent No. 4,842,866 discloses sustained release release including active substance, alginic acid, calcium and the like. U.S. Patent Nos. 4,199,560 and 4,163,777 also disclose pharmacologically active substances using alginic acid and sustained release for drug delivery. In addition, U.S. Patent Nos. 4,401,456 and 4,400,391 announced that alginate beads can be used to release sustained release of bioactive substances. In particular, U.S. Patent No. 4,401,456 states that when producing alginic acid beads, bioactive substances are dispersed and air is dispersed, if necessary, so that the surface is suspended to obtain sustained release from the ground or lake. U.S. Patent No. 5,141,927 discloses that the alginate extracted from seaweed and the ion exchange capacity of alginate can be used to treat hypertension by making capsules containing vitamin D and alginic acid. The above patents on sustained release use a mixture of alginic acid, a bioactive substance, and water in making alginate gels or beads, but do not use structural starches that can give rigid stiffness as in the present invention. It also does not suggest any means for controlling the release rate, including delayed release of the drug or bioactive substance.

Examples of the use of alginic acid in health beverages include "Methods for Producing Alginate-Additional Beverages for Prevention of Obesity" and "Preparation of Alginate-protection Supplements for Prevention of Obesity" Method "and" Animal feed and its manufacturing method "of the Republic of Korea Patent Publication No. 94-023659, there is a manufacturing method of animal feed in the form of jelly containing the feed material and calcium alginate. In addition, Choi Su-bu et al. Published a novel alginic acid derivative having an antithrombotic effect and a method for producing the same in Korean Patent Publication No. 94-021458. Korean Patent Publication No. 96-000053 discloses a low calorie noodle for diet foods containing calcium alginate with a carbohydrate content of 20% or less in a jelly state. The patent focuses on lowering the carbohydrate content to lower energy relative to wet growth, and there is no mention of alginic acid + starch bead preparation or mention of satiety due to the swelling of alginic acid beads. In addition, Korean Patent Publication Nos. 96-016745, 96-016529, and 95-026403 add ramen, yogurt, and dietary fiber mixtures such as sodium alginate / plydextrose to a beverage, respectively. And the preparation of beverages, and claimed to be effective in preventing obesity and adult diseases by reducing cholesterol content and inhibiting the production of lipid peroxide in terms of effectiveness. Korean Patent Publication No. 96-015301 discloses a method for preparing alginic acid jelly confectionery by mixing alginic acid and gelatin into confectionery.

Long-release sustained release drugs are an important factor in many drug delivery. Sustained delivery of various medicines has the advantage of maintaining a constant concentration of active ingredients in the blood by prolonged release in a constant and sustained form. By obtaining stable concentrations in the blood, various physiological environments can be advantageously maintained. In addition, when such an active substance is delivered by injection as in the past, it always visits a hospital or makes the mind of the user uncomfortable. In the case of oral delivery, there is a simple advantage, but like injections, it cannot reduce or eliminate the toxicity or side effects caused by peaks and lowering of the concentration of active substances in the blood. Thus, until now, to obtain a convenient and controlled sustained release sustained release, the dried powder is extruded or a water-soluble viscosity enhancer is used to make pharmaceutical tablets. In general, drug release by alginic acid forms a gel film on the surface of tablets at low pH, such as gastric acid, which inhibits the diffusion of active substances. As pH increases, alginic acid rapidly dissolves and accelerates diffusion. Therefore, it is thought that the slow release of the active substance can be achieved by reducing the dissolution rate by coating the alginic acid layer in several layers.

Alginate beet not only completely decayed and contracted when dried, but also hardly increased again at room temperature even when soaked again in a mole. Therefore, alginic acid beets containing a physiologically active pharmaceutical substance as described above may be taken undried, but this is very inconvenient in sales or transportation, and when taken in a dried state, it is difficult to expect a sustained release effect. .

The inventors of the present invention can exhibit a sustained release effect of the medicinal and physiologically active substances, provide a feeling of satiety through the ingestion of dietary fiber of alginic acid to show the effect of diet foods and to remove by removing the impurities in the body of cholesterol or heavy metals Alginic acid beads and alginic acid coated alginic acid bead coated with alginic acid can be further developed.

