KR20070119297A - Rapid-acting fomulation containing nateglinide as an active ingredient - Google Patents

Abstract

A pharmaceutical composition is provided to effectively exert the efficacy of a medicine due to rapid disintegration and a fast dissolution rate of nateglinide, and be usable as a rapid-acting type hypoglycemic agent. A pharmaceutical composition includes nateglinide represented by the following formula 1, soybean polysaccharide, and a pharmaceutically acceptable additive. The nateglinide is contained in an amount of 5-50wt% of the pharmaceutical composition. The soybean polysaccharide is 70-80% dietary fiber containing at least one selected from the group consisting of cellulose, hemicellulose, pectin, gums, and mucilage. The soybean polysaccharide is contained in an amount of 5-50wt% of the pharmaceutical composition. The pharmaceutically acceptable additive is contained in an amount of 15-90wt% of the pharmaceutical composition.

Description

Rapid-acting fomulation containing nateglinide as an active ingredient}

1 is a graph showing the dissolution rate according to the presence of soybean polysaccharide according to an embodiment of the present invention;

Figure 2 is a graph showing the dissolution rate of soybean polysaccharide-containing formulations and prior art prescriptions according to an embodiment of the present invention; And

Figure 3 is a graph showing the dissolution rate of soybean polysaccharide and conventional disintegrant according to an embodiment of the present invention.

The present invention relates to a pharmaceutical composition containing nateglinide having improved fastness as an active ingredient.

Nateglinide; 3-phenyl-2-[(4-propan-2-ylcyclohexanecarbonyl) amino] propanoic acid] is a meglitinide-based white crystalline powder approved in 1999 by the US FDA. The nateglinide stimulates pancreatic beta cells to promote insulin secretion and is known to be useful as a therapeutic agent for diabetes because it exhibits an excellent hypoglycemic effect by oral administration (Japanese Patent Publication No. 4-15221). Compared to other hypoglycemic agents, it is known to have a low incidence of hypoglycemia and high safety in patients with older or renal function, and is effective in type 2 diabetes, which is poorly controlled by diet or exercise therapy. In particular, the nateglinide is widely used when fasting blood sugar is normal and postprandial hyperglycemia is a problem because the effect of normalizing hyperglycemia is excellent.

However, since nateglinide is a poorly water-soluble substance, satisfactory elution does not occur in the case of oral administration with a conventional solid preparation, and thus, it may not exhibit the characteristic effect of nateglinide that lowers blood sugar level within a short time, that is, fast efficacy. Therefore, in order to enhance the fast-acting efficacy of nateglinide, it is necessary to immediately release the drug from the preparation, and therefore, the study of the preparation is necessary.

In order to quickly release the drug from the formulation, first the rapid disintegration of the formulation must take place and show rapid dissolution with the rapid disintegration.

Therefore, a lot of studies of fast-acting disintegrants causing rapid disintegration have been made recently.

Korean Patent Publication No. 2006-0039934 discloses one or more disintegrants selected from nateglinide, camels or salts thereof, sodium carboxymethyl starch, croscarmellose sodium, crospovidone, partially gelatinized starch and low-substituted hydroxypropyl cellulose. It describes about the formulation containing these.

International Publication No. 2005-092319 also describes a formulation containing a disintegrant selected from nateglinide and sodium starch glycoates, crospovidone and mixtures thereof.

However, disintegrants used in such various conventional formulations speed up the rate of disintegration, but are not proportional to the dissolution rate.

On the other hand, soy polysaccharide means a dietary fiber containing cellulose, hemicellulose, pectin, gum, mucilage and the like. As a conventional technique using the same, US Patent Publication No. 2004-0105903 and US Pat. No. 6,669,956 disclose a purification and purification method based on isoflavone, which is a plant extract, as an excipient with soy polysaccharide. However, the effect of the soy polysaccharide on the immediate release has not been published so far.

Therefore, while the present inventors are studying a method for improving the fastness of the pharmaceutical composition containing nateglinide, in the pharmaceutical composition using the soybean polysaccharide as a disintegrant, as well as rapid disintegration, the active ingredient nateglinide is eluted in a short time. It was confirmed that the drug can be effectively exhibited and completed the present invention.

The present invention is to provide a pharmaceutical composition containing nateglinide with improved efficacy as an active ingredient.

