KR0142924B1 - Peonig microcapsules and ttheir preparing method - Google Patents

Abstract

The present invention relates to a horseshoe microcapsule and a method for producing the same which changes the formulation of the horseshoe ring to greatly improve the dose to the unique taste of horseshoe, and has a rapid medicinal effect. Leaching with water, ethanol and water-ethanol mixture and removing the solvent if necessary by spray drying, freeze drying or solvent volatilization, or spray drying, freeze drying or solvent volatilization of the solution leached with organic solvents such as ether, methylene chloride, etc. Extract the organic solvent by one or more of the three extraction methods of horseshoe medicinal herbs, such as by removing the organic solvent, and add water and ethanol to it, add the coating material to the solution to dissolve it, and do not add the usual additives or the usual additives A high molecular compound to increase the taste and fluidity of the microcapsules obtained by adding and spray drying It includes a horseshoe microcapsules obtained by suspending the microcapsules prepared in a solution previously dissolved or swelled in an organic solvent that does not dissolve dextrin and spray-dried, and a preparation method thereof.

Description

Manufacturing method of horseshoe microcapsules

The present invention relates to a horseshoe microcapsules made by grinding raw herbal medicines of horseshoe rings and a method for manufacturing the same, and more particularly, powdered fine powders of musk, cow sulfur, whole wheat, and Saddam, which are raw materials of horseshoe rings, are finely powdered and then extracted with a solvent. Alternatively, by dissolving the coating material in a solution suspended in a solvent and instantaneous drying using a spray dryer, the microcapsules are prepared by removing the secondary capsule material with a second coating material to prepare a horseshoe microcapsule. The present invention relates to a horseshoe microcapsule of a new formulation and to a method for preparing the same, which greatly improves the dose to and can be rapidly absorbed into the body.

Horseshoe ring is one of the representative herbal medicines known to be effective for the treatment of acute hepatitis, otitis, ophthalmitis and gingivitis. It is mainly formulated in the form of a large pill and incision is taken in a certain amount if necessary.

According to the 1985 drug evaluation, such a horseshoe ring usually contains 90 mg of musk, 150 mg of sulphur, 2,550 mg of saccharin and 210 mg of Saddam in one ring, and this prescription may vary slightly depending on the content of each ingredient. .

In general, the amount of horseshoe ring is known to be taken hot water 2-3 times a day, 1 1/20 ~ 1/10 pills once for infants and children, 1/5 pills once for adults Incision is to be taken. However, these horseshoe rings are so hard that they cannot be incised to the exact dose size, and above all, they have a very bitter taste and disgusting smell than any of the existing herbal medicines. There is a problem that the elution and absorption of the component is late.

As part of trying to solve this problem, some pharmaceutical companies recently filled the gelatin hard capsules with 1/10 doses of horseshoe pill, such as musk 9mg, sulfur sulfur 15mg, 255mg and Saddam 21mg, in order to eliminate the bitter taste. Single horse capsules are commercially available (Medical Index, 1992).

However, these capsules can be evaluated in terms of improving the difficulty of incision, inaccurate dose, and uncomfortable dosage method, but by simply changing the formulation of the conventional pills into capsules, the crude powders of animals and plants are administered in a circular manner. As a result, the problem of content uniformity and dissolution of active ingredients in the body, which is a problem of herbal medicines, remains a problem to be improved.

Accordingly, the present inventors have conducted a long study to solve the problems of the conventional horseshoe ring or horseshoe capsules and to improve the dose and drug efficacy, and as a result of the increase of the solubility of poorly soluble drugs, the manufacturing principle of the microcapsules by the spray drying method When the microcapsule is applied to the horseshoe ring, it is convenient to carry and take, and in particular, it is possible to alleviate the disgusting and bitter taste of the herbal medicine as well as to realize that the drug appears very quickly, thereby completing the present invention.

Therefore, the present invention is more convenient to carry and take the horseshoe ring, which has been used as one of the representative herbal medicines for many years, which is convenient to carry and take, and especially the strong taste of the herbal medicine is alleviated. It is an object of the present invention to provide a horseshoe microcapsules in the form of ultrafine spherical particles and a method of manufacturing the same.

