KR20180054955A - The Solid Active Pharmaceutical Ingredients Comprising Glyceryl phosphoryl choline for Improving the Stability of Hygroscopic Drug Substance, Use or Method for Preparing Thereof - Google Patents

Abstract

The present invention relates to a solid preparation comprising glyceryl phosphoryl choline using orotic acid as an adsorbent, and to uses or a manufacturing method thereof. The solid preparation containing the glyceryl phosphoryl choline and orotic acid of the present invention can be prepared as a solid type by overcoming the disadvantages related to the stability and production cost of a conventional soft capsule formulation and improving the hygroscopicity, and can be used as a pharmaceutical composition for preventing or treating cranial nerve diseases including brain dysfunction, cognitive disorder, and the like.

Description

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a solid preparation containing glyceryl phosphoryl choline having improved hygroscopicity,

The present invention relates to a solid preparation comprising glycerylphosphorylcholine and orotic acid, wherein the hygroscopicity of glyceryl phosphoryl choline is improved by using orotic acid as an adsorbent, a use thereof or a preparation method thereof .

The orotic acid represented by the following formula (1) can improve the hygroscopicity of glycerylphosphorylcholine (formula (2)) to help develop it as a solid agent, and the present invention can be applied to a solid preparation And the improvement of hygroscopicity.

Formula 1

(2)

L-α-glyceryl phosphorylcholine (GPC) represented by the above-mentioned formula 2 is a semisynthetic derivative of lecithin and is a precursor of the cholinergic system and also called chloline alfoscerate Loses.

Glycerylphosphorylcholine is the main compound for producing new acetylcholine in the brain, which naturally exists in all cells of the body, but decreases as the aging progresses, resulting in decreased cognitive ability, vascular dementia and Alzheimer ' s dementia Of the neurodegenerative diseases.

These glycerylphosphorylcholine are effective for improvement of cognitive ability, improvement of brain function and treatment, secondary drugs for cerebrovascular deficiency and degeneration or degenerative brain syndrome, It is also known to be useful for senile cognitive disturbances such as sensory disturbance and concentration reduction, emotional and behavioral changes such as anxiety, irritability, and senile depression.

In Korea, soft capsule preparations such as glyatorine soft capsules, alpoatiline soft capsules, and solid preparations such as glycyrrhizin and glutathione are prescribed. However, soft capsules are mainly sold in the market due to limitations in formulation.

However, the soft capsule containing glycerylphosphorylcholine has a possibility that the main ingredient, which is in a liquid state at the time of production, is transferred to a gelatin soft capsule shell which is water-soluble over time, which may cause a decrease in the drug efficacy. In addition, the possibility of microorganism alteration is higher than those of other formulations such as tablets and powders, and it is weak against moisture and heat, and storage stability is very low. In addition, since a soft capsule manufacturing facility is required, an additional process and a manufacturing apparatus are required in comparison with a general preparation such as a tablet, and the production cost is relatively high.

To overcome this disadvantage, tablets containing solid type glyceryl phosphoryl choline have been developed. However, there is a problem that the solid raw material itself is too strong in hygroscopicity and is converted into a liquid phase within a few hours when the raw material is left in the atmosphere. Tablets made from solid raw materials are also weak against heat and humidity, and therefore, formulation defects such as swelling and swelling of tablets are frequently reported.

With respect to a preparation containing glycerylphosphorylcholine or a method for producing the same, Korean Patent Laid-Open No. 10-2009-0088564 discloses a pharmaceutical preparation characterized in that glycerylphosphorylcholine is adsorbed on colloidal silicon dioxide and granulated And Korean Patent No. 10-1172699 discloses a pharmaceutical preparation which can be solidified by adsorption on magnesium aluminosilicate. Korean Patent Laid-Open Publication No. 10-2016-0005971 discloses a solid preparation comprising glycerylphosphorylcholine and calcium silicate and a method for producing the same, which can form a solid form by adsorbing glycerylphosphorylcholine by calcium silicate .

Formulations containing glycerylphosphorylcholine are prescribed as prescription medicines in Korea and China and are intended to replicate soft capsules containing 400 mg of glycerylphosphorylcholine and tablets 2-3 times a day. On the other hand, glycerylphosphorylcholine is classified as a dietary supplement in most countries including the US and Europe. In the United States, the choline alfoscerate raw material in liquid form is blended with flow agents such as di-calcium phosphate dihydrate, magnesium stearate, silicon dioxide and magnesium silicate to produce an adsorbate having a content of 50% And is commercially available. The United States recommends taking 600 mg of the adsorbent preparation containing 300 mg of glycerylphosphorylcholine twice a day, 2 capsules, and it is readily available in online and offline stores without a prescription.