The present invention provides a pharmaceutical composition containing nateglinide having improved fastness as an active ingredient.

Hereinafter, the present invention will be described in detail.

The pharmaceutical composition of the present invention comprises nateglinide represented by the following formula (1), soybean polysaccharide which is a fast disintegrating agent, and a pharmaceutically acceptable additive.

The nateglinide according to the present invention may be selected and synthesized by methods or known in the art or commercially available, and preferably 5 to 50 wt%, more preferably based on the pharmaceutical composition. 20 to 30% by weight is included.

Soybean polysaccharide according to the present invention is a 70 to 80% dietary fiber containing cellulose, hemicellulose, pectin, gum, mucilage, and the like, preferably 5 to 50% by weight, more preferably to the pharmaceutical composition 5 to 40% by weight, most preferably 5 to 30% by weight.

The soy polysaccharide contains a sufficient amount of fiber. White rice contains 0.3 g per 100 g and brown rice has 1 g of fiber per 100 g, while soybean contains 5 g of fiber per 100 g, and sufficient fiber is heavy metal. It adsorbs toxic substances such as pesticides and releases them into the body, and also proliferates lactic acid bacteria in the large intestine, eliminating diarrhea and constipation and normalizing intestinal function. In addition, the fiber improves the hyperlipidemia in the blood by several functions, and prevents the blood sugar rises sharply when eating, thereby lowering the glycemic index is helpful in the prevention of adult diseases such as diabetes.

In particular, the soybean polysaccharide used as a tablet disintegrating agent of the present invention dissolves a pharmaceutical preparation containing nateglinide in water in a short time as compared to the prior art, and serves to elute the components of nateglinide in the preparation in a short time. do.

The soy polysaccharide is prepared by a special process from defatted soybean pieces without threshing. The degreased bean flakes are first extracted with lime water in a slurry tank, and then the soluble fraction and the insoluble fraction are separated. The soluble fraction contains proteins, the insoluble fraction contains carbohydrates and other components, and soy polysaccharides can be obtained from the insoluble fraction. The separation can be carried out by conventional methods. The insoluble portion is diluted with purified water and the pH is adjusted with acid or base to give a neutralized product. It can be added to the treatment using appropriate chemical, microbiological and physical techniques. The product can then be spray-dried and mixed to produce soy polysaccharides.

The disintegrant used in the present invention may further add a disintegrant commonly used in addition to the soybean polysaccharide. The disintegrants include sodium starch glycolate, crospovidone, croscarmellose sodium, alginic acid, sodium alginate, calcium carboxymethyl cellulose, sodium carboxymethyl cellulose, chitosan, guar gum, low-substituted hydroxypropyl cellulose, magnesium aluminum silicate, Polyacrylic calcium, and the like.

Pharmaceutically acceptable additives according to the invention include starch, partially gelatinized starch, microcrystalline cellulose, lactose, povidone, colloidal silicon dioxide, calcium hydrogen phosphate, lactose, mannitol, malt, gum arabic, hydroxypropyl cellulose, carbox Nauba lead, synthetic aluminum silicate, stearic acid, magnesium stearate and talc may be used, and preferably corn starch, microcrystalline cellulose, lactose, povidone, colloidal silicon dioxide, magnesium stearate, and the like may be used.

The pharmaceutically acceptable additive according to the present invention is preferably included 15 to 90% by weight based on the pharmaceutical composition.

As a result of the dissolution test of the pharmaceutical composition containing nateglinide as an active ingredient, the dissolution rate of the composition containing the soybean polysaccharide according to the present invention is almost 100%, such as 95.82 ~ 102.49%, while not containing soy polysaccharide In the case of the composition, the dissolution rate is about 23.28 ~ 68.60%, it can be seen that the fastness is increased when the soy polysaccharide is used as a disintegrant.

In addition, as a result of comparing the pharmaceutical composition according to the present invention with conventional disintegrants known to be excellent in disintegration, the dissolution rate is higher than the dissolution rate (20.32 ~ 63.95%) of the conventional disintegrant, the fastness of the pharmaceutical composition of the present invention Confirmed high.

Therefore, in the pharmaceutical composition of the present invention, by using the soybean polysaccharide as a disintegrating agent, not only rapid disintegration, but also active ingredient nateglinide can be eluted in a short time to effectively exhibit the drug efficacy.

