KR20050098440A - Rapid-acting oral formulation of artemisia extract using solid dispersion, processing method thereof - Google Patents

Abstract

The present invention relates to a fast-acting solid dispersion oral preparation of a leaf extract and a method for preparing the same. More specifically, the present invention provides a pharmaceutical composition that does not have a carrier function of a leaf extract, a water-soluble polymer, and a solid dispersion effective for treating gastrointestinal diseases. The present invention relates to a fast-acting oral preparation and preparation method thereof of a leaf extract, wherein an acceptable excipient is added to dissolve together in a solvent, followed by spray drying to prepare a solid dispersion.

The fast-acting solid dispersion oral preparation of the lobar extract according to the present invention is an agent which shows the fast-acting effect on gastrointestinal diseases by improving the solubility, dissolution rate and bioavailability in the gastrointestinal tract, compared to the pharmaceutical composition of the conventional lobar extract.

Description

Fast-acting solid dispersion oral preparation of leafy leaf extract and preparation method therefor {RAPID-ACTING ORAL FORMULATION OF ARTEMISIA EXTRACT USING SOLID DISPERSION, PROCESSING METHOD THEREOF}

The present invention relates to a fast-acting solid dispersion oral preparation of a leaf extract, improved dissolution rate and bioavailability, and a preparation method thereof.

The leaf lobe used in the present invention is a perennial herbaceous plant belonging to the family of compositae , the leaf leaf extract extends the blood coagulation time (Pharmaceutical Journal 28 (2): 69-77, 1984), and the flavone extracted from the leaf Anticancer activity ( Chem. Pharm. Bull. 32 (2): 723; 1984), platelet aggregation inhibitory activity ( Zhongguo Zhongyao Zazhi , 17 (6): 353, 1992), antifungal activity ( J. of Chemical Ecology , 19 (11) ), 1993), which are anti-complementary to help the host's defense system and are effective in allergies and inflammation ( Chem. Pharm. Bull. 33 (5): 2028-2034, 1985), lowering blood pressure and sedation ( Indian J. Med. Res. 60, 1972). In addition, eupatilin extracted from the leaves can be used for antitumor (WO 8803805), psoriasis treatment (WO 8803800), allergy treatment (JP 84155314) and aphthous ulcer treatment (CA 2065496 AA) It is known.

The present inventors have found that eupatillin is effective in gastrointestinal diseases in addition to the above-described antitumor and anti-allergic effects, and has filed a patent application for the use of eupatilin as a therapeutic agent for gastrointestinal diseases (Korean Patent Application No. 94-00147). In a continuing study, pharmacologically active ingredient, jaceosidin, was isolated from the leaves and patented for its preparation and its use as a therapeutic agent for gastrointestinal diseases (Korean Patent Application No. 94-39337). It was found that the leaf extract of Ossidine has an effect on inflammatory bowel disease, and patented its use as an agent for treating inflammatory bowel disease (Korean Patent Application No. 96-28230).

In addition, the present inventors have recently removed only the harmful components while maintaining the active ingredient of the leaf extract as it is, the prevention or treatment effect of gastrointestinal diseases or inflammatory bowel disease is superior to conventional leaf extracts that do not remove the harmful components The extraction method was developed and patented for its manufacturing method (Korean Patent Application No. 2003-41628).

By the way, even though the leaf extract has an excellent effect on the prevention or treatment of gastrointestinal diseases or inflammatory bowel disease, the dissolution rate in the gastrointestinal tract is about 40-50%. Although the solubility and elution rate in Esau and low biomembrane permeability are low, the absorption of the drug is delayed, so that the bioavailability is low, but there is no prior art for solubilizing the formulation containing the leaf extracts and the specific formulation. .

Moreover, the prevention or treatment of gastrointestinal diseases or inflammatory bowel disease should be taken in the long run, but patients should take medications in response to symptomatic symptoms such as heartburn, stomach pain, or random discontinuation of medication due to medication insufficiency. As a result, there is a problem in that gastrointestinal diseases are not treated and relapse, and therefore, a fast-acting formulation which is administered in combination with a sustained release formulation has been required.