[Purpose of invention]

It is an object of the present invention to provide alginic acid beads for pharmaceutical delivery systems which can exhibit sustained release effects of pharmaceuticals and bioactive substances.

Another object of the present invention is to provide an alginic acid bead that can exhibit the effect of diet food by providing a feeling of satiety through the ingestion of alginic acid dietary fiber.

It is still another object of the present invention to provide an alginate bead that can adsorb and remove cholestol or heavy metals that are impurities in the body.

Another object of the present invention is to improve alginic acid coated alginic acid beads coated with alginic acid alginic acid beads to improve the properties of alginic acid beads.

Another object of the present invention is to provide a method for preparing the alginic acid beads and alginic acid coated alginic acid beads.

The above and other objects can be achieved by the present invention described below.

[Summary of invention]

Alginic acid beads for the sustained release pharmaceutical delivery system of the present invention are characterized by consisting of alginic acid, a structural substance, and a pharmaceutically active substance.

Alginate beads for sustained-release pharmaceutical delivery system of the present invention by mixing a structural material in an aqueous alginate solution to prepare an aqueous solution slurry, the desired medicinal active material is mixed in the aqueous solution slurry, and the slurry solution is dropwise polyvalent cation solution It is prepared by the step of injecting into the cured, washing the cured beads, and drying the washed beads.

The alginate may be used in the form of ammonium or potassium salt, but mainly in the form of sodium alginate.

As the structural material, fine flour, soy flour, starch powder, or the like may be preferably used.

Pharmaceutically active substances that may be contained in the alginic acid beads include vitamins, essential nutrients, proteins and other pharmaceutical substances, as well as pesticides such as herbicides, fertilizers or growth hormones of plants and animals.

As the polyvalent cation solution, a solution such as CaCl ₂ , SrCl ₂ , BaCl ₂ , AlCl ₃ may be preferably used.

The alginic acid beads prepared above are coated with an aqueous alginate solution to improve properties such as sustained release effect of the alginic acid beads, adsorption effect of heavy metals, and the like.

The alginic acid beads prepared above were immersed in an aqueous alginate solution to give an alginate coating having a thickness of about 0.5 mm, and the coated alginic acid beads were injected into a polyvalent cation solution to cure the coating film, wash the cured beads, and wash the beads Alginic acid coated alginic acid beads are prepared by drying. Depending on the degree of effect desired, this coating process is repeated to produce multi-layer coated alginic acid beads.

Alginic acid beads of the present invention, including the sustained release effect of the medicinal and physiologically active substances contained, can adsorb and remove cholesterol or heavy metals, and provide a feeling of satiety through the intake of dietary fiber of alginic acid can exhibit the effect of diet food. Therefore it can be applied to each application.

Hereinafter, with reference to the accompanying drawings will be described in detail the contents of the present invention.

Detailed Description of the Invention

Alginic acid beads for the sustained release pharmaceutical delivery system of the present invention contain a pharmaceutically active substance in an alginic acid bead consisting of alginic acid and a structural substance. The alginic acid beads have a form in which structural starch is mixed with beads of alginate cured by a polyvalent cation. The pharmaceutically active substance needs to delay the release effect depending on its use. For example, when a pharmaceutically active substance is released from alginic acid beads, the initial release should be delayed, slowed down, or prolonged, as required. Conventional alginic acid beads cannot exhibit this sustained release effect of the pharmaceutically active substance.

Alginic acid beads for a sustained release pharmaceutical delivery system of the present invention are prepared by mixing a structural material in an aqueous solution of alginate. Structural materials that can be used here include wheat flour, soy flour, and starch flour. It is believed that the structural material plays a structural role of alginic acid beads as well as shrinks the processing of alginic acid beads in an aqueous solution to slow down the diffusion rate of the pharmaceutically active substance.

Pharmaceutically active substances that can be used in the present invention include vitamins, essential nutrients, proteins, pharmaceuticals, pesticides, fertilizers, growth hormones of plants and animals. Vitamins, essential nutrients, proteins or other medicinal substances for oral use may be used for oral use (taken by mouth) contained in alginic acid beads. The pharmaceutically active substance is used in the form of a water-soluble or water-insoluble solid, liquid or slurry.

