KR970011272B1 - A process for the preparation of guiryungwon formulations - Google Patents

Abstract

The "Kuilyongwon" medicament is prepared by the following method. (1) Powder 93.75 of Korean angelica root, 93.75 of deer antlers and 18.75 of mume fruit flesh in respective or mixed state. Each component is pre-treated and measured before powdering. (2) Reflux and extract with the solvent mixing alkali inorganic salts as extraction supplementary agent, cyclodextrines as stabilizer and tweens nonionic surfactant with 30~70wt% of soluble low-level alcohol. (3) Concentrate soluble low-level alcohol obtained by filtering with decreasing pressure and then obtain extract, and formulate with more than 1 species formulating carrier.

Description

Guiryongwon Pharmaceutical Manufacturing Method

Figure 1 is a process summary of the main treatment of Angelica Angelica, Deer Antler, Omae meat pretreatment, numerical value and powdering method.

2 to 4 is a process summary for extracting the main drug extract by extracting with a mixed solvent containing 30%, 50% and 70% ethanol.

5 to 11 is a summary of the manufacturing process of the preparation, 5-1 and 5-2 are granules, 6 is a liquid, 7 is a syrup, 8-1 to 8-3 is a suspension, 9 is a tablet, FIG. 10 is a hard capsule, and FIG. 11 is a manufacturing process summary of a soft capsule.

The present invention has been used to treat symptoms such as dark blood, darkening of the face, darkening of the ears, darkening of the eyes, weakening of the legs, pain in the lower back, and whitening of the urine. The present invention relates to a formulation and a method for producing the same.

In general, the pharmacological action of the active or active ingredient of the herbal medicine is due to the addition of aliphatic (aromatic) organic compounds, oxygen-based hetero compounds, hetero compounds, alkaloids, glycosides, proteins, resins, polysaccharides, amino acids, minerals and other minor components, and the like. It has been found that it is expressed due to the synergistic effect, and in the case of Guiryongwon, which is the object of the present invention, the active ingredient of the prescription constituent herbal is as follows.

The water-soluble components of Angelica are aromatic hydrocarbons (organic acid), vitamins (nicotinamide, vitamins, A, B, etc.), sucrose, polysaccharides, amino acids, and essential oils such as organic components, phthalides, pyranocamines (coumarins) It is composed of polyacetylene, etc., and antler is water-soluble ingredient (pantoclean, complex lipid, neutral sugar, free fatty acid, sulfuric acid, mineral, amino acid, polysaccharide, collagen, chondroitin, protein, colloid, etc.) and fat soluble ingredient (Follicular hormones, sterol esters, prostaglandins, etc.). On the other hand, the plum meat consists of aliphatic organic acids (citric acid, malic acid, tartaric acid), steroids, colloids, and carbohydrates.

Therefore, by maximizing the use of the active ingredients of these prescription medicinal herbs, it is easier to take than the traditional medicinal herb pill and absorbed quickly in the gastrointestinal tract, resulting in fast drug efficacy and improved stability and efficacy in the formulation. It is a feature of the present invention, developed by ear dragon juice, ear dragon syrup, ear dragon suspension, ear dragon chewable tablet, ear dragon hard and soft capsule.

Guiryongwon (Reimbursement), which is listed in the traditional Chinese medicine, such as consent reimbursement, contains only the matters related to the prescription constituent medicines, such as 『Separation of 當歸 · 하고 and 製 法 and 服法]. Dosage doses according to prescription and age, especially for pediatric doses, problems with efficacy effects, and daily doses of 50-70 pills of paulownia fruit (375 mg) should be taken. Since there were no specific details on the problem (22.5 grams per day) and its manufacturing method, there have been many difficulties in formulating the drug. However, the amount of herbal medicine prescribed for pill, the dosage for each age, and the manufacturing method were determined. As a result of two rounds of deliberation by the Pharmacological Review Committee, the license for manufacturing items of the hospital was formally obtained from the Ministry of Health and Social Affairs.

Accordingly, the present inventors decided the following about the prescription ingredients of Guilong Ryongwon, age-specific usage, dosage, and packing unit at the end of a long period of research based on pills.

The preparation method according to each formulation is described in detail in the following examples, and it is easy to use for adults or women, children and infants who do not take a large amount of pills by supplementing and improving the various problems described above, and in the gastrointestinal tract As a result of the research to improve the efficacy of the drug and improve the stability of the drug by facilitating absorption, the active ingredient, such as extractive adjuvant, stabilizer, and nonionic surfactant, is added to the prescription composition herbal to maximize the active ingredient by temperature and solvent. The extracted X was used to change the pharmaceutical formulation to maximize the efficacy of the drug, and the preparations of the ear dragon granules, ear dragon liquid, ear dragon syrup, ear dragon suspension, ear dragon chewable tablets, ear dragon hard and soft capsules according to the present invention The present invention has been completed by discovering that the efficacy and stability are improved over the existing pills.

