KR20100070261A - Rapidly releasing preparation comprising a magnolia officinalis extract - Google Patents

Abstract

PURPOSE: An immediate release oral administration containing Magnoliae Cortex extracts is provided to maintain internal dissolution rate of magnoliae Cortex extracts. CONSTITUTION: An immediate releae composition with high disintegration and high dissolubility effect contains Magnoliae Cortex extracts. A dry granule composition is manufactured by mixing Magnoliae Cortex extracts dry powder and additive ingredient. The Magnoliae Cortex extracts is from root, stem, rhytidome, leaf, flower of the Magnoliae Cortex. The additive ingredient is organic acid, alkali, anti-wetting agent, disintegrant or lubricant.

Description

Rapidly releasing preparation comprising a Magnolia officinalis extract}

The present invention relates to a formulation for rapid release oral administration of thick extract, specifically, the present invention relates to a rapid release formulation prepared by adding an auxiliary component to the extract of thick extract.

[Document 1] Lee Young-mi and 2 others, Chinese herbal medicine

[Document 2] Commissioner of Food and Drug Safety, Criteria and Test Methods for Drugs, Korea Food and Drug Administration Notification No. 1998-127, 1998

[Document 3] The Commissioner of the Korea Food and Drug Administration, Regulations on the Review of Application for Permission for Import of Manufactured Import Items of Non-Pharmaceutical Products, Notification of Food and Drug Administration 2007-18, 2007

[Document 4] Park, Jong-hee, Encyclopedia of Herbal Medicine (Ha), Book Publishing Company

References Kun Yen Ho, et al., Phytother. Res., 15 , pp. 139-141, 2001)

[6] Wei-Wei Zhang, et al., World J. Gastroenterol, 11 (28) , pp. 4414-4418, 2005

Jun ho Park, et al., European Journal of Pharmacology, 496, pp. 189-195, 2004

8 Koji Ikeda, et al., Phytother. Res., 17 , pp. 933-937, 2003

Natural medicines are mostly used as medicines or raw materials of medicines through simple processing such as natural products (animals, plants, minerals, etc.) produced in nature or dried, sliced or powdered. Traditional manufacturing methods such as boiling by boiling alcohol or making powder into powder (Lee Young-mi and 2 people, medicinal herb medicine) have been used, but recently, the immersion liquid was concentrated to solidify the groceries, such as solid preparations or Banhahubaktang. Prescriptions containing herbal medicines are extracted with water to make powders or granules (Ministry of Food and Drug Safety, Standards and test methods such as medicines, Korean Food and Drug Administration Notification No. 1998-127, 1998).

Generally, excipients, disintegrants, etc. are allowed to be used to make solid preparations (Regulations on Review of Application for Approval of Import and Manufacture of Imported Items for Non-Pharmaceutical Products, Korea Food and Drug Administration, and Korea Food & Drug Administration 2007-18 (2007), but the disintegration, dissolution and stability are unpredictable according to the composition ratio. Moreover, the immersion extract of the herbal medicine is extracted with cellulose-based components, and its disintegration is deteriorated due to the increase in the binding strength for long-term storage. There is a need for improvement in terms of stability as well.

Magnoliae Cortex is an evergreen tree of the dicotyledonous plant of the genus Amphitaceae. It is distributed in Korea, Japan, Taiwan, and southern China, and becomes more viscous when wet with water with bark and leaves as powder. Due to the incense (線香) as a binder. Machilus thunbergii from Korea, Magnolia obovata from Japan, and Magnolia officinalis from China are mainly used as herbal medicines. Danghubak contains about 1% of essential oils, the main ingredient is sesquiterpenoid machilol (= β-eudesmol), other α- eudesmol (α-eudesmol), γ-eudesmol, caryophyllene epoxide, cryptomeridiol, eudesobovatol A, B, α-pinene, β-pinene (β-pinene), camphene, limonene, bornyl acetate, and the phenolic component is magnool (magnolol; bis-chavicol), honokiol, and magnolo. There are magnolosides A, B, and C (Park Jong Hee, Encyclopedia of Herbal Medicine (Bottom), Book Publishing Shinil Corp., 2002). Traditionally, he is known to have all the five organs, including warm, tasteful, non-toxic, old-fashioned chills, stomach swellings, brain storms, hunger hunger, warming crises, and stopping the transfer of earth and sand eggs. Kun Yen Ho, et al., Phytother.Res., 15 , pp. 139-141, 2001), the weiring of gut smooth muscle (Wei-Wei Zhang, et al., World J. Gastroenterol, 11 (28) , pp. 4414-4418, 2005), anti-inflammatory (Jun ho Park, et al., European Journal of Pharmacology, 496, pp. 189-195, 2004), inhibition of cancer metastasis (Koji Ikeda, et al., Phytother.Res., 17 , pp.933-937, 2003), but it has been known to exert a variety of pharmacological effects. Nothing has been taught or described for the rapid release formulations containing the developed latex extract. .

Accordingly, the present inventors confirmed that the magnool and honokiol components contained in the Hakku immersion extract showed anti-cancer effects on bladder cancer and colorectal cancer during the development of a solid cancer treatment using the Hakpak extract. While developing a formulation using an additive for use in the study, by studying a rapid release formulation containing a thick extract extract that compensates for the disintegration phenomenon in the stability test, as well as the high disintegration and high-solubilizing effect, the drug is eluted during administration. A rapid release formulation for oral administration having a stable effect of maintaining a constant rate was completed in the present invention.

In order to achieve the above object, the present invention provides a fast-release formulation composition having a high disintegration, and a high solubility effect containing a thick extract.

As one embodiment of the present invention, the present invention provides a dry dried granule composition by mixing (1) thick powder extract dry powder and (2) auxiliary ingredients.

As another embodiment of the present invention, the present invention provides a dry mixed dry granule composition by mixing (1) the dry granule composition and (2) the dry granule composition.

As another embodiment of the present invention, the present invention provides a rapid-release composition for oral administration comprising (1) the dry granulated composition and (2) auxiliary components.

As used herein, a "hughu extract" is a Magnolia officinalis or Magnolia obovata and is preferably a variety of organs or parts (eg roots, stems, bark, leaves, flowers and fruits) ), Preferably means an extract obtained from the bark (cortex). As used herein, the term "extract" includes water containing purified water or a solvent selected from lower alcohols having 1 to 4 carbon atoms such as methanol and ethanol or a mixed solvent thereof, preferably an extract available in water.