Hereinafter, the present invention will be described in detail.

The present invention, in the manufacture of a drug containing horseshoe herbal medicine ingredients mainly musk, cow sulfur, whole wheat and Saddam, ethanol content of the final solution by adding water and ethanol to the horseshoe herbal extracts or horseshoe herbal extracts extracted from the horseshoe herbal medicines The film is added to dissolve the coating material in an amount of 5% to 80%, and then dissolved by instantaneous drying using a spray dryer.

The present invention will be described in more detail with reference to the manufacturing method as follows.

The present invention is to prepare a formulation containing a horseshoe herbal medicine ingredients, mainly musk, cow sulfur, whole lacquer and Saddam, to prepare a horseshoe herbal extract or horseshoe herbal extracts from the horseshoe herbal ingredients first. In the present invention, a method of extracting a horseshoe-ring herbal medicine may be used to finely powder some or all of the herbal ingredients of the horseshoe ring to 200 μm or less, or to cut or remove some or all of the herbal medicines of each of the horseshoe rings. Or rinsing with water, ethanol or water-ethanol mixed solvent, or if necessary, removing the solvent by spray drying, lyophilization, or solvent volatilization, or cutting out some or all of the herbal components of the horseshoe ring. The leachate may be prepared by pulverization or semal, and then leached with an organic solvent such as ether or methylene chloride, and then any of these methods may be used by removing the solvent by spray drying, freeze drying or solvent volatilization.

In order to increase the taste and fluidity, the microcapsules are prepared by suspending the microcapsules in a solution in which a high molecular compound is dissolved in an organic solvent that does not dissolve dextrin in advance or swelling, and then spray-dried to obtain a second coating material. .

Water and ethanol are added to the extract or extract extracted by the above extraction method so that the ethanol content of the final solution is 5 to 80% to form a solution or suspension.

If the content of ethanol in the final solution exceeds 80% there is a problem that the coating material does not melt.

Then, 30-70% of the coating material is added to the solution or suspension based on the total amount of horseshoe microcapsules. The coating material is dissolved in pure ethanol and water but is dissolved in pure ethanol alone. use. In the present invention, as the coating material, at least one selected from dextrin, soluble starch, gum arabic, gelatin, sodium alginate, tragacanta, xanthan gum and guar gum is used. If the amount is less than 30%, all the herbal ingredients are coated. It is not possible to reduce the bitterness and disgusting smell of the herbal medicine for the purpose of the present invention, and when used in excess of 70% is not good because the dose is excessive.

In the present invention, one or more selected from conventional surfactants, dissolution aids, flavoring agents, stabilizers, suspending agents and the like may be added to the coating material.

Surfactants are used to homogenize the suspension and use sodium lauryl sulfate, polyoxyethylene-based surfactants or polyoxyethylene-polyoxypropylene adduct-based surfactants. Stabilizers such as silicon dioxide are used to keep the product moisture resistant without sticking to it, and high sealants such as opaggloss, shellac and polyethylene glycol are used to make the product moisture resistant. Flavoring agents that can be used in the formulation, such as flavoring, are used.

In addition, carboxymethyl cellulose sodium, carboxymethyl cellulose calcium, crystalline cellulose, and hydroxide are used as film forming additives to control the homogeneity, fluidity and physical strength of particles by changing the film formation time, film thickness, film surface shape and film strength. High molecular compounds such as hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, methyl cellulose, polyvinyl alcohol, polyvinylpyrrolidone and the like and sugars such as white sugar, mannitol, sorbitol, fructose, lactose, glucose and galactose It may be. At this time, it is preferable that the film forming additive is 30 to 70% of the total amount of the microcapsules. If the amount is excessively used, the production time is long, the production rate of the microcapsules is reduced, the resulting microcapsules are agglomerated and the fluidity is reduced.

The horseshoe microcapsules of the present invention thus prepared may be coated with a secondary coating material in order to improve taste and fluidity.