The structural material is preferably contained in an amount of 5 to 25% by weight based on the total alginic acid beads, and the pharmaceutically active material may be up to 50% by weight based on the concentration of the alginic acid slurry, but 0.1 to 20% by weight is preferable.

Alginate beads for sustained-release pharmaceutical delivery system of the present invention by mixing a structural material in an aqueous alginate solution to prepare an aqueous solution slurry, the desired medicinal active material is mixed in the aqueous solution slurry, and the slurry solution is dropwise polyvalent cation solution It is prepared by the step of injecting into the cured, washing the cured beads, and drying the washed beads.

The alginate may be used in the form of ammonium or potassium salt, but mainly in the form of sodium alginate.

As the multi-group cation solution, a solution such as CaCl ₂ , SrCl ₂ , BaCl ₂ , AlCl ₃ may be preferably used.

The alginic acid beads of the present invention became very hard white beads when dried, and the volume was reduced to about 40% or less and gradually restored to 90% or more of the volume in the aqueous state. This volume expansion can accelerate the release of the medicinal active substance to help delivery and provide a feeling of satiety by ingesting alginic acid dietary fiber can be expected the effect of diet foods.

It is preferable that the alginate aqueous solution used above contains 0.1-5.0 weight% of alginate salts. An aqueous solution slurry is prepared by mixing 5 to 25% by weight of the structural substance in the aqueous alginate solution, and the mixture is mixed so that the concentration of the pharmaceutically active substance is 1 to 200 mg / ml. Bubbles are removed from the slurry using an ultrasonic wave. Using a separatory funnel having an internal diameter of about 3 to 10 mm, the nozzle was dropped dropwise into the aqueous polyvalent cation solution. The concentration of the polycation aqueous solution is preferably 0.1 to 2.0 M. After all the slurry was dropped, the mixture was allowed to stand for 5 to 30 minutes to sufficiently cure the alginic acid beads, and then sufficiently washed with distilled water. The washed beads are dried in an oven at about 60 ° C. for at least 3 hours.

When L-phenylalanine, one of the amino acids, is mixed as a pharmaceutically active substance in the preparation of alginic acid beads, it may further contain about 2.5 times more L-phenylalanine than when L-phenylalanine is absorbed later. This means that in the manufacture of alginic acid beads, mixing the medicinal active material from the outset may contain a greater amount of the medicinal active material.

The alginic acid beads prepared above are coated with an aqueous alginate solution to improve properties such as sustained release effect of the alginic acid beads, adsorption effect of heavy metals, and the like.

The alginic acid beads prepared above were immersed in an aqueous alginate solution to give an alginate coating having a thickness of about 0.5 mm, and the coated alginic acid beads were injected into a polyvalent cation solution to cure the coating film, wash the cured beads, and wash the beads. Alginic acid coated alginic acid beads are prepared by drying. Depending on the degree of effect desired, this coating process is repeated to produce multi-layer coated alginic acid beads.

The coating is performed to immerse the alginate-uncoated alginic acid beads prepared according to the present invention in an aqueous solution in which 0.1-5.0 weights of alginate is dissolved to form a coating film having a thickness of about 0.5 mm. The coated alginic acid beads are dropped dropwise into a stirring 0.1-2.0 M polyvalent aqueous solution, thereby curing the coating film. Alginic acid beads cured of the coating film is washed with distilled water and dried in an oven at about 60 ℃. If necessary, the second coating, the third coating, and the fourth coating may be repeated in the same manner to form a coating film of multiple layers. Beads coated with alginic acid retained the gloss of the surface than uncoated beads, and the thickness of the coated film after drying was kept below 0.1 mm even after repeated coatings.

