KR20120077004A - Curcumin-containing solid dispersion and composition comprising the same - Google Patents

Abstract

PURPOSE: A pharmaceutical composition or food composition containing curcurmin-containing solid dispersion is provided to enhance solubility and elution rate and to improve bioavailability. CONSTITUTION: A soild dispersion contains curcurmin and hydrophilic non-ionic surfactant with 10 or more of HLB value. The weight ratio of the curcurmin and hydrophilic non-ionic surfactant is 1:1-50. The solid dispersion is prepared by dissolving curcurmin and hydrophilic non-ionic surfactant in an organic solvent, or is prepared by drying the solution. The organic solvent is ethanol, methanol, dichloromethane, acetone, acetonitrile, or chloroform. The surfactant is polyethylene glycol, hydroxyl stearate, polyethylnene glycol hydrogenated castor oil, stearoyl macrogol glyceride, polyethylene glycol, sorbitan monooleate, or polyoxyethylene polyoxypropylene block copolymers. A pharmaceutical composition or food composition contains the solid dispersion.

Description

Curcumin-containing solid dispersion and composition comprising the same

The present invention relates to a curcumin-containing solid dispersion and a composition comprising the same, and more particularly to a solid dispersion consisting of curcumin and a hydrophilic nonionic surfactant having an HLB value of 10 or more, and a pharmaceutical composition or a food composition comprising the same. will be.

Curcuma longa (L) is cultivated in Asia, including China, mainly in India, and has been used since ancient times for food, medicinal use, and dyeing. In Korea, Eulgeum, Geumgeum, Okrum, Wanggeum, deepening, also called, has been used as a herbal medicine with excellent efficacy. The bioactive substance of turmeric currently used as a medicinal herb in Korea is a curcuminoid, which is a yellow pigment component containing about 3-6%, and is a mixture composed of curcumin and its derivatives. Of these, curcumin is known to have the strongest pharmacological action.

Curcumin is a water-insoluble polyphenol and exhibits various physiological and pharmacological actions. In other words, antioxidant, anti-inflammatory, antibiotic and anticancer activities have been reported, and liver and kidney protective actions, thrombus formation inhibition, antirheumatic and senile dementia treatment and prevention effects have also been reported. In addition, various animal models and clinical trials have reported that curcumin shows very high safety even at high doses (Anand, P., Kunnumakkara, AB, Newman, RA, Aggarwal, BB, 2007. Bioavailability of Curcumin: Problems and Promises Mol.Pharmaceutics, 4 (6), 807-818).

However, curcumin is extremely low in water solubility, unstable in neutral and alkaline environments and readily degrades. Because of this, curcumin shows low bioavailability due to low solubility and instability in the gastrointestinal tract, even though curcumin has various medicinal effects and safety. Clinical pilot studies have reported that patients who have taken oral 3600 mg of curcumin have a blood level of 11.1 nM. In another study, plasma peaks of 0.41 oral administration of 4-8 g of curcumin were 0.41. To 1.75 μM (Anand, P., Kunnumakkara, AB, Newman, RA, Aggarwal, BB, 2007. Bioavailability of Curcumin: Problems and Promises.Mol.Pharmaceutics, 4 (6), 807-818 ). However, since such high dose oral administration can lower the medication compliance of patients, it is required in the art to improve the bioavailability by improving the solubility and stability in the gastrointestinal tract.

In an attempt to increase the solubility of curcumin, Korean Patent Registration No. 10-0523336 and Korean Patent Registration No. 10-0621741 disclose a water-soluble curcumin covalently bonded to a sugar or mannose such as glucoside in alpha form. It has been disclosed. However, the synthesis of sugar-derivatives by covalent bonds may be difficult to use economically due to the complicated manufacturing method and low yield.

WO 2007/101551 discloses a phospholipid complex of curcumin or an extract comprising the same. US Patent Publication No. 2006/0067998 also discloses a colloidal drug delivery system comprising curcumin or curcumin analogues, wherein the colloidal drug delivery system is a polymer based nanoparticle (or nanoparticle). Spheres), microparticles (or microspheres). However, the phospholipid complex may contain curcumin only in the lipid layer, and the colloidal drug transport system may also have limited curcumin content since the curcumin is enclosed inside the nanoparticles or the microparticles.