The method of coating is to prepare a coating solution by dissolving or swelling a secondary coating material in an organic solvent in which the prepared microcapsules are not dissolved, and suspending the previously prepared microcapsules in this coating solution and spray drying. If less than 30% is suitable, less than this, the taste and fluidity cannot be improved, and if the excess is exceeded, the horseshoe microcapsules do not exhibit rapid efficacy.

As the secondary coating material used in the coating process, Eudragit, polyvinylpyrrolidone, methyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, hydroxypropyl methyl cellulose-phthalate and hydroxypropyl methyl cellulose- One or two or more high molecular compounds selected from acetosuccinate are previously dissolved or swelled in an organic solvent. At this time, the organic solvent is selected from methanol, ethanol, isopropanol or methylene chloride.

In addition, the prepared horseshoe microcapsules of the present invention or the exfoliated horseshoe microcapsules may be prepared by adding a powdered flavoring agent that can be used in the preparation, such as an orange flavor, and an excipient that can be used in the preparation, such as crystalline cellulose, white sugar, and lactose. Fine granules, granules, capsules and tablets can be prepared, and excipients that can be used in preparations such as water, white sugar, glycerin, banana flavor, sorbitol liquid, citric acid, etc. can be added to prepare suspensions, syrups, and the like. Can be.

Just as a drug once dissolved or wetted in water or ethanol in the formulation is faster to dissolve than the dry powder of the drug, horseshoe rings or horseshoe capsules take considerable time for the herbal drug itself to wet, elute, and absorb the active ingredient. The horseshoe microcapsules of the present invention prepared by the same manufacturing method are dispersed and dissolved almost instantaneously when contacted with water, so that the herbal component of the horseshoe ring, which is the content, is dissolved or suspended, so that the horseshoe microcapsules dissolve faster than conventional horseshoe rings or horseshoe capsules. have.

Hereinafter, the present invention will be described in detail with reference to Examples, but the present invention is not limited to the Examples.

[Production Example 1]

20.4 g of powdered poultry was extracted with 200 ml of 30% (v / v) ethanol for 2 hours in a heat-circulating extractor and dissolved in 20 g of dextrin, 1 g of lauryl sulfate, and 2 ml of opa glass. 720 mg of musk, 1200 mg of sulfur and 1680 mg of Saddam were suspended and then microcapsules were prepared by spraying. This product contains 1% by weight of ethanol and 870mg is one adult dose (one-fifth equivalent).

[Production Example 2]

20.4 g of powdered poultry is cooled by cooling with 100 ml of 50% (v / v) ethanol for 10 days, and then filtered by filtrating again with 100 ml of 50% (v / v) ethanol for 10 days and combined. . 50 g of dextrin is added to the filtrate, and it is dissolved in musk 720 mg, 1200 mg of sulfur and 1680 mg of mud beforehand made of fine powder (less than 200 μm), and then microcapsules are prepared by spraying. This product contains about 3% by weight of ethanol and 1.65g is one adult (one-fifth equivalent).

[Manufacture example 3]

Four powders of musk 720 mg, 1200 mg of sulfur, 20.4 g of whole wheat, and 1680 mg of Saddam are sprayed into 100 ml of 10% (v / v) ethanol with fine powder (less than 200 μm) in a suspension of 30 g of dextrin, 0.4 g of sodium lauryl sulfate and white sugar. 2.0 g is added to melt, and then microcapsules are prepared by spraying. This product contains about 5% by weight of ethanol and 1.55g is one adult (one-fifth equivalent).

[Production Example 4]

Combine crude medicines, such as 20.4 g of whole wheat and 1680 mg of Saddam, and combine them with 100 ml of water and extract and filter with a heated circulation extractor for 2 hours. To this filtrate, 0.5 g of carboxymethylcellulose sodium was dissolved, 30 ml of ethanol, which had previously been dissolved in 30 g of dextrin, was added, and then 720 mg of musk, made of fine powder (less than 200 μm), and 1200 mg of sulfur sulfur were suspended to prepare microcapsules by spraying. This product contains about 2% by weight of ethanol and 1.05g is one adult dose (one-fifth equivalent).