“Auxiliary component” as defined herein includes one or more additive components selected from (1) organic acids, (2) alkalis, (3) desiccants, (4) disintegrants, or (5) lubricants;

The organic acid is represented by the formula of C _a H _b O _c , a is 1 to 18, and b and c are numbers that constitute at least one carboxylic acid group and have a chemically stable structure. Preferably an organic acid such as citric acid or ascorbic acid, or a mixture thereof, more preferably 0.001% or more in the composition as citric anhydride;

In the alkali, when the formula is expressed as M _a C _b H _c O _d P _e S _f Si _g , M is the aforementioned metal, and b to g are each a number capable of forming chemically stable alkali around M. It is a component selected from 0-18, Preferably it is sodium-containing alkali, such as sodium bicarbonate, sodium monohydrogen phosphate, magnesium containing magnesium, such as potassium, magnesium stearate, calcium containing alkali, such as precipitated calcium carbonate, aluminum, or carbonate, An alkaline substance containing at least one metal, more preferably at least one alkali selected from sodium bicarbonate, calcium carbonate, or magnesium carbonate, the amount of which uses the equivalent amount required to neutralize the preceding organic acid;

As the preferred desiccant, 0.01% or more of at least one desiccant selected from colloidal silica gel or silicic acid oxide which can be expressed as SiO ₂ when expressed in a formula is added;

Preferred disintegrants include at least 0.1% of at least one disintegrant selected from gelatinized starch, lactose, microcrystalline cellulose or sodium starch glycolate;

Preferred glidants include magnesium stearate, talc, stearic acid, or light silicic anhydride and include at least 0.1% of one or more optional glidants.

“Thick leaf extract dry powder” as defined herein includes a dry powder in which the thick powder extract is dried by a drying method commonly known in the art, for example, a hot air drying method, a freeze drying method, a natural drying method, and the like.

The fast-release preparation composition of the present invention has a high disintegration and high-solubility effect during the administration of a drug containing a thick leaf extract as an active ingredient, and by using both a dry active ingredient and an auxiliary ingredient simultaneously, the dissolution rate of the drug during the administration of the drug during the administration of the drug is kept constant. It has an effect that can be stably maintained.

Oral dosage form composition comprising an extract according to the present invention, powder, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols and the like, oral formulations, suppositories, and sterile injectable solutions, respectively, according to a conventional method. Formulated in the form of can be used.

Carriers, excipients and diluents that may be included in the composition comprising the extract include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate , Cellulose rose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. When formulated, diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents and surfactants are usually used.

Solid preparations for oral administration include tablets, pills, powders, granules, capsules and the like, and such solid preparations may include at least one excipient such as starch, calcium carbonate and sucrose in the extract. Or lactose, gelatin and the like. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used.

Oral liquid preparations include suspensions, solvents, emulsions, and syrups, and may include various excipients, such as wetting agents, sweeteners, fragrances, and preservatives, in addition to commonly used simple diluents such as water and liquid paraffin. . Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, suppositories. As the non-aqueous solvent and suspending agent, propylene glycol, polyethylene glycol, vegetable oils such as olive oil, injectable esters such as ethyl oleate and the like can be used.

As the base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.

Preferred dosages of the compositions of the present invention vary depending on the condition and weight of the patient, the extent of the disease, the form of the drug, the route of administration and the duration, and may be appropriately selected by those skilled in the art.

The components of the composition of the present invention and the principles of the invention will be described in more detail below.

As an example of the manufacturing process of such a thick extract,

(1) extracting the thick gourd with a lower alcohol such as water, methanol, ethanol or a mixed solvent thereof, and then concentrating to obtain a thick gourd extract;

(2) preparing a granule or tablet by adding an auxiliary component to the thick extract of step 1;

Additives known in the art that can be further added to the compositions of the present invention include binders, lubricants, disintegrants, colorants, preservatives, sweeteners, flavors, stabilizers, moisturizers or diluents, and the like.

Binders usable herein include, as conventional binders, preferably polyvinylpyrrolidone, hydroxypropylcellulose, microcrystalline cellulose, hydroxypropylmethylcellulose, dextrin, gelatin, methylcellulose, hydroxycellulose, hydroxymethylcellulose, poly May further comprise one or more ingredients selected from vinyl alcohol, pregelatinized starch, gum arabic,

As a disintegrating agent, as a disintegrating agent, sodium starch glycolate, crospovidone, cross-linked sodium carboxymethyl cellulose, low-substituted hydroxypropyl cellulose, Hydroxypropylmethylcellulose, polyvinylpyrrolidone, starch, carboxymethylcellulose calcium and combinations thereof, and may include one or more

As the lubricant, a mixture of at least one of magnesium stearate, talc, stearic acid and light silicic acid may be preferably used as a conventional lubricant.

As the moisturizing agent, as a general moisturizing agent, polyethylene glycol or a substance containing an alcoholic hydroxyl group in the structure can be used a mixture of one or more kinds of compounds having a molecular weight of 20,000 or less.

In addition, if necessary, a colorant may be included in the tablet, and titanium dioxide, iron oxide, magnesium carbonate, calcium sulfate, magnesium oxide, magnesium hydroxide, aluminum lake, for example, blue No. 1 aluminum lake, red No. 40 Aluminum Lake, Yellow No. 203 Aluminum Lake, etc. may include one or more selected.

Preservatives may be added one or more selected from benzoic acid, methyl paraben, ethyl paraben, propyl paraben and the like, and may further contain sweetening agents, flavoring agents, stabilizers, diluents.

Various oral fast-release compositions can be prepared using the compositions of the present invention, including, for example, tablets compressed into tablets by mixing the pharmaceutically acceptable additives described above, as well as those described in the Korean Pharmacopoeia. Oral preparations, ie, powders, granules, capsules, pills, and the like.

As described above, the rapid-release preparation composition of the present invention as a high disintegration and high-solubility effect of the extract of the thick extract, by confirming a stable effect of maintaining a constant dissolution rate of the drug during in vivo administration, as a fast-release composition for oral administration It can be usefully used.

Hereinafter, the present invention will be described in detail. However, the following Examples, Reference Examples and Experimental Examples are merely illustrative of the present invention, but the content of the present invention is not limited thereto.