The pharmaceutical composition of the present invention is preferably in an oral solid form, more preferably tablets and the like can be used.

The pharmaceutical composition of the present invention can be formulated by a conventional pharmaceutical method, and the formulating method includes a direct compression method and a granule compression method, and an appropriate method can be used without being limited thereto.

The direct compression method is a method of directly tableting a uniform dry mixture made by adding and mixing excipients, binders, disintegrants, etc. to the crystals of medicines and powders, and the granulation compression method is a method of preparing and granulating granules. The granules compression method can be divided into dry method and wet method.

The dry method is a method of mixing and compressing a slug made of dry granulation and a sheet-like material by crushing and sizing to form a lubricating agent, and the wet method is a granulated product by adding an excipient, a disintegrant to a medicine and then adding a binder. It is then dried, and then granulated using a granulator, and then compressed into tablets.

The dosage of the pharmaceutical composition of the present invention varies in the range depending on the weight, age, sex, health condition, diet, time of administration, administration method, excretion rate and severity of disease of the patient. The daily dose of nateglinide is 30 mg to 1 g, preferably 90 to 270 mg, preferably administered once to several times a day.

Hereinafter, preferred examples are provided to aid in understanding the present invention. However, the following examples are merely provided to more easily understand the present invention, and the contents of the present invention are not limited thereto.

< Example  1 to 6 Of the present invention Nateglinide  Preparation of Containing Tablets

Example  One:  Of the present invention Nateglinide  Preparation of containing tablets 1

Tablets containing nateglinide were prepared using soy polysaccharide as a disintegrant and corn starch and microcrystalline cellulose as excipients as follows.

After 25 g of nateglinide, 20 g of soy polysaccharide, 23.5 g of corn starch, 23.5 g of microcrystalline cellulose, and 4.5 g of colloidal silicon dioxide were mixed with a stirrer for 2 minutes, 70 ml of purified water dissolved in 1.5 g of povidone was added, followed by association for 3 minutes. , Granulated. It was dried, stipulated, 2 g of magnesium stearate was added thereto, mixed for 2 minutes, and then compressed into 360 mg, thereby preparing a tablet.

Example  2:  Of the present invention Nateglinide  Preparation of containing tablets 2

Tablets containing nateglinide were prepared in the same manner as in Example 1 except that 31.5 g of corn starch and 15.5 g of microcrystalline cellulose were used as an excipient and 60 ml of purified water was used.

Example  3:  Of the present invention Nateglinide  Preparation of containing tablets 3

Tablets containing nateglinide were prepared in the same manner as in Example 1 except that 25 g of soy polysaccharide as a disintegrant, 21 g of corn starch and 21 g of microcrystalline cellulose were used as excipients.

Example  4:  Of the present invention Nateglinide  Preparation of Containing Tablets 4

Tablets containing nateglinide were prepared in the same manner as in Example 1, except that 30 g of soy polysaccharide as a disintegrant, 18.5 g of corn starch and 18.5 g of microcrystalline cellulose were used as excipients.

Example  5:  Of the present invention Nateglinide  Preparation of Containing Tablets 5

As an excipient, 24.5 g of lactose and 12.5 g of microcrystalline cellulose were used instead of corn starch, 30.0 g of soy polysaccharide as a disintegrating agent, and nateglinide was prepared in the same manner as in Example 1 except that 40 ml of purified water was used. Tablets containing were prepared.

Example  6:  Of the present invention Nateglinide  Preparation of Containing Tablets 6

Tablets containing nateglinide were prepared in the same manner as in Example 5 except that 12.5 g of corn starch was used as an excipient and 30 ml of purified water was used.

Table 1 shows the composition of the components of Examples 1 to 6.

Ingredient Content (g) Example 1 Example 2 Example 3 Example 4 Example 5 Example 6 Nateglinide 25 25 25 25 25 25 Soy Polysaccharide 20 20 25 30 30 30 Corn starch 23.5 31.5 21 18.5 - 12.5 Microcrystalline Cellulose 23.5 15.5 21 18.5 12.5 - Lactose - - - - 24.5 24.5 Povidone 1.5 1.5 1.5 1.5 1.5 1.5 Colloidal silicon dioxide 4.5 4.5 4.5 4.5 4.5 4.5 Magnesium Stearate 2 2 2 2 2 2

Next, to determine the immediate release according to the presence or absence of soybean polysaccharides were prepared tablets according to Comparative Examples 1 to 4 below.