In order to solve the above problems, the present inventors have conducted a number of studies to formulate fast-acting oral preparations by increasing the bioavailability by excellent dissolution rate and oral absorption rate of leaf extracts that have an excellent effect in the prevention or treatment of gastrointestinal diseases or inflammatory bowel disease. It was. As a result, by adding a pharmaceutically acceptable excipient that does not have a carrier function of a leaf extract, a water-soluble polymer and a solid dispersion, dissolved in a solvent and then spray-dried to prepare a solid dispersion by excellent dissolution rate and oral absorption rate It was confirmed that the utilization rate can be increased, and thus, the present invention was completed by preparing a fast-acting oral preparation of the leaf extract showing rapid drug release.

Accordingly, an object of the present invention is to provide a rapid dissolving solid dispersion oral preparation capable of rapidly eluting a leaf extract, and having an excellent oral absorption rate so as to increase bioavailability.

It is another object of the present invention to provide a method for preparing a fast dissolving solid dispersion oral preparation of a leaf extract.

In order to achieve the above object, the present invention provides a fast-acting oral preparation of a leaf extract, which comprises a solid dispersion prepared by containing a water-soluble polymer as a leaf extract and a carrier.

In addition, the present invention is prepared by preparing a solid dispersion by preparing a solid dispersion by dissolving together in a solvent by adding a pharmaceutically acceptable excipient that does not have a carrier function of a leaf extract, a water-soluble polymer and a solid dispersion. Provided is a method for preparing a fast-acting oral preparation of an extract.

Hereinafter, the present invention will be described in detail.

The present invention adds one or more water-soluble polymers and pharmaceutically acceptable excipients that do not have a carrier function of the solid dispersion, dissolved together in one or more solvents, and then spray-dried to prepare a solid dispersion. The fast-acting oral preparations of the leaf extracts are formulated by the formulation method.

The leaf extract can use the leaf extract obtained by a conventional extraction method, in addition to

1) extracting the leaves of the leaf with alcohol or an aqueous solution of alcohol (step 1)

2) adding an alkaline solution to the extract obtained in step 1 and reacting at 80 ° C. for at least 12 hours (step 2)

3) neutralizing by adding an acidic solution to the extract obtained in step 2 (step 3), or

4) The extract obtained in step 3 may be obtained through a method for preparing a leaf extract, which comprises a step (step 4) of lyophilization after concentration under reduced pressure.

Extracting method of the leaf extract is described in detail in the Republic of Korea Patent Application No. 2003-41628 which the applicant has applied for a patent.

The leaf extract is known to have an excellent effect in the treatment of gastrointestinal diseases, gastritis and gastric ulcer, the effective dose is 60mg once, 180mg per day.

The water-soluble polymers used in the present invention exhibit hydrophilicity, and when these are spray-dried together with the leaf extract, they increase the solubility by hydrophilizing the environment around the leaf extract, and also serve to minimize the activation energy required to dissolve the drug. It also plays a role in maximizing the solubility and dissolution rate of the leaf extract, enhancing the membrane permeability and maintaining physical and chemical stability.

Preferred examples of the water-soluble polymer include methyl cellulose, ethyl cellulose, hydroxymethyl cellulose, hydroxyethyl cellulose, hydroxyethyl methyl cellulose, hydroxypropyl methyl cellulose, carboxymethyl cellulose, sodium carboxymethyl cellulose, and these carboxymethyl Cellulose derivatives including polyvinyl cellulose, polyvinyl alcohol, polyvinylpyrrolidone or copolymers containing the same, polyvinylacetate, polyalkene oxide or polyalkeneglycol, polyethylene-polypropylene polymer, and the like. Two or more types can be used together.

The water-soluble polymer is preferably contained 0.5 to 300 parts by weight relative to the leaf extract.

