KR20200033773A - Composition for Dampproofing Coating - Google Patents

Abstract

The present invention provides a composition for moisture-proof coating capable of securing stability and a moisture-proof effect of an active component by using the composition for moisture-proof coating. The composition for moisture-proof coating according to the present invention can provide stability of a tablet by effectively blocking moisture penetration by double coating the active component.

Description

Composition for moisture-proof coating {Composition for Dampproofing Coating}

The present invention relates to a composition for moisture-proof coating, and more particularly, to a composition for moisture-proof coating that can secure the stability and moisture-proof effect of the active ingredient by using the composition for moisture-proof coating.

In general, the coating film is used to smooth the surface of solid preparations such as tablets and pellets and to take the drug easily without taking it on the neck or to improve the quality of the product. In addition, the coating film is used to improve the stability of the contents, to shield the bitter taste or unpleasant odor of the drug, or to control the release and dissolution rate of the drug through the film to sustain the sustained release.

The coating film can be classified into a general coating film, an enteric coating film, and a sustained release coating film according to the purpose of use. The general coating film is a film used for the purpose of improving the quality of the product and convenience when masking or taking a bitter taste, as disclosed in Korean Patent Publication No. 1986-0001118. The general coating film is designed to dissolve easily in water regardless of the pH of the solution so that the drug can be readily absorbed by disintegrating easily in all gastrointestinal tract environments. (For example, a film is formed using hydroxypropyl cellulose, hydroxypropyl methyl cellulose, and the like).

The enteric coating film is a polymer that does not dissolve at low pH and dissolves well in intestinal fluids above pH 5 to protect drugs that are highly unstable to gastric acid from stomach acid, such as omeprazole and protein, as disclosed in U.S. Patent Nos. 6,420,473 or 4,704,295. It is a coating on the surface of the drug. Polymers such as methacrylic acid copolymers (eg, methacrylic acid-ethyl acrylate copolymers and methacrylic acid-methyl methacrylic acid copolymers), which mainly form an enteric coating, are used alone, or with ethyl cellulose, etc. Use with the same water-insoluble polymer. When these enteric coating-forming polymers are used for the formation of a general coating film, since the drug does not dissolve because it does not melt in the stomach, drugs that are absorbed mainly in the upper part of the stomach or small intestine may affect absorption in the body.

The sustained release coating film, as disclosed in Korean Patent Publication No. 10-2005-0044545, is used as a sustained release of the drug by controlling the disintegration rate and drug release rate of the tablet by coating the water-insoluble film on the tablet surface. On the other hand, the general coating film formed of a water-soluble film coating agent is relatively easy to manufacture, but has the disadvantage of being unstable in temperature and moisture. That is, when exposed to high temperature and high humidity conditions for a long time, the film weakens or moisture easily penetrates into the film, thereby causing problems such as deterioration of tablet properties due to moisture absorption or a decrease in the content of the active ingredient. In particular, in the case of tablets containing vitamins or herbal ingredients, the properties of the tablets may be deformed or the content may be reduced by moisture.

To improve these problems, U.S. Patent Nos. 5,885,617 and 6,448,323 disclose using polyvinyl alcohol and lecithin, which are water-soluble polymers, as a coating base, and U.S. Patent Nos. 6,051,255, 6,235,311, etc. A method of combining propyl methylcellulose and polyethylene glycol or forming a double coating layer has been disclosed.

However, despite the above disclosure, there is a limit to maintaining stability when exposed to moisture for a long time.

U.S. Patent No. 4,798,724 discloses a solid formulation coated with an elastic film coating prepared by mixing hydroxypropyl cellulose, which is a water-soluble film coating agent, with an acrylic resin. As the acrylic resin, a copolymer of ethyl acrylate and methyl methacrylate or a copolymer of methyl acrylate and methyl methacrylate was used.

However, in US Pat. No. 4,798,724, hydroxypropyl cellulose used as a water-soluble film coating agent has a property of absorbing moisture in the air and has a high equilibrium moisture content under conditions of high temperature and high humidity, thereby limiting the effect of blocking moisture penetration. As a result, it can cause problems in the stability of the formulation under high temperature and high humidity conditions (Handbook of Pharmaceutical Excipients, Paul J. Sheskey, Raymond C. Rowe, Sian C. Owen, published in 2005), and affect the disintegration rate and drug release rate. Can be crazy.