Reference Example 1. Preparation of Thick Extract

      After extracting the bark of Danghu bakkuk as a herbal standard product at Seoul Gyeongdong Market, the hoobak extract of the present invention was added to 10 parts by weight of water based on 1 dry weight of hoobak and left at room temperature under reduced pressure at 100 mmHg or less for 3 days. Extracted by heating at 80 ~ 100 ℃ for ~ 4 hours, and concentrated by reduced pressure to 100 mmHg or less filtered filtrate using 100 mesh net to give 0.2 parts by weight (average 25% dry weight loss) (hereinafter referred to as Mx 117) box)

Example 1 Preparation of Thick-Containing Dry Granule Composition

1-1.Preparation of Thick Extract and Auxiliary Ingredients (1)

To prepare a composition having a weight ratio as shown in Table 1 below (1) 1kg each of (b) lactose and starch to (1) dried powder extract (a) thick extract obtained in Reference Example 1-1, and then homogeneously prepared the mixture 14 Granulated using a mesh net, dried at 50 ~ 60 ℃, and then sifted through the 16 mesh net to form granules.

ingredient Content (% by weight) 1: 0.5 1: 1 1: 1.5 Dry granules (a) Thick Extract 66 50 34 (b) Lactose and starch 34 50 66 Total amount 100 100 100

1-2. Preparation of Thick Extract and Auxiliary Ingredient Mixture (2)

To prepare a granule of (a) thick extract and (b) lactose and starch 1kg and (c) 70% ethanol, respectively, having a weight ratio as shown in Table 2. In the manufacturing method, 1kg each of lactose and starch was added to 1kg of dried powder extract, and the mixture was homogeneously prepared. After granulation using 14 mesh nets, the same amount of 70% ethanol (alcohol) was mixed, followed by Example 1-1. It was prepared under the same conditions.

ingredient Content (% by weight) 1: 1 Dry granules (a) Thick Extract 34 (b) Lactose and starch 33 (C) 70% ethanol (alcohol) 33 Total amount 100

1-3. Preparation of Thickening Extract Auxiliary Ingredient Mixture (3)

The granules were prepared using (a) thick extract, (b) lactose and starch, (c) polyethylene glycol 4000, and (d) binder 70% ethanol (alcohol) having a weight ratio as shown in Table 3 below. In the manufacturing method, 1kg each of lactose and starch is added to 1kg of dried powder extract, and the mixture is homogeneously prepared. After granulation using 14 mesh nets, polystyrene glycol 4000 is dissolved in 70% ethanol (alcohol), and the weight ratio is 10%. It was prepared under the same conditions as in Example 1-1.

ingredient Content (% by weight) 1: 1: 1 Dry granules (a) Thick Extract 34 (b) Lactose and starch 33 (C) Polystyrene Glycol 4000 33 (d) 70% ethanol (alcohol) Total amount 100

1-4. Preparation of Thickening Extract Auxiliary Ingredient Mixture (4)

The granules were prepared using (a) thick extract and (b) lactose and starch, (c) sodium bicarbonate, and (d) alcohol having a weight ratio as shown in Table 4 below. In the manufacturing method, 1kg each of lactose and starch is added to 1kg of dried powder extract, and the mixture is homogeneously prepared. After granulation using 14 mesh nets, 70% ethanol (alcohol) is used. It was prepared under the same conditions as in Example 1-1 so that the weight ratio was 5%.

ingredient Content (% by weight) 1: 1: 1 Dry granules (a) Thick Extract 34 (b) Lactose and starch 33 (c) baking soda 33 (d) 70% ethanol Total amount 100

1-5. Preparation of Thickening Extract Auxiliary Ingredient Mixture (5)

The granules were prepared using (a) thick gourd extract and (b) lactose and starch, (c) precipitated calcium carbonate, and (d) 70% ethanol (alcohol) having a weight ratio as shown in Table 5 below. In the manufacturing method, 1kg of lactose and starch are added to 1kg of dried powder extract, and the mixture is homogeneously prepared. After granulation using 14 mesh net, precipitated calcium carbonate (20-100 mesh, 90% or more) is 70% ethanol. It was prepared under the same conditions as in Example 1-1 to dissolve in (alcohol) and to have a weight ratio of 5%.

ingredient Content (% by weight) 1: 1: 1 Dry granules (a) Thick Extract 34 (b) Lactose and starch 33 (c) Precipitated calcium carbonate 33 (d)  70% ethanol (alcohol) Total amount 100

1-6. Preparation of Thickening Extract Auxiliary Ingredient Mixture (6)

The granules were prepared by using the following weight ratios (a) thick extract and (b) lactose and starch, (c) sodium hydrogen phosphate, and (d) 70% ethanol (alcohol). The method is prepared by homogeneously preparing the mixture by adding 1 kg each of lactose and starch to 1 kg of the dry powder extract powder, and then granulating using 14 mesh nets. Sodium dihydrogen phosphate (20-100 mesh, 90% or more, based on anhydride) Was prepared in the same conditions as in Example 1-1 to dissolve in 70% ethanol (alcohol) to a weight ratio of 5%.

ingredient Content (% by weight) 1: 1: 1 Dry granules (a) Thick Extract 34 (b) Lactose and starch 33 (c) Sodium hydrogen phosphate 33 (d) 70% ethanol (alcohol) Total amount 100

1-7. Preparation of Thickening Extract Auxiliary Ingredient Mixture (7)

The granules were prepared using (a) thick extract and (b) lactose and starch, (c) anhydrous citric acid, and (d) 70% ethanol (alcohol) having a weight ratio as shown in Table 7 below. In the manufacturing method, 1 kg of lactose and starch were added to 1 kg of dried powder extract, and the mixture was homogeneously prepared. After granulation using 14 mesh nets, citric anhydride (20-100 mesh, 90% or more) was added to 70% ethanol ( It was prepared under the same conditions as in Example 1-1 to dissolve in alcohol) to 5% by weight.

ingredient Content (% by weight) 1: 1: 1 Dry granules (a) Thick Extract 34 (b) Lactose and starch 33 (c) Anhydrous Citric Acid 33 (d) 70% ethanol (alcohol) Total amount 100

1-8. Preparation of Thickening Extract Auxiliary Ingredient Mixture (8)

The granules were prepared using (a) thick extract and (b) lactose and starch, (c) sodium bicarbonate, and (d) 70% ethanol (alcohol) having a weight ratio as shown in Table 9 below. The method is prepared by homogeneously preparing the mixture by adding 1 kg of lactose and starch to 1 kg of the dry powder extract, and then granulating it using 14 mesh nets, and then ascorbic acid (20-100 mesh, 90% or more) 70% ethanol. It was prepared under the same conditions as in Example 1-1 to dissolve in (alcohol) and to have a weight ratio of 5%.

