Pharmaceutical preparation and preparation method thereof

Abstract

The present invention relates to a pharmaceutical preparation with improved productivity and uniformity and a method for preparing the same.

Description

[0001] DESCRIPTION

[0002] Title

[0003] PHARMACEUTICAL PREPARATION AND PREPARATION METHOD THEREOF

[0004] Technical Field

[0005] The present invention relates to a pharmaceutical preparation with improved productivity and uniformity and a method for preparing the same.

[0006] Background

[0007] Anorexia is a state in which a desire for food, water, or beverages has decreased, thus resulting in a voluntary decrease in food intake. If such loss of appetite persists, it may cause a nutritional deficiency state or weight loss, and in particular, the weight loss related to malnutrition may lower the health-related quality of life and cause secondary medical problems. Thus, it was confirmed that there are systemic effects such as improvement of physical indicators, an increase in exercise capacity, an increase in health-related quality of life, a decrease in fatigue and the like through amelioration of anorexia, and in particular, it was observed that pediatric patients with anorexia show better growth accompanied by significant improvement in physical indicators such as weight and BMI by ameliorating anorexia. Taken together, anorexia and its resulting nutritional deficiency are one of diseases which need to be solved for the healthy growth of infants and children and the improvement of quality of life in adults and the elderly.

[0008] Cyproheptadine exhibits an appetite-promoting effect by inhibiting serotonin (5- hydroxytryptamine, 5-HT). When a large amount of nutrients are ingested, a ratio of tryptophan increases to promote serotonin synthesis in the brain, and peripheral satiety factors (a factor for indicating a satiety state) such as cholecystokinin act on the hypothalamus of the brain to promote the release of serotonin. The released serotonin acts on the receptors of the hypothalamus to inhibit neuropeptide Y (NPY), thereby causing satiety and suppressing appetite. Cyproheptadine has an effect of delaying satiety and promoting appetite by inhibiting such serotonin to promote the action of NPY.

[0009] "Trestan® capsule" is a complex which combines four ingredients that help appetite promotion and growth, such as cyproheptadine orotate, which exhibits an appetite-promoting effect through the above functional mechanisms, DL-camitine hydrochloride, which helps fatty acids be used as energy necessary for the body as an auxiliary factor in fat metabolism, lysine hydrochloride, which is essential for growth and health maintenance as an essential amino acid, cyanocobalamin (vitamin B12), which is a vitamin essential for nucleoprotein synthesis, cell replication, and maintenance of normal hematopoietic function in the human body, promotes the production of red blood cells, and is involved in metabolism of proteins to prevent anemia and help improve growth, appetite, concentration and memory. Unlike other appetite-promoting ingredients, it may be used for ordinary people and children, and thus is a drug with high clinical utility for appetite promotion.

[0010] Detailed Description of the Invention

[0011] Technical Problem

[0012] The present inventors have found that a sticking phenomenon, in which a raw material adheres to a facility surface, occurs when producing a preparation including said active ingredients, and thus process efficiency and productivity are deteriorated or it becomes difficult to uniformly maintain a weight of the preparation. Accordingly, there is a need to develop a pharmaceutical preparation with improved productivity and uniformity. Technical Solution

[0013] The present invention provides a pharmaceutical preparation which contains dry granules comprising: cyproheptadine orotate hydrate; DL-carnitine hydrochloride; L-lysine hydrochloride; and cyanocobalamin as active ingredients, and microcrystalline cellulose; anhydrous calcium hydrogen phosphate; and magnesium aluminometasilicate as additives, in which a weight ratio of a total weight of the active ingredients to anhydrous calcium hydrogen phosphate in the dry granules is 1 :0.082 to 1 :0.199, and a weight ratio of a total weight of the active ingredients to magnesium aluminometasilicate in the dry granules is 1 :0.099 to 1 :0.215.