Accordingly, the problem to be solved by the present invention is to provide a composition for moisture-proof coating excellent in stabilization and moisture-proof effect of the active ingredient.

As a result of repeated studies to develop a new moisture-proof coating liquid, the present inventors effectively prevent the penetration of moisture without significantly affecting the disintegration time of the tablet when forming a film coating layer with the moisture-proof coating liquid, thereby improving tablet stability. Found something that can be maintained.

The moisture-proof coating composition of an embodiment of the present invention comprises a tablet containing an active ingredient and a pharmaceutically acceptable additive; A first coating layer coated with a first coating base including a hydroxypropyl methylcellulose-based water-soluble coating agent and a moisture adsorbent on the outside of the tablet; And a second coating layer coated with a second coating base including polyvinyl alcohol and a moisture barrier on the outside of the first coating layer. And the total weight of the first coating agent is less than the total weight of the second coating agent.

The moisture-proof coating composition of an embodiment of the present invention comprises a tablet containing an active ingredient and a pharmaceutically acceptable additive; A first coating layer coated with a first coating base including a hydroxypropyl methylcellulose-based water-soluble coating agent and a moisture adsorbent on the outside of the tablet; And a second coating layer as a second coating base including polyvinyl alcohol and a moisture barrier on the outside of the first coating layer. And the first coating base and the second coating base comprises a 1: 2 to 1: 4 weight ratio. Preferably, the first coating base and the second coating base comprise a weight ratio of 1: 2.5 to 1: 4.

In one embodiment of the present invention, it is characterized in that the hydroxypropyl methylcellulose-based water-soluble coating agent of the first coating agent and the water adsorbent are in a weight ratio of 2: 1 to 40: 1.

In one embodiment of the present invention, it is characterized in that the hydroxypropyl methylcellulose-based water-soluble coating agent of the first coating agent and the water adsorbent are in a weight ratio of 5: 1 to 30: 1.

In one embodiment of the present invention, the second coating base is characterized in that the polyvinyl alcohol-based water-soluble coating agent and the moisture barrier agent are in a weight ratio of 2: 1 to 20: 1.

In one embodiment of the present invention, the polyvinyl alcohol-based water-soluble coating agent and the moisture barrier agent of the second coating agent are characterized by being in a weight ratio of 3: 1 to 18: 1.

In one embodiment of the present invention, the hydroxypropyl methylcellulose-based water-soluble coating agent of the first coating agent and the water adsorbent are included in a weight ratio of 5: 1 to 30: 1, the polyvinyl alcohol-based water-soluble coating agent of the second coating agent, and It characterized in that it comprises a water blocking agent in a 3: 1 to 18: 1 weight ratio.

In one embodiment of the invention, the active ingredient is choline alfoscerate, Pravastatin, L-Carnitine, Rabeprazole, Telmisartan ethambutol ), Citicoline, Pyridostigmine, Ranitidine, Furosemide, Cefuroxime Axetil, Fluvastatin, Acetyl-L-Carnitine -L-Carnitine, Clopidogrel, Amlodipine, Cyanocobalamin, Limaprost, Losartan, Aspirin, Fesoterodine, Bupropion ), Ropinirole, Cefetamet Pivoxil, Rosuvastatin, Sarpogrelate, Aripiprazole, and Ramipril do.

In one embodiment of the present invention, the water adsorbent is characterized in that at least one selected from calcium silicate, magnesium metaaluminate, and colloidal silicon dioxide.

In one embodiment of the invention, the moisture barrier is characterized in that at least one selected from mannitol, pregelatinized starch, erythritol, isomalt, xylitol, sorbitol and maltitol.

In one embodiment of the present invention, the water adsorbent is characterized in that at least one selected from calcium silicate, magnesium metaaluminate, and colloidal silicon dioxide, and the water blocking agent is mannitol, pregelatinized starch, erythritol, isomalt, xylitol, sorbitol And one or more selected from maltitol.

In the present invention, "hydroxypropyl methylcellulose-based (hydroxypropyl methylcellulose-based) water-soluble coating agent" is a coating agent containing hydroxypropyl methylcellulose, a commercially available hydrophilic matrix system Opadry ^TM 03B28796 (Opadray ^TM 03B28796, Colorcon, Inc, USA), Opadray ^TM 03K192290 (Opadray ^TM 03K192290, Colorcon, Inc, USA).