Therefore, the object of the present invention is to determine the prescribed amount of Guiryongwon, extract the main herbal medicine to obtain the X, then formulated it is easy to take and easy to use because it is quickly absorbed in the gastrointestinal tract, the drug expression is not only fast, but also of the formulation It is to provide new chyloyong granules, liquids, syrups, suspensions, chewable tablets, capsules (hard and soft capsules) with improved efficacy and stability.

Summary of the Invention The present invention is a manufacturing method for extracting the active ingredients of prescription main medicines, such as new ear granules, ear dragon liquid, ear dragon syrup, ear dragon suspension, ear dragon chewable tablets, and ear dragon capsules (hard and soft capsules). 30-70% water-soluble medicinal herb prepared by powdering the main herb obtained individually or mixed by pretreatment process such as selection, washing, cutting, sterilization and drying of antler and maeyun meat Reflux extraction is performed with a mixed solvent containing lower alcohols, alkali inorganic salts as extraction aids, cyclodextrins as stabilizers, and twins as nonionic surfactants, and refined into essential oils, fats, steroids, phthalides, and pyranocoumarins. (Coumarin), acetylacetylene, steroids, pantocrine, saponins, fatty acids, carbohydrates, sugars, mucus, proteins, salts, organic acids, chondroitin and amino acids Extracted and then, after the filtration was concentrated under reduced pressure, the aqueous alcoholic extract is obtained by obtaining the X, it is to prepare them as an acceptable formulation in a pharmaceutical formulation along with one or more carriers.

Subsequently, as a method for preparing a pharmaceutically acceptable formulation, 1) the main herbal extract obtained by the above extraction method is added to purified water to dissolve it, and then the cyclodextrins, which are nonionic surfactants and stabilizers, are added to the solution and stirred. In the main herbal solution obtained by mixing, optionally add excipients, sweeteners, preservatives, solvents, fragrances and emulsifiers and other excipients, and then mix homogeneously, and add homogeneous pH, and then adjust the pH to 3.5-6.0 After cooling, the precipitate formed by cooling is filtered (centrifuged), added to a suitable amount of purified water to a total amount of 15 liters, and then filled, sterilized and aged to prepare a new earing or chyryon syrup solution, or 2) main medicine extract The main herbal powder obtained by apologizing and dispersing the solution obtained by sequentially adding a suspending agent and an emulsifier to purified water in advance and dispersing After preparing the acid solution, the sweetener, aluminum magnesium silicate dispersion, and fragrance liquid prepared in advance are added to the mixture sequentially and uniformly mixed.The pH is adjusted with an organic acid as a pH adjuster, the volume is adjusted, filtered, homogenized, filled, and sterilized. 3) Add the excipient, sweetener, disintegration and glidant obtained by apology to the main herbal extract in advance, and mix and mix the main herbal powder obtained by apologies in a passionate dilution in advance. After dispersing the mixture, add the combined solution prepared by cooling, stirring, and aging to make homogeneous association, and then make it into granules, and then dry and fill the dried granules, granulated granules, and apple granules in the cloth to prepare granules. ) Put the main herbal extract X and the excipient obtained by apologies in advance in purified water and stir and mix to make it homogeneous. To the main herbal powder obtained by apology, add a solution of an appropriate amount of sweetener, stabilizer, suspending agent, and citric acid to passionate water, mix it homogeneously, and aged it. After mixing, prepare into granules, add the fragrance and mix it homogeneously, and then prepare it as an ear dragon chewable tablet, or 5) Add the lactose and corn starch with the excipient obtained by apology with 80-120 body in X. The main herbal powder obtained by mixing is compacted by adding a lubricating agent, and then filled into capsules to prepare a hard dragon capsule, or 6) dissolving soybean oil and wax as excipients at 60-70 ° C, followed by stirring by adding the remaining soybean oil. Main medicine obtained by completely removing bubbles under reduced pressure after filtering It is prepared. Glycerin, paraoxybenzoic acid methyl, paraoxybenzoic acid propyl, ethylvanillin and pigments were added to the enzymatic solution in advance, and then gelatin was rapidly added to the excipient solution obtained by cooling to room temperature, stirred, mixed, swelled, and then warmed and dissolved. The foam is completely removed under reduced pressure, and then the viscosity is adjusted to form a film with a capsule base. The main herbal solution prepared above is added to form a capsule, followed by washing, drying and redrying to prepare a soft capsule.