WO 2009/101263 discloses a curcumin complex formed by 2-hydroxypropyl-beta-cyclodextrin, sulfobutylether-beta-cyclodextrin, gamma-cyclodextrin. However, since the curcumin complex has to form a complex with the cyclodextrin by lowering the pH using a high pH solution of pH 11 or higher, the curcumin decomposes during the manufacturing process, considering that the curcumin is easily degraded in neutral and alkaline. In the manufacturing process, since the pH must be adjusted in several steps, the manufacturing method may be complicated and inefficient.

In addition, Tønnesen has disclosed micelles using ionic surfactants such as sodium dodecyl sulfate and triton X-100 at neutral pH (Tønnesen, HH, 2002. Solubility, chemical and photochemical stability of curcumin in surfactant solutions.Study of curcumin and curcuminoids VIII.Pharmazie, 57 (12), 820-824), the ionic surfactants used in the study are generally limited in their use due to their toxicity in the gastrointestinal tract. .

Meanwhile, WO 2006/022012 discloses a curcumin-containing solid dispersion obtained by dissolving curcumin and polyvinylpyrrolidone in alcohol and spray drying the same. The curcumin-containing solid dispersion has an advantage of effectively improving the solubility of curcumin. However, in order to increase the bioavailability of curcumin, it is required to increase not only the solubility of curcumin but also the stability in the gastrointestinal tract, but the solid dispersion of curcumin and polyvinylpyrrolidone may increase There is a disadvantage that is not satisfactory yet.

The present invention not only improves the solubility of curcumin in water, but also improves stability, thereby lowering the rate of decomposition in the gastrointestinal tract during oral administration, thereby resulting in improved curcumin-containing solid dispersion and oral administration. It provides a composition comprising.

That is, an object of the present invention is to provide a curcumin-containing solid dispersion having improved solubility and stability at the same time.

It is also an object of the present invention to provide a pharmaceutical composition or a food composition comprising the curcumin-containing solid dispersion.

According to one aspect of the invention, there is provided a solid dispersion consisting of curcumin and a hydrophilic nonionic surfactant having an HLB value of 10 or more.

In the solid dispersion, the weight ratio of the curcumin and the hydrophilic nonionic surfactant may be in the range of 1: 1-50.

The solid dispersion is a solution obtained by dissolving curcumin in a hydrophilic nonionic surfactant having an HLB value of 10 or more; Or a solution obtained by dissolving curcumin and a hydrophilic nonionic surfactant having an HLB value of 10 or more in an organic solvent. Preferably, the organic solvent may be selected from one or more selected from the group consisting of ethanol, methanol, dichloromethane, acetone, acetonitrile and chloroform, and the drying may be performed under reduced pressure drying, spray drying, freeze drying, or fluidized bed spray drying. Can be performed by

The hydrophilic nonionic surfactants having an HLB value of 10 or more include polyethylene glycol hydroxystearate, polyethylene glycol castor oil, polyethylene glycol hydrogenated castor oil, polyethylene glycol conglyceride, polyethylene glycol almond glyceride, polyethylene glycol trioleate, Polyethylene glycol palm kernel oil, polyethylene glycol capryl / capric triglyceride, lauryl macrogol glyceride, stearoyl macrogol glyceride, polyethylene glycol sorbitan monolaurate, polyethylene glycol sorbitan monostearate, polyethylene glycol sorb Non-triggered tristearate, polyethylene glycol sorbitan tetrastearate, polyethylene glycol sorbitan monooleate, polyethylene glycol sorbitan trioleate, polyethylene glycol Le sorbitan tetra-oleate, polyethylene glycol, sorbitan isostearate, polyethylene glycol sorbitol hexa oleate, and polyoxyethylene polyoxypropylene can be at least one selected from the group consisting of a propylene block copolymer and; Preferably one from the group consisting of polyethylene glycol hydroxystearate, polyethylene glycol hydrogenated castor oil, stearoyl macrogol glyceride, polyethylene glycol sorbitan monooleate, and polyoxyethylene polyoxypropylene block copolymer Can be selected.

In addition, according to another aspect of the present invention, there is provided a pharmaceutical composition or food composition comprising the solid dispersion.