In Korea, the content of glycerylphosphorylcholine contained in one preparation is 400 mg, which is 100 mg more than that of the United States, and it is common to take one capsule at a time, so that the size issue of the preparation is greatly highlighted. This is because older adults have difficulty in swallowing large-sized medicines because their swallowing ability is lowered. In particular, the inconvenience of taking soft capsules is more severe than that of tablets.

As a result, the present inventors have sought to satisfy such unmet demand, and as a result, they are superior in hygroscopicity and stability to conventional solid raw materials while having a volume smaller than that of conventional adsorbates, , Production efficiency, hygroscopicity, and so on.

On the other hand, the present inventors have researched solidification of liquid glyceryl phosphoryl choline and disclosed a new crystal form newly discovered in Korea Patent Registration No. PCT / KR2015 / 000446.

In the case of the new crystalline form of solid glycerylphosphorylcholine produced by the present invention, there is an advantage in that the hygroscopicity is low as compared with the crystalline form which is conventionally known in Korean Patent Registration No. 10-1287422 and is named as crystal form 1, In both conditions, both of the crystal forms had problems of gel formation within a few hours and still needed improvement in stability and hygroscopicity.

Accordingly, the present inventors developed a solid raw material improved in hygroscopicity by adding orotic acid, which is widely used as a pharmaceutical agent, and not as an excipient commonly known as an adsorbent.

Orotic acid is a pharmacologically acceptable salt that is used as an acid addition salt of pharmaceutical raw materials. As a food, magnesium orotate is used as 1,000 to 2,000 mg daily for symptom relief due to magnesium deficiency. As such, it is used as an acid addition salt of mineral Safety is a widely proven material.

The present inventors have developed a solid preparation containing glycerylphosphorylcholine which is improved in stability and hygroscopicity compared to conventional liquid and solid preparations. As a result, a solid preparation containing glycerylphosphorylcholine was produced by using orotic acid, which is not an excipient commonly known as an adsorbent, as an adsorbent. As a result, stability and hygroscopicity were improved, And thus it is possible to formulate solid dosage forms of appropriate sizes, thus completing the present invention.

It is therefore an object of the present invention to provide a solid preparation comprising glyceryl phosphoryl choline and orotic acid.

Another object of the present invention is to provide a pharmaceutical composition for preventing or treating brain diseases, which comprises the above-mentioned solid preparation of the present invention.

It is still another object of the present invention to provide a method for producing a solid preparation comprising glyceryl phosphoryl choline.

Other objects and advantages of the present invention will become more apparent from the following detailed description of the invention, claims and drawings.

According to one aspect of the present invention, there is provided a solid preparation comprising glycerylphosphorylcholine and orotic acid.

The glycerylphosphorylcholine contained in the present invention is also referred to as choline alfoscerate and is a drug that promotes the production of acetylcholine as a neurotransmitter as a cholinesterase precursor compound and can be used as a cognitive ability improving agent, .

The orotic acid contained in the present invention is also referred to as vitamin B13, and acts as an intermediate when an enzyme that converts saccharides into energy is synthesized in the body. It helps prevent hepatic disorders, prevents aging, and is known to be involved in growth promotion. It is known to be contained in vegetables, wheat germ, yeast, etc., especially in milk, in raw milk, and especially in chlorine or amniotic milk at a high content of 15-118 mg / ml on average. Such orotic acid is one of the pharmaceutically acceptable salts and is used as amlodipine orotate or carnitine orate.

According to one embodiment of the present invention, the orotic acid contained in the present invention is characterized by adsorbing the glycerylphosphorylcholine.

The glycerylphosphorylcholine is usually present in a liquid state and contains 14 to 16% of water. And even when it is solidified and solidified, it is unstable in temperature and humidity. Therefore, it absorbs moisture in the air and easily changes into a liquid phase. Thus, in order to prepare a solid preparation containing glycerylphosphorylcholine, it is important to reduce the hygroscopicity of the raw material to ensure stability.

In the present invention, by using orotic acid as an adsorbent, stability against temperature and humidity is greatly improved.