The main herbal medicine used in the present invention is obtained by pretreatment such as pre-selection, washing, cutting, sterilization, drying, and so on, using a certain amount of medicinal liquor, red wine or soju, soaked for 4-6 hours and dried. Dried (washed), dried with alcohol (washed), cooled by heating until the surface becomes slightly yellow in culture for 3-4 hours (runner), heated by neutralization using powdered liver of liver At the same time, put the donkey to be indifferent (tocho) or it is heated by neutralization to make it super black. When the outside becomes super black, take out the dried one and choose it. Alternatively, use one of the following methods: burn the hair with a fire, remove it, and use an enemy of cows or sheep to thin the softened and soften it.

On the other hand, the maeyuk meat can be used by selecting one method from among the vinegar (vinegar, herbicide), thickened or crushed (briquette).

In carrying out the present invention, it is more preferable in view of extraction and stability of the herbal medicine to select the numerical method of digging the guinea pig, the antler, and the maeyuk meat.

In the present invention, the main herbal medicines are those obtained by pulverizing the pretreated and numerically treated main herbal medicines.

Here, if the manufacturing method of the present invention will be described in detail.

Among the main herbal medicines that have been pre-selected, washed, cut, sterilized and dried, the Angelica is soaked for 4-6 hours using a certain amount of medicinal liquor, yellow liquor or soju, and then dried and dried. Use the fire to remove the hair by burning it with silver, and use it to thin the softened and dried (water polo), which is desired to be the milk of a cow or sheep.In addition, the falcon meat is immersed in purified water. And dry meat. Figure 1 shows the flow chart of the main herbal medicine pretreatment process and numerical method of the present invention.

In this way, the main herbal medicine prepared by powdering method was put into the filter cloth, and 30-30% of the water-soluble low alcohol 20-30 liters, which is 10 times the total amount of the herbal medicine, was added as an alkali inorganic salt 0.01-0.04% as an extraction aid. Cyclodextrins as stabilizers 0.3-1.5% and 0.07-0.09% of nonionic surfactants were added to reflux at 80-100 degrees for 4-6 hours, and the active ingredients such as essential oils, fats, steroids and phthalides Water-soluble alcohol extract obtained by filtration of phytanokumarin-based (coumarin-based), polyacetylene-based, steroids, pantocrine, saponins, fatty acids, carbohydrates, sugars, mucus, proteins, salts, organic acids, chondroitin and amino acids (30%, 50% and 70%) were decompressed and concentrated to obtain the main herbal extract.

In the extraction method, as the water-soluble lower alcohol, methanol, ethanol, propanol, butanol, etc. are used, and ethanol is most preferred, wherein the concentration of the water-soluble lower alcohol is 30%, 50% and 70%, respectively. do. Alkali inorganic salts, which are extraction aids, are selected from heavy oils, ammonia, calcium carbonate, calcium hydroxide, etc., and neutral oils are the most preferred among heavy oils, ammonia, calcium carbonate, and calcium hydroxide. It is preferable to select and use one of alpha, beta, and gamma bodies. In addition, the nonionic surfactant uses Tween 20, Tween 40, Tween 60, Tween 80 and the like having a HLB (hydrophilic Lipophilic Balance) value of 12-18, among which Tween 40 is most preferred. Pressure reduction and concentration method is a conventional method in the field of the present invention, the description thereof will be omitted. Process diagrams for extracting with 30%, 50% or 70% ethanol according to the present invention are shown in FIGS. 2 to 4, respectively.

At this time, the extraction container is a double part equipped with a liquid meter, a thermometer, a cooler, and an agitator. The inner surface is made of glass or stainless steel, and the separation is effective under pressure or pressure filtration.

The formulation method is described in more detail below.

1) After dissolving the main herbal extract obtained by the above extraction method in purified water, add 0.005 to 0.08% of nonionic surfactant and 0.8 ~ 2.0% of cyclodextrin as a stabilizer, and stir and mix to the main herbal liquid obtained Optionally, add excipients such as sweeteners, preservatives, solvents, fragrances, emulsifiers, and other excipients, mix them homogeneously, adjust the pH to 3.5-6.0 by adding 0.03 to 0.06% of an organic pH adjuster. After allowing to stand for 6 hours, the precipitate formed by cooling to room temperature is filtered (centrifuged).