[0014] The present invention provides a method for preparing a pharmaceutical preparation, the method comprising: mixing cyproheptadine orotate hydrate; DL-carnitine hydrochloride; L-lysine hydrochloride; and cyanocobalamin as active ingredients, and microcrystalline cellulose; anhydrous calcium hydrogen phosphate; and magnesium aluminometasilicate as additives, and preparing the resulting mixed composition into dry granules, in which a weight ratio of a total weight of the active ingredients to anhydrous calcium hydrogen phosphate in the dry granules is 1 :0.082 to 1:0.199, and a weight ratio of a total weight of the active ingredients to magnesium aluminometasilicate in the dry granules is 1 :0.099 to 1 :0.215.

[0015] Specific embodiments of the present invention are as follows, but the scope of the present invention is not limited thereto.

[0016] (1) A pharmaceutical preparation according to the present invention is a pharmaceutical preparation comprising dry granules comprising: cyproheptadine orotate hydrate; DL-carnitine hydrochloride; L-lysine hydrochloride; and cyanocobalamin as active ingredients, and microcrystalline cellulose; anhydrous calcium hydrogen phosphate; and magnesium aluminometasilicate as additives, in which a weight ratio of a total weight of the active ingredients to anhydrous calcium hydrogen phosphate in the dry granules is 1 :0.082 to 1 :0.199, and a weight ratio of a total weight of the active ingredients to magnesium aluminometasilicate in the dry granules is 1 :0.099 to 1 :0.215.

[0017] (2) In above (1), it may be provided that the weight ratio of the total weight of the active ingredients to microcrystalline cellulose in the dry granules is 1 :0.016 to 1 :0.232.

[0018] (3) In above (1) or (2), it may be provided that cyproheptadine orotate hydrate is comprised in an amount of 1 mg to 3 mg, DL-camitine hydrochloride is comprised in an amount of 100 mg to 200 mg, L-lysine hydrochloride is comprised in an amount of 100 mg to 200 mg, and cyanocobalamin is comprised in an amount of 0.5 mg to 2 mg.

[0019] (4) In any one of above (1) to (3), it may be provided that microcrystalline cellulose is comprised in an amount of 5 mg to 70 mg, anhydrous calcium hydrogen phosphate is comprised in an amount of 25 mg to 60 mg, and magnesium aluminometasilicate is comprised in an amount of 30 mg to 65 mg.

[0020] (5) In any one of above (1) to (4), it may be provided that the weight ratio of the total weight of the active ingredients to anhydrous calcium hydrogen phosphate in the dry granules is 1 :0.099 to 1 :0.166, and the weight ratio of the total weight of the active ingredients to magnesium aluminometasilicate in the dry granules is 1 :0.132 to 1 :0.199.

[0021] (6) In any one of above (1) to (5), it may be provided that the weight ratio of the total weight of the active ingredients to microcrystalline cellulose in the dry granules is 1 :0.033 to 1 :0.166.

[0022] (7) In any one of above (1) to (6), it may be provided that at least one selected from the group consisting of silicon dioxide, light anhydrous silicic acid, magnesium stearate and talc is further comprised as additives.

[0023] (8) In any one of above (1) to (7), it may be provided that the pharmaceutical preparation is formulated into one type selected from the group consisting of tablets, powders, granules, pills and capsules.

[0024] (9) In any one of above (1) to (8), it may be provided that the pharmaceutical preparation is for preventing or treating anorexia.

[0025] (10) A method for preparing a pharmaceutical preparation according to the present invention is a method for preparing a pharmaceutical preparation comprising: mixing cyproheptadine orotate hydrate; DL-carnitine hydrochloride; L-lysine hydrochloride; and cyanocobalamin as active ingredients, and microcrystalline cellulose; anhydrous calcium hydrogen phosphate; and magnesium aluminometasilicate as additives, and preparing the resulting mixed composition into dry granules, in which a weight ratio of a total weight of the active ingredients to anhydrous calcium hydrogen phosphate in the dry granules is 1 :0.082 to 1 :0.199, and a weight ratio of a total weight of the active ingredients to magnesium aluminometasilicate in the dry granules is 1 :0.099 to 1 :0.215.