ingredient Content (% by weight) 1: 1: 1 Dry granules (a) Thick Extract 34 (b) Lactose and starch 33 (c) Ascorbic acid 33 (d) 70% ethanol (alcohol) Total amount 100

1-9. Preparation of Thick Extract Extract Mixture (9)

To prepare a granule using (A) Example 1-4 and (B) Example 1-7 having a weight ratio as shown in Table 4. The preparation method was prepared by mixing the granules of Example 1-7 in a ratio of 1: 0.5 to 1 part of the granules of Example 1-4.

ingredient Content (% by weight) 1: 0.5 Mixed granules (A) (a) Thick Extract 66 (b) Lactose and starch (c) baking soda (d) 70% ethanol (alcohol) (B) (a) Thick Extract 34 (b) Lactose and starch (c) Anhydrous Citric Acid (d) 70% ethanol (alcohol) Total amount 100

1-10. Preparation of Thick Extract Extract Mixture (10)

To prepare a granule using (A) Example 1-4 and (B) Example 1-8 having a weight ratio as shown in Table 10. The preparation method was prepared by mixing the granules of Example 1-8 in a 1: 0.5 ratio to 1 part by weight of the granules of Example 1-4.

ingredient Content (% by weight) 1: 0.5 Mixed granules (A) (a) Thick Extract 66 (b) Lactose and starch (c) baking soda (d) 70% ethanol (alcohol) (B) (a) Thick Extract 34 (b) Lactose and starch (c) Ascorbic acid (d)  70% ethanol (alcohol) Total amount 100

1-11. Preparation of Thick Extract Extract Mixture (11)

To prepare a granule using (A) Example 1-5 and (B) Example 1-7 having a weight ratio as shown in Table 11. The preparation method was prepared by mixing the granules of Example 1-7 in a 1: 0.5 ratio to 1 part by weight of the granules of Example 1-5.

ingredient Content (% by weight) 1: 0.5 Mixed granules (A) (a) Thick Extract 66 (b) Lactose and starch (c) Precipitated calcium carbonate (d)  70% ethanol (alcohol) (B) (a) Thick Extract 34 (b) Lactose and starch (c) Anhydrous Citric Acid (d) 70% ethanol (alcohol) Total amount 100

1-12. Preparation of Thick Extract Extract Mixture (12)

To prepare a granule using (A) Example 1-5 and (B) Example 1-8 having a weight ratio as shown in Table 12. The preparation method was prepared by mixing the granules of Example 1-8 in a 1: 0.5 ratio to 1 part by weight of the granules of Example 1-5.

ingredient Content (% by weight) 1: 0.5 Mixed granules (A) (a) Thick Extract 66 (b) Lactose and starch (c) Precipitated calcium carbonate (d) 70% ethanol (alcohol) (B) (a) Thick Extract 34 (b) Lactose and starch (c) Ascorbic acid (d) 70% ethanol (alcohol) Total amount 100

1-13. Preparation of Thick Extract Extract Mixture (13)

To prepare a granule using (A) Example 1-6 and (B) Example 1-7 having a weight ratio as shown in Table 13. The preparation method was prepared by mixing the granules of Example 1-7 in a ratio of 1: 0.5 to 1 part of the granules of Example 1-6.

ingredient Content (% by weight) 1: 1 Mixed granules (A) (a) Thick Extract 50 (b) Lactose and starch (c) Sodium hydrogen phosphate (d) 70% ethanol (alcohol) (B) (a) Thick Extract 50 (b) Lactose and starch (c) Anhydrous Citric Acid (d) 70% ethanol (alcohol) Total amount 100

1-14. Preparation of Thick Extract Extract Mixture (14)

To prepare a granule using (A) Example 1-6 and (B) Example 1-8 having a weight ratio as shown in Table 4. The preparation method was prepared by mixing the granules of Example 1-8 in a 1: 0.5 ratio to 1 part by weight of the granules of Example 1-6.

ingredient Content (% by weight) 1: 1 Mixed granules (A) (a) Thick Extract 50 (b) Lactose and starch (c) Sodium hydrogen phosphate (d) 70% ethanol (alcohol) (B) (a) Thick Extract 50 (b) Lactose and starch (c) Ascorbic acid (d) 70% ethanol (alcohol) Total amount 100

Example 2. Preparation of Rapid Release Composition

2-1. Rapid release composition example (1)

0.1 mg of (b) magnesium stearate corresponding to 0.1% of 1 part of dried granules prepared in Example 1-1 was mixed homogeneously, and then directly put into a tablet press to give 500 mg / tablet (hardness 3). Tablets having a composition corresponding to ˜6 Kp) were prepared.

ingredient Content (weight) (a)  Thick Extract 99.9  Lactose and starch (b) Magnesium stearate 0.1 sum 100

2-2. Rapid release composition example (2)

0.1 mg of (b) magnesium stearate corresponding to 1% of dry granules prepared in Example 1-2 was added homogeneously, and then mixed with a tableting machine to give 500 mg / tablet (hardness 3). Tablets having a composition corresponding to ˜6 Kp) were prepared.

ingredient Content (weight) (a) Thick Extract 99.9 Lactose and starch 70% ethanol (alcohol) (b) Magnesium stearate 0.1 sum 100

2-3. Rapid release composition example (3)

0.1 mg of (b) magnesium stearate corresponding to 1% of dry granules prepared in Example 1-3 was added to the mixture, homogeneously mixed, and then spun with a tableting machine to give 500 mg / tablet (hardness 3). Tablets having a composition corresponding to ˜6 Kp) were prepared.

ingredient Content (weight) (a) Thick Extract 99.9 Lactose and starch Polystyrene Glycol 4000 70% ethanol (alcohol) (b) Magnesium stearate 0.1 sum 100

2-4. Rapid release composition example (4)

0.1 mg of (b) magnesium stearate corresponding to 1% of dry granules prepared in Examples 1-4 was added and mixed homogeneously, followed by a tablet press to give 500 mg / tablet (hardness 3). Tablets having a composition corresponding to ˜6 Kp) were prepared.

ingredient Content (weight) (a) Thick Extract 99.9 Lactose and starch baking soda 70% ethanol (alcohol) (b) Magnesium stearate 0.1 sum 100

2-5. Rapid release composition example (5)

0.1 mg of (b) magnesium stearate corresponding to 1% of dry granules prepared in Example 1-5 was added and mixed homogeneously, followed by a tablet press to give 500 mg / tablet (hardness 3). Tablets having a composition corresponding to ˜6 Kp) were prepared.