After adjusting the filtrate to 15 liters of total volume and filling it, sterilize at 90-95 degrees for an instant or 30 minutes, and aged at 30-45 degrees for 2-7 days to prepare a new earling or earling syrup solution, or 2) The main herbal powder obtained by apology is previously added to the purified water by suspending agent and emulsifying agent, and then dispersed in a solution obtained by dissolving it. Then, the preliminary preparative dispersion is prepared, and the sweetener, aluminum magnesium silicate dispersion, and fragrance prepared in advance are added sequentially and homogeneously. After mixing, adjust pH to 4.5-5.0 with organic acid as PH adjuster, filter and homogenize by adjusting the volume, and then fill, sterilize and mature to prepare Huilong Suspension, or To the homogeneous main medicine powder obtained by adding and mixing the excipient, sweetener, disintegration and lubricant, which were obtained from The resulting binder was homogeneously dispersed at 90 degrees, cooled to room temperature, stirred and aged at 40 degrees. The binding solution was prepared. After homogeneous association, it was made into granules and dried at 50 degrees for 8 hours to dry granules. Prepare the granulated granules, and then prepare apple granules by filling apples with 12-45 sieves and filling the granules, or 4) Add the main medicine extract and the excipients obtained by apples with 60-80 sieves in purified water beforehand and stir and mix them. After homogenizing, add the solution of sweetener, cyclodextrin as a stabilizer, suspending agent and citric acid as an organic acid, and mix it homogeneously in 5 liters. After aging for 24 hours, disintegrating and lubricating agents were added to the granules, and then stirred and mixed. Crab, then compressed into tablets to prepare as ear dragon chewable tablets, or 5) Add the excipient obtained by apologies with 80-120 apples in the main herbal extract X in advance, and mix it homogeneously in the mixer for about 30 minutes with talc, which is a lubricant, Magnesium stearate is added and compacted, followed by filling into a capsule to prepare a hard dragon hard capsule.6) Also, after dissolving the soybean oil and lead as excipients at 60-70 ° C, add the main herbal extract and stir for 30 minutes while adding the remaining soybean oil and stirring. The main herbal liquid obtained by pulverizing in a colloid mill and then filtered through a No. 80 sieve is prepared by removing the air bubbles completely at 760 mmHg for 2 hours. Glycerin, paraoxybenzoic acid methyl, paraoxybenzoic acid propyl, ethylvanillin and a suitable amount of pigment were added to 2 liters of passion water, and gelatin was rapidly added to the excipient solution obtained by cooling to room temperature, stirred, mixed and swelled for 20 minutes. Next, dissolve for 6 hours while warming to 70 degrees, depressurize at 70 degrees under 10-20mmHg to completely remove the bubbles, adjust the viscosity to form a film with a capsule base, add the main herbal liquid to form a capsule, and then use naphtha. After washing, the capsule is dried for 2-3 hours at a temperature of 20-25 degrees and a humidity of 30-50%, and then dried for 10-15 hours at a humidity of 20-40% at 30 degrees to prepare a soft dragon capsule.

As the nonionic surfactant used in the present invention, TLB 20, Tween 40, Tween 60, Tween 80, etc. having a HLB (Hydrophilic Lipophilic Balance) value of 12-18 may be used, and Tween 40 is most preferred. Cyclodextrins, which are stabilizers, are selected from one of alpha, beta, and gamma bodies.

Preservatives used in the present invention are benzoic acids (benzoic acid, sodium benzoate), parabens (paraoxybenzoic acid methyl, paraoxybenzoic acid propyl, etc.), dehydroacetic acid (dehydroacetic acid, sodium dehydroacetic acid), sorbic acid (sorbic acid) , Sodium sorbate, potassium sorbate) and other one or two or more kinds of preservatives generally accepted for the manufacture of pharmaceuticals can be used.

The solvent used for this invention can use purified water, ethanol, etc.

The fragrance used in the present invention may be used as a natural or artificial fragrance by mixing one or two or more kinds of fragrances commonly used in the manufacture of medicines.

Suspending agents and emulsifiers include one or two of carboxymethyl cellulose sodium carboxymethyl cellulose, polysorbates or Celtex (cyclodextrin) solutions, and polyvinylpyrrolidone or other pharmaceutical agents commonly used in the manufacture of pharmaceuticals. It can mix and use on paper.

As other excipients used in the present invention, lactose, glucose, soy phospholipids, soybean oil, lead, propylene glycol and the like may be used alone or in combination of two or more thereof.

As a disintegration and glidant used for this invention, it can be used 1 type or in mixture of 2 or more types, such as Avicel, crystalline cellulose, stearic acid, magnesium stearate.

