KR100524700B1 - Pharmaceutical compositions for Hyperlipidemia treatment using of Self Emulsifying drug delivery system - Google Patents

Abstract

The present invention relates to a pharmaceutical composition for treating hyperlipidemia using a self-emulsifying drug delivery system, and more particularly, to improve the bioavailability of poorly soluble hyperlipidemia treatment agent having high hydrophobicity and crystallinity In order to improve the stability of certain surfactants, solubilizers, co-surfactants, and formulations, antioxidants are formulated to prepare nanoemulsion concentrates, and when the drugs are administered to humans, they form nanoemulsions with digestive or bodily fluids. The present invention relates to a pharmaceutical composition for treating hyperlipidemia using a self-microemulsifying drug delivery system that greatly improves bioabsorption and prevents oxidization of an active ingredient into acid during long-term storage.

Description

Pharmaceutical compositions for hyperlipidemia treatment using of Self Emulsifying drug delivery system

The present invention relates to a pharmaceutical composition for treating hyperlipidemia using a self-emulsifying drug delivery system, and more particularly, to improve the bioavailability of poorly soluble hyperlipidemia treatment agent having high hydrophobicity and crystallinity In order to improve the stability of certain surfactants, solubilizers, co-surfactants, and formulations, antioxidants are formulated to prepare nanoemulsion concentrates, and when the drugs are administered to humans, they form nanoemulsions with digestive or bodily fluids. The present invention relates to a pharmaceutical composition for treating hyperlipidemia using a self-microemulsifying drug delivery system that greatly improves bioabsorption and prevents oxidization of an active ingredient into acid during long-term storage.

Simvastatin, a drug for treating hyperlipidemia, is synthesized by introducing a methyl group from the metabolite of the fungus Aspergillus fungus. It not only inhibits biosynthesis, but also reduces unnecessary LDL and triglycerides in patients with hyperlipidemia and also increases HDL, which is necessary for the body, and has great effects on the treatment of many complications caused by atherosclerosis and hyperlipidemia. It is shown.

However, the drug for treating hyperlipidemia is very hydrophobic, so that its solubility in water is only 400 ng / ml, and its solubility in ethanol, methanol and acetone is also poor. In addition, since the drug can cause headache, muscle pain and kidney failure, it should provide a uniform dosage and proper bioavailability.

Currently, the preparations for the treatment of hyperlipidemia are in the form of tablets and have a half-life of 1.1 to 1.7 hours in the blood and a high crystallinity of the drug, so that the absorption rate is 60%, but the actual bioavailability is only 5%.

As described above, the conventional hyperlipidemic drug simvastatin has a low bioavailability due to slow dissolution due to crystallinity and poor solubility of the drug.

In order to compensate for these drawbacks, a technique for increasing the absorption rate and bioavailability by making the formulation into a nano size by simulating simvastatin has been developed, and related arts include the following.

US Pat. No. 4,592,859 uses a method of providing cationic or anionic materials as colloidal particles as a way to enhance the stability of oil / water emulsion systems. U.S. Patent No. 5,965,160 also refers to a system consisting of cationic lipids, oils, fat-soluble fatty alcohols and surfactants as oil components as self-emulsifying oil compositions containing poorly soluble drugs. As triglycerides and long chain triglycerides, those having 8 to 12 carbon atoms are used. However, this is a drug used in the present invention simvastatin is a component to remove the triglyceride component is to reduce their levels, which is a violation of the oil components that can be used in the present invention, and the non-ionic surfactant and It is completely different from the method using auxiliary nonionic surfactants. U.S. Patent 5,753,264 uses vitamin E and sunscreen as active ingredients as a system comprising an emulsion of chitosan microcapsules and an oil / water. However, the purpose of this formulation has been for long periods of time or for sustained mass transfer. In the present invention, simvastatin as an active ingredient, rather than the concept of persistence, aimed at fast-acting drug delivery. U. S. Patent No. 5,744, 155 discloses a method for attaching mucoadhesive polymeric materials to mucosa using an oil / water emulsion. However, the present invention does not aim for mucoadhesiveness, and also does not use a polymer material, but the method of using the emulsion is a similar but completely different system. U. S. Patent No. 5,993, 858 discloses a self-emulsifying drug composition comprising a poorly water-soluble drug and a surfactant, a co-surfactant and a solvent to increase bioavailability. However, since oil or lipids are thermoreversible by temperature, they exist in the solid phase at room temperature, so that oil or lipids disintegrate in the human body and drug is absorbed at the same time as the general drug powder. However, in the present invention, the self-emulsifying system is a liquid, which disintegrates upon human administration, and has a very short time for dissolving the drug, resulting in a rapid peak blood concentration compared to a general formulation, and also in terms of improving bioavailability. In addition, Korean Patent Publication No. 02-42218 invented by the present inventors has developed a pharmaceutical composition for treating hyperlipidemia using a self-emulsifying drug delivery system using a statin active ingredient, a surfactant, a dissolving agent, and a cosurfactant. In this case, however, there was an improvement effect in bioavailability, but there is still room for improvement in terms of stability.