In the present invention, "polyvinyl alcohol-based (polyvinyl alcohol-based) water-soluble coating agent" is a coating agent containing polyvinyl alcohol, for example, commercially sold Opadry ^TM Yellow 85F92177 (Opadray ^TM Yellow 85F92177, Colorcon, Inc. , USA), water-soluble Opadry ^TM 88A620001 (Opadray ^TM 88A620001, Colorcon, Inc, USA).

The moisture-proof coating composition according to the present invention can provide a tablet stability by effectively blocking moisture penetration without significantly affecting the disintegration time of the tablet by using the active ingredient as a double coating.

[Composition for moisture-proof coating]

Moisture-proof coating composition according to an embodiment of the present invention is a tablet containing an active ingredient and a pharmaceutically acceptable additive; A first coating layer coated with a first coating base including a hydroxypropyl methylcellulose-based water-soluble coating agent and a moisture adsorbent on the outside of the tablet; A second coating layer coated with a second coating base including a polyvinyl alcohol-based water-soluble coating agent and a moisture barrier on the outside of the first coating layer.

Active ingredients

The active ingredient for applying the composition for moisture-proof coating according to an embodiment of the present invention is a moisture sensitive active ingredient or a stability-lowering active ingredient, and is not limited thereto.

The stability-lowering active ingredient refers to a decrease in the content of the active ingredient according to moisture or an increase in related substances.

The moisture sensitive active ingredient is Choline alfoscerate, Pravastatin, L-Carnitine, Rabeprazole, Telmisartan Ethambutol, Citicholine ( Citicoline), pyridostigmine, Ranitidine, and Furosemide, but is not limited thereto.

The stability-lowering active ingredients include Cefuroxime Axetil, Fluvastatin, Acetyl-L-Carnitine, Clopidogrel, Amlodipine, Cyanocobalamin , Limaprost, Losartan, Aspirin, Fesoterodine, Bupropion, Ropinirole, Cefetamet Pivoxil, Rosuvastatin (Rosuvastatin), Sapogrelate, Aripiprazole, and Ramipril, but is not limited thereto.

Coating base

The moisture-proof coating composition according to an embodiment of the present invention is double-coated on the active ingredient to prevent problems of deliquescent and stability of the active ingredient generated during long-term storage.

In one embodiment of the present invention, when both the first coating agent or the second coating agent is used, there is no problem of deliquescent of an active ingredient than a single coating, and a phenomenon in which moisture is formed on the surface of the final formulation and a drug is derived. It shows excellent formulation effect that does not occur.

The first coating agent and the second coating agent are 1: 1 to 1: 4 weight ratio, 1: 2 to 1: 4 weight ratio, 1: 2.5 to 1: 4 weight ratio, and 1: 3 to 1: 4 weight ratio, but are not limited thereto. Does not work.

Within the weight range of the first coating agent and the second coating agent, an excellent formulation is realized in which the problem of deliquescent of the active ingredient does not occur, and a phenomenon in which moisture is formed on the surface of the final formulation and a drug is not induced is generated.

In one embodiment of the present invention, the moisture adsorbent adsorbs moisture originating from the inside of the formulation and promotes property stability such as prevention of drug derivation.

In one embodiment of the present invention, the water adsorbent is at least one component selected from calcium silicate, magnesium metaaluminate, and colloidal silicon dioxide, preferably calcium silicate.

In one embodiment of the present invention, the hydroxypropyl methylcellulose-based water-soluble coating agent and the water adsorbent based on the first coating agent are 2: 1 to 40: 1 weight ratio, 5: 1 to 30: 1 weight ratio, 10: 1 to 30: 1 weight ratio, 10: 1 to 25: 1 weight ratio, but is not limited thereto.

Within the weight range of the hydroxypropyl methylcellulose-based water-soluble coating agent and water adsorbent, the moisture contained in the tablet is absorbed, so that no problem of deliquescent of the active ingredient occurs, and drug release of the active ingredient is facilitated.

In one embodiment of the present invention, the moisture barrier has the advantage of strengthening the moisture-proofing power by preventing moisture from penetrating from the outside.

In one embodiment of the present invention, the moisture blocking agent is at least one component selected from mannitol, pregelatinized starch, erythritol, isomalt, xylitol, sorbitol and maltitol, preferably mannitol.