The pH adjuster used in the present invention may be used by mixing one or two or more organic acids such as phosphoric acid and citric acid.

As the binder used in the present invention, hydroxypropyl cellulose may be used.

5 to 11 are summarized the process of preparing the ear dragon or syrup solution, suspensions, granules, chewable tablets, hard capsules and soft capsules.

The present invention will be described in detail with reference to the following examples.

In addition, the present invention is not limited to the number by the following examples, antler, Angelica, and maeyang meat in the context of the present invention means a number of herbal medicines and the dosage of each age in the dosage of each formulation is based on adults As such, 15-7 years of age 1/2, 7-4 years of age 1/3, less than 4 years old means 1/4 dose.

Nutraceutical Levels and Powdering Methods

Example 1

1. Angelica: After picking, washing, cutting, drying, sterilizing and pretreatment, steep for 4-6 hours using a certain amount of medicinal liquor, yellow liquor or soju, and then use it. .

2. Deer antler: The one obtained through the selection, washing, cutting, drying, sterilization and pretreatment in advance is burned with fire and removed by using a cow or sheep milking.

3. Omae meat: After distillation, cutting, washing, drying, sterilization and pretreatment, immerse in purified water, and then increase the flesh to make it soft. Remove nuclei and dry meat individually or mixed to make powder. .

In the grinder, mix the main herb assorted 9.656 kilogram and antler 9.656 kilogram measured by the numerical method of the main herbal medicine, pulverize it in small amounts, and then pulverize it. 20.63 kilograms (96%) of triturated granules were added to the mixture.

Manufacturing method of main herbal medicine X

Example 2

1) Add 2.063 kilograms of the main herbal mixture powder prepared in Example 1 to a filter cloth, add 2,400 mg of sodium bicarbonate, 7.0 g of cyclodextrin, and 1.5 g of Tween40 to 20.6 liters of 30% ethanol, 10 times the total amount of herbal medicine, and then 5 hours. The mixture was extracted at reflux, then cooled and filtered to give 30% of the extract.

2) The concentrated extract extract obtained by depressurizing and concentrating the 30% ethanol extract to 1/3 of the total amount of the extract was dried using a spray dryer to obtain 297 grams of dried extract (yield 14.14%).

Example 3

1) Add 2.063 kilograms of the main herbal medicine powder prepared in Example 1 to a filter cloth, add 400 mg of sodium bicarbonate, 7.0 g of cyclodextrin, and 1.5 g of Tween40 to 20.6 liters of 50% ethanol, 10 times the total amount of herbal medicine, and then 5 hours. Extraction was carried out at reflux followed by cold filtration to yield a tanol extract at 50%.

2) The concentrated extract extract obtained by depressurizing and concentrating the 50% ethanol extract to 1/3 of the total amount of the extract was dried to obtain 303 grams of dry extract (yield 14.7%) using a spray dryer.

Example 4

1) Add 2.063 kilograms of the main herbal medicine powder prepared in Example 1 into a filter cloth, add 400 mg of heavy sodium bicarbonate, 7.0 g of cyclodextrin, and 1.5 g of Tween40 to 20.6 liters of 70% ethanol, 10 times the total amount of herbal medicine, and then 5 hours. Extraction was carried out at reflux followed by cold filtration to obtain 70% of the extract.

2) The concentrated extract extract obtained by depressurizing and concentrating the 70% ethanol extract to 1/3 of the total amount of the extract was dried to obtain 311 grams of dry extract (yield 15.1%) using a spray dryer.

Manufacturing method of granule

Example 5

1) Add 54 grams of hydroxypropyl cellulose, previously apologized with No. 60 sieve, to 1 liter of passion distillate, disperse at 90 ° C, cool and dissolve while stirring, and then mature at 40 ° C.

2) Add 120 grams of lactose and 60 grams of D-mannitol 42 grams of crystalline cellulose to apple for 2 hours to the main drug x 297 grams prepared in Example 2 in a coalescer, and mix for 1 hour. The solution is added and homogeneously combined (main medicine powder).

3) Using the granulator, the main drug mixture powder prepared in 2) is prepared into granules of a suitable size.

4) Dry the granules for 8 hours at 50 ° C to prepare dried granules, sizing them, add 20 grams of strawberry flavor powder to the granules obtained by apples with 12-45 sieves, mix them evenly, and pack them in sachets (2.0 grams). do.