Production Example 5

20.4 g of pre-diluted pre-galvanized with 100 ml of 30% (v / v) ethanol was extracted by distillation in a filtrate for 2 hours in a filtrate, and 20 g of dextrin and 0.3 g of gelatin were dissolved in musk 720 mg of fine powder (less than 200 μm). Suspension, 1200 mg of sulfur and 1680 mg of Saddam were suspended, and microcapsules were prepared by spraying. This product contains about 5% by weight of ethanol and 0.87g is one adult dose (one-fifth equivalent).

[Manufacture example 6]

15 g of dextrin, 0.02 g of silicon dioxide and 0.4 g of sodium lauryl sulfate were dissolved in a filtrate obtained by extracting filtrate extracted with 204 g of whole grains and 16.8 g of Saddam with 1000 ml of 25% (v / v) ethanol in a heating circulation extractor for 2 hours. The dried product obtained by spray-drying the liquid extracted from 7.2 g of ether for 2 hours in a heating circulation extractor and 12 g of sulfur powder made of fine powder (less than 200 μm) were suspended, and then microcapsules were prepared by spray drying. This product contains 2% by weight of ethanol and 1.13g is one adult dose (one-fifth equivalent).

Example 1

The sprayed and dried solution of 35 g of the microcapsules prepared in Preparation Example 1 was spray-dried to prepare a coated microcapsule in a solution of 10 g of Eudragit E in 300 ml of ethanol. This product contains 1% by weight of ethanol and 1.13g is one adult dose (equivalent to 1/5 of a horseshoe ring).

Example 2

The sprayed and dried solution of 35 g of the microcapsules prepared in Preparation Example 1 was spray-dried to prepare a coated microcapsule in a solution of 10 g of Eudragit S in 300 ml of ethanol. This product contains 1% by weight of ethanol and 1.13g is one adult dose (equivalent to 1/5 of a horseshoe ring).

Example 3

5 g of polypyrrolidone was previously dissolved in 300 ml of ethanol, and the liquid suspension of 35 g of the microcapsules prepared in Preparation Example 1 was spray-dried to prepare a coated microcapsule. This product contains 1% by weight of ethanol and 1g is one adult dose (1/5 of a horseshoe ring).

Example 4

5 g of hydroxypropylmethylcellulose was dissolved in 150 ml of isopropanol and 150 ml of methylene chloride, and then spray-dried 35 g of the microcapsules prepared in Preparation Example 1 was spray dried to prepare a coated microcapsule. This product contains 1% by weight of ethanol and 1.13g is one adult dose (equivalent to 1/5 of a horseshoe ring).

Example 5

To 45 g of the microcapsules prepared in Example 3, 0.5 g of talc is added and the capsules are filled.

Example 6

To 45 g of the microcapsules prepared in Example 1 was added 0.5 g of talc and filled into a cloth.

Example 7

100 g of white sugar, 10 g of sorbitol solution, 200 mg of citric acid, 4 g of sodium carboxymethylcellulose, and 100 g of honey were dissolved in 500 ml of water, 200 mg of methyl paraoxybenzoate, 400 mg of propyl paraoxybenzoate, and 4 ml of ethanol, 0.3 ml of peppermint, were dissolved. 45 g of the microcapsules prepared in Example 8 and water were added thereto, and the mixture was stirred to 800 ml. 20 ml of this product is one adult dose (1/5 equivalent of horseshoe ring).

Example 8

50 g of white sugar, 10 g of concentrated glycerin, 200 mg of citric acid, 200 g of sodium chloride, 2 g of pectin, 1 g of crystalline cellulose and 200 g of honey were added to 500 ml of water, 200 mg of paraoxybenzoate, 400 mg of paraoxybenzoate and 400 ml of banana, and 4 ml of ethanol pre-dissolved. After stirring and dissolving, 45 g of microcapsules prepared in Example 2 and water were added thereto, and the mixture was stirred to 800 ml. 20 ml of this product is one adult dose (1/5 equivalent of horseshoe ring).