In one embodiment of the present invention, the polyvinyl alcohol-based water-soluble coating agent and the moisture barrier agent of the second coating base are 2: 1 to 20: 1 weight ratio, 3: 1 to 18: 1 weight ratio, 6: 1 to 18: 1 weight ratio , 6: 1 to 15: 1 weight ratio, but is not limited thereto.

Within the weight range of the polyvinyl alcohol-based water-soluble coating agent and the moisture barrier agent, an external moisture barrier is excellent and provides an excellent coated tablet that does not generate cracks in the final coated tablet. In one embodiment of the present invention, for moisture-proof coating Tablets with a film-coated layer formed by moisture-proof coating using a composition in a conventional pharmaceutical formulation containing an active ingredient, for example, tablets, pellets, etc., using a conventional method (for example, coating using a film coating machine or a fluidized bed granulator). , Pellets and the like.

In one embodiment of the present invention, the hydroxypropyl methylcellulose-based water-soluble coating agent of the first coating agent and the water adsorbent are included in a weight ratio of 5: 1 to 30: 1, the polyvinyl alcohol-based water-soluble coating agent of the second coating agent, and Moisture barrier may be a composition for moisture-proof coating comprising a 3: 1 to 18: 1 weight ratio.

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

Preparation Example 1: Preparation of active ingredient tablets

Preparation Examples 1-1 to 1-2

With the ingredients and contents listed in Table 1 below, a tablet was prepared using a roller compaction method according to the following method.

Calcium hydrogen phosphate anhydrous, croscarmellose sodium and povidone are mixed with the active ingredient, and the obtained mixture is roller speed 1.5 to 2.5 rpm, screw speed 8 to 10 rpm and pressure 8 to 12 MPa using a roller compactor (Seoul Hi-Tech, RC80). The mixture was compressed in to prepare a compact. The compact was passed through 20 mesh to prepare granules having an average particle diameter of 100 to 850 μm. This granule was lubricated with talc and magnesium stearate passed through a 40 mesh sieve, and then compressed into a target hardness of 15 to 25 kP with a 16 mm x 8 mm rectangular punch. All processes were carried out in a laboratory dehumidified below 35% relative humidity.

Ingredient (mg / tablet) Manufacturing example 1-1 1-2 Active ingredients Choline alfoscerate 600 -  L-carnitine - 600 Calcium hydrogen phosphate anhydrous 100 100 Croscarmellose sodium 40 40 Povidone 20 20 Talc 20 20 Magnesium stearate 20 20 Gross weight 800 800

Example 1. Moisture absorption and moisture barrier evaluation of moisture

The moisture-proof evaluation of the moisture-proof coating composition according to the present invention was performed.

With the ingredients and contents shown in Tables 2 to 3, coated tablets were prepared according to the following method.

A hydroxypropyl methylcellulose-based water-soluble coating agent (Opadry 03K192290) and a water adsorbent were added and stirred in 80% ethanol and purified water to prepare a first coating substrate, and polyvinyl alcohol-based water-soluble coating agent (Opadry 88A620001) and a water blocking agent were added to the purified water. A second coating base was prepared by injecting and stirring. After putting the uncoated tablet prepared in Preparation Example 1-1 into the coating machine, spray the first coating agent with a supply temperature of 40 to 50 ° C, a product temperature of 33 to 37 ° C, a spray rate of 3 rpm, and a spray pressure of 3.2 bar to coat the uncoated tablet. A first coated tablet was prepared. After drying the first coating tablet for 10 minutes at a supply temperature of 60 ° C, the second coating tablet is sprayed with a second coating agent at a supply temperature of 50 to 60 ° C, a product temperature of 35 to 40 ° C, a spray rate of 3 rpm, and a spray pressure of 3.2 bar. Was coated. After the coating was completed, it was cured at a supply temperature of 60 ° C for 2 hours.

division Ingredient (mg / tablet) Comparative example Example One 1-1 1-2 1-3 1-4 1-5 1-6 1-7 1-8 Example 1-1 800 800 800 800 800 800 800 800 800 1st
coating
Mechanism Opadry 03K19229 24 24 24 24 24 24 24 24 24 Calcium silicate 0 1.6 - - 1.6 1.6 1.6 1.6 1.6 Magnesium metaaluminate - - 1.6 - - - - - - Colloidal silicon dioxide - - - 1.6 - - - - - ethanol q.s q.s q.s q.s q.s q.s q.s q.s q.s Purified water q.s q.s q.s q.s q.s q.s q.s q.s q.s 2nd
coating
Mechanism Opadry 88A620001 72 72 72 72 72 72 72 72 72 Mannitol 0 8 8 8 - - - - - Erythritol - - - - 8 - - - - Isomalt - - - - - 8 - - - Xylitol - - - - - - 8 - - Sorbitol - - - - - - - 8 - Maltitol - - - - - - - - 8 Purified water q.s q.s q.s q.s q.s q.s q.s q.s q.s Gross weight 896 920.8 888.8 884.8 905.6 901.6 924.8 908.8 904.8