< Comparative example  1-4> Soy Polysaccharides Not Used Nateglinide  Preparation of Containing Tablets

Comparative example  One:  Without soy polysaccharide Nateglinide  Preparation of containing tablets 1

Tablets containing nateglinide were prepared using corn starch and microcrystalline cellulose as excipients, except for the soybean polysaccharide as a disintegrant.

After 25 g of nateglinide, 33.5 g of corn starch, 33.5 g of microcrystalline cellulose, and 4.5 g of colloidal silicon dioxide were mixed with a stirrer for 2 minutes, 70 ml of purified water in which 1.5 g of povidone was dissolved was added and granulated for 3 minutes. It was dried, stipulated, 2 g of magnesium stearate was added thereto, mixed for 2 minutes, and then compressed into 360 mg, thereby preparing a tablet.

Comparative example  2:  Without soy polysaccharide Nateglinide  Preparation of containing tablets 2

Tablets containing nateglinide were prepared in the same manner as in Comparative Example 1 except that 22.3 g of corn starch and 44.7 g of microcrystalline cellulose were used, and 85 ml of purified water was used.

Comparative example  3:  Without soy polysaccharide Nateglinide  Preparation of containing tablets 3

Tablets containing nateglinide were prepared in the same manner as in Comparative Example 1 except that 40.2 g of corn starch and 26.8 g of microcrystalline cellulose were used, and 55 ml of purified water was used.

Comparative example  4:  Without soy polysaccharide Nateglinide  Preparation of Containing Tablets 4

Tablets containing nateglinide were prepared in the same manner as in Comparative Example 1 except that 44.7 g of corn starch and 22.3 g of microcrystalline cellulose were used, and 45 ml of purified water was used.

The composition of the components of Comparative Examples 1 to 4 is shown in Table 2.

Ingredient Content (g) Comparative Example 1 Comparative Example 2 Comparative Example 3 Comparative Example 4 Nateglinide 25 25 25 25 Corn starch 33.5 22.3 40.2 44.7 Microcrystalline cellulose 33.5 44.7 26.8 22.3 Povidone 1.5 1.5 1.5 1.5 Colloidal silicon dioxide 4.5 4.5 4.5 4.5 Magnesium Stearate 2 2 2 2

Next, the tablets according to Comparative Examples 5 to 8 were prepared in order to determine the degree of rapid release of the present invention as compared with the prior art.

< Comparative example  5 to 8> according to the prior art Nateglinide  Preparation of Containing Tablets

Comparative example  5: Nateglinide  Preparation of Containing Tablets 1 ( JP10194969 of Example  One)

Tablets containing nateglinide were prepared by the method described in Japanese Patent No. 10194969 as follows.

25 g of nateglinide, 54 g of lactose, and 20 g of low-substituted hydroxypropyl cellulose were mixed with a high speed stirrer for 2 minutes, and 70 ml of purified water was added thereto, followed by association and granulation for 3 minutes. It was dried, stipulated, and mixed with 1 g of magnesium stearate, and then compressed into 360 mg to prepare a tablet.

Comparative example  6: Nateglinide  Preparation of containing tablets 2 ( WO2005092319 of Example  One)

Tablets containing nateglinide were prepared by the method described in International Publication No. 2005-092319 as follows.

18.3 g of nateglinide, 49.6 g of lactose, 13.1 g of microcrystalline cellulose, 3.8 g of sodium starch glycolate, and 4.2 g of colloidal silicon dioxide were mixed with a high speed stirrer for 2 minutes, and then 1.8 g of povidone and 1.8 g of sodium lauryl sulfate were dissolved. 45 ml of purified water was added, and the mixture was granulated for 3 minutes. It was dried, stipulated, 1.7 g of magnesium stearate, 2 g of colloidal silicon dioxide, and 3.5 g of sodium starch glycolate were added thereto, mixed for 2 minutes, and tableted to 360 mg to prepare a tablet.

Comparative example  7: Nateglinide  Preparation of Containing Tablets 3 ( WO2005092319 of Example  4)

Tablets containing nateglinide were prepared by the method described in International Publication No. 2005-092319 as follows.