The solid dispersions according to the invention show high bioavailability by significantly increasing the solubility and dissolution rate of curcumin. In particular, the solid dispersion according to the present invention has a markedly improved stability according to pH, thereby lowering the decomposition rate in the gastrointestinal tract, thereby exhibiting further improved bioavailability. Therefore, the solid dispersion according to the present invention can be usefully used in pharmaceutical compositions and food compositions.

Figure 1 shows the results of comparative dissolution test in a pH 6.8 buffer of the solid dispersion (Example 3) and curcumin (Comparative Example 1) obtained according to the present invention.
Figure 2 shows the profile of the curcumin concentration in blood over time when orally administered to rats of solid dispersions (Examples 1 and 3) and curcumin (Comparative Example 1) obtained according to the present invention.

In the present specification, "curcumin" is a compound having a structure of Formula 1 below, and its chemical name is 1,7-bis (4-hydroxy-3-methoxyphenyl) -1,6-heptada Ene-3,5-dione. Curcumin can be chemically synthesized as a known compound or extracted from herbal medicines such as Curcuma longa.L. Thus, the term "curcumin" herein includes chemically synthesized or extracted from a herbal medicine, and further includes a herbal extract including curcumin.

The present invention provides a solid dispersion consisting of curcumin and a hydrophilic nonionic surfactant having an HLB value of 10 or more.

In the solid dispersion, the weight ratio of the curcumin and the hydrophilic nonionic surfactant is preferably in the range of 1: 1 to 50, more preferably in the range of 1: 3 to 20. When the content of the hydrophilic nonionic surfactant is less than 1 weight ratio with respect to the curcumin, not only satisfactory solubility improvement of curcumin is obtained, but also the recrystallization of curcumin, which has been amorphously dispersed in the solid dispersion, may proceed with time. Can be. In addition, when the content of the hydrophilic nonionic surfactant exceeds 50 weight ratio with respect to the curcumin, the viscosity of the solution during the manufacturing process is high and the drying time takes a long time, not only can increase the manufacturing cost but also use excess surfactant Adverse events in the gastrointestinal tract may occur.

The solid dispersion is a solution obtained by dissolving curcumin in a hydrophilic nonionic surfactant having an HLB value of 10 or more; Or a solution obtained by dissolving curcumin and a hydrophilic nonionic surfactant having an HLB value of 10 or more in an organic solvent. For example, when the hydrophilic nonionic surfactant is in liquid form at room temperature, a solid dispersion may be prepared by drying a solution obtained by directly dissolving curcumin in the hydrophilic nonionic surfactant without using an organic solvent. In addition, when the hydrophilic nonionic surfactant is in a non-liquid form at room temperature, a solid dispersion may be prepared by drying a solution obtained by dissolving curcumin and a hydrophilic nonionic surfactant using an appropriate organic solvent. Preferably, the organic solvent may be at least one selected from the group consisting of ethanol, methanol, dichloromethane, acetone, acetonitrile and chloroform. The drying may be carried out by a drying method commonly used in the pharmaceutical field, preferably by vacuum drying, spray drying, lyophilization or drying with fluid bed granulator.

The hydrophilic nonionic surfactant having an HLB value of 10 or more includes polyethylene glycol hydroxystearates; Polyethylene glycol caster oils; Polyethylene glycol hydrogenated caster oils; Polyethylene glycol corn glycerides; Polyethylene glycol almond glycerides; Polyethylene glycol trioleates; Polyethylene glycol palm kernel oils; Polyethylene glycol caprylic / capric triglycerides; Lauryl macrogol glycerides; Stearoyl macrogol glycerides; Polyethylene glycol sorbitan monolaurates; Polyethylene glycol sorbitan monostearates; Polyethylene glycol sorbitan tristearates; Polyethylene glycol sorbitan tetrastearates; Polyethylene glycol sorbitan monooleates; Polyethylene glycol sorbitan trioleates; Polyethylene glycol sorbitan tetraoleates; Polyethylene glycol sorbitan monoisostearates; Polyethylene glycol sorbitol hexaoleates; And polyoxyethylene polyoxypropylene block copolymers (polyoxyethylene / polyoxypropylene block co-polymers) may be selected from the group consisting of one or more, preferably polyethylene glycol hydroxystearate, polyethylene glycol hydrogenated castor oil, stearate One or more selected from the group consisting of royl macrogol glyceride, polyethylene glycol sorbitan monooleate, and polyoxyethylene polyoxypropylene block copolymer, more preferably polyethylene glycol 660 hydroxystearate (e.g., For example, Solutol ^TM HS15, BASF).