In addition, the solid dispersion prepared according to the present invention may disperse a pharmaceutically acceptable excipient in a solution in order to perform a desired process, and the excipient used herein is simply irrelevant to the carrier of the solid dispersion. This is to facilitate the granulation operation. Excipients added to the present invention include surfactants, additives such as fatty acids or fatty alcohols, sugars such as white sugar, macion syrup, white sugar, gelatin, sugar and starch syrup, glidants such as magnesium stearate, talc, colloidal silicon dioxide, Excipients such as microcrystalline cellulose, calcium dihydrogen phosphate, starch, mannitol, polyvinylpyrrolidone, sodium starch glycolate, crospovidone, low-substituted hydroxypropyl cellulose, calcium carboxymethylcellulose, It may further include antioxidants, flavoring agents, preservatives, fragrances, sweeteners, pigments, pH adjusting agents and viscosity adjusting agents to prevent oxidation, these are preferably added in the usual amount of use commonly used for the leaf extract .

The surfactant added to the present invention may use various surfactants including pharmaceutically acceptable anionic, cationic, nonionic or amphoteric surfactants. Specifically, polyoxyethylene sorbitan fatty acid ester, sorbitan fatty acid ester, polyoxyethylene fatty acid ester, polyoxyethylene polyoxypropylene block copolymer (polyoxyethylene polyoxypropylene block copolymer), polyoxyethylene polyoxypropylene copolymer, reactant of natural or hydrogenated vegetable oil and ethylene glycol, sodium dioctyl sulfosuccinate (dioctylsulfosuccinic acid sodium salt), lauryl sulfonic acid sodium salt, phospholipids, propylene glycol mono or di fatty acid esters, natural vegetable oils of triglycerides and polyalkylene polyols Trans Esterification products, mono-, di- or mono / di glycerides, of propylene glycol mono or di fatty acid esters with mono-, di- or mono / diglycerides One or more selected from the group consisting of mixtures and derivatives thereof can be used.

Preferably the surfactant is a polyoxyethylene polyoxypropylene block copolymer, a reaction product of natural or hydrogenated vegetable oils with ethylene glycol, polyoxyethylene sorbitan fatty acid esters and propylene glycol mono or di fatty acid esters with mono-, di- Or a mixture of mono / diglycerides.

Fatty acids or fatty alcohols that may be used in the composition of the present invention include citric acid, oleic acid, stearyl alcohol, stearyl alcohol, myristic acid, linoleic acid or lauric acid. (lauric acid), capric acid (capric acid), caprylic acid (caprylic acid), caproic acid (caproic acid) and the like can be used, but is not limited thereto.

Antioxidants that can be used in the compositions of the present invention are butylated hydroxytoluene, sodium bisulfite, α-tocopherol, vitamin C (ascorbic acid), β-carotene (β-carotin), tocopherol acetate, fumaric acid, nalic acid, butylated hydroxyanisole, propyl galate and sodium ascorbate (sodium ascorbate) and the like can be used, but is not limited thereto.

Flavoring agents that can be used in the composition of the present invention may be mixed fruit flavor, apple flavor, strawberry flavor, cherry flavor, peppermint flavor, vanilla flavor, yogurt flavor, drink flavor and the like, but are not limited thereto.

Preservatives that can be used in the composition of the present invention may be used, but are not limited to benzoic acid, sodium benzoate, ethyl paraben, methyl paraben, propyl paraben and the like.

Perfume that can be used in the composition of the present invention may be used, but is not limited to peppermint brain, peppermint oil, orange oil, clove oil, cinnamon oil, strawberry essence and other common fruit flavor and plant essence.

Sweeteners that may be used in the compositions of the present invention may be used, but are not limited to, white sugar, glucose, fructose, aspartame, stevioside, sorbitol, mannitol, oligosaccharide, syrup, macion syrup, and the like.

 The pigments that can be used in the compositions of the present invention are green No. 3, red No. 2, red No. 3, blue No. 1, blue No. 2, yellow No. 4, yellow No. 5, water-soluble mannitol, caramel, titanium oxide, ferric oxide, etc. Can be used, but is not limited to these.

PH adjusting agent that can be used in the composition of the present invention may be used, but is not limited to sodium carbonate, sodium hydroxide, potassium hydroxide, triethanolamine, monoethanolamine and the like.

Viscosity modifiers that may be used in the compositions of the present invention are acacia, bentonite, alginic acid, propylene glycol alginate, polyvinylpyrrolidone, polyvinylalcohol ), Carbopol, polycarbopil, tragacanth gum, xanthan gum, and the like may be used, but are not limited thereto.