18.3 g of nateglinide, 49.6 g of lactose, 13.1 g of microcrystalline cellulose, 3.8 g of crospovidone, and 4.2 g of colloidal silicon dioxide were mixed with a high speed stirrer for 2 minutes, followed by purified water of 1.8 g of povidone and 1.8 g of sodium lauryl sulfate. ㎖ was added and the mixture was granulated for 3 minutes. It was dried, stipulated, 1.7 g of magnesium stearate, 2 g of colloidal silicon dioxide, and 3.5 g of crospovidone were added thereto, mixed for 2 minutes, and tableted to 360 mg to prepare a tablet.

Comparative example  8: Nateglinide  Preparation of Containing Tablets 4 ( WO2005016315 of Example  3)

Tablets containing nateglinide were prepared by the method described in WO 2005-016315.

18.6 g of nateglinide and 52.9 g of lactose, 15.4 g of white sugar, 3 g of croscarmellose sodium and 2.4 g of colloidal silicon dioxide were mixed with a high speed stirrer for 2 minutes, and 20 ml of purified water dissolved in 1.8 g of povidone was added thereto, followed by 3 minutes of association. , Granulated. It was dried, stipulated, 2 g of croscarmellose sodium, 2 g of colloidal silicon dioxide, and 1.8 g of magnesium stearate were added thereto, mixed for 2 minutes, and tableted to 360 mg to prepare a tablet.

The composition of the components of Comparative Examples 5 to 8 is shown in Table 3.

Ingredient Content (g) Comparative Example 5 Comparative Example 6 Comparative Example 7 Comparative Example 8 Nateglinide 25 18.3 18.3 18.6 Microcrystalline cellulose - 13.1 13.1 - Lactose 54 49.6 49.6 52.9 Low Substituted Hydroxypropyl Cellulose 20 - - - White sugar - - - 15.4 Povidone - 1.8 1.8 1.8 Colloidal silicon dioxide - 6.2 6.2 4.4 Sodium starch glycolate - 7.3 - - Crospovidone - - 7.3 - Croscarmellose sodium - - - 5.0 Sodium lauryl sulfate - 1.8 1.8 - Magnesium Stearate One 1.7 1.7 1.8

Next, the tablets according to Comparative Examples 9 to 11 were prepared in order to find out the immediate release degree of the soybean polysaccharide used as the disintegrant in the present invention compared to the conventional disintegrant.

< Comparative example  9 to 11 Conventional Disintegrant  Used Nateglinide  Preparation of Containing Tablets

Comparative example  9:  Conventional Disintegrant  Used Nateglinide  Preparation of containing tablets 1

Tablets containing nateglinide were prepared using other conventional disintegrants instead of soybean polysaccharides as disintegrants and corn starch and microcrystalline cellulose as follows.

After mixing 25 g of nateglinide, 23.5 g of corn starch, 23.5 g of microcrystalline cellulose, 4.5 g of colloidal silicon dioxide and 20 g of low-substituted hydroxypropyl cellulose with a high-speed stirrer, 70 ml of purified water in which 1.5 g of povidone was dissolved. It was added and granulated for 3 minutes. It was dried, stipulated, 2 g of magnesium stearate was added thereto, mixed for 2 minutes, and then compressed into 360 mg, thereby preparing a tablet.

Comparative example  10:  Conventional Disintegrant  Used Nateglinide  Preparation of containing tablets 2

Tablets containing nateglinide were prepared in the same manner as in Comparative Example 9 except that 20 g of crospovidone was used instead of low-substituted hydroxypropyl cellulose as a disintegrant.

Comparative example  11:  Conventional Disintegrant  Used Nateglinide  Preparation of containing tablets 3

Tablets containing nateglinide were prepared in the same manner as in Comparative Example 9 except that 20 g of croscarmellose sodium was used instead of low-substituted hydroxypropyl cellulose as a disintegrant.

The composition of the components of Comparative Examples 9 to 11 is shown in Table 3.

Ingredient Content (g) Comparative Example 10 Comparative Example 11 Comparative Example 12 Nateglinide 25 25 25 Corn starch 23.5 23.5 23.5 Microcrystalline cellulose 23.5 23.5 23.5 Povidone 1.5 1.5 1.5 Colloidal silicon dioxide 4.5 4.5 4.5 Low Substituted Hydroxypropyl Cellulose 20 - - Crospovidone - 20 - Croscarmellose sodium - - 20 Magnesium Stearate 2 2 2

< Experimental Example  1> Soy Polysaccharide Presence  According Nateglinide  Dissolution Rate Measurement

In order to determine the immediate release rate of nateglinide according to the presence of soy polysaccharide, the dissolution rate of nateglinide was measured as follows.