Accordingly, the present invention, in order to improve the above problems, a specific surfactant that can solubilize the drug to improve the bioabsorption and bioefficiency of the statin active ingredient used as a hyperlipidemia treatment agent and a dissolving agent and coplanar surface for improving the absorption rate In order to increase the stability of the drug, a nanoemulsion concentrate containing an active agent is effectively prepared to increase the stability of the formulation, and the drug is delivered to the human body using the concept of a self-emulsifying drug delivery system. It is an object to provide an improved pharmaceutical composition.

The present invention relates to a pharmaceutical composition for treating hyperlipidemia, which contains an active ingredient of statins as an active ingredient, 1 to 20% by weight of an active ingredient of statins, 5 to 60% by weight of a surfactant, 20 to 60% by weight of a solvent, and a cosurfactant. A pharmaceutical composition for treating hyperlipidemia using a self-emulsifying drug delivery system comprising a nanoemulsion concentrate composed of 10 to 50% by weight and 1 to 5% by weight of an antioxidant is characterized by the above.

Referring to the present invention in more detail as follows.

In order to improve the poor solubility of statins active ingredients used in the treatment of hyperlipidemia, the present invention adds a surfactant, a dissolving agent, and a co-surfactant to form a nanoemulsion concentrate to form a self-emulsifying drug delivery system. A pharmaceutical composition configured to improve solubilization and bioavailability. It is also a pharmaceutical composition for enhancing the stability by adding an antioxidant to increase the stability of the formulation.

In the present invention, as an active ingredient, statins, which are effective drugs for treating hyperlipidemia, are used. For example, lovastatin or simvastatin may be preferably used, and their content is 1 in the total content of the nanoemulsion concentrate. 20 weight% is preferable. If the content is less than 1% by weight, it is impossible to formulate due to the large amount of excipients and there is a problem in that the dosage is increased.If the content is more than 20% by weight, it is difficult to dissolve the drug and the size of the particles increases and the body There is a problem in that the absorption rate is reduced.

In the present invention, the pharmaceutically acceptable surfactant used to improve the bioabsorption and bioefficiency of the effective drug is mainly used because of its high irritation and toxicity when ionic. In particular, the surfactant can be used as a dissolving agent that dissolves poorly soluble drugs, and also prevents the recrystallization of drugs in the gastrointestinal tract and stably disperses at pH and temperature to form a stable emulsion, thus making a self-emulsifying drug delivery system (Self Microemulsifying). Drug Delivery System (SMEDDS). The surfactant used in the self-microemulsifying drug delivery system preferably has a water solubility of 7 or more, and more preferably 10 to 15 HLB (Hydrophilic Lipophilic Balance). Mainly used nonionic surfactants are preferably selected from, for example, caster oils, substituted caster oils, twins, spans, lavorasol, lavorafil, brij, more preferably polyoxyl 35 castor oil may be used. Polyoxyl 35 castor oil may be used in the preparation of fat soluble vitamin preparations with an HLB value of about 14 and is preferred for achieving stable oil-in-water emulsions. In addition, polyoxyl 35 castor oil has 83% of hydrophobic polyethyleneglycol ricinoleate and 17% of fatty acid portion of hydrophilic polyethyleneglycol, which is very well soluble in water and has other hydrophobic properties such as chloroform, toluene, xylene, It blends well with the same strong organic solvents and has very good solubility in other alcoholic solvents, castor oil, olive oil and natural and synthetic oils such as fatty acids and fatty alcohols. Polyoxyl 35 castor oil has a viscosity of 650-800 mPas and a critical micelle concentration of 0.009%, which can form micelles even in very small amounts.It is very stable in acidic and electrolyte solutions and can be used for beverages and cosmetics. It can also be used together with 30-50% alcohol to make perfumes. Polyoxyl 35 castor oil is also highly dependent on the amount of surfactant and can be used in water-insoluble drugs such as Micronazole, Hexedetine, Clotrimazole, and Benzocaine. It can also be used as an oral dosage form.