[0026] (11) In above (10), it may be provided that the weight ratio of the total weight of the active ingredients to microcrystalline cellulose in the dry granules is 1 :0.016 to 1 :0.232.

[0027] (12) In above (10) or (11), it may be provided that at least one selected from the group consisting of silicon dioxide, light anhydrous silicic acid, magnesium stearate and talc is further mixed as additives.

[0028] (13) In any one of above (10) to (12), it may be provided that the method for preparing the pharmaceutical preparation further comprises formulating the prepared dry granules into a dosage form.

[0029] (14) A method for preventing or treating anorexia according to the present invention comprises administering to a subject in need thereof the pharmaceutical preparation according to any one of above (1) to (8).

[0030] (15) A use according to the present invention is a use of the pharmaceutical preparation according to any one of above (1) to (8) for preventing or treating anorexia.

[0031] (16) A use according to the present invention is a use of the pharmaceutical preparation according to any one of above (1) to (8) for preparing a medication for preventing or treating anorexia.

[0032] Advantageous Effects

[0033] A pharmaceutical preparation of the present invention can show excellent productivity and uniformity, and thus can be economical and suitable for mass production.

[0034] Brief Description of the Drawings

[0035] FIG. l is a view showing an individual mass deviation of capsules of Examples 1 to 6 and Comparative Examples 1 to 6.

[0036] Best Mode for Invention

[0037] Hereinafter, the present invention will be described in more detail. All the combinations of various elements disclosed in the present invention fall within the scope of the present invention. In addition, it cannot be seen that the scope of the present invention is limited to the specific description below.

[0038] The present invention provides a pharmaceutical preparation which contains dry granules comprising: cyproheptadine orotate hydrate; DL-carnitine hydrochloride; L-lysine hydrochloride; and cyanocobalamin as active ingredients, and microcrystalline cellulose; anhydrous calcium hydrogen phosphate; and magnesium aluminometasilicate as additives, in which a weight ratio of a total weight of the active ingredients to anhydrous calcium hydrogen phosphate in the dry granules is 1 :0.082 to 1 :0.199, and a weight ratio of a total weight of the active ingredients to magnesium aluminometasilicate in the dry granules is 1 :0.099 to 1 :0.215.

[0039] A pharmaceutical preparation of the present invention shows excellent productivity and uniformity, and thus may be economical and suitable for mass production.

[0040] The pharmaceutical preparation of the present invention has excellent process efficiency and productivity, and easily secures quality since the preparation with a uniform weight is reproducibly prepared.

[0041] According to one specific embodiment of the present invention, the pharmaceutical preparation of the present invention may have a good degree of sticking to a facility surface during a dry granulation process, so that the dry granulation process may be smoothly performed, the powder properties of the obtained granules, such as flowability, dustability, etc., are suitable for the formulation, and a uniform preparation may be reproducibly prepared.

[0042] The pharmaceutical preparation of the present invention comprises cyproheptadine orotate hydrate as an active ingredient. Cyproheptadine exhibits an appetite-promoting effect by inhibiting serotonin (5-hydroxytryptamine, 5-HT). When a large amount of nutrients are ingested, a ratio of tryptophan increases to promote serotonin synthesis in the brain, and peripheral satiety factors (a factor for indicating a satiety state) such as cholecystokinin act on the hypothalamus of the brain to promote the release of serotonin. The released serotonin acts on the receptors of the hypothalamus to inhibit neuropeptide Y (NPY), thereby causing satiety and suppressing appetite. Cyproheptadine has an effect of delaying satiety and promoting appetite by inhibiting such serotonin to promote the action of NPY.

[0043] The pharmaceutical preparation of the present invention comprises DL-carnitine hydrochloride as an active ingredient. DL-carnitine hydrochloride is a cofactor in fat metabolism and helps fatty acids to be used as energy needed for the living body.

[0044] The pharmaceutical preparation of the present invention comprises L-lysine hydrochloride as an active ingredient. L-lysine hydrochloride is an essential amino acid, which is essential for growth and health maintenance.