The dissolution rates of the Examples 1 to 6 and Comparative Examples 1 to 4 were measured according to the 8th Amendment Dissolution Test Method No. 8 of the KP. As the eluate, 500 ml of the second solution of the KEPCO 8 Disintegration Test Method was used, and the elution temperature was 37 ° C., the rotation speed of the paddle was 50 rpm, and the elution rate was measured for 30 minutes . And in Table 5.

Dissolution rate (%) 5 minutes 10 minutes 15 minutes 30 minutes Example 1 49.60 69.79 81.91 96.53 Example 2 46.66 69.92 80.82 95.82 Example 3 55.05 79.92 92.11 101.31 Example 4 76.02 90.43 97.39 102.49 Example 5 48.22 74.61 87.35 101.38 Example 6 47.52 77.93 90.37 100.45 Comparative Example 1 8.02 13.23 17.84 35.75 Comparative Example 2 31.22 45.55 54.47 68.60 Comparative Example 3 31.10 44.08 51.37 64.82 Comparative Example 4 9.20 13.95 17.32 23.28

As shown in Figure 1 and Table 5, the dissolution rate (95.82 ~ 102.49%) for 30 minutes of the embodiment according to the present invention using the soybean polysaccharide as a disintegrant is the dissolution rate (23.28 ~ 68.60%) of the comparative examples without using the soy polysaccharide It was higher than about 30-50%.

Therefore, the pharmaceutical composition according to the present invention can be usefully used as a fast-acting short-acting hypoglycemic agent by increasing the dissolution rate in a short time.

< Experimental Example  2> according to the prescription containing soy polysaccharide and the prior art prescription Nateglinide  Dissolution Rate Measurement

In order to determine the degree of rapid release of nateglinide according to the soybean polysaccharide-containing formulation and the prior art prescription of the present invention, the dissolution rate was measured in the same manner as in Experimental Example 1 for Example 4 and Comparative Examples 5 to 8, and The results are shown in Figure 2 and Table 6.

Dissolution rate (%) 5 minutes 10 minutes 15 minutes 30 minutes Example 4 76.02 90.43 97.39 102.49 Comparative Example 5 4.78 9.57 12.59 20.32 Comparative Example 6 9.57 23.62 35.89 63.95 Comparative Example 7 6.52 13.05 17.17 27.71 Comparative Example 8 9.42 23.24 35.30 62.91

As shown in FIG . 2 and Table 6, the dissolution rate of the dissolution test result of Example 4 according to the present invention using soy polysaccharide as a disintegrant (102.49%) is the dissolution rate (20.32 ~ 63.95) of the comparative examples without using the soy polysaccharide. About 40 ~ 80% higher than%).

Therefore, the pharmaceutical composition according to the present invention can be usefully used as a fast-acting short-acting hypoglycemic agent by increasing the dissolution rate in a short time.

< Experimental Example  3> Formulated with Soy Polysaccharide and Fast-acting Disintegrant  Nateglinide according to prescription of  Dissolution Rate Measurement

In order to determine the rapid release degree of nateglinide according to the soybean polysaccharide-containing formulation of the present invention and the conventional fast-acting disintegrant formulation, the dissolution rate was measured in the same manner as in Experiment 1 for Example 1 and Comparative Examples 9 to 11 The results are shown in FIG. 3 and Table 7.

Dissolution rate (%) 5 minutes 10 minutes 15 minutes 30 minutes Example 1 49.60 69.79 81.91 96.53 Comparative Example 9 21.62 31.17 38.28 52.08 Comparative Example 10 48.35 58.34 64.32 74.91 Comparative Example 11 15.93 21.92 26.46 37.65

As shown in FIG . 3 and Table 7, the dissolution rate (96.53%) of Example 1 according to the present invention using the soybean polysaccharide as a disintegrant as a result of the dissolution test is the dissolution rate (37.65 ~ 74.91%) of the comparative examples using a conventional disintegrant 20 ~ 60% higher than

Therefore, the pharmaceutical composition according to the present invention can be usefully used as a fast-acting short-acting hypoglycemic agent by increasing the dissolution rate in a short time.