According to another embodiment of the present invention, the equivalent ratio of the glycerylphosphoryl choline to the orotic acid is 1: 0.5 to 1: 2, more preferably the equivalent ratio is 1: 0.9 to 1: 1.5, Equivalent ratio of 1: 0.95 to 1: 1.05.

The present inventors have tested the preparation of hygroscopic material and hygroscopicity according to the content of orotic acid to glycerylphosphorylcholine. When the amount of orotic acid is less than 0.5 equivalent molar ratio, the effect of improving hygroscopicity is weak. It has been confirmed that the volume of the preparation becomes large and the convenience of taking the product becomes poor.

As used herein, the term " solid formulation " means a formulation having the shape of a solid state, preferably including tablets (more preferably film-coated tablets), pills, powders, coatings, granules, It is not.

As used herein, the term " chewable tablet " refers to a formulation that is chewy in the mouth and makes its hardness so that it does not need to be taken with water.

According to another embodiment of the present invention, the solid preparation further comprises a disintegrant.

The disintegrant included in the present invention serves to absorb water when taking the solid preparation to accelerate disintegration of the solid preparation, and the disintegrant is selected from the group consisting of croscarmellose sodium, sodium starch glycolate, microcrystalline cellulose, crospovidone, Polyvinylpyrrolidone, low-substituted hydroxypropylcellulose, alginic acid, powdered cellulose, starch or sodium alginate are preferable, and more preferable are cocamelose sodium, crospovidone, sodium starch glycolate, etc., And most preferably a mixture of croscarmellose sodium and crospovidone.

According to another aspect of the present invention, there is provided a pharmaceutical composition for preventing or treating cerebrovascular diseases comprising the above-mentioned solid preparation of the present invention.

The composition has a prophylactic or therapeutic use for cranial nerve diseases that may occur due to an acetylcholine deficiency.

The cerebrovascular disease includes cerebral dysfunction or cognitive disorder, preferably cerebrovascular deficiency, degenerative brain syndrome, dementia, memory loss, delirium, desire and spontaneity, decrease in concentration, , Irritable hypersensitivity, or ambient indifference, senile pseudorabies, and the like.

When the composition of the present invention is manufactured from a pharmaceutical composition, the pharmaceutical composition of the present invention includes a pharmaceutically acceptable carrier. The pharmaceutically acceptable carriers to be contained in the pharmaceutical composition of the present invention are those conventionally used in the formulation and include lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia rubber, calcium phosphate, alginate, gelatin, But are not limited to, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrups, methylcellulose, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. It is not. The pharmaceutical composition of the present invention may further contain a lubricant, a wetting agent, a sweetening agent, a flavoring agent, an emulsifying agent, a suspending agent, a preservative, etc. in addition to the above components. Suitable pharmaceutically acceptable carriers and formulations are described in detail in Remington ' s Pharmaceutical Sciences (19th ed., 1995).

The pharmaceutical composition of the present invention can be preferably administered orally.

The appropriate dosage of the pharmaceutical composition of the present invention may vary depending on factors such as the formulation method, administration method, age, body weight, sex, pathological condition, food, administration time, administration route, excretion rate, . On the other hand, the dosage of the pharmaceutical composition of the present invention is preferably 0.01-400 mg / kg (body weight) per day.

The pharmaceutical composition of the present invention may be formulated into a unit dose form by formulating it using a pharmaceutically acceptable carrier and / or excipient according to a method which can be easily carried out by a person having ordinary skill in the art to which the present invention belongs. Or may be prepared by penetration into a multi-dose vessel, and may additionally comprise a dispersant or stabilizer.

According to another aspect of the present invention, the present invention provides a process for preparing a solid preparation comprising glycerylphosphorylcholine, comprising the steps of: (a) adding an organic solvent to glycerylphosphorylcholine and orotic acid Adding and stirring, followed by filtration and washing with an organic solvent; And (b) drying the product of step (a).

Hereinafter, the method of the present invention for preparing a solid preparation containing glycerylphosphorylcholine will be described in detail as follows:

The solid preparation of the present invention can be prepared through a solvent mediated method.

(a) glyceryl Phosphorylcholine and orotic acid Addition of organic solvent and stirring , and filtration thereof and washing with organic solvent

First, the method of the present invention comprises the steps of (a) adding an organic solvent to glycerylphosphorylcholine and orotic acid, stirring, followed by filtration and washing with an organic solvent.