Multilayered alginic acid beads coated with alginic acid in the present invention exhibit a significant delayed radiation effect of the pharmaceutically active substance. For example, multilayered alginic acid beads containing starch as a structural substance and L-phenylalanine as a medicinal active substance have a delayed release effect of 1 hour or more. When the initial release inhibition caused by the multilayer coating is used in the drug delivery system (DDS) by oral absorption of the active substance, it is necessary to adjust the release delay time to suppress the release from the stomach and release the small intestine or the large intestine. It is possible. In addition, the release rate of phenylalanine tended to be lower as the multilayer coating was applied, and thus the release time could be extended due to the sustained release. Therefore, it can be seen that the release of the pharmacologically active substance by the alginic acid coating, the release rate of the pharmacologically active substance, and the long-term release in the body can be expected.

Alginic acid bead of the present invention, including the sustained release effect of the drug and the bioactive substances contained, can absorb and remove cholesterol or heavy metals, can provide the feeling of diet by providing satiety through the intake of dietary fiber of alginic acid. Therefore it can be applied to each application.

Alginic acid uncoated beads and alginic acid coated beads of the present invention exhibit heavy metal removal effects. In the heavy metal adsorption experiment using multi-alginated alginate beads, the weight of lead that can be adsorbed per unit weight increases as the multi-layer coating of alginic acid beads is conducted. In the first coating, the adsorption amount of lead was greatly increased, but the adsorption amount of lead per unit weight of the beads did not increase significantly due to the additional coating. This is because the adsorption of lead is mainly due to alginic acid rather than starch, and the primary coated alginic acid beads have a higher content of alginic acid due to the addition of alginic acid on the coated surface than the uncoated alginic acid beads, and directly contact the alginic acid without any diffusion resistance. This is because adsorption is rapid. However, alginic acid coating above the secondary coating does not have any synergistic effect on the adsorption of heavy metals because the increase in the content of alginic acid per unit weight is not greater. The digestive fluid in the body undergoes the catabolism of the structural substances, and alginic acid is in the form of released polymers because it lacks digestive enzymes, which then capture cholesterol. Cholesterol trapped in the alginic acid is not released under the conditions of the body, but is discharged out of the body through the large intestine can lower the cholesterol, a harmful compound in the body. Reproducing the above situation when taking alginic acid bead in the present invention, once the alginic acid bead enters the water by intestinal motility and digestive fluid secretion, expands and the separation of structural substance and alginic acid causes the alginic acid polymer to You will be in a gin. At this time, a portion of the cholesterol contained in the food is trapped between the alginic acid polymer and the collected cholesterol is not digested in the digestive system of the body because it is discharged out of the body eventually leads to a decrease in cholesterol intake by food. In this experiment, cholesterol, which is assumed to be trapped between alginic acid polymers, is released from the body rather than released from the body.

Alginic acid is a polysaccharide, and it is well known to provide various benefits such as anti-aging, anti-obesity dietary food, lowering cholesterol, and removing heavy metals from the body. In the present invention, the addition of a structural material to the alginic acid beads to simplify the operation after drying and to facilitate re-expansion by moisture, and to make the multi-layer alginic acid beads by adding a bioactive substance or medicines to reduce the initial release delay, release rate In addition, it is possible to control the extension of the release time. The multilayer coating of the present invention enables oral delivery of pharmacologically active substances, such as vitamin C, antibiotics, insulin, which easily deteriorate the stomach, damage the stomach wall, and require sustained sustained release. In addition, alginic acid beads can be expanded in an aqueous solution to provide a feeling of satiety to the stomach, and thus can be a good dietary fiber. The structural components of alginic acid beads are used as nutrients and structures, and alginic acid provides the feeling of satiety mentioned above, while trapping cholesterol in the body as impurities, and adsorbing heavy metals in the body. The purpose of the present invention is the development of a high functional complex diet food, and a Smart and Soft Delivery System as a delivery system of medicine, and more specifically, the present invention is slowly controlled release and release of bioactive substances and medicines useful to the human body, Hazardous substances (cholesterol, heavy metals) can be applied to complex multifunctional drug delivery systems that are released out of the body.

The present invention will be further illustrated by the following examples, which are only described for the purpose of illustrating the present invention and are not intended to limit the protection scope of the present invention.