The other pharmaceutically acceptable additives are preferably included in 100 parts by weight or less based on the leaf extract.

On the other hand, the present invention provides a method for the preparation of fast-acting oral preparations of leaf extracts, characterized in that the solid extract is prepared by dissolving the leaf extract and the water-soluble polymer in a suitable solvent and then spray drying. In this case, for the purpose of improving the fluidity of the spray dried product, an appropriate excipient may be added and dispersed, followed by spray drying. In particular, in the present invention, by adopting the spray drying as a single process, it is possible to improve the economics and productivity according to the production of leaf extract containing solid dispersion.

When spray drying, the viscosity and solid content of the spray drying liquid, the appearance and flowability of the spray drying product, the particle size of the spray drying product, the particle size distribution, etc. should be taken into consideration. This greatly influences the physical properties of the spray dried material. The injection temperature should be set within a range that does not cause any physical and chemical changes to the leaf extract and the polymer used, and the injection speed and spray pressure of the spray liquid should be carried out in consideration of the drying capacity of the spray dryer. In particular, the exhaust temperature is most closely related to the optimization of the whole process and needs to be carefully controlled. The higher the spray pressure, the lower the solids content of the spray drying liquid, the smaller the particle size of the spray dried material. The higher the intake and exhaust temperatures, the higher the fluidity of the particles, but the higher the bulk density.

When the final spray dried product is formulated into tablets or capsules, it is important not only to have physical properties that can satisfy the pharmaceutical properties such as disintegration and dissolution of the formulation itself, but also to ensure that these properties are not lost during the formulation process. Therefore, the present invention provides a method of optimizing spray drying conditions and other conditions to increase the solubility of the leaf extract and at the same time to have a pharmaceutically acceptable characteristic.

The preparation method according to the preferred spray drying conditions are specifically

1) dissolving the leaf extract and the water-soluble polymer and optionally other pharmaceutically acceptable additives in a solvent (step 1); And

2) the spray drying solution of step 1

Spray drying liquid injection amount: 30-700 ml / min,

Spray drying pressure: 0.5-7 kg / cm 2,

Spray drying intake temperature: 80-250 degreeC,

Spray drying exhaust temperature: 40-150 degreeC,

Solid content of spray drying liquid: 0.5 to 30.0%

Spray drying is carried out under the conditions of (step 2).

At this time, the solvent for dissolving the drug and the water-soluble polymer in the present invention can be used both pharmaceutically acceptable solvent that can dissolve at the same time, for example, dichloromethane, chloroform, ethanol, methanol, acetone, isoprotanol , A liquid obtained by mixing propanol and the like alone or in combination of two or more kinds thereof is not limited to the solvents exemplified above.

The present invention also provides a formulation in which the leaf extract-containing solid dispersion is formulated into tablets, pills, tablets, hard capsules, soft capsules, suspensions, suspension syrups, dry syrups and the like by conventional pharmaceutical methods. do.

Hereinafter, the present invention will be described in detail by examples. However, the following examples are only for illustrating the present invention, and the scope of the present invention is not limited by the examples.

<Example 1> Preparation of the leaf extract containing solid dispersion 1

According to the method described in Korean Patent Application No. 2003-41628, 100 grams of leaf extracts and hydroxypropyl methyl cellulose from which noxious components were removed were dissolved in 1750 grams of 1: 1 (mass ratio) mixed solvent of dichloromethane and ethanol. 10 grams of talc was added and well dispersed to prepare a spray dried liquid. The spray drying solution was spray dried using a spray dryer (Mobile Minor ™) under the following conditions to prepare a leaf extract-containing solid dispersion.

Spray drying liquid injection amount: 50-60 ml / min,

Spray drying pressure: 3 kg / cm 2,

Spray drying intake temperature: 105-115 degreeC,

Spray drying exhaust temperature: 55-65 degrees Celsius,

<Example 2> Preparation of the leaf extract containing solid dispersion 2

Except that 100 grams of polyvinylpyrrolidone was used as the water-soluble polymer, the same procedure as in Example 1 was carried out under the same conditions to prepare a leaf extract-containing solid dispersion.