[0045] The pharmaceutical preparation of the present invention comprises cyanocobalamine as an active ingredient. Cyanocobalamin is a vitamin essential for nucleoprotein synthesis, cell replication, and maintenance of normal hematopoietic function in the human body, which promotes the production of red blood cells, and is involved in metabolism of proteins to prevent anemia and help improve growth, appetite, concentration and memory.

[0046] The pharmaceutical preparation of the present invention comprising: cyproheptadine orotate hydrate; DL-camitine hydrochloride; L-lysine hydrochloride; and cyanocobalamin as active ingredients may be advantageously used for preventing or treating anorexia.

[0047] As used herein, the term “prevention” refers to all the acts, which inhibit or delay the occurrence of diseases by administering the pharmaceutical preparation of the present invention.

[0048] As used herein, the term “treatment” refers to all the acts, by which a suspicious symptom of a subject likely to develop a disease or a symptom of a subject suffering from a disease gets better or takes a favorable turn by administering the pharmaceutical preparation of the present invention.

[0049] In one embodiment of the present invention, cyproheptadine orotate hydrate may be comprised in an amount of 1 mg to 3 mg, specifically in an amount of 1 mg to 2 mg.

[0050] In one embodiment of the present invention, DL-carnitine hydrochloride may be comprised in an amount of 100 mg to 200 mg, specifically in an amount of 120 mg to 180 mg, 130 mg to 170 mg, or 140 mg to 160 mg.

[0051] In one embodiment of the present invention, L-lysine hydrochloride may be comprised in an amount of 100 mg to 200 mg, specifically in an amount of 120 mg to 180 mg, 130 mg to 170 mg, or 140 mg to 160 mg.

[0052] In one embodiment of the present invention, cyanocobalamin may be comprised in an amount of 0.5 mg to 2 mg, specifically in an amount of 0.5 mg to 1.5 mg.

[0053] In one embodiment of the present invention, cyproheptadine orotate hydrate may be comprised in an amount of 1 mg to 3 mg, DL-carnitine hydrochloride may be comprised in an amount of 100 mg to 200 mg, L-lysine hydrochloride may be comprised in an amount of 100 mg to 200 mg, and cyanocobalamin may be comprised in an amount of 0.5 mg to 2 mg.

[0054] In one embodiment of the present invention, cyproheptadine orotate hydrate may be comprised in an amount of 1 mg to 2 mg, DL-carnitine hydrochloride may be comprised in an amount of 120 mg to 180 mg, L-lysine hydrochloride may be comprised in an amount of 120 mg to 180 mg, and cyanocobalamin may be comprised in an amount of 0.5 mg to 1.5 mg.

[0055] In one embodiment of the present invention, cyproheptadine orotate hydrate may be comprised in an amount of 1 mg to 2 mg, DL-carnitine hydrochloride may be comprised in an amount of 130 mg to 170 mg, L-lysine hydrochloride may be comprised in an amount of 130 mg to 170 mg, and cyanocobalamin may be comprised in an amount of 0.5 mg to 1.5 mg.

[0056] In one embodiment of the present invention, cyproheptadine orotate hydrate may be comprised in an amount of 1 mg to 2 mg, DL-carnitine hydrochloride may be comprised in an amount of 140 mg to 160 mg, L-lysine hydrochloride may be comprised in an amount of 140 mg to 160 mg, and cyanocobalamin may be comprised in an amount of 0.5 mg to 1.5 mg.

[0057] In one embodiment of the present invention, microcrystalline cellulose may be comprised in an amount of 5 mg to 70 mg, specifically in an amount of 5 mg to 65 mg, 5 mg to 60 mg, or 5 mg to 55 mg.

[0058] In one embodiment of the present invention, anhydrous calcium hydrogen phosphate may be comprised in an amount of 25 mg to 60 mg, specifically in an amount of 25 mg to 55 mg.

[0059] In one embodiment of the present invention, magnesium aluminometasilicate may be comprised in an amount of 30 mg to 65 mg, specifically in an amount of 35 mg to 65 mg.