The amount of the surfactant used is preferably 5 to 60% by weight in the total content of the nanoemulsion concentrate. If the content of these is less than 5% by weight, the drug is absorbed into the human body to prevent the formation of a stable emulsion, and if it exceeds 60% by weight, it may cause disorders of the gastrointestinal tract, and the formed nanoemulsion may coalesce to precipitate. There may be a phenomenon.

In addition, as a dissolving agent used to improve the absorption rate of the effective drug and reduce the dosage, fatty acid esters, vegetable oils, refined fish oil, pharmaceutically acceptable dissolving agents having strong hydrophobicity, and the like may be used. As monoethyl ester, among fatty acid esters are propylene glycol mono or di fatty acid ester derivatives such as propylene glycol monocaprylate and propylene glycol monolaurate, and polyglyceryl di fatty acid esters such as propylene glycol and polyglyceryl dioleate. The selected one is preferred, and more preferably diethylene glycol monoethyl ether may be used. The amount of these used is preferably 20 to 60% by weight in the total content of the nanoemulsion concentrate. If the content thereof is less than 20% by weight, there is a problem that the drug is not completely dissolved, and if it exceeds 60% by weight, a problem of unstable stable emulsion formation occurs.

In the present invention, the co-surfactant used to improve the dissolution and stability of the nanoemulsion concentrate is a polyhydric alcohol such as polyethylene glycol, alpicoat canal oil, dimethylisosorbide, diethylene glycol monoethyl ether (transcutol) and tetraglycol. The substituted ones are preferable, and their content is preferably 10 to 50% by weight of the total content constituting the nanoemulsion concentrate. If the content thereof is less than 10% by weight, there is a problem in dissolving. If the content exceeds 50% by weight, crystals are precipitated when the nanoemulsion concentrate is diluted in an aqueous phase.

The antioxidant used in the present invention for the stability of the formulation contains 1 to 5% by weight of the total content of the nanoemulsion concentrate, if the content is less than 1% by weight there is a problem that can not exhibit the effect of the antioxidant When it exceeds 5% by weight, there is a problem in that the particles become large in forming the prepared microemulsion. Antioxidants inhibit the reaction to free radicals and inhibit many reactions to heart disease, cancer and other aging. Among these antioxidants, tocopherol acetate is a fat-soluble vitamin and a large amount in fat tissues and liver muscles, and a small amount is stored in platelets, adrenal glands, pituitary gland, testes, ovaries, etc., and is mainly present in the biofilm. Oxidation of biological membranes is also caused by the attack of free radicals occurring inside the membrane (lipid layer). In the present invention, the antioxidant may be used tocopherol acetate, tocopherol acetate is the only antioxidant in the biofilm by inhibiting the oxidation of the biofilm by prolonging the survival of various adult diseases and red blood cells, including cancers such as lung cancer, stomach cancer, bladder cancer, It is known to be effective in strengthening blood vessel walls and inhibiting platelet adhesion. The recommended daily dose varies according to age, gender, and country. However, it is usually prescribed as 15 IU per day for adults and 30 IU for pregnant women.

As described above, the present invention uses the antioxidant tocopherol, which is an antioxidant, in order to prevent the statin active ingredient from being oxidized to be acid, so that the content of the drug can be made constant, thereby obtaining stabilization of the preparation.

In addition, the weight ratio of surfactant, solubilizer, co-surfactant, and antioxidant used in the preparation of the nanoemulsion of the composition according to the present invention is to be used by mixing 25 to 35: 15 to 25: 25 to 35: 1 to 5. desirable.

In the present invention, when the nanoemulsion concentrate is injected into a soft capsule and administered to a human body, the emulsion is rapidly emulsified in the gastrointestinal tract by itself, and the drug causes the absorption of the body in the body in a few minutes by using a self-emulsifying drug delivery system and enhances the absorption power. It can be formulated in a form that maximizes bioavailability. That is, the present invention includes a soft capsule containing the pharmaceutical composition as an active ingredient and containing a conventional excipient.

Pharmaceutical compositions according to the invention may be formulated in the form of transdermal absorbents, or solidified emulsions.