ingredient Content (weight) (a) Thick Extract 99.9 Lactose and starch Precipitated calcium carbonate  70% ethanol (alcohol) (b) Magnesium stearate 0.1 sum 100

2-6. Rapid release composition example (6)

0.1 mg of (b) magnesium stearate corresponding to 0.1% of 1 part of dried granules prepared in Example 1-6 was mixed homogeneously, followed by a tablet press to give 500 mg / tablet (hardness 3). Tablets having a composition corresponding to ˜6 Kp) were prepared.

ingredient Content (weight) (a) Thick Extract 99.9 Lactose and starch Sodium hydrogen phosphate 70% ethanol (alcohol) (b) Magnesium stearate 0.1 sum 100

2-7. Rapid release composition example (7)

0.1 mg of (b) magnesium stearate corresponding to 1% of dry granules prepared in Examples 1-7 was added homogeneously, followed by homogeneous mixing with a tableting machine to give 500 mg / tablet (hardness 3). Tablets having a composition corresponding to ˜6 Kp) were prepared.

ingredient Content (weight) (a) Thick Extract 99.9 Lactose and starch Anhydrous Citric Acid 70% ethanol (alcohol) (b) Magnesium stearate 0.1 sum 100

2-8. Rapid release composition example (8)

0.1 mg of (b) magnesium stearate corresponding to 1% by weight of (1) dry granules prepared in Example 1-8 was mixed homogeneously, and then directly put in a tablet press to give 500 mg / tablet (hardness 3). Tablets having a composition corresponding to ˜6 Kp) were prepared.

ingredient Content (weight) (a) Thick Extract 99.9 Lactose and starch Ascorbic acid 70% ethanol (alcohol) (b) Magnesium stearate 0.1 sum 100

2-9. Rapid release composition example (9)

0.1 mg of (b) magnesium stearate corresponding to 1% by weight of the mixed granules prepared in Examples 1-9 was added homogeneously, and then mixed directly with a tablet press to give 500 mg / tablet (hardness 3). Tablets having a composition corresponding to ˜6 Kp) were prepared.

ingredient Content (weight) (a) Thick Extract 99.9 Lactose and starch baking soda 70% ethanol (alcohol) Thick Extract Lactose and starch Anhydrous Citric Acid 70% ethanol (alcohol) (b) Magnesium stearate 0.1 sum 100

2-10. Rapid release composition example (10)

0.1 mg of (b) magnesium stearate corresponding to 1% by weight of the mixed granules prepared in Example 1-10 was added homogeneously, and then mixed directly with a tablet press to give 500 mg / tablet (hardness 3). Tablets having a composition corresponding to ˜6 Kp) were prepared.

ingredient Content (weight) (a) Thick Extract 99.9 Lactose and starch baking soda  70% ethanol (alcohol) Thick Extract Lactose and starch Ascorbic acid 70% ethanol (alcohol) (b) Magnesium stearate 0.1 sum 100

2-11. Rapid release composition example (11)

0.1 mg of (b) magnesium stearate corresponding to 1% by weight of (a) the mixed granules prepared in Example 1-11 was added to the mixture, and then mixed homogeneously. Tablets having a composition corresponding to ˜6 Kp) were prepared.

ingredient Content (weight) (a) Thick Extract 99.9 Lactose and starch Precipitated calcium carbonate 70% ethanol (alcohol) Thick Extract Lactose and starch Anhydrous Citric Acid 70% ethanol (alcohol) (b) Magnesium stearate 0.1 sum 100

2-12. Rapid release composition example (12)

0.1 mg of (b) magnesium stearate corresponding to 1% by weight of the mixed granules prepared in Examples 1-12 was added homogeneously, and then mixed directly with a tablet press to give 500 mg / tablet (hardness 3). Tablets having a composition corresponding to ˜6 Kp) were prepared.

ingredient Content (weight) (a) Thick Extract 99.9 Lactose and starch Precipitated calcium carbonate 70% ethanol (alcohol) Thick Extract Lactose and starch Ascorbic acid 70% ethanol (alcohol) (b) Magnesium stearate 0.1 sum 100

2-13. Rapid release composition example (13)

0.1 mg of (b) magnesium stearate corresponding to 1% of the mixed granules prepared in Examples 1-13 was added homogeneously, and then mixed homogeneously with a tableting machine to give 500 mg / tablet (hardness 3). Tablets having a composition corresponding to ˜6 Kp) were prepared.

ingredient Content (weight) (a) Thick Extract 99.9 Lactose and starch Sodium hydrogen phosphate 70% ethanol (alcohol) Thick Extract Lactose and starch Anhydrous Citric Acid 70% ethanol (alcohol) (b) Magnesium stearate 0.1 sum 100

2-14. Rapid release composition example (14)

0.1 mg of (b) magnesium stearate corresponding to 1% by weight of the mixed granules prepared in Examples 1-14 was added to the mixture, and then mixed homogeneously, followed by a tablet press to give 500 mg / tablet (hardness 3). Tablets having a composition corresponding to ˜6 Kp) were prepared.

ingredient Content (weight) (a) Thick Extract 99.9 Lactose and starch Sodium hydrogen phosphate 70% ethanol (alcohol) Thick Extract Lactose and starch Ascorbic acid 70% ethanol (alcohol) (b) Magnesium stearate 0.1 sum 100

2-15. Rapid release composition example (15)

Mx 117 (thick extract) of Reference Example 1 was dried and pulverized while maintaining 40 to 60 ° C. under reduced pressure of 100 mmHg or less again (a) Dry extract (yield) of average particle size of 50 to 100 mesh (90% or more) 1.4 → 1), and 1 part by weight of this dry extract corresponds to (b) 0.7 part by weight of lactose for direct hitting, 0.3 part by weight of microcrystalline cellulose for direct hitting, (c) 0.1 part by weight of colloidal silica gel and 0.1% of the total amount. (d) Magnesium stearate was mixed homogeneously and then tableted with a tableting machine to make a tablet corresponding to 500 mg / tablet (hardness 3-6 Kp) having the composition shown in Table 29 below.

ingredient Content (weight) Mixed substrate (a) Thick Extract (Dry Extract) 50.9 (b) Lactose 35 Microcrystalline cellulose 10 (c) Colloidal Silica Gel 4 (d) Magnesium Stearate 0.1 sum 100

2-16. Rapid release composition example (16)