EXAMPLE

Example 1-4

In order to make alginate beads containing L-phenylalanine, an aqueous slurry containing 20% starch powder and 1.5% sodium alginate was prepared, and then L-phenylalanine was mixed to a concentration of 3 mg / ml. . In order to remove bubbles, bubbles were removed by an ultrasonic wave for 10 minutes, and then dropped in a 100 ml separatory funnel dropwise into a 1M CaCl ₂ aqueous solution. After all the slurry was dropped, the mixture was allowed to stand for 5 minutes, washed well with distilled water, and then dried in an oven at 60 ° C. for at least 10 hours. Meanwhile, the alginic acid beads which were completely dried in order to make double-layered alginic acid beads were immersed in 1.0% aqueous sodium alginate solution, coated with an alginate coating having a thickness of about 0.5 mm, and then dropped into the stirred 1M CaCl ₂ aqueous solution. It was washed in distilled water and dried again in an oven at 60 ℃.

Alginic acid beads prepared above are beads which are not coated with alginic acid [Example 1]. The alginic acid beads were again coated with an alginate solution and injected dropwise into 1M CaCl ₂ aqueous solution to prepare primary coated beads [Example 2]. The coating process was continued to produce secondary coated and quaternary coated beads [Examples 3 and 4].

Delayed Release Effect Test:

Initial release delay effects and release rates were measured for the alginic acid beads prepared in Examples 1-4. The beads were placed in a stirring PBS solution (0.01 M phosphate buffered saline, pH 7.4) and samples were taken over time to measure the concentration of L-phenylalanine. All L-phenylalanine was detected at 275 nm of the UV spectrometer. The measurement results are shown in FIG.

As can be seen in Figure 1 it was confirmed that the L-phenylalanine does not elute at all until the 15 minutes have passed the primary coated beads it takes a long time to pass through the primary coating membrane. It was confirmed that L-phenylalanine was not eluted at all for 30 minutes for the secondary coated beads and 70 minutes for the fourth coated beads. In addition, the release rate of L-phenylalanine tended to be lower as the multilayer coating was applied, thereby extending the release time due to sustained release. The release rate of L-phenylalanine in the absence of alginic acid coating was 9.1 × 10 ^-5 M / h, 5.8 × 10 ^-5 M / h in the primary coating, and 2.7 × 10 ^-5 M / in the secondary coating. It can be seen that the release rate decreases by more than 60% for each alginic acid coating as h.

Heavy metal adsorption test:

Heavy metal adsorption test was performed on the alginic acid beads prepared in Example 1-4, and the results are shown in FIG.

A certain amount of the beads of Example 1-4 were taken, placed in a Erlenmeyer flask with 200 ppm of leaded water solution, and adsorption experiments were carried out using a shaker at 25 ° C. and 100 rpm. Samples were taken at regular intervals and subjected to quantitative analysis using an atomic absorption spectrometer. As shown in Figure 2 it can be seen that the weight of lead that can be adsorbed per unit weight increases as the self-weight coating on the alginic acid beads. In the first coating, the adsorption amount of lead increased by about 30%, but the adsorption amount per unit weight of lead did not increase significantly due to the additional coating. In the absence of coating, the initial adsorption rate was 1.9 mg Pb / g-beads · h, which was increased by more than 50% to 2.9 mg Pb / g-beads · h when the first coating was applied. The rise was minor.

Example 5-6

0.025 g / ml of cholesterol was dissolved in chloroform, added to the alginic acid slurry, mixed well, and then mixed in an oven at 60 ° C. for 1 minute to evaporate chloroform to prepare alginic acid beads in the same manner as in Example 1. [Example 5] Starch powder was contained in Example 5 to prepare alginic acid beads containing starch powder [Example 6].