Example 6

1) Add 250 grams of hydroxypropyl cellulose, previously apologized with No. 60 sieve, to 2 liters of passion distillate, disperse at 90 ° C, dissolve by cooling, stir and homogenize and mature at 40 ° C (binder solution)

2) Add 572 grams of lactose and 615 grams of apple starch previously appled with a No. 60 sieve to 2.063 kilograms of the main herbal mixture powder prepared in Example 1 in a coalescer, mix homogeneously for 1 hour, and then combine the mixture prepared in 1) above. Add solution and homogeneously combine (main medicine powder)

3) Using the granulator, the main herbal powder prepared in 2) is prepared into granules of appropriate size.

4) Dry the granules at 50 ° C for 8 hours to prepare dried granules, sizing, add 40 grams of lemon flavor powder to the granules obtained by apples with 12-45 sieves, mix them evenly, and pack them in sachets (3.5 grams). do.

5) Adults take 3 times a day, 1 packet once in water or milk, or take granules as it is.

Manufacturing method of liquid

Example 7

1) Add 482 grams of sodium glutamate, 3.75 grams of sodium benzoate, and 1.8 grams of sodium dehydroacetate to add 5 liters of passion distillate, add 1.8 kilograms of isomerized sugar, dissolve completely, and cool. )

2) Add 1 x 297 grams of the main drug prepared in the same manner as in Example 2, mix and dissolve homogeneously, and add 16.5 grams of Tween 40 and 207 grams of cyclodextrin, dissolve completely, and cool to room temperature. (Main medicine)

3) Dissolve 12 grams of drink flavor in an appropriate amount of ethanol.

4) Add the main herbal liquid prepared in 2) to the sweetener and preservative of 1) above, add the fragrance solution prepared by stirring slowly with stirring, add purified water, and adjust the pH to 4.5-5.5 by adding citric acid as a PH adjuster. After adding the appropriate amount of purified water to adjust the total amount to 15 liters, homogenize, filter, fill in a 30ml bottle and sterilize at 90 degrees and aged at 35 degrees for 7 days.

5) Adults take 30 milliliters of a bottle three times a day.

Method of Preparation of Syrup

Example 8

1) Add 3.5 grams of paraoxybenzoic acid methyl and 1.8 grams of paraoxybenzoic acid to 3 liters of passion distillate, add 1.8 kilograms per bag to the dissolved solution, mix and dissolve at 80 ° C for 30 minutes, and then dissolve the D-sorbitol solution. (70%) Add 1.34 kilograms, mix, filter, and cool to room temperature (syrup and stock solution).

2) Add 1 x 297 grams of the main herbal medicine prepared in the same manner as in Example 2, mix and dissolve the mixture evenly, dissolve it, add 207 grams of Tween 40 and 207 grams of cyclodextrin to dissolve completely, and then cool to room temperature. (Main medicine)

3) Add 50 milliliters of strawberry flavor to an appropriate amount of ethanol and dissolve it (fragrance solution).

4) Add the syrup and preservative solution of 1) and the aromatic solution of 3) prepared by dissolving in the main herbal solution of 2) while stirring. Add the appropriate amount of purified water, adjust the total amount to 5 liters, homogenize, filter, and fill into a 10 ml bottle. After sterilization at 90 degrees and aged at 35 degrees for 7 days.

5) Adults take one bottle 10 milliliters three times a day.

Manufacturing method of suspending agent

Example 9

1) Put 200 grams of polyvinyl phytolidone in 2 liters of passion distillate, dissolve it, cool it to 50 degrees, add 100 grams of polysorbate 혼합 80, and mix it in a homogeneous mixture. Put the main medicine powder obtained by apologizing the herbal medicine extract 297 grams into No. 60 sieve, mix and disperse it, and then cool and adjust the PH and viscosity to prepare a preliminary dispersion of pharmaceutical preparations.

2) Add 1.6 kilograms of sugar per hundred liters to 2 liters of purified water, mix and dissolve at 80 degrees for 30 minutes, add 1.4 kilograms of D-sorbitol solution (70%), mix, and filter, and 52 grams of sodium carboxymethylcellulose. To this solution, 3.5 grams of sodium dehydroacetate was added to the completely dissolved solution, and then cooled to room temperature with homogenous stirring to prepare a white sugar solution.

3) Put 120 grams of aluminum magnesium dispersion silicate in 500 milliliters of zeolite, stir at 90 ° C for 2 hours, cool to room temperature, allow to stand for 1 day, and adjust pH and viscosity to prepare a dispersion. Silicate dispersion)

4) Dissolve 60 grams of strawberry flavor in an appropriate amount of ethanol.