[0060] In one embodiment of the present invention, microcrystalline cellulose may be comprised in an amount of 5 mg to 70 mg, anhydrous calcium hydrogen phosphate may be comprised in an amount of 25 mg to 60 mg, and magnesium aluminometasilicate may be comprised in an amount of 30 mg to 65 mg.

[0061] In one embodiment of the present invention, microcrystalline cellulose may be comprised in an amount of 5 mg to 65 mg, anhydrous calcium hydrogen phosphate may be comprised in an amount of 25 mg to 55 mg, and magnesium aluminometasilicate may be comprised in an amount of 35 mg to 65 mg.

[0062] In one embodiment of the present invention, microcrystalline cellulose may be comprised in an amount of 5 mg to 60 mg, anhydrous calcium hydrogen phosphate may be comprised in an amount of 25 mg to 55 mg, and magnesium aluminometasilicate may be comprised in an amount of 35 mg to 65 mg.

[0063] In one embodiment of the present invention, microcrystalline cellulose may be comprised in an amount of 5 mg to 55 mg, anhydrous calcium hydrogen phosphate may be comprised in an amount of 25 mg to 55 mg, and magnesium aluminometasilicate may be comprised in an amount of 35 mg to 65 mg.

[0064] In one embodiment of the present invention, a weight ratio of a total weight of the active ingredients to microcrystalline cellulose in the dry granules may be 1 :0.016 to 1 :0.232, specifically 1 :0.016 to 1 :0.215, 1 :0.016 to 1 :0.199, or 1 :0.016 to 1 :0.182, and more specifically 1 :0.033 to 1 :0.166.

[0065] In one embodiment of the present invention, a weight ratio of a total weight of the active ingredients to anhydrous calcium hydrogen phosphate in the dry granules may be 1 :0.082 to 1 :0.199, specifically 1 :0.082 to 1 :0.182, and more specifically 1 :0.099 to 1 :0.166.

[0066] In one embodiment of the present invention, a weight ratio of a total weight of the active ingredients to magnesium aluminometasilicate in the dry granules may be 1 :0.099 to 1 :0.215, specifically 1 :0.115 to 1 :0.215, and more specifically 1 :0.132 to 1 :0.199.

[0067] In one embodiment of the present invention, a weight ratio of a total weight of the active ingredients to anhydrous calcium hydrogen phosphate in the dry granules may be 1 :0.082 to 1 :0.199, a weight ratio of a total weight of the active ingredients to magnesium aluminometasilicate in the dry granules may be 1 :0.099 to 1 :0.215, and a weight ratio of a total weight of the active ingredients to microcrystalline cellulose in the dry granules may be 1 :0.016 to 1 :0.232.

[0068] In one embodiment of the present invention, a weight ratio of a total weight of the active ingredients to anhydrous calcium hydrogen phosphate in the dry granules may be 1 :0.082 to 1 :0.199, a weight ratio of a total weight of the active ingredients to magnesium aluminometasilicate in the dry granules may be 1 :0.099 to 1 :0.215, and a weight ratio of a total weight of the active ingredients to microcrystalline cellulose in the dry granules may be 1 :0.016 to 1 :0.215.

[0069] In one embodiment of the present invention, a weight ratio of a total weight of the active ingredients to anhydrous calcium hydrogen phosphate in the dry granules may be 1 :0.082 to 1 :0.199, a weight ratio of a total weight of the active ingredients to magnesium aluminometasilicate in the dry granules may be 1 :0.099 to 1 :0.215, and a weight ratio of a total weight of the active ingredients to microcrystalline cellulose in the dry granules may be 1 :0.016 to 1 :0.199.

[0070] In one embodiment of the present invention, a weight ratio of a total weight of the active ingredients to anhydrous calcium hydrogen phosphate in the dry granules may be 1 :0.082 to 1 :0.199, a weight ratio of a total weight of the active ingredients to magnesium aluminometasilicate in the dry granules may be 1 :0.099 to 1 :0.215, and a weight ratio of a total weight of the active ingredients to microcrystalline cellulose in the dry granules may be 1 :0.016 to 1 :0.182.