< Experimental Example  4> Disintegration time  Comparison of Dissolution Rates

For the preparations prepared by the methods of Examples 1 to 6 and Comparative Examples 1 to 11 above, the time for which the tablet completely disintegrated was measured according to the KEPCO Revised Disintegration Test Method. In the test, water was used as the test solution, and the temperature of the test solution was 37 ° C. The measurement results are shown in Table 8.

Disintegration time (seconds) 30 min dissolution rate (%) Example 1 25 96.53 Example 2 25 95.82 Example 3 25 101.31 Example 4 53 102.49 Example 5 130 101.38 Example 6 215 100.45 Comparative Example 1 128 35.75 Comparative Example 2 28 68.60 Comparative Example 3 37 64.82 Comparative Example 4 120 23.28 Comparative Example 5 54 20.32 Comparative Example 6 1160 63.95 Comparative Example 7 1720 27.71 Comparative Example 8 151 62.91 Comparative Example 9 33 52.08 Comparative Example 10 40 74.91 Comparative Example 11 210 37.65

As shown in Table 8, Comparative Examples 1 to 11 that do not use soy polysaccharide as a disintegrant have a slow disintegration rate (Comparative Examples 1, 4, 6, 7, 8, 11), or dissolution rate compared to a fast disintegration rate. Was found to be unsatisfactory (Comparative Examples 2, 3, 5, 9, 10). In contrast, in the case of the soybean polysaccharide-containing preparation according to the present invention, not only rapid disintegration but also a 30-minute dissolution rate of 95% or more, it was confirmed that the active ingredient nateglinide in a short time to effectively exhibit the drug efficacy.

Therefore, the pharmaceutical composition according to the present invention can be usefully used as a fast-acting short-acting hypoglycemic agent by high dissolution rate in a short time.

As described above, the pharmaceutical composition containing nateglinide using soy polysaccharide as a disintegrating agent according to the present invention can not only fast disintegration but also the active ingredient nateglinide is eluted in a short time to effectively exhibit the medicinal effects It can be usefully used as a hypoglycemic agent.

Claims (12)

A pharmaceutical composition comprising nateglinide, a soybean polysaccharide, and a pharmaceutically acceptable additive represented by Formula 1 below. <Formula 1>

According to claim 1, wherein the nateglinide is a pharmaceutical composition, characterized in that 5 to 50% by weight relative to the pharmaceutical composition. The pharmaceutical composition according to claim 1, wherein the nateglinide is included in an amount of 20 to 30% by weight based on the pharmaceutical composition. The pharmaceutical composition of claim 1, wherein the soybean polysaccharide is 70-80% dietary fiber containing at least one selected from the group consisting of cellulose, hemicellulose, pectin, gum and musila mice. According to claim 1, wherein the soybean polysaccharide is a pharmaceutical composition, characterized in that 5 to 50% by weight relative to the pharmaceutical composition. According to claim 1, wherein the soybean polysaccharide is a pharmaceutical composition, characterized in that 5 to 40% by weight relative to the pharmaceutical composition. According to claim 1, wherein the soybean polysaccharide is a pharmaceutical composition, characterized in that 5 to 30% by weight based on the pharmaceutical composition. The method of claim 1, wherein the pharmaceutically acceptable additive is starch, partially gelatinized starch, microcrystalline cellulose, lactose, povidone, colloidal silicon dioxide, calcium hydrogen phosphate, lactose, mannitol, malt, gum arabic, hydroxypropyl cellulose Carnauba lead, synthetic aluminum silicate, stearic acid, magnesium stearate and talc pharmaceutical composition characterized in that at least one member selected from the group consisting of. The pharmaceutical composition of claim 1, wherein the pharmaceutically acceptable additive is at least one selected from the group consisting of corn starch, microcrystalline cellulose, lactose, povidone, colloidal silicon dioxide, and magnesium stearate. The pharmaceutical composition of claim 1, wherein the pharmaceutically acceptable additive is included in an amount of 15 to 90% by weight based on the pharmaceutical composition. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition is an oral preparation. The pharmaceutical composition according to claim 11, wherein the oral preparation is a tablet.

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