Specific examples of the hydrophilic nonionic surfactant having an HLB value of 10 or more include: polyethylene glycol 660 hydroxystearate (eg, Solutol ^™ HS15, BASF), polyethylene glycol 35 castor oil (Cremophor ^™ EL or Cremophor ^™ ELP, BASF) Emulphor ^™ EL or Incrocas ^™ 35, Croda; Emulgin ^™ RO35, Henkel), polyethylene glycol 38 castor oil (Emulgante ^™ EL65, Condea), polyethylene glycol 40 castor oil (Emalex ^™ C-40, Nihon Emulsion; Alkamulus ^™ EL719, Rhone-Poulenc), Polyethylene glycol 50 castor oil (Emalex ^TM C-50, Nihon Emulsion), Polyethylene glycol 60 castor oil (Nikkol ^TM CO-60TX, Nikko), Polyethylene glycol 100 castor oil (Thorney ^TM ), Polyethylene glycol 200 caster Oil (Eumulgin ^TM PRT200, Pulcra SA), Polyethylene Glycol 20 Hydrogenated Castor Oil (Nikkol ^TM HCO-20, Nikko), Polyethylene Glycol 25 Hydrogenated Castor Oil (Simulsol ^{T M} 1292, Seppic; Cerex ^™ ELS 250, Auschem SpA), Polyethyleneglycol 40 Hydrogenated Castor Oil (Cremophor ^™ RH40, BASF; Croduret ^™ , Croda; Emulgin ^™ HRE, Henkel), Polyethyleneglycol 45 Hydrogenated Castor Oil ( Cerex ^TM ELS 450, Auschem Spa), Polyethylene Glycol 50 Hydrogenated Castor Oil (Emalex ^TM HC-50, Nihon Emulsion), Polyethylene Glycol 60 Hydrogenated Castor Oil (Cremophor ^TM RH60, BASF; Nikkol ^TM HCO-60, Nikko Polyethyleneglycol 80 Hydrogenated Castor Oil (Nikkol ^TM HCO-80, Nikko), Polyethyleneglycol 100 Hydrogenated Castor Oil (Nikkol ^TM HCO-100, Nikko), Polyethyleneglycol 20 Corn Glyceride (Crovol ^TM M40, Croda), polyethylene glycol 20 almond glycerides (Crovol ^TM A40, Croda), polyethylene glycol 25 trioleate (TAGAT TO ^TM , Goldschmidt), polyethylene glycol 40 palm kernel oil (palm) kernel oil) (Crovol ^TM PK70, Croda), polyethylene glycol 60 corn glycerides (Crovol ^TM M70, Croda), polyethylene glycol 60 almond glycerides (Crovol ^TM A70, Croda), polyethylene glycol 6 capryl / capric triglycerides (SOFTIGEN ^™ 767, Huls; Glycerox ^TM 767, Croda), lauryl macrogol 32 glycerides (Gelucire ^TM 44/14, Gattefosse), stearoyl macrogol glycerides (Gelucire ^TM 50/13, Gattefosse), polyethylene glycol 20 sorbitan monolaurate ( Tween ^TM 20, Atlas / ICI; Crillet ^TM 1, Croda; DACOL ^TM MLS20, Condea), polyethylene glycol 4 sorbitan monolaurate (Tween ^TM 21, Atlas / ICI; Crillet ^TM 11, Croda), polyethylene glycol 6 sorbitan Monolaurate (Nikkol ^TM GL-1, Nikko), polyethylene glycol 20 sorbitan monopalmitate (Tween ^TM 40, Atlas / ICI; Crillet 2, Croda), polyethylene glycol 20 sorbitan monostearate (Tween ^TM 60, Atlas / ICI; Crillet ^TM 3, Croda), Polyethylene glycol 8 sorbitan monostearate (DACOL ^TM MS, Codea), Polyethylene glycol 6 sorbitan monostearate (Nikkol ^TM TS106, Nikko), polyethylene glycol sorbitan tristearate ( Tween ^™ 65, Atlas / ICI; Crillet ^TM 35, Croda), polyethylene glycol 60 sorbitan tetra stearate (Nikkol ^TM GS460, Nikko), polyethylene glycol 5 sorbitan monooleate ^{(Tween TM 81, Atlas / ICI} ; Crillet TM 41, Croda), polyethylene glycol 6 Sorbitan monooleate (Nikkol ^TM TO-106, Nikko), polyethylene glycol 20 sorbitan monooleate (Tween ^TM 80, Atlas / ICI; Crillet ^TM 4, Croda), polyethylene glycol 40 sorbitan monooleate (Emalex ^TM ET8040, Nihon Emulsion), polyethylene glycol 20 sorbitan trioleate (Tween ^™ 85, Atlas / ICI; Crillet ^TM 45, Croda), polyethylene glycol 30 sorbitan tetraoleate (Nikkol ^TM GO-430, Nikko), polyethylene glycol 40 sorbitan tetraoleate (Nikkol ^TM GO-440, Nikko), polyethylene glycol 20 sorbitan monoiso Stearate (Tween ^™ 120, Atlas / ICI; Crillet 6, Croda), polyethylene glycol sorbitol hexaoleate (Atlas ^™ G-1086, ICI), polyoxyethylene polyoxypropylene block copolymers (Poloxamer ^™ ), and the like. .