<Example 3> Preparation of the leaf extract containing solid dispersion 3

Except that 100 grams of methyl cellulose was used as the water-soluble polymer, the same procedure as in Example 1 was carried out under the same conditions to prepare a solid extract containing the leaf extract.

Example 4 Preparation of Solid Dispersion Containing Petal Extract 4

Except that 100 grams of polyvinyl alcohol was used as the water-soluble polymer, the same method as in Example 1 was carried out under the same conditions to prepare a leaf extract-containing solid dispersion.

<Example 5> Preparation of the leaf extract containing solid dispersion 5

Except that 100 grams of carboxymethyl cellulose sodium was used as the water-soluble polymer, the same procedure as in Example 1 was carried out under the same conditions to prepare a solid extract containing a leaf extract.

Example 6 Preparation of Petite Extract-Containing Solid Dispersion 6

As a water-soluble polymer, 100 grams of hydroxypropylmethylcellulose and 50 grams of polyoxyethylene polyoxypropylene block copolymer were dissolved in a solvent, and 10 grams of precipitated calcium carbonate was added thereto to disperse well. Dispersions were prepared.

Example 7 Preparation of Petite Extract-Containing Solid Dispersion 7

A solid dispersion containing a leaf extract was prepared by the same method as in Example 1, except that 100 grams of hydroxypropyl cellulose and 30 grams of a reaction product of a natural or hydrogenated vegetable oil and ethylene glycol were used as a polymer. It was.

Example 8 Formulation of Solid Dispersion 1

After homogeneously mixing 34.0 grams of the solid dispersion composition prepared in Example 1 with 39.1 grams of microcrystalline cellulose and 26.0 grams of calcium carboxymethyl cellulose, granules were prepared by using a roller compactor by dry granulation. 1.0 g of magnesium stearate was mixed with a lubricant, and then filled in an automatic capsule charger to prepare a capsule.

Example 9 Formulation of Solid Dispersion 2

After homogeneously mixing 38.6 grams of the solid dispersion composition prepared in Example 6 with 29.0 grams of microcrystalline cellulose and 21.7 grams of calcium carboxymethyl cellulose, granules were prepared using a roller compactor by dry granulation. After mixing 0.8 grams of magnesium stearate as a lubricant, the capsules were prepared by filling in an automatic capsule filling machine.

Example 10 Formulation of Solid Dispersion 3

30.5 grams of the solid dispersion composition prepared in Example 7 was homogeneously mixed with 29.0 grams of microcrystalline cellulose, 25.8 grams of lactose, and 5.0 grams of calcium carboxymethyl cellulose, and then granulated using a roller compactor by dry granulation. After the preparation, tablets were prepared by mixing 4.5 grams of crospovidone with a disintegrant and 0.8 grams of magnesium stearate with a lubricant.

Example 11 Formulation of Solid Dispersion 4

20.5 grams of the solid dispersion composition prepared in Example 7 was homogeneously mixed with 50.0 grams of lactose and 5.0 grams of calcium carboxymethyl cellulose, and then granules were prepared using a roller compactor by dry granulation. A tablet was prepared by mixing 5.0 grams of low-substituted hydroxypropyl cellulose and 0.5 grams of magnesium stearate with a lubricant.

Comparative Example

8 kg of lactose and 4 kg of corn starch were mixed in a high speed mixer. The mixture was mixed with 3 Kg of leaf extracts prepared in the same manner as in Example 1, combined in a coalescer, and then assembled into No. 20 sieves. After hot-air drying at 60 degreeC, it granulated in No. 20 sieve and obtained granules. The granules were prepared by filling the granules into an automatic capsule filling machine.

Experimental Example 1 Solubility Comparison Experiment

The solubility of the oral test preparations comprising the pharmaceutical compositions of the leaf extracts by the spray drying method of the present invention and the comparative compositions for oral preparations containing the pharmaceutical compositions of the leaf extracts prepared by a conventional wet granulation method were measured and compared.