Cholesterol Capture Effect Test:

The beads of Example 5 were prepared in 8 samples of 1 g each, and 4 samples were added to each of 1) distilled water, 2) pH 7.4 PBS aqueous solution, 3) pH 2.0 HCl aqueous solution, and 4) 10 ml of ethanol (FIG. 3). (a)), each of the remaining four samples in 1) distilled water, 2) aqueous solution of pH 7.4 PBS, 3) aqueous solution of pH 2.0 HCl, and 4) 10 ml of ethanol (FIG. 3 (b)), and these were added for 13 hours. The mixture was shaken at 30 ° C. and 30 rpm shaker. After the extraction experiment was detected by separating (mobile phase; ethyl acetate: hexane = 50: 50) using silica thin layer chromatography (TLC). Samples were taken from the extraction solution and tested for detection of cholesterol (Figs. 3 (b) and (d)). In addition, each bead was dissolved in 20 ml of 0.1 M EDTA (ethylenediaminetetraacetic acid) solution. 3 ml of chloroform was added to the dissolved bead solution, and the mixture was extracted with extreme mixing. Then, a sample was taken from the chloroform of the liquid-separated lower layer, and cholesterol detection experiments were performed (FIG. 3 (a) and (c)).

As can be seen from the photograph of FIG. 3, it can be seen that all of them have the same cholesterol trapping effect with or without starch powder. It was confirmed that the beads collected cholesterol did not elute in the cholesterol dissolution test by distilled water, pH 7.4 PBS aqueous solution, pH 2.0 HCl aqueous solution, with or without starch. PBS aqueous solution is the elution condition corresponding to the body fluids of the human body, pH 2.0 HCl aqueous solution is to simulate the elution conditions corresponding to stomach acid in the stomach. On the other hand, in the elution conditions using ethanol, it was confirmed that cholesterol is eluted from alginic acid and alganic acid + starch beads (line 4 in Figure 3 (b) and (d)). However, ethanol elution is thought to only elute cholesterol on the surface of alginic acid and alginic acid + starch beads, which can be confirmed that a lot of cholesterol still remains in the fourth row of (a) and (c).

[Example 7-8]

Alginate beads containing no starch powder were prepared in the same manner as in Example 1 [Example 7]. Alginate beads containing starch powder were prepared in Example 7 [Example 8]

Volumetric measurement after drying:

The beads of Example 7 had an average diameter of 5.0 mm before drying, but shrank to a negligible volume after drying. After drying, the beads of Example 8 had a very solid white bead having an average diameter of 3.6 mm and an average weight of 0.02 dried g, and when expanded in an aqueous solution, the average diameter was 5.1 mm and the average weight was 0.103 wet g. Increased by about three times. This means that the alginic acid beads of the present invention can accelerate the release of medicinal actives due to volume expansion.

All simple modifications or changes of the present invention can be easily carried out by those skilled in the art, and all such modifications or changes can be seen to be included in the scope of the present invention.

Claims (7)

An alginate bead for a sustained release pharmaceutical delivery system, comprising a pharmacologically active substance and comprising a structural starch mixed with a bead in a state in which the alginate is cured by a polyvalent cation. The alginic acid bead for sustained release medicine delivery system according to claim 1, wherein the alginic acid beads adsorb heavy metal and collect cholesterol. The alginate bead for sustained release pharmaceutical delivery system according to claim 1, wherein the pharmaceutically active substance is selected from the group consisting of vitamins, essential nutrients, proteins, pharmaceuticals, pesticides, fertilizers and growth hormones. Mixing aqueous starch with an aqueous alginate solution to form an aqueous slurry; Mixing a desired medicament substance into the aqueous slurry; Pouring the slurry solution into the polyvalent cation solution drop by drop to cure; Washing the cured beads; And drying the washed beads; A process for preparing alginic acid beads for a sustained release pharmaceutical delivery system, comprising the steps. The method of claim 4, wherein the alginic acid beads prepared by the method are immersed in an aqueous alginate solution to form an alginic acid coating film having a thickness of about 0.5 mm; Injecting the coated beads into the polyvalent cation solution dropwise to cure the coating film; Washing the cured beads; Drying the washed beads; And repeating the above steps to produce multiple layers of beads; A method for producing alginic acid beads for sustained release medicine delivery system, further comprising the step. The method of claim 4 or 5, wherein the polyvalent cation solution is selected from the group consisting of CaCl ₂ , SrCl ₂ , BaCl ₂ and AlCl ₃ solutions. Alginate beads for sustained release pharmaceutical delivery systems, which are prepared according to any one of claims 4 to 6.

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