5) Add the main preliminary dispersion prepared in 1) to the white sugar solution prepared in 2) while mixing with stirring, mix the aluminum magnesium silicate dispersion prepared in 3), 4) the aromatic solution and mix it homogeneously, and add citric acid as a PH regulator. Adjust the pH to 4.5-5.0, add a suitable amount of purified water to it, adjust the total amount to 5 liters, filter it with No. 60 sieve, homogenize it, fill it with a 10ml bottle, sterilize at 90 degrees, and mature for 35 days. .

6) Adults take one bottle 10 milliliters three times a day.

Manufacturing method of chewable tablet

Example 10

1) Add 220 grams of white sugar, 400 grams of lactose, 204 grams of glucose, obtained by apologies in the No. 297 grams of the main herbal extract X prepared in the same manner as in Example 2, stir and homogeneously mix it, Apologize to obtain mixed herbal medicine powder. (Main herbal powder)

2) Add 155 grams of cyclodextrin, 45 grams of dextrin, and citric acid in a solution of 5 liters of passion, and mix it homogeneously in the solution of 1) the main herbal powder. Mix it homogeneously, leave, swell, and mature at 40 degrees for 24 hours. Manufacture by assembly.

3) Add 18 grams of crystalline cellulose, 23 grams of Avicel and 30 grams of magnesium stearate, stir to homogenize, and apologize to No. 60. (Disintegration and lubricant)

4) Mix 2) and 3) homogeneously for 30 minutes, add 10 grams of strawberry-flavored powder to it, mix it homogeneously, and then tablet it to make tablets (700 milligrams per tablet).

5) Adults take 3 tablets 3 times a day.

Manufacturing method of capsule

Example 11

1) Apologize 34 grams of corn starch using 80 mesh net.

2) Mix 66 grams of lactose and 34 grams of apple starch apples from 1) with homogeneous mixture for 30 minutes, and then add X 297 grams of the main drug prepared in the same manner as in Example 2 and continue for 30 minutes. Mix with further stirring to equalize the whole. (Main herb mixed powder)

3) Add 43 g of magnesium stearate and 10 grams of talc to the main powder mixture of 2), mix it homogeneously, compact it using a roller compactor, and fill it with a capsule (450 milligrams of capacity) and pack it with light. .

4) Adults take 2 capsules 3 times a day.

Manufacturing method of soft capsule

Example 12

1) After dissolving 10 grams of soybean oil and 29 grams of sulfur in 60-70 degrees, dissolving it, and then adding 192 grams of the remaining soybean oil and stirring, adding the main herbal medicine X 297 grams prepared in the same manner as in Example 2 and stirring for 30 minutes. The main herbal medicine obtained by pulverizing in a small amount in the colloid mill and then filtered through No. 80 sieve is completely removed by air bubbles at 760 mmHg for 2 hours to prepare the main herbal liquid.

2) Add 107 grams of glycerin, 12 grams of paraoxybenzoic acid methyl, 12 grams of paraoxybenzoic acid propyl, eqylaniline and a pigment in 2 liters of passion distillate, and cool to room temperature (excipient solution).

3) Rapidly add 131.6 grams of gelatin to the excipient of 2), stir and mix, swell for 20 minutes, dissolve for 6 hours while heating to 70 degrees under vacuum, and decompress under 70 degrees and 10-20mmHg to completely remove the bubbles. After the removal, after adjusting the viscosity to form a film with a capsule base, add the main drug solution prepared in 1) to form a capsule (content 500 milligrams), wash with naphtha, temperature 20-25 degrees, humidity 30-50% After drying the capsule for 2-3 hours at 30 ° C it is dried for 10-15 hours at 20-40% humidity.

4) Printed capsules are dried and then sorted and packed.

5) Adults take 2 capsules 3 times a day.

With the preparation of Guiryongwon prepared according to the above example, the stability test according to the change over time, the stability test according to long-term preservation, and the dissolution test were performed. The results are as follows.

Experimental Example 1

Stability Test of Guiryongwon Formulations over Time

1. Sample

The test was carried out by using the sample of the ear dragon granules prepared by the method of the present invention, brushed ear dragon liquid, ear dragon syrup and ear dragon suspension, ear dragon chewable tablet, ear dragon hard and soft capsule.

2. Experimental method

1) Confirmation test

Identification of antler was tested by color reaction according to Bosa No. 87-86 Herbal Standards.

2) Content test

The content of decursin in Angelica gigas was quantitatively analyzed by liquid chromatography.

3) Disintegration test

The test was carried out according to the disintegration test method of the six general test methods of the Korean Pharmacopoeia.

4) Preservation of Specimen

Sample preservation was tested at 40 degrees (humidity 75%) at room temperature and in the life tester.