[0071] In one embodiment of the present invention, a weight ratio of a total weight of the active ingredients to anhydrous calcium hydrogen phosphate in the dry granules may be 1 :0.082 to 1 :0.182, a weight ratio of a total weight of the active ingredients to magnesium aluminometasilicate in the dry granules may be 1 :0.115 to 1 :0.215, and a weight ratio of a total weight of the active ingredients to microcrystalline cellulose in the dry granules may be 1 :0.016 to 1 :0.182.

[0072] In one embodiment of the present invention, a weight ratio of a total weight of the active ingredients to anhydrous calcium hydrogen phosphate in the dry granules may be 1 :0.099 to 1 :0.166, a weight ratio of a total weight of the active ingredients to magnesium aluminometasilicate in the dry granules may be 1 :0.132 to 1 :0.199, and a weight ratio of a total weight of the active ingredients to microcrystalline cellulose in the dry granules may be 1 :0.033 to 1 :0.166.

[0073] In one embodiment of the present invention, at least one selected from the group consisting of silicon dioxide, light anhydrous silicic acid, magnesium stearate and talc may be further comprised as additives. In one embodiment of the present invention, the pharmaceutical preparation may be formulated into one type selected from the group consisting of tablets, powders, granules, and capsules. In this case, an additive required for formulation may be further comprised in the pharmaceutical preparation of the present invention, which may be formulated according to a conventional method used in the art or a method disclosed in Remington's Pharmaceutical Science (19th ed., 1995).

[0074] In one embodiment of the present invention, the pharmaceutical preparation may be administered once to several times a day, specifically once to six times a day, more specifically once or five times a day, and still more specifically twice to four times a day, but is not limited thereto, and may be appropriately adjusted according to a patient’s state, a content of active ingredients included in the preparation, and the like.

[0075] The present invention may provide a method for preparing a pharmaceutical preparation, the method comprising: mixing cyproheptadine orotate hydrate; DL-camitine hydrochloride; L- lysine hydrochloride; and cyanocobalamin as active ingredients, and microcrystalline cellulose; anhydrous calcium hydrogen phosphate; and magnesium aluminometasilicate as additives, and preparing the resulting mixed composition into dry granules, in which a weight ratio of a total weight of the active ingredients to anhydrous calcium hydrogen phosphate in the dry granules is 1 :0.082 to 1:0.199, and a weight ratio of a total weight of the active ingredients to magnesium aluminometasilicate in the dry granules is 1 :0.099 to 1 :0.215.

[0076] In the method for preparing the pharmaceutical preparation of the present invention, the contents described above may be equally applied as long as there is no contradiction. Thus, the ingredients included in the pharmaceutical preparation described above, the content of respective ingredients, the weight ratio of respective ingredients, uses, effects, etc. may be directly applied to the method for preparing the pharmaceutical preparation as long as there is no contradiction.

[0077] In one embodiment of the present invention, at least one selected from the group consisting of silicon dioxide, light anhydrous silicic acid, magnesium stearate and talc may be further mixed as additives.

[0078] In one embodiment of the present invention, the dry granules may be prepared through a conventional dry granulation method used in the art.

[0079] In one embodiment of the present invention, the method for preparing the pharmaceutical preparation may further comprise formulating the prepared dry granules into a dosage form.

[0080] In one embodiment of the present invention, the pharmaceutical preparation may be formulated into one type selected from the group consisting of tablets, powders, granules, pills and capsules.

[0081] In one embodiment of the present invention, the formulating of the prepared dry granules may comprise mixing additives required for the formulation.

[0082] One example of the formulating of the prepared dry granules may be filling the prepared dry granules into capsules to formulate the same into the capsules, but is not limited thereto.

[0083] The present invention provides a method for preventing or treating anorexia, comprising administering to a subject the pharmaceutical preparation of the present invention.