The present invention also provides a pharmaceutical composition or food composition comprising the solid dispersion.

The pharmaceutical composition or food composition may be in the form commonly used in the pharmaceutical and food fields, for example, oral preparations such as powders, granules, tablets, capsules, liquids or parenteral preparations such as injections and external preparations. It may be in the form. Preferably, it may be in the form of solid oral preparations such as powders, granules, tablets, capsules and the like. Compositions in the form of oral or parenteral preparations may contain additives such as diluents, disintegrants, binders, lubricants and the like commonly used in the pharmaceutical and food fields.

Hereinafter, the present invention will be described in more detail through Examples and Test Examples. However, these Examples and Test Examples are for illustrating the present invention, and the present invention is not limited to these Examples and Test Examples.

Examples 1-8

To prepare a solid dispersion according to the ingredients and contents of Table 1 below. That is, after curcumin and a hydrophilic nonionic surfactant were mixed, it was dissolved by adding acetone. The resulting solution was dried under reduced pressure at room temperature (about 25 ° C.) to prepare a solid dispersion.

Example One 2 3 4 5 6 7 8 Curcumin (mg) 5 5 5 5 5 5 5 5 Polyethylene glycol 660 hydroxy
Tearate
(Solutol HS15 ^TM) (mg) 25 40 50 100 Polyethylene Glycol 40 Hydrogenated
Castor oil
(Cremophor ^TM RH40) (mg) 50 Polyethylene glycol 20 sorbitan
Monooleate
(Tween ^TM 80) (mg) 50 Stearoyl Macrogol Glyceride
(Gelucire ^TM 50/13) (mg) 50 Polyoxyethylene polyoxypropylene
Block copolymer
(Poloxamer ^TM 407) (mg) 50 Acetone (ml) One One One One One One One One

Comparative Example 1-6

To prepare a solid dispersion (Comparative Examples 2-6) according to the components and contents of Table 2. That is, after curcumin and hydrophobic nonionic surfactant or a hydrophilic polymer were mixed, it was dissolved by adding acetone. The resulting solution was dried under reduced pressure at room temperature (about 25 ° C.) to prepare a solid dispersion.

Comparative example One 2 3 4 5 6 7 Curcumin (mg) 5 5 5 5 5 5 5 Span ^TM 80 (mg) 50 Imwitor ^TM 370 (mg) 50 Labrasol ^TM mg 50 Polyethylene glycol 20000 (mg) 50 Hydroxypropylmethylcellulose (mg) 50 Polyvinylpyrrolidone (mg) 50 Acetone (ml) - One One One One One One

Test Example 1. Solubility Measurement

55 mg of the solid dispersions obtained in Examples 3, 5 to 8, and Comparative Examples 2 to 6, respectively, and 5 mg of Comparative Example 1 were taken in 2 ml of pH 1.2 buffer, 400 rpm at room temperature using a magnetic bar. After stirring for 12 hours at the rate of centrifugation, filtered with a 0.45 μm filter and then each solubility was measured using HPLC. The results are shown in Table 3 below.