((A) + (b) + (c)) mixed dry composition and (d) sodium bicarbonate (20-100 mesh, 90% or more), except for magnesium stearate prepared in Example 2-15, were added and mixed. And tableted to make tablets. In this case, the tablets corresponding to 500 mg / tablet (hardness 3 to 6 Kp) having the composition shown in Table 30 were produced by directly mixing with a tableting machine after mixing homogeneously (e) magnesium stearate corresponding to 0.1% of the total amount.

ingredient Content (weight) Mixed substrate (a) Thick Extract 89.9 (b) Lactose Microcrystalline cellulose (c) Colloidal Silica Gel (d) baking soda 10 (e) Magnesium Stearate 0.1 sum 100

2-17. Rapid release composition example (17)

0.1 part by weight of ((a) + (b) + (c)) mixed dry granulated composition and (d) precipitated calcium carbonate (20-100 mesh, 90% or more), except for magnesium stearate prepared in Example 2-15. And homogeneously mixing (e) magnesium stearate corresponding to 0.1% of the total amount, followed by a tablet press to make a tablet corresponding to 500 mg / tablet (hardness 3 to 6 Kp) having the composition shown in Table 31 below.

ingredient Content (weight) Mixed substrate (a) Thick Extract 89.9 (b) Lactose Microcrystalline cellulose (c) Colloidal Silica Gel (d) Precipitated Calcium Carbonate 10 (e) Magnesium Stearate 0.1 sum 100

2-18. Rapid release composition example (18)

0.1 weight of ((a) + (b) + (c)) mixed dry granulated composition and (d) sodium hydrogen phosphate (20-100 mesh, 90% or more) except for magnesium stearate prepared in Example 2-15 (E) Magnesium stearate corresponding to 0.1% of the total and total amount was mixed homogeneously, followed by a tablet press to make a tablet corresponding to 500 mg / tablet (hardness 3 to 6 Kp) having the composition shown in Table 32 below.

ingredient Content (weight) Mixed substrate (a) Thick Extract 89.9 (b) Lactose Microcrystalline cellulose (c) Colloidal Silica Gel (d) Sodium hydrogen phosphate 10 (e) Magnesium Stearate 0.1 sum 100

2-19. Rapid release composition example (19)

(E) Citric anhydride (20 to 100 mesh), which corresponds to half the amount of ((a) + (b) + (c) + (d)) mixed dry granulated composition and neutral bath except for magnesium stearate prepared in Example 2-16. , More than 90%) and (f) magnesium stearate corresponding to 0.1% of the total amount homogeneously, and then hit by a tablet press to correspond to 500 mg / tablet (hardness 3 to 6 Kp) having the composition shown in Table 33. Tablets were made.

ingredient Content (weight) Mixed substrate (a) Thick Extract 94.9 (b) Lactose Microcrystalline cellulose (c) Colloidal Silica Gel (d) baking soda (e) Anhydrous Citric Acid 5 (f) Magnesium Stearate 0.1 sum 100

2-20. Rapid release composition example (20)

(E) Ascorbic acid (20-100), which corresponds to half the amount of ((a) + (b) + (c) + (d)) mixed dry granulated composition and neutral bath except for magnesium stearate prepared in Example 2-16. Mesh, 90% or more) and (f) magnesium stearate corresponding to 0.1% of the total amount homogeneously mixed, and then hit by a tablet press to correspond to 500 mg / tablet (hardness 3 to 6 Kp) having the composition shown in Table 34 below. Made tablets.

ingredient Content (weight) Mixed substrate (a) Thick Extract 94.9 (b) Lactose Microcrystalline cellulose (c) Colloidal Silica Gel (d) baking soda (e) Ascorbic acid 5 (f) Magnesium Stearate 0.1 sum 100

2-21. Rapid release composition example (21)

(E) Citric anhydride (20-), which corresponds to half the amount of ((a) + (b) + (c) + (d)) mixed dry granulated composition and precipitated calcium carbonate except the magnesium stearate prepared in Example 2-17. 100 mesh, 90% or more) and (f) magnesium stearate corresponding to 0.1% of the total amount was mixed homogeneously, and then hit by a tablet press to 500 mg / tablet (hardness 3 to 6 Kp) having the composition shown in Table 35 below. The corresponding tablet was made.

ingredient Content (weight) Mixed substrate (a) Thick Extract 94,9 (b) Lactose Microcrystalline cellulose (c) Colloidal Silica Gel (d) Precipitated Calcium Carbonate (e) Anhydrous Citric Acid 5 (f) Magnesium Stearate 0.1 sum 100

2-22. Rapid release composition example (22)

(E) Ascorbic acid (20), which corresponds to half the amount of ((a) + (b) + (c) + (d)) mixed dry granulated composition and precipitated calcium carbonate except for magnesium stearate prepared in Example 2-17. ~ 100 mesh, 90% or more) and 500 mg / tablet (hardness 3 ~ 6 Kp) having the composition shown in Table 36 by homogeneously mixing (f) magnesium stearate corresponding to 0.1% of the total amount, followed by a tablet press. Tablets made for this.

ingredient Content (weight) Mixed substrate (a) Thick Extract 94.9 (b) Lactose Microcrystalline cellulose (c) Colloidal Silica Gel (d) Precipitated Calcium Carbonate (e) Ascorbic acid 5 (f) Magnesium Stearate 0.1 sum 100

2-23. Rapid release composition example (23)

(E) Citric anhydride (20), which corresponds to half the amount of ((a) + (b) + (c) + (d)) mixed dry granulated composition and sodium dihydrogen phosphate except for magnesium stearate prepared in Examples 2-18. ~ 100 mesh, 90% or more) and 500 mg / tablet (hardness 3 ~ 6 Kp) having the composition shown in Table 37 by homogeneously mixing (f) magnesium stearate corresponding to 0.1% of the total amount, followed by a tablet press. Tablets made for this.

ingredient Content (weight) Mixed substrate (a) Thick Extract 94.9 (b) Lactose Microcrystalline cellulose (c) Colloidal Silica Gel (d) Sodium hydrogen phosphate (e) Anhydrous Citric Acid 5 (f) Magnesium Stearate 0.1 sum 100

2-24. Rapid release composition example (24)

(E) Ascorbic acid corresponding to half the amount of ((a) + (b) + (c) + (d)) mixed dry granulated composition and sodium dihydrogen phosphate except for magnesium stearate prepared in Examples 2-18 ( 20 to 100 mesh, 90% or more) and 500 mg / tablet (hardness 3 to 6 Kp) having the composition shown in the following Table 38 by homogeneously mixing (f) magnesium stearate corresponding to 0.1% of the total amount with a tableting machine. Tablets).