Specifically, the pH condition (pH = 1.2) in the gastrointestinal tract of the capsule test formulation containing the pharmaceutical composition of the leaf extract prepared from Example 8 and the capsule composition comprising the pharmaceutical composition of the leaf extract prepared from the comparative example The solubility of the drug was measured at pH conditions (pH = 6.8) in the small and large intestine.

The experimental method is as follows.

In an oral preparation prepared in Example 8 and Comparative Example, an amount corresponding to 60 mg of leaf extracts was taken, and a buffer solution of pH 1.2 and pH 6.8 was added (2.0 g of sodium chloride solution of pH 8 solution of KEPCO, 7.0 ml of hydrochloric acid and water). To 1 L. A pH 6.8 solution of 0.2 mol / L potassium dihydrogen phosphate solution was added to 250 mL of 118 mL of 0.2 mol / L sodium hydroxide solution and water to make 1 L.) After the solution was stirred at 37 ° C. for 1 hour, the solubility was measured. Solubility was measured using HPLC after centrifugation.

The results are shown in Table 1.

Solubility and comparison at pH = 1.2 and pH = 6.8 (unit: µg / ml) Formulation pH 1.2 pH 6.8 Comparative Preparation 1.5 3.4 Test formulation 8.1 8.7 Test / Comparison x 100 (%) 540% 256%

As shown in Table 1, the solubility of the oral test preparation prepared from Example 8 of the present invention was 8.1 μg / ml and 8.7 μg / ml at pH = 1.2 and pH = 6.8, respectively, The solubility of the oral comparative formulation was 1.5 μg / ml and 3.4 μg / ml, respectively. In addition, it can be seen that the solubility of the oral preparation according to the present invention is 5.4 times and 2.6 times higher at pH = 1.2 and pH = 6.8 when the solubility is compared.

Therefore, the fast-acting oral preparation by the solid dispersion according to the present invention can be seen that the solubility is very high in the gastrointestinal small intestine and large intestine pH conditions, compared to the preparation prepared by the conventional method, it is constantly dissolved in various pH conditions It can be seen that.

Experimental Example 2 Dissolution Rate Comparison Experiment

The dissolution rates of the oral preparations comprising the pharmaceutical compositions of the fast-acting solid dispersion oral preparations of the leaf extracts of the present invention and the leaf extracts prepared by conventional wet granulation methods were measured and compared.

The experimental method is as follows.

Taking the amount corresponding to 60 mg leaf leaf extract in the oral preparation comprising the pharmaceutical composition of leaf leaf extract prepared in Example 8 and Comparative Example, prepared in the same manner as in Experimental Example 1 of pH = 1.2 and pH = 6.8 500 ml of buffer solution was added to the dissolution tester vessel and stirred at 100 rpm. The content of the leaf extract extracted from the eluted by the paddle method was measured.

The dissolution rate measured at pH = 1.2 is shown in FIG. 1, and the dissolution rate measured at pH = 6.8 is shown in FIG. 2.

As shown in Figure 1 and Figure 2, the oral preparation prepared in Example 8 of the present invention (test formulation) showed a dissolution rate of more than 70% for 10 minutes at pH 1.2 and pH 6.8, 20 minutes to 60 minutes Showed a constant dissolution rate.

On the other hand, the oral preparation prepared in Comparative Example (comparative) showed a lower dissolution rate for each stirring time compared to the oral preparation prepared in Example 8.

Thus, as shown in Figures 1 and 2 oral preparations according to the present invention has a higher dissolution rate at pH = 1.2 and pH = 6.8 compared to the oral preparations prepared from the comparative example, in particular a constant dissolution rate even at various pH It has excellent elution characteristics.

Experimental Example 3 Blood Concentration Comparison Experiment

When the oral preparations according to the present invention and the oral preparations prepared from Comparative Examples were administered to rats, blood concentrations were measured and compared.

The experimental method is as follows.