Solubility (μg / ml) Example 3 536.38 Example 5 444.35 Example 6 400.18 Example 7 319.83 Example 8 138.40 Comparative Example 1 <0.01 Comparative Example 2 0.01 Comparative Example 3 0.02 Comparative Example 4 19.24 Comparative Example 5 13.13 Comparative Example 6 9.31

From the results in Table 3, it can be seen that the solubility of the solid dispersion obtained using the hydrophilic nonionic surfactant according to the present invention was significantly increased compared to the solid dispersion obtained using the hydrophobic nonionic surfactant or the hydrophilic polymer. have.

Test Example 2 Measurement of Solubility by Content

The solubility of the solid dispersions obtained in Examples 1 to 4 was measured in the same manner as in Test Example 1, and the results are shown in Table 4 below.

Solubility (μg / ml) Example 1 281.65 Example 2 453.57 Example 3 536.38 Example 4 1046.63

From the results of Table 4, it can be seen that the solubility of curcumin increases proportionally as the content of the hydrophilic nonionic surfactant increases.

Test Example 3 Evaluation of Stability of Curcumin According to pH

The stability of the solid dispersions of Examples 3, 5 and 6, curcumin (Comparative Example 1), and the solid dispersions of Comparative Example 7 was evaluated. Samples were taken after 0, 2, 4, 6, 12, and 24 hours while each sample was placed in a buffer of pH 1.2, 6.8, or 7.4 in a 37 ° C. thermostat, and the content of curcumin in the solution was determined using HPLC. It was. The results are shown in Table 5 below.

Sample Buffer content(%) 0 hours 2 hours 4 hours 6 hours 12 hours 24 hours Comparative Example 1 pH1.2 100 97.7 93.2 88.1 83.4 81.8 pH6.8 100 72.4 57.5 52.2 45.4 26.3 pH7.4 100 17.8 13.5 10.4 8.1 2.3 Comparative Example 7 pH1.2 100 95.2 93.8 91.9 83.0 80.0 pH6.8 100 77.9 56.7 46.5 32.4 19.2 pH7.4 100 48.8 22.8 15.7 3.5 3.0 Example 3 pH1.2 100 100 99.9 99.7 98.7 98.3 pH6.8 100 99.8 99.2 98.5 97.7 96.2 pH7.4 100 100 99.7 99.1 95.9 94.9 Example 5 pH1.2 100 99.4 99.3 86.9 81.6 79.9 pH6.8 100 93.0 88.4 87.2 83.5 80.4 pH7.4 100 87.8 87.38 86.9 81.65 79.9 Example 6 pH1.2 100 95.8 92.8 85.1 79.7 72.6 pH6.8 100 95.6 94.3 92.6 89.4 83.4 pH7.4 100 94.0 92.8 85.1 79.7 72.6

From the results in Table 5, curcumin shows a relatively good stability at low pH, but at neutral pH, the decomposition rate is very fast when pure curcumin is present. In addition, the solid dispersion (Comparative Example 7) obtained using polyvinylpyrrolidone, a hydrophilic polymer, exhibited a very similar decomposition rate to Curcumin (Comparative Example 1) without any treatment because the decomposition rate of curcumin was very fast. . In contrast, the solid dispersions obtained according to the invention exhibited excellent stability. Especially in the case of the curcumin of Comparative Example 1 and the solid dispersion of Comparative Example 7 in the condition of pH 7.4, the content of the solid dispersion obtained according to the present invention was maintained at 70% or more after 24 hours. In addition, it can be seen that the solid dispersion obtained according to Example 3 is particularly excellent in stability, since at least about 95% of curcumin is present at all pHs even after 24 hours.