ingredient Content (weight) Mixed substrate (a) Thick Extract 94.9 (b) Lactose Microcrystalline cellulose (c) Colloidal Silica Gel (d) Sodium hydrogen phosphate (e) Ascorbic acid 5 (f) Magnesium Stearate 0.1 sum 100

2-25. Rapid release composition example (25)

Mx 117 (thick extract) of Reference Example 1 was vacuum dried and pulverized while maintaining 40 to 60 ° C. at a reduced pressure of 100 mmHg or less again, and the dry extract (a yield of 1.4 → 1) having an average particle size of 50 to 100 mesh (90% or more). (A) 0.3 parts by weight of lactose for direct hitting, 0.1 part by weight of microcrystalline cellulose for direct hitting, (c) 0.1 part by weight of sodium starch glycolate, 0.1 weight by weight of starch Part, (d) 0.1 parts by weight of colloidal silica gel and 0.1% of the total amount of (e) 500 mg / tablet having a composition shown in the following Table 39 by homogeneous mixing with a tableting machine and then (hardness 3 ~ 6 Kp).

ingredient Content (weight) Mixed substrate (a) Thick Extract (Dry Extract) 50.9 (b) Lactose 20 Microcrystalline cellulose 7 (c) Sodium starch glycolate 7 Gelatinized starch 7 (d) Colloidal silica gel 7 (e) Magnesium Stearate 0.1 sum 100

Experimental Example 1. Content Measurement

In order to determine the content of the fast-release preparation of the pakbak extract, the content of the contents was measured by the following experimental method using high-speed liquid chromatography (HPLC, Younglin equipment).

The tablets prepared by the manufacturing method of Reference Example 1 were each placed in an airtight container (a plastic container which did not leak when left at 100 mmHg for 30 minutes), and placed in a life tester having a relative humidity of 60 ± 5% at 40 ° C. for 6 months. The specimens were left standing and examined at 2-month intervals. Grind each sample to fine powder, precisely weigh about 1.0mg of magnool, place it in a 100 ml volumetric volumetric flask, add 70 ml of methanol, ultrasonically extract for 10 minutes, and add a small amount of methanol. Fit. This solution was filtered through a membrane filter and tested according to the high performance liquid chromatography conditions as shown in Table 40 below.

High performance liquid chromatography (HPLC, Waters) conditions column Agilent C18, 4.6mm id x 150mm Mobile phase Acetonitrile: Water: Acetic acid = 50: 50: 1 Flow rate  1.0 ml / min Detector 289 nm absorbance detector

As a result of the experiment, as shown in Figure 1, it can be seen that the main peaks of honokiol and magnool, which are the constituents of the hooted extract at 11.1 and 17.6 minutes, respectively. g, magnol 1,3 mg / g), the content of each formulation contained 98.0 to 102.0% in terms of the corresponding weight, indicating that the pickies of the two components are completely separated and are sufficient under the conditions of the quantitative method. can do.

Experimental Example 2. Disintegration Test

In order to compare the disintegration rate according to the disintegration time of the granules and tablets prepared in the above examples, each granule and tablets obtained in the above examples were each placed in an airtight container (a plastic container which did not leak when left at 100 mmHg for 30 minutes). It was put in a life tester (40 ° C, 60 ± 5% relative humidity) and left for 6 months. Each sample was examined at 2 month intervals and tested with purified water according to the disintegration test method of the Korean Pharmacopoeia. Six tablets were used for the tablets and six (1 g) each for the granules (each value; average value, n = 6).

As a result, as shown in Table 41 it was confirmed excellent disintegration effect.

In addition, as a result of the experiment to compare the disintegration rate according to the disintegration time, as shown in Figure 2, when comparing the Example 1-1 and Example 1-9, the disintegration while leaving for 6 months as the addition of auxiliary components Even if the test was carried out, Example 1-1 had a longer disintegration time, resulting in poor disintegration, while Example 1-9 maintained the disintegration without any difference from the initial production state. Examples 2-1 and Example 2- Comparing to 9 it can be seen that the addition of such a disintegrant to maintain the initial disintegration properties over time to maintain the pharmaceutical properties, Examples 2-15, Examples 2-19 and Example 2 Comparing to -25, the stability of the formulation could be maintained as the disintegration by these auxiliaries in the tablet was maintained.