According to another embodiment of the present invention, the equivalent ratio of glycerylphosphorylcholine and orotic acid in step (a) is 1: 0.5-2.0, more preferably 1: 0.9-1.5, And more preferably an equivalent ratio of 1: 0.95 to 1.05.

The organic solvent in step (a) may be selected from a variety of organic solvents known in the art, and preferably methanol, ethanol, butanol, isopropyl alcohol, pentane, hexane, heptane, cyclohexane, toluene, Is selected from the group consisting of acetone, methylene chloride, chloroform, ether, petroleum ether, benzene, ethylene glycol, propylene glycol, butylene glycol, acetonitrile and acetone, more preferably isopropyl alcohol, ethyl acetate or acetone, Most preferably ethyl acetate or acetone.

According to another embodiment of the present invention, the stirring is carried out at a temperature of 45-55 ° C for 1 hour to 3 hours, more preferably at 50-55 ° C for 1 hour to 3 hours.

(b) drying the resultant product of step (a)

Finally, the process of the present invention comprises (b) drying the product of step (a).

According to another embodiment of the present invention, the drying is carried out at 40-50 DEG C for 12-20 hours.

In this way, a solid preparation containing glycerylphosphorylcholine can be prepared.

When a solid raw material containing glyceryl phosphoryl choline is prepared by using orotic acid as an adsorbent as in the present invention, hygroscopicity can be improved, and thus, it is possible to help solid formulations.

The features and advantages of the present invention are summarized as follows:

(a) The present invention provides a glycerylphosphorylcholine solid preparation using orotic acid as an adsorbent, its use and preparation method.

(b) The present invention provides a solid preparation comprising glycerylphosphorylcholine by using orotic acid, which is not an excipient commonly known as an adsorbent, as an adsorbent, and as a result, the stability and hygroscopicity are improved, And it was confirmed that solid dosage form of appropriate size is possible.

(c) The solid preparation of the present invention is improved in stability and hygroscopicity as compared with conventional liquid and solid preparations, and cost reduction can be expected because no additional production facility is required.

Figures 1 and 2 illustrate the water content pattern of solid raw material mixed with glyceryl phosphoryl choline and orotic acid prepared according to one embodiment of the present invention.
Figures 3a-3i and 4a-4h illustrate the effect of equivalents of the conventional solid crystalline glyceryl phosphoryl choline and the glyceryl phosphoryl choline-orotic acid of the present invention on the conditions of relative humidity 64% and 75% The obtained adsorbates were photographed and compared at each time point.
In Figures 1 to 4, GPC Form-I is L-α-glycerylphosphorylcholine solid Form 1, GPO 0.5eq is glycerylphosphorylcholine-orotic acid (0.5eq) adsorbate, GPO 1eq is glycerylphosphate (1.5 eq) adsorbed with glycerylphosphorylcholine-orotic acid (1.5 eq) and GPO 2eq adsorbed with glycerylphosphorylcholine-orotic acid (2 eq) adsorbate .

Hereinafter, the present invention will be described in more detail with reference to Examples. It is to be understood by those skilled in the art that these embodiments are only for describing the present invention in more detail and that the scope of the present invention is not limited by these embodiments in accordance with the gist of the present invention .

The orotic acid used in the following examples was 99% pure material purchased from China Asta chemical, and glycerylphosphorylcholine manufactured by Fushilai Pharmaceutical was used. The remaining solvents and inorganic reagents were purchased from Daejeong Chemical.

Example

Example 1: Preparation of solid raw materials by mixing glycerylphosphorylcholine and orotic acid (0.5 eq) via solvent-mediated method

In a 100 ml reactor, 5 g of glycerylphosphorylcholine, 1.52 g of orotic acid and 26 ml of acetone were added at room temperature, followed by stirring at 50 ° C for 2 hours. After cooling to room temperature, the mixture was filtered, washed with 10 ml of acetone, and then dried with hot air at 45 ° C for 16 hours to obtain 6.16 g of a mixture of glycerylphosphorylcholine and orotic acid (0.5 eq).

Example 2: Preparation of solid raw materials by mixing glycerylphosphorylcholine and orotic acid (1 eq) via solvent-mediated method

25 g of glycerylphosphorylcholine, 15.2 g of orotic acid and 100 ml of acetone were added to a 250 ml reactor at room temperature, followed by stirring at 50 ° C for 2 hours. After cooling to room temperature, the mixture was filtered, washed with 40 ml of acetone, and then dried with hot air at 45 ° C for 16 hours to obtain 38.6 g of a mixture of glycerylphosphorylcholine and orotic acid (1 eq).