In addition, the pharmaceutical composition according to the present invention may further contain pharmaceutically acceptable additives such as lecithin, viscosity modifier, fragrance, preservative, pigment, glycerin, sorbitol, gelatin, etc., which can be easily selected by those skilled in the art. .

The effective dosage of the composition according to the present invention can be varied depending on the age, physical condition, weight, etc. of the patient, but is generally administered within the range of 1 to 100 mg / kg (weight) / day. In addition, within a daily effective dosage range is divided into once a day or several times a day.

As such, the composition according to the present invention uses a statin active ingredient as an active ingredient, and a surfactant to improve the bioabsorption and bioefficiency of the drug, a dissolving agent and a cosurfactant and a drug to improve the absorption rate of the drug. In order to enhance the stability of the anti-hyperlipidemic drugs were prepared by the addition of antioxidants to prepare a nanoemulsion concentrate, the drug was absorbed into the body using a self-emulsifying drug delivery system.

Hereinafter, the present invention will be described in more detail based on the following examples, but the present invention is not limited by the examples.

Examples 1-4

Next, a soft capsule was prepared by the composition shown in Table 1 and the following method. Simvastatin was dissolved in diethylene glycol monoethyl ether and Alpicoat Kenal oil while warming to a temperature of about 40 ° C., then cooled at room temperature to add antioxidant and surfactant polyoxyl 35 castor oil (Cremophor EL). After uniformly mixing, the resulting nanoemulsion concentrate was poured into a soft capsule maker as it was prepared in a conventional manner.

Examples 5-10

Next, a soft capsule was prepared by the composition shown in Table 1 and the following method. Simvastatin was dissolved in diethylene glycol monoethyl ether and transcutol, polyethylene glycol, and dimethyl isosorbide cosurfactant, respectively, while warmed to a temperature of about 40 ° C. Tocopherol acetate, an antioxidant, was added and uniformly mixed, and then, the resultant nanoemulsion concentrate was added to a soft capsule preparation by adding a pharmaceutically acceptable additive commonly used in the preparation of the soft capsule.

division Ingredient (% by weight) drug Surfactants Solvent Cosurfactant Antioxidant Simvastatin Cremophor EL Diethylene glycol monoethyl ether Transcutol Alpicoat Canal Oil Dimethylisosorbide Polyethylene glycol Tocopherol Acetate room city Yes One 5.8 34.8 23.1 - 34.8 - - 1.5 2 5.8 34.8 23.1 - 33.3 - - 3 3 5.8 34.8 23.1 - 31.3 - - 5 4 5.8 31.8 23.1 - 34.3 - - 5 5 5.8 34.8 23.1 34.8 - - - 1.5 6 5.8 34.8 23.1 33.3 - - - 3 7 5.8 34.8 23.1 - - - 34.8 1.5 8 5.8 34.8 23.1 - - - 33.3 3 9 5.8 34.8 23.1 - - 34.8 - 1.5 10 5.8 34.8 23.1 - - 33.3 - 3

Test Example 1

The size of the emulsion formed when Examples 1 to 10 meet the water phase was observed and the results are shown in Table 2. The uniformity and size distribution of the relics were measured using the ELS-8000 (Otsuka Electronics) instrument using dynamic light scattering and the average size and distribution according to the laser intensity. In general, the smaller the size of the emulsion is stable and the absorption of the drug is improved, the pharmaceutical composition according to the present invention was found to form a small emulsion of micro or less as shown in the results of Table 2.

division Average size and distribution (nm) Dilute 1/10 in distilled water Dilute 1/10 in artificial gastric juice Dilute 1/10 in artificial intestine room city Yes One 24.1 (22.8-30) 25.9 (25.6-26.9) 25.4 (27.8-29.3) 2 40.1 (39-41.3) 65.9 (63.4-68.4) 93.4 (89.2-97.6) 3 100.8 (100.1 to 105.5) 100.4 (100.1 to 100.9) 101.8 (100.5-102.5) 4 150.2 (149-155) 138 (131-146) 190 (178-202) 5 75.3 (72.2 to 77.3) 80.3 (79.9-45.7) 51.1 (49.8-52.8) 6 58.8 (40.2-80.4) 60.8 (55.1-65.4) 68.7 (60.1 ~ 85.4) 7 173 (34-300) 133 (50-250) 206 (192-220)

In addition, dilution of the nanoemulsion concentrates prepared in Examples 1 and 6 by 1/10 in artificial intestine from those measured by the dynamic light scattering method according to Test Example 1 is shown in FIGS. 1 and 2, respectively. Looking at Figures 1 and 2 it was also found that because the size of the emulsion is small as described above is stable and the absorption of the drug is improved.