0 2 months 4 months 6 months Example 1-1 17.1 ± 1.6 21.3 ± 2.6 23.8 ± 4.4 32.0 ± 3.4 Example 1-2 16.2 ± 1.5 19.4 ± 1.3 21.3 ± 3.5 21.3 ± 3.5 Example 1-3 9.7 ± 1.0 11.3 ± 1.5 12.1 ± 1.6 13.0 ± 1.4 Example 1-4 8.8 ± 1.0  8.8 ± 1.0  9.2 ± 0.7 10.9 ± 2.9 Example 1-5 8.3 ± 0.8 10.5 ± 2.6 11.2 ± 2.3 12.8 ± 1.7 Example 1-6 9.0 ± 1.0 11.1 ± 2.2 12.2 ± 2.1 12.9 ± 1.7 Example 1-7 11.0 ± 1.5 11.0 ± 1.5 11.1 ± 1.3 12.9 ± 1.7 Example 1-8 13.0 ± 1.0 12.5 ± 0.9 12.9 ± 0.6 12.8 ± 1.6 Example 1-9 5.5 ± 0.6 5.7 ± 1.0 5.7 ± 1.0 5.2 ± 0.8 Example 1-10 5.7 ± 0.8 5.3 ± 1.0 5.8 ± 1.0  6.2 ± 0.8 Example 1-11 5.5 ± 0.9 5.7 ± 1.0 5.7 ± 1.0 5.5 ± 0.9 Example 1-12 5.5 ± 0.9 5.5 ± 1.1 6.0 ± 0.8 6.2 ± 0.8 Example 1-13 5.5 ± 0.9 5.3 ± 1.0  5.5 ± 1.1 5.8 ± 1.0 Example 1-14 5.7 ± 0.8 23.0 ± 1.5 5.5 ± 0.9 5.5 ± 0.9 Example 2-1 23.6 ± 1.6 23.7 ± 1.9 24.2 ± 2.3 22.8 ± 0.5 Example 2-2 23.2 ± 1.9 21.5 ± 2.4 26.6 ± 1.8 27.2 ± 1.3 Example 2-3 20.5 ± 1.3 19.2 ± 1.3 21.8 ± 1.7 22.3 ± 1.9 Examples 2-4 19.2 ± 1.3 18.4 ± 1.2 20.3 ± 1.9 20.5 ± 0.8 Example 2-5 18.4 ± 1.2 18.6 ± 1.4 18.8 ± 0.8 19.2 ± 0.5 Example 2-6 18.6 ± 1.4 18.7 ± 1.4 20.0 ± 1.8 20.8 ± 1.9 Example 2-7 18.7 ± 1.4 18.5 ± 1.2 19.4 ± 1.5 19.5 ± 1.2 Example 2-8 18.5 ± 1.2 6.0 ± 0.8 18.7 ± 1.0 18.7 ± 1.0 Example 2-9 5.5 ± 0.9  5.2 ± 0.8 5.3 ± 1.0 5.5 ± 1.1 Example 2-10 5.2 ± 0.8 5.3 ± 1.0  5.3 ± 0.8 5.5 ± 0.9 Example 2-11 5.5 ± 0.9 5.8 ± 0.8 5.8 ± 1.0 5.8 ± 1.0 Example 2-12 5.3 ± 0.8 5.7 ± 1.0 5.7 ± 0.8 5.7 ± 1.0 Example 2-13 5.5 ± 0.9  5.5 ± 0.9 6.5 ± 0.0 6.2 ± 0.8 Example 2-14 5.5 ± 0.9 19.8 ± 1.3 5.8 ± 1.0 5.7 ± 1.0 Example 2-15 19.8 ± 1.3 18.7 ± 1.5 19.8 ± 1.3 19.2 ± 1.6 Example 2-16 18.7 ± 1.5 19.3 ± 1.2 18.7 ± 1.5 18.8 ± 1.4 Example 2-17 19.3 ± 1.2 17.9 ± 0.7 19.3 ± 1.2 20.3 ± 0.3 Example 2-18 17.9 ± 0.7 5.7 ± 1.0 17.9 ± 0.7 18.0 ± 0.8 Example 2-19 5.7 ± 1.0 5.5 ± 0.9 6.3 ± 0.4 6.2 ± 0.8 Example 2-20 5.7 ± 1.0 5.8 ± 0.8 6.2 ± 0.8 6.2 ± 0.8 Example 2-21 5.5 ± 0.9 5.8 ± 1.0 5.8 ± 0.8 5.8 ± 0.8 Example 2-22 5.8 ± 0.8 5.5 ± 0.9 6.0 ± 0.8 6.2 ± 0.5 Example 2-23 5.5 ± 0.9 5.8 ± 0.8  5.7 ± 0.8 6.5 ± 0.0 Example 2-24 5.5 ± 0.9 5.5 ± 1.1  5.8 ± 1.0 6.0 ± 0.8 Example 2-25 18.5 ± 1.2 18.8 ± 1.0 19.5 ± 1.4 19.8 ± 0.5

Experimental Example 3. Dissolution Test

In order to compare the difference between the granules and the tablet dissolution rate immediately after the preparation of the granules and tablets prepared in the above example (blank display) and after 6 months (full display), the above Examples 1-1 and Example 1-9, Example 2-1, Example 2-8 and Example 2-19, respectively, prepared in airtight containers (plastic containers that did not leak when left standing at 100 mmHg for 30 minutes) at 40 ° C. and relative humidity of 60 ± 5 It was placed in a life tester (%) and left for 6 months. The samples were examined at intervals of 2 months and tested with purified water according to the Dissolution Test Method 2 (paddle method). Six tablets were used for tablets, and 6 granules were used for each 1 g, and the quantitative method was performed according to the method of high performance liquid chromatography (HPLC) test of Experimental Example 1 ((A, B are each value; mean value, n = 6), (c is each value; mean ± standard deviation, n = 6)).

As a result of the experiment, as shown in Figure 3, the granules and tablets of the embodiment was able to confirm the dissolution rate that is constantly released.

[National R & D project supporting this invention]

[Task unique number]

10018327

[Name of Buddha]

Ministry of Knowledge Economy

[Name of research project]

Development of treatment for intractable diseases using natural products of regional industrial technology development task

[Name of Research Project]

Development and Commercialization of Solid Cancer Treatment Using Natural Magnolia

[Host]

Hanseo Pharmaceutical

[Research period]

October 01, 2004 to September 30, 2008

1 is a diagram showing the chromatogram and the integration result by high-performance liquid chromatography of the tablet prepared by the reference method 1,

Figure 2 shows the granules (Example 1-1, Example 1-9) and tablets (Example 2-1, Example 2-9, Example 2-15, Example 2-19 and Example 2-25 Is a diagram comparing the disintegration effect of

Figure 3 compares the dissolution effect of the granules (Example 1-1, Example 1-9) and tablets (Example 2-1, Example 2-9, and Example 2-19) (white symbols; preparation Immediately after, the calibration symbol: 6 months after manufacture).

Claims (12)

A fast-release preparation composition having a high disintegrating and high-solubility effect containing a thick extract. Dry granule composition which dried by mixing (1) thick powder extract dry powder and (2) auxiliary component. The mixed dry granule composition of (1) the dry granule composition of claim 2 and (2) the dry granule composition of claim 2, which are mixed with each other and dried. A rapid-release composition for oral administration comprising (1) the dry granulated composition of claim 2 and (2) ancillary components. The composition according to claim 1 or 2, wherein the hummus extract is Magnolia officinalis or Magnolia obovata, and the composition is obtained from the root, stem, bark, leaf, flower or fruit of the hummus. The composition of claim 5, wherein the extract is an extract available in water including purified water or a solvent selected from a lower alcohol having 1 to 4 carbon atoms such as methanol, ethanol, or a mixed solvent thereof. The composition of claim 2 or 4, wherein the auxiliary component comprises at least one additive component selected from organic acids, alkalis, desiccants, disintegrants or lubricants. 8. The composition of claim 7, wherein said organic acid is at least one organic acid selected from organic acids such as citric acid or ascorbic acid, or mixtures thereof.  8. The composition of claim 7, wherein said alkali is at least one alkali selected from sodium bicarbonate, calcium carbonate, or magnesium carbonate. 8. The composition of claim 7, wherein the desiccant is at least one desiccant selected from colloidal silica gel or silicic acid oxide which can be expressed as SiO ₂ when expressed in an acidic formula. 8. The composition of claim 7, wherein the disintegrant is at least one disintegrant selected from gelatinized starch, lactose, microcrystalline cellulose or sodium glycolate starch. 8. The composition of claim 7, wherein the lubricant is at least one disintegrant selected from magnesium stearate, talc, stearic acid, or light silicic anhydride.

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