Example 2. Moisture-proof evaluation of double coating

The moisture-proof evaluation of the moisture-proof coating composition according to the present invention was performed.

With the ingredients and contents shown in Tables 3 to 5, coated tablets were prepared according to the method of Example 1.

Examples 2-1 to 2-9

With the ingredients and contents shown in Table 3 below, a double coated coated tablet was prepared by the manufacturing method of Example 1.

division Ingredient (mg / tablet) Comparative example Example One 2-1 2-2 2-3 2-4 2-5 2-6 2-7 2-8 2-9 Example 1-1 800 800 800 800 800 800 800 800 800 800 1st
coating
Mechanism Opadry 03K19229 24 24 24 24 24 24 24 24 24 24 Calcium silicate 0 0.8 0.8 0.8 1.6 1.6 1.6 4.8 4.8 4.8 ethanol q.s q.s q.s q.s q.s q.s q.s q.s q.s q.s Purified water q.s q.s q.s q.s q.s q.s q.s q.s q.s q.s 2nd
coating
Mechanism Opadry 88A620001 72 72 72 72 72 72 72 72 72 72 Mannitol 0 24 8 4 24 8 4 24 8 4 Purified water q.s q.s q.s q.s q.s q.s q.s q.s q.s q.s Gross weight 896 920.8 904.8 900.8 921.6 905.6 901.6 924.8 908.8 904.8

Examples 2-10 to 2-18

With the ingredients and contents shown in Table 4 below, a double coated coated tablet was prepared by the manufacturing method of Example 1.

division Ingredient (mg / tablet) Comparative example Example One 2-10 2-11 2-12 2-13 2-14 2-15 2-16 2-17 2-18 Example 1-2 800 800 800 800 800 800 800 800 800 800 1st
coating
Mechanism Opadry 03K19229 24 24 24 24 24 24 24 24 24 24 Calcium silicate 0 0.8 0.8 0.8 1.6 1.6 1.6 4.8 4.8 4.8 ethanol q.s q.s q.s q.s q.s q.s q.s q.s q.s q.s Purified water q.s q.s q.s q.s q.s q.s q.s q.s q.s q.s 2nd
coating
Mechanism Opadry 88A620001 72 72 72 72 72 72 72 72 72 72 Mannitol 0 24 8 4 24 8 4 24 8 4 Purified water q.s q.s q.s q.s q.s q.s q.s q.s q.s q.s Gross weight 896 920.8 904.8 900.8 921.6 905.6 901.6 924.8 908.8 904.8

Test Example 1.

Examples 1-1 to 1-8 and 2-1 to 2-18 were subjected to hygroscopicity test by exposing for 31 days in air without packaging under room temperature storage conditions (25 ° C, 60% RH). The results of the test and the observation of properties are as shown in Tables 5 to 7 below.

The comparative example 1 and the comparative example 2 were compared with the moisture proof evaluation of the double coated coated tablet of the present invention.

time Hygroscopicity (%) Comparative example Example One 1-1 1-2 1-3 1-4 1-5 1-6 1-7 1-9 14 days 2.41 0.93 1.24 1.41 1.20 1.33 1.27 1.34 1.38 31 days 5.06 2.04 2.72 2.93 2.71 2.83 2.76 2.91 2.89 Change of nature (31 days) Constellation
Change No property change

time Hygroscopicity (%) Comparative example Example One 2-1 2-2 2-3 2-4 2-5 2-6 2-7 2-8 2-9 14 days 2.41 1.20 1.08 1.15 0.98 0.93 0.96 1.31 1.25 1.28 31 days 5.06 2.64 2.40 2.52 2.16 2.04 2.08 2.88 2.76 2.82 Change of nature (31 days) Constellation
Change No property change

time Hygroscopicity (%) Comparative example Example 2 2-10 2-11 2-12 2-13 2-14 2-15 2-16 2-17 2-18 14 days 2.87 1.29 1.06 1.22 1.04 1.00 1.01 1.49 1.39 1.41 31 days 5.72 2.91 2.62 2.84 2.45 2.25 2.33 3.16 3.06 3.12 Constitutional change
(31 days) Constellation
Change No property change