5) Experiment result

Each experimental data was the average of the results of three or more experiments.

3. Preparation of Sample

1) Ear dragon granules (KYG): was prepared according to the method of Example 5 of the present invention.

2) ear dragon liquid (KYL): was prepared according to the method of Example 7 of the present invention.

3) Cute dragon syrup (KYS): was prepared according to the method of Example 8 of the present invention.

4) cute dragon suspension (KYSY): was prepared according to the method of Example 9 of the present invention.

5) Cute dragon chewable tablets (KYT): was prepared according to the method of Example 10 of the present invention.

6) cute dragon hard capsule (KYC): was prepared according to the method of Example 11 of the present invention.

7) cute dragon soft capsule (KYSC): was prepared according to the method of Example 12 of the present invention.

[Table 1] Stability test of the solids with time

Content: Decursin (mg / liter) in Angelica

[Table 2] Stability test of the liquid solution with time

Content: Decursin (mg / liter) in Angelica

Experimental Example 2

Stability Test of Long-term Preservation of Guiryongwon Formulations

1. Sample, 2. Experimental Method, 3. Preparation of Sample is Same as Experimental Example 1

[Table 3] Stability test of long-term storage of solids

Content: Decursin (mg / liter) in Angelica

[Table 4] Stability test of long term preservation

Content: Decursin (mg / liter) in Angelica

Experimental Example 3

Comparative Dissolution Test of Guiyongwon by Formulation

1. Sample

The test was carried out by using a sample of the ear dragon liquid, ear dragon syrup, ear dragon granule, ear dragon chewable tablet, ear dragon capsule (including soft capsule) and ear dragon ring prepared by the method of the present invention.

2. Experimental method

1) Content test

The content of decursin in Angelica gigas was quantitatively analyzed by liquid chromatography.

2) Dissolution test

Standard pills prepared by the general pill preparation method and preparations of the present invention were tested in the artificial gastric juice according to the six pharmacopeia dissolution test methods for each dissolution time period.

3) Experiment result

Each experimental data was the average of the results of three or more experiments.

Table 5 according to the present invention, worms granules, liquids, syrups, suspensions, cheongbrugs and

Results of elution test of decursin in capsules (soft) and guinea pig pills

Experimental Example 4

For the acute toxicity test, the ear dragon solution prepared according to Example 7 was observed for 7 days after direct injection into a 6-7 week-old healthy mouse using a catheter, but there were no deaths and temporary symptoms such as respiratory and gait disorders were found. It never happened.

In this experiment, LD ₅₀ value is negligible, and other drugs such as granule syrup are considered to be very stable drugs as well as liquids.

Claims (8)

In the Guiryeongwon herbal medicine consisting of Angelica, Deer Antler and Omaeus, powdered by pre-treatment and shaping Angelica 93.75mg, Deer Antler 93.75mg and 18.75mg of Omae meat, individually or mixed, and then extracted as 30-70% water-soluble low alcohol. The mixture was refluxed with a mixed solvent of alkaline inorganic salts, cyclodextrins as stabilizers and twins as nonionic surfactants, and then concentrated under reduced pressure to obtain an extract, and then the extract was extracted. A method of preparing a pharmaceutically acceptable Guiryongwon medicament, characterized in that it is formulated together. The method according to claim 1, wherein the main medicine is guinea guinea pig, antler sperm water, five maeyuk meat increases the number. The method of claim 1, wherein 30 to 70% of the water-soluble lower alcohol is selected from methanol, ethanol, propanol or butanol, and in particular, 30%, 50% or 70% of ethanol is used. According to claim 1, Alkali inorganic salts as an extraction aid is selected from sodium bicarbonate, ammonia, calcium carbonate, calcium hydroxide, in particular, the manufacturing method of cute dragon, characterized in that the use of sodium bicarbonate. The method of claim 1, wherein the cyclodextrins as stabilizers are selected from the group consisting of alpha, beta, gamma body, and the method for preparing chyryonwon medicament. The method of claim 1, wherein the nonionic surfactant is selected from Tween 20, Tween 40, Tween 60, and Tween 80 having an HLB value of 12-18, in particular Tween 40. According to claim 1, wherein the preparation carrier is prepared by using the at least one agent carrier selected from nonionic surfactants, suspending agents, stabilizers, sweeteners, preservatives, solvents, fragrances, emulsifiers and other excipients Way. The method of claim 1, wherein the formulation of Guiyongwon medicament is granules, liquids, syrups, suspensions, chewable tablets, hard capsules or soft capsules.