Test Example 4 Comparative Dissolution Test

A comparative dissolution test was performed on the solid dispersion obtained in Example 3 and the curcumin of Comparative Example 1. The comparative dissolution test was performed using 900 ml of pH 6.8 buffer at 37 ° C. and 50 rpm using the method of the Korean Pharmacopoeia Elution Test, and the amount of curcumin eluted at 10, 15, 30, 45, and 60 minutes. Was measured using HPLC. Dissolution test results are shown in Table 6 and FIG. 1.

Time (min) Dissolution rate (%) Example 3 Comparative Example 1 10 42.8 0 15 63.1 0 30 84.1 0 45 89.9 0 60 92.1 0

From the results in Table 6, the solid dispersion obtained in accordance with the present invention shows a dissolution rate of 90% or more in 60 minutes, while the curcumin of Comparative Example 1 hardly elutes.

Test Example 5 Comparison of Bioavailability in Rats

The solid dispersions obtained in Examples 1 and 3 were dissolved in water to prepare a solution. In addition, the curcumin of Comparative Example 1 was suspended in an aqueous solution containing 5% polyethylene glycol 400 to prepare a suspension. The solution and suspension were administered using oral gabbage to male rats (250 g) fasted overnight at a dose of 50 mg / kg on a curcumin basis, respectively. After administration, blood was collected at 15 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, 4 hours, 8 hours, and 12 hours, centrifuged, plasma was collected, and the amount of curcumin in the blood was analyzed using HPLC. . The profile of blood curcumin concentration with time is shown in FIG. 2, and the results of calculating the pharmacokinetic parameters obtained are shown in Table 7.

Cmax (ng / ml) Tmax (hr) AUC _0-12 (ngh / ml) Example 1 55.15 0.25 24.62 Example 3 95.60 0.33 72.84 Comparative Example 1 15.65 0.45 15.31

From the results in Table 7, it can be seen that the solid dispersions prepared according to the present invention exhibit significantly superior bioavailability.

Claims (9)

A solid dispersion consisting of curcumin and a hydrophilic nonionic surfactant having an HLB value of 10 or more. The solid dispersion according to claim 1, wherein a weight ratio of the curcumin and the hydrophilic nonionic surfactant is 1: 1-50. The solution of claim 1, wherein the solid dispersion is a solution obtained by dissolving curcumin in a hydrophilic nonionic surfactant having an HLB value of 10 or more; Or a curcumin obtained by drying a solution obtained by dissolving a hydrophilic nonionic surfactant having an HLB value of 10 or more in an organic solvent. 4. The solid dispersion according to claim 3, wherein the organic solvent is selected from the group consisting of ethanol, methanol, dichloromethane, acetone, acetonitrile and chloroform. The solid dispersion according to claim 3, wherein the drying is performed by reduced pressure drying, spray drying, freeze drying, or fluidized bed spray drying. The method of claim 1, wherein the hydrophilic nonionic surfactant having an HLB value of 10 or more is polyethylene glycol hydroxystearate, polyethylene glycol castor oil, polyethylene glycol hydrogenated castor oil, polyethylene glycol conglyceride, polyethylene glycol almond glyceride, Polyethylene glycol trioleate, polyethylene glycol palm kernel oil, polyethylene glycol capryl / capric triglyceride, lauryl macrogol glyceride, stearoyl macrogol glyceride, polyethylene glycol sorbitan monolaurate, polyethylene glycol sorbitan mono Stearate, polyethylene glycol sorbitan tristearate, polyethylene glycol sorbitan tetrastearate, polyethylene glycol sorbitan monooleate, polyethylene glycol sorbitan trioleate, poly Solid dispersion characterized in that at least one selected from the group consisting of ethylene glycol sorbitan tetraoleate, polyethylene glycol sorbitan monoisostearate, polyethylene glycol sorbitol hexaoleate, and polyoxyethylene polyoxypropylene block copolymer . The method of claim 6, wherein the hydrophilic nonionic surfactant having an HLB value of 10 or more is polyethylene glycol hydroxystearate, polyethylene glycol hydrogenated castor oil, stearoyl macrogol glyceride, polyethylene glycol sorbitan monooleate, and Solid dispersion, characterized in that at least one selected from the group consisting of polyoxyethylene polyoxypropylene block copolymer. A pharmaceutical composition comprising the solid dispersion according to any one of claims 1 to 7. A food composition comprising the solid dispersion according to any one of claims 1 to 7.

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