Test Example 2

The drug absorption rate in beagle dogs was investigated by comparing the soft capsules prepared in Example 1 with the simvastatin tablets of the control agent (Zoko-Co., Ltd., MSD).

As test animals, healthy mature beagle dogs (males) weighing 10.20 to 12.20 kg (10.99 ± 0.87 kg) were used and basal reared in each cage for about two weeks prior to testing. Basic physical examination, blood and serum tests, abdominal radiography, and abdominal ultrasonography confirmed clinical health and fasted 24 hours prior to drug administration. Beagle dogs were divided into two groups, and the soft capsules according to Example 1 and the simvastatin tablet as a control agent were administered, and a crossover test was performed after a sufficient period of rest (three weeks).

In the test method, first, 10 mg of the soft capsule according to Example 1, 20 mg of the soft capsule according to Example 1 and 20 mg of the simvastatin tablet, a control agent, were administered to a beagle dog, followed by 0 minutes, 20 minutes, 40 minutes, and 1 hour. 5 ml of blood with a heparinized disposable syringe in the neck vein at time, 1 hour 20 minutes, 1 hour 40 minutes, 2 hours, 2 hours 20 minutes, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours Was taken. 100 μl of the internal standard substance solution was added to 1.0 ml of plasma, shaken, and methanol and water were sequentially flowed through a C18 solid-phase extraction column (Sep-pak, waters). Next, the plasma sample was packed into a column, vacuumed, and washed with 3 ml of water twice, followed by 0.5 ml of methanol twice, and the eluate was collected. The solvent of the eluate was evaporated to dryness under a nitrogen stream of 35 ° C.

0.2 ml of acetonitrile: water 40:60 mixture was completely dissolved in the residue for 1 minute, and analyzed by HPLC (HPLC: column fluorofix, mobile phase (ACN: buffer = 55:45), detection 238 nm, column temperature 50 ℃, injection volume 100 μl).

The results of blood concentration of simvastatin acid with time after administration of the soft capsule and the control agent of Example 1 are shown in FIG. 3.

As shown in FIG. 3, the soft capsule of the nanoemulsion concentrate according to the present invention had a higher bioavailability than the control tablet 20 mg despite the administration of 10 mg. It was confirmed that high.

In addition, the results of drug absorption over time after the soft capsule and the control agent of Example 1 are shown in Table 3.

Metric Control agent Formulation of Example 1 (self-microemulsifying type 10 mg) Formulation of Example 1 (20 mg of self-emulsifying type) ¹⁾ AUC _{0 →} 10hr (ng · hr / mL) 91.57 ± 17.13 105.30 ± 22.59 173.06 ± 40.32 ²⁾ C _max (ng / ml) 18.18 ± 1.61 20.07 ± 3.03 35.35 ± 3.03 ³⁾ T _max (hr) 3 ± 1.36 1.4 ± 0.09 1.4 ± 0.09 Bioavailability (%) 115% 189% 1) shows the area under the blood-time curve; 2) shows the highest blood concentration; and 3) shows the time to reach the highest blood concentration.

Looking at Table 3, it can be seen that the soft capsule of the nanoemulsion concentrate according to the present invention has a much higher bioavailability than the control agent.

As can be seen in Test Examples 1 and 2, the nanoemulsion concentrate according to the present invention has a small size of the emulsion formed when it is in contact with the water phase and is stable, and the absorption of the drug is fast. Therefore, the bioavailability was also high. Therefore, Examples 2 to 10 having an emulsion size similar to that of Example 1 can also be expected to improve the bioabsorption rate of the drug.

Test Example 3

In order to confirm the stability of the formulation, the soft capsule self-microemulsifying drug prepared in Example 1 was formed at 40 ° C. and 75% relative humidity for two months under the conditions of precipitation, change in turbidity, color change, Observed visual changes such as phase separation, but it was confirmed that it maintains a stable phase with a clear pale yellow light without change. In addition, the samples were taken one at a time and dissolved in acetonitrile to compare the area ratio obtained by HPLC to confirm the change in the content of simvastatin over time, the results are shown in FIG.

As shown in FIG. 4, the content of simvastatin at the time of initial measurement was 105%, and after 150 days, the content was maintained at 101.8%. When calculating the degradation rate of simvastatin, up to 90%, which is less than the standard of the US pharmacopoeia, is estimated at 16 months. It was determined that the designed drug is very stable. After two months, there was only a slight decrease in the drug content and no significant change, so the formulation of the designed drug was able to confirm that the drug was kept stable. It was confirmed.