Example 3 Preparation of Solid Raw Material Mixed with Glycerylphosphorylcholine and Orotic Acid (1.5 eq) via Solvent-Mediated Method

A 250 ml reactor was charged with 20 g of glycerylphosphorylcholine, 22.76 g of orotic acid and 100 ml of acetone at room temperature, followed by stirring at 50 ° C for 2 hours. After cooling to room temperature, the mixture was filtered, washed with 40 ml of acetone, and then dried with hot air at 45 ° C for 16 hours to obtain 37.6 g of a mixture of glycerylphosphorylcholine and orotic acid (1.5 eq).

Example 4 Preparation of Solid Raw Material Mixed with Glycerylphosphorylcholine and Orotic Acid (2 eq) via Solvent-Mediated Method

A 100 ml reactor was charged with 5 g of glycerylphosphorylcholine, 6.22 g of orotic acid and 45 ml of acetone at room temperature, followed by stirring at 50 ° C for 2 hours. After cooling to room temperature, the mixture was filtered, washed with 20 ml of acetone, and then dried with hot air at 45 ° C for 16 hours to obtain 10.8 g of a mixture of glycerylphosphorylcholine and orotic acid (2 eq).

Example 5: Preparation of solid raw materials mixed with orotic acid (1 eq) using liquid glycerylphosphoryl choline

10 g of glycerylphosphorylcholine, 10 g of sodium sulfate and 80 ml of anhydrous ethanol were added to a 250 ml reactor at room temperature, followed by stirring at 40 to 50 ° C for 1 hour. The mixture was cooled to room temperature, filtered, and the filtrate was concentrated under reduced pressure. To this was added 5.158 g of orotic acid, 50 ml of acetone and 50 ml of ethyl acetate, and the mixture was heated under reflux for 1 hour and then stirred at room temperature for 16 hours. After concentration under reduced pressure, 50 ml of acetone and 50 ml of methanol were added, followed by stirring at room temperature for 2 hours. Washed with 20 ml of acetone and then hot-air dried at 45 ° C for 16 hours to obtain 8.7 g of a mixture of glycerylphosphorylcholine and orotic acid (1 eq).

Example 6: Preparation of a solid preparation according to the equivalence of orotic acid

ingredient A B C D Glycerylphosphorylcholine 400 400 400 400 Orotic Mountain 121.4 242.7 364.1 485.5 Microcrystalline cellulose 35 35 35 35 Lactose baggage 80 80 80 80 Crospovidone 50 50 50 50 Croscarmellose sodium 10 10 10 10 Sodium stearyl fumarate 10 10 10 10

The glycerylphosphorylcholine orotic acid adsorbates prepared in Examples 1 to 4 were used for the preparation of the compositions of Formulations A, B, C and D, respectively. According to the composition of Table 1, The ingredients were used to prepare solid tablets.

Example 7: Manufacture of Film Coated Definition

One equivalent of aurous acid and one equivalent of glycerylphosphorylcholine were added to the high-speed synergist, and glycerylphosphorylcholine was adsorbed to orotic acid while mixing at a high speed. To this, microcrystalline cellulose was added, and purified water was added thereto. After drying and sizing the associated material, colloidal silicon dioxide, crospovidone, low-substituted hydroxypropylcellulose, and magnesium stearate were added to the sized product, and the mixture was compressed and film coated to obtain a glycerylphosphorylcholine film coated tablet . This was named Prescription F. Table 2 shows the composition of each equivalent weight.

ingredient E F G H Glycerylphosphorylcholine 400 400 400 400 Orotic Mountain 121.4 242.7 364.1 485.5 Microcrystalline cellulose 35 35 35 35 Colloidal silicon dioxide 10 10 10 10 Crospovidone 55 55 55 55 Low-substituted HPMC 15 15 15 15 Magnesium stearate 10 10 10 10

Example 8: Comparison of the stability of the prepared solid preparation with the equivalent amount of orotic acid

In order to compare the stability of the solid preparations containing glyceryl phosphoryl choline with the equivalents of orotic acid, the solid preparations prepared in Examples 6 and 7 were stored for 6 months in long-term storage (25 ° C, 60% relative humidity) After storage under the conditions of the test (40 ± 2 ° C., 75 ± 5% relative humidity), the results are shown in Table 3 below.