Experimental Example 1

Bitter Taste Reduction Experiment of Horseshoe Microcapsules

Experimental Method

In order to compare the bitterness of the conventional horseshoe capsule and the horseshoe microcapsules of the present invention, each of the horseshoe capsule and the horseshoe microcapsules containing 4 g of horseshoe medicinal herbs is suspended in 100 ml of purified water to prepare a test solution A and a test solution B and perform a sensory experiment. Continue stirring until And a caffeine solution of 1%, 0.75%, 0.50%, 0.35%, 0.24%, 0.10% is prepared as a control solution. First, in order to savor the taste of the control solution, 3 ml of the control solution is put on the back of the tongue, the taste is remembered, swallowed after 5 seconds, the mouth is washed with water and the bread is tasted to remove the bitter taste of the mouth. In this way, the degree of bitterness of the caffeine solution of each concentration is continuously memorized, and 3 ml of Test Solution A is placed on the back of the tongue, and the bitterness is tasted, where the degree of bitterness corresponds to a similar bitter taste in the control solution. (Use the following survey form).

Wash the mouth with water and taste the bread to remove the bitter taste of the mouth, and then put 3 ml of the test solution B on the back of the tongue and taste the bitter taste and mark the same bitter taste in the control solution as in the test solution A.

* 1: 1% caffeine solution

2: caffeine solution 0.75%

3: caffeine solution 0.5%

4: caffeine solution 0.35%

5: 0.25% caffeine solution

6: caffeine solution 0.1%

The experiment was conducted on 11 healthy men and women aged 19 to 22 years old. If the taste is between numbers, it is indicated as [.5].

In order to process the data with the above experimental results, the bitter taste of Control 1 was 100, 1.5 was 87, 2 was 75, 2.5 was 63, 3 was 50, 3.5 was 43, 4 was 35, and 4.5 was 30 points, 5 points were 25 points, 5.5 points were 18 points, and 6 points were 10 points.

As a result, the score of the horseshoe capsule was 42.38 points (± 22.70, corresponding to 0.42% of caffeine), while the horseshoe microcapsule was 25.24 points (± 14.76, corresponding to 0.25% of caffeine). It was found that the decrease below.

Experimental Example 2

Stability test according to the slope change of horseshoe microcapsules

Experimental Method

The prototype of Example 6 was stored for 2 years at room temperature, for 6 months at uv lamp-45 degrees, 45 degrees and 37 degrees-RH75% for 6 months and at 60 degrees for 2 months, respectively, to test the appearance, taste, solubility and content. . Appearance is visual, taste is taste, solubility was tested by dispersing and dissolving the equivalent amount of product in 50 minutes in purified water and 50 ml of 1 liquid (Korean Pharmacopoeia) within a few minutes. 90.6.5, according to the Republic of Korea process, quantitatively determined as bound bilirubin in cow sulfur and musk in musk.

[Experiment result]

As shown in the following table, the horseshoe microcapsules were not significantly affected by light, humidity and temperature and were stable for 2 years at room temperature.

Claims (2)

In the manufacture of a drug containing horseshoe herbal medicines mainly composed of musk, cow sulfur, whole wheat and Saddam, the ethanol content of the final solution is 5 ~ by adding water and ethanol to the horseshoe herbal extract or horseshoe herbal extract extracted from the horseshoe herbal medicine. 80% of the coating material was added to dissolve it, followed by instantaneous drying using a spray dryer to prepare a microcapsule, which was dissolved in a ethanol, methanol, isopropanol or methylene chloride, or a swollen coating solution. A method for producing horseshoe microcapsules characterized by suspending in a suspension and spray drying to coat in a 5 to 30% coating amount. The method of claim 1, wherein the secondary coating material is Eudragit, polyvinylpyrrolidone, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, hydroxypropyl methyl cellulose-phthalate and hydroxypropyl methyl cellulose-acetostone A method for producing a horseshoe microcapsule, characterized by using one or two or more selected from among sinates.