As a result of observing Examples 1-1 to 1-8 containing a water absorbent and a water blocking agent for 31 days, calcium silicate, magnesium metaaluminate and colloidal silicon dioxide as the water absorbent, mannitol and pregelatinized starch as the water blocking agent , Erythritol, isomalt, xylitol, sorbitol and maltitol were all satisfied with hygroscopicity and properties. Among them, calcium silicate as a water absorbent and mannitol as a water blocker were found to have low hygroscopicity and excellent properties.

Examples 2-1 to 2-double coated with a hydroxypropylmethylcellulose-based water-soluble coating agent having various mixed weight ratios and a first coating agent comprising calcium silicate and a second coating agent comprising polyvinyl alcohol-based water-soluble coating agent and mannitol As a result of observing 18 for 31 days, low moisture absorption and excellent properties were confirmed.

Claims (11)

A tablet containing an active ingredient and a pharmaceutically acceptable additive;
A first coating layer coated with a first coating base including a hydroxypropyl methylcellulose-based water-soluble coating agent and a moisture adsorbent on the outside of the tablet;
A second coating layer coated with a second coating base including a polyvinyl alcohol-based water-soluble coating agent and a moisture barrier on the outside of the first coating layer; And
The total weight of the first coating agent is a moisture-proof coating composition comprising less than the total weight of the second coating agent. According to claim 1,
The first coating agent and the second coating agent is a moisture-proof coating composition comprising a 1: 2 to 1: 4 weight ratio. According to claim 1,
A moisture-proof coating composition comprising a hydroxypropyl methylcellulose-based water-soluble coating agent and a water adsorbent in the first coating base in a weight ratio of 2: 1 to 40: 1. The method of claim 3,
A moisture-proof coating composition comprising a hydroxypropyl methylcellulose-based water-soluble coating agent and a water adsorbent in the first coating base in a weight ratio of 5: 1 to 30: 1. According to claim 1,
A moisture-proof coating composition comprising a polyvinyl alcohol-based water-soluble coating agent and a moisture barrier agent in the second coating base in a weight ratio of 2: 1 to 20: 1. The method of claim 5,
A moisture-proof coating composition comprising a polyvinyl alcohol-based water-soluble coating agent and a moisture barrier agent in a weight ratio of 3: 1 to 18: 1 in the second coating base. According to claim 1,
The hydroxypropyl methylcellulose-based water-soluble coating agent of the first coating base and the water adsorbent comprising a 5: 1 to 30: 1 weight ratio,
A moisture-proof coating composition comprising a polyvinyl alcohol-based water-soluble coating agent and a moisture barrier agent in a weight ratio of 3: 1 to 18: 1 in the second coating base. The method according to any one of claims 1 to 7,
The moisture absorbent composition for moisture-proof coating, characterized in that at least one selected from calcium silicate, magnesium metaaluminate and colloidal silicon dioxide. The method according to any one of claims 1 to 7,
The moisture barrier composition for moisture-proof coating, characterized in that at least one selected from mannitol, pregelatinized starch, erythritol, isomalt, xylitol, sorbitol and maltitol. The method according to any one of claims 1 to 7,
The moisture adsorbent is characterized in that at least one selected from calcium silicate, magnesium metaaluminate and colloidal silicon dioxide,
The moisture barrier composition for moisture-proof coating, characterized in that at least one selected from mannitol, pregelatinized starch, erythritol, isomalt, xylitol, sorbitol and maltitol. According to claim 1,
The active ingredients are Choline alfoscerate, Pravastatin, L-Carnitine, Rabeprazole, Telmisartan Ethambutol, Citicoline , Pyridostigmine, Ranitidine, Furosemide, Cefuroxime Axetil, Fluvastatin, Acetyl-L-Carnitine, Clopidogrel (Clopidogrel), Amlodipine, Cyanocobalamin, Limaprost, Losartan, Aspirin, Fesoterodine, Bupropion, Ropinirole ), Cefetamet Pivoxil, Rosuvastatin, Sarpogrelate, Aripiprazole, and Ramipril.