- A B C D E F G H Appearance (white rectangular tablet) fitness fitness fitness fitness fitness fitness fitness fitness Content (95% ~ 105%) fitness fitness fitness fitness fitness fitness fitness fitness Elution (30 minutes 80% or more (water)) fitness fitness fitness fitness fitness fitness fitness fitness

Example 8: Elution test of solid preparation

In order to compare the dissolution rates of the solid preparations prepared in Examples 6 and 7 with the conventional soft capsule formulation, glycitalin soft capsule (Chong Kun Dang), the results were shown in Table 4 below. :

Eluent Temperature Test method Paddle rotation speed Water 900 ml 37 ± 0.5 ° C Korea Pharmacopoeia dissolution test, second method (paddle method) 50 rpm

Analytical methods are described in Journal of the Korea Academia-Industrial cooperation Society Vol. 14, No. 12 pp. 6324-6329 and 2013, the following procedure was carried out.

Specifically, the eluate was collected at 5, 10, 15 and 30 minutes and filtered with a 0.45 μm PVDF syringe filter (Whatman, USA). Separately, 444 mg of choline alfoscerate standard was weighed and placed in a 100-mL volumetric flask. 10 mL of this solution was placed in a 100-mL volumetric flask, filled with a pH 6.8 solution, and used as a standard solution. It was analyzed by HPLC analysis under the following conditions. Specifically, the HPLC system was HPLC-20A series (Shimadzu, Japan) and the detector was RID-10A (Shimadzu, Japan). The column used was a Zorbax NH2 column (4.6 x 250 mm, 5 μm), the mobile phase was 60% acetonitrile, the detector was a refractive index detector (RID-10A), the flow rate was 1.5 mL / min and the injection volume was 50 μL.

Test solution (water) Average dissolution rate (%) 5 minutes 10 minutes 15 minutes 30 minutes Treaty 2.8 58.6 91.0 97.6 A 25.0 78.4 92.3 98.7 B 43.8 80.0 94.5 99.5 C 36.5 78.3 92.5 98.5 D 20.6 69.5 91.6 97.9 E 35.5 80.5 92.8 98.2 F 42.8 81.2 92.9 99.3 G 38.5 75.5 92.0 98.9 H 25.6 75.1 91.5 98.0

As can be seen from the above Table 5, the tablets prepared using the orotic acid adsorbent prepared in the present invention had a better dissolution rate than the control drug in all time zones as compared with the glycitalin soft capsules of Chong Kun Dang, Respectively. This is because, in the case of soft capsules, it takes time for the initial coating to decompose. It was confirmed that the tablets of the present invention had a relatively small variation with time and eluted more than 90% in 15 to 30 minutes.

While the present invention has been particularly shown and described with reference to exemplary embodiments thereof, it is to be understood that the same is by way of illustration and example only and is not to be construed as limiting the scope of the present invention. Accordingly, the actual scope of the present invention will be defined by the appended claims and their equivalents.

Claims (9)

A solid preparation comprising glyceryl phosphoryl choline and orotic acid.
The solid preparation according to claim 1, wherein the orotic acid adsorbs the glycerylphosphorylcholine.
The solid preparation according to claim 1, wherein the equivalent ratio of glycerylphosphorylcholine to orotic acid is 1: 0.5 to 1: 2.
The solid preparation according to claim 1, wherein the solid preparation is a tablet, a pill, a powder, a coating, a capsule, a granule or a chewable tablet.
A pharmaceutical composition for the prophylaxis or treatment of neurological diseases comprising the solid preparation of claim 1.
A process for preparing a solid preparation comprising glycerylphosphorylcholine comprising the steps of:
(a) adding an organic solvent to glycerylphosphorylcholine and orotic acid, stirring, followed by filtration and washing with an organic solvent; And
(b) drying the product of step (a).
7. The method of claim 6, wherein the equivalence ratio of glycerylphosphorylcholine and orotic acid in step (a) is from 1: 0.5 to 1: 2.
The method of claim 6, wherein the organic solvent of step (a) is selected from the group consisting of methanol, ethanol, butanol, isopropyl alcohol, pentane, hexane, heptane, cyclohexane, toluene, methyl acetate, ethyl acetate, methylene chloride, chloroform, ether, Is selected from the group consisting of ether, benzene, ethylene glycol, propylene glycol, butylene glycol, acetonitrile and acetone.
The method according to claim 6, wherein the drying of step (b) is carried out at 40-50 ° C for 12-20 hours.

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