250-300 g of experimental male white rats (Sprague-Dawely series) were used for the experiment after adapting for about 1 to 2 weeks. Mice fasted for at least 24 hours prior to the start of the experiment were anesthetized with ether and the canal of the left femoral artery was inserted to insert a tube to which a 50 IU / ml heparin-filled syringe was connected. After about 2 hours, when the rat awoke from anesthesia, the solid dispersant prepared in Example 8 and the formulation prepared in Comparative Example were administered with a dose of 20 mg / kg of eupatini using an oral sonde. 0, 5, 10, 20, 30, 1, 2, 4, 6, 8 and 12 hours after administration of the formulation, blood was collected from the left femoral artery at 10,500 rpm. Centrifuged for minutes and plasma was separated and stored at -20 ° C until analysis.

The content of eupatillin in the blood was quantified using HPLC.

The results are shown in FIG.

As shown in FIG. 3, the blood concentration when the solid dispersion preparation (test preparation) of the present invention prepared from Example 8 was administered to a rat was measured by the blood concentration when the preparation (comparative preparation) prepared from the comparative example was administered. It can be seen that higher than the concentration. In addition, it can be seen that the solid dispersion preparation according to the present invention has a maximum blood concentration of 2 times or more and a blood surface area (AUC) of 10 times or more compared to the preparation prepared from the comparative example.

Through such experiments, it can be seen that the solid dispersion according to the present invention has a higher bioavailability than the preparation prepared from the comparative example.

As described above, the present invention provides a fast-acting solid dispersion oral preparation and a preparation method thereof of the lobar extract, which has improved and improved dissolution rate and bioavailability, thereby increasing the solubility and dissolution rate in the gastrointestinal tract and enhancing the biomembrane permeability. It can be usefully absorbed in vivo and can significantly increase the bioavailability. In addition, by presenting a solubilization method and a specific formulation method of the formulation containing the leaf foliar extract, which is a poorly soluble drug, in combination with a sustained release formulation in the prevention or treatment of diseases of the gastrointestinal tract or inflammatory bowel disease can be treated to fundamental gastrointestinal disease treatment .

1 is a dissolution rate according to time after stirring the fast-acting solid dispersion oral preparation of the present invention (test preparation) and the preparation according to the comparative example (comparison preparation) containing 60 mg of leaflets extract in the pH = 1.2 buffer solution of Experimental Example 8 Is a comparison

Figure 2 is a dissolution rate according to time after stirring the fast-acting solid dispersion oral preparation of the present invention (test preparation) and the preparation according to the comparative example (comparison preparation) containing 60 mg of leaf extract in the pH = 6.8 buffer solution of Experimental Example 8 Is a comparison

3 is a comparison of blood concentrations over time after oral administration of a fast-acting solid dispersion oral preparation of the present invention (test preparation) and a comparative preparation (comparison preparation) according to the present invention containing 20 mg of eufatlin of Experimental Example 8 It is.

Claims (6)

Fast-acting oral preparations of a leaf extract comprising a leaf extract and a solid dispersion prepared by containing a water-soluble polymer as a carrier The method of claim 1, wherein the water-soluble polymer is methyl cellulose, hydroxymethyl cellulose, hydroxyethyl cellulose, hydroxyethyl methyl cellulose, hydroxypropyl methyl cellulose, carboxymethyl cellulose, sodium carboxymethyl cellulose and these carboxymethyl Cellulose Derivatives Including Chill Cellulose, Polyvinyl Alcohol, Polyvinyl Pyrrolidone Or Copolymers Comprising The Same, Fast-acting oral preparations of leaf extracts, characterized in that at least one selected from the group consisting of According to claim 2, wherein the water-soluble polymer is a fast-acting oral preparation of the leaf extract, characterized in that 0.5 to 300 parts by weight relative to the leaf extract 4. The leaf extract according to claim 1, wherein the oral preparation is selected from the group consisting of tablets, powders, granules, pills, hard capsules, soft capsules, and oral solutions containing aqueous solutions. Fast-acting oral preparation of The fast-acting oral extract of the leaf extract, characterized in that the solid extract is prepared by adding a pharmaceutically acceptable excipient that does not have a carrier function of the leaf extract, the water-soluble polymer and the solid dispersion, and then dissolving it in a solvent. Method of Preparation for Preparation 6. The method of claim 5, wherein the solvent is at least one selected from the group consisting of dichloromethane, chloroform, ethanol, methanol, acetone, isopropanol and propanol.