Test Example 4

To check the stability of the self-emulsifying microemulsion-type emulsion, the distribution of the emulsion region and the distribution of the particle size, simvastatin, solubilizer, surfactant, and co-surfactant were mixed with water dropwise. Water is added dropwise to the point where the mixed microemulsion solution becomes transparent, and the area where the microemulsion is formed by connecting the point where the mixed solution becomes transparent after floating the point is shown in FIG. 5. In the blue emulsion region shown in Figure 5 it can be seen that the stable aspect of the drug and the particle size was also confirmed that small.

As shown in FIG. 5, the stable region of the microemulsion was confirmed.

As described above, the pharmaceutical composition for treating hyperlipidemia according to the present invention is formulated with a specific surfactant, a dissolving agent, a co-surfactant, and an antioxidant in an active ingredient for treating hyperlipidemia of statins to prepare a nanoemulsion concentrate, and to prepare a self-emulsifying type By delivering the drug to the human body using the concept of drug delivery system, solubilization and bioavailability of the poorly soluble drug is improved compared to the prior art has the effect of reducing the cost due to the reduced dose of the drug and improve the stability of the formulation.

1 is a graph measuring the size distribution of the emulsion by diluting the simvastatin nanoemulsion concentrate prepared in Example 1 according to the present invention in artificial intestine solution 1/10 by the dynamic light scattering method.

Figure 2 is a graph of the size distribution of the emulsion by diluting the simvastatin nanoemulsion concentrate prepared in Example 6 according to the present invention in artificial intestine solution by dynamic light scattering method.

Figure 3 shows the change in blood concentration of simvastatin acid over time after oral administration of 10 mg, 20 mg of the soft capsules prepared by Example 1 according to the present invention and 20 mg of simvastatin tablets commercially available as control. The graph shown.

Figure 4 is a graph showing the change in the content of simvastatin over time of the soft capsule prepared by Example 1 according to the present invention.

FIG. 5 is a graph showing the stability of the self-emulsifying microemulsion type microemulsion according to Example 1 according to the present invention and the distribution of the size and the area where the emulsion is formed.

Claims (9)

In the pharmaceutical composition for the treatment of hyperlipidemia containing the active ingredient of statins as an active ingredient, 1 to 20% by weight of statins active ingredient 5 to 60% by weight of surfactant selected from nonionic surfactants consisting of castor oils, substituted castor oils, twins, spans, lavorasol, lavorafil and bridges, diethylene glycol monoethyl ether, propylene glycol Fatty acid ester selected from monolaurate, polyglyceryl dioleate, coconut oil, olive oil, corn oil, castor oil, macadamia nut oil, vegetable oil selected from apricot oil, coconut oil and oil containing unsaturated fatty acids, and purified 20 to 60% by weight hydrophobically pharmaceutically acceptable solubilizer selected from fish oil, 10 to 50% by weight of cosurfactant selected from polyethylene glycol, alpicoat canal oil, dimethylisosorbide, diethylene glycol monoethyl ether and tetraglycol %, And nanoemulsion consisting of 1 to 5% by weight of antioxidant of tocopherol acetate Concentrate Pharmaceutical composition for the treatment of hyperlipidemia using a self-emulsifying drug delivery system comprising a. 2. The pharmaceutical composition for treating hyperlipidemia according to claim 1, wherein the active ingredient of the statins is lovastatin or simvastatin. delete delete delete The self-microemulsifying type according to claim 1, wherein the pharmaceutical composition is a mixture of surfactant: solvent: cosurfactant: antioxidant in a weight ratio of 25 to 35:15 to 25:25 to 35: 1 to 5. A pharmaceutical composition for treating hyperlipidemia using a drug delivery system. The pharmaceutical composition for treating hyperlipidemia according to claim 1, wherein the pharmaceutical composition additionally contains a pharmaceutically acceptable additive. 8. The hyperlipidemia treatment according to claim 7, wherein the pharmaceutically acceptable additive is at least one selected from lecithin, viscosity modifier, fragrance, preservative, pigment, glycerin, sorbitol and gelatin. Pharmaceutical composition. A soft capsule comprising the pharmaceutical composition for treating hyperlipidemia according to claim 1 as an active ingredient and a conventional excipient.