[0084] The present invention provides a use of the pharmaceutical preparation of the present invention for preventing or treating anorexia. The present invention provides a use of the pharmaceutical preparation of the present invention for preparing a medication for preventing or treating anorexia.

[0085] Matters mentioned in the pharmaceutical preparation, treatment method and use of the present invention may be applied the same, if not contradictory to each other.

[0086] Mode for Invention

[0087] Hereinafter, the present invention will be described in more detail through exemplary embodiments. These exemplary embodiments are provided only for the purpose of illustrating the present invention, and thus it will be apparent to those skilled in the art that the scope of the present invention is not limited thereto.

[0088] <Example>

[0089] Examples 1 to 3. Preparation of dry granules according to component ratio of anhydrous calcium hydrogen phosphate and magnesium aluminometasilicate

[0090] According to a component ratio in table 1 below, cyproheptadine orotate hydrate, DL- camitine hydrochloride, L-lysine hydrochloride, and then cyanocobalamin were sieved through a 32-mesh sieve and mixed with microcrystalline cellulose (Heweten 102, average particle size of 130 pm), anhydrous calcium hydrogen phosphate (A-Tab), magnesium aluminometasilicate (Neusilin US2), and magnesium stearate at 15 RPM for 15 minutes. The completely mixed raw materials were put into a dry granulator to prepare dry granules under the conditions of a roll pressure of 50 kgf / cm2; a side seal pressure of 35 kgf / cm2; a roll speed of 15 RPM; a powder feed screw speed of 40 RPM; an oscillator; a 16-mesh sieve and 60 RPM.

[0091] [Table 1]

[0092]

[0093] Examples 4 to 6. Preparation of dry granules according to component ratio of microcrystalline cellulose

[0094] Mixing and dry granulation process were performed in the same manner as in Examples

[0095] 1 to 3 according to a component ratio of table 2 below.

[0096] [Table 2]

[0097] <Comparative Example>

[0098] Comparative Examples 1 to 4. Preparation of dry granules according to component ratio of anhydrous calcium hydrogen phosphate and magnesium aluminometasilicate

[0099] Mixing and dry granulation process were performed in the same manner as in Examples 1 to 3 according to a component ratio of table 3 below.

[0100] [Table 3]

[0101] Comparative Examples 5 to 8. Preparation of dry granules according to component ratio of microcrystalline cellulose

[0102] Mixing and dry granulation process were performed in the same manner as in Examples 1 to 3 according to a component ratio of table 4 below.

[0103] [Table 4]

[0104] <Test Example>

[0105] Test Example 1. Comparison and evaluation for productivity of dry granulation process and powder properties of granules according to component ratio of anhydrous calcium hydrogen phosphate and magnesium aluminometasilicate The productivity of a dry granulation process and the powder properties of obtained granules were evaluated with regard to compositions of Examples 1 to 3 and Comparative Examples 1 to 4. An individual mass deviation of capsules was calculated based on a weight of the filled granules by opening the capsules after the completion of capsule filling process. The results thereof are shown in table 5 below.

[0106] [Table 5]

[0107] As can be confirmed from the above results, in the case of Examples 1 to 3, it was found that the dry granulation process is smoothly performed, and the powder properties of the obtained granules are also suitable for capsule filling. It was also found that the individual mass deviation of the filled capsules is 5.0% or less, which is appropriate, making it possible to reproducibly fill the capsules with a target amount of 415 mg. In contrary, in the case of Comparative Examples 1 and 2, it was found that a proportion of small particle sizes in the granules increases (the proportion of particles passing through 80 mesh exceeds 40%), resulting in poor flowability of powder, which increases powder dustability during the capsule filling process, and the individual mass deviation of the filled capsules also exceeds 5.0%, which is inappropriate, making it impossible to reproducibly fill the capsules with the target amount of 415 mg.

[0108] In addition, in the case of Comparative Examples 3 and 4, it was confirmed that a phenomenon of main ingredients sticking to a roll surface during the dry granulation process is intensified.

[0109] Test Example 2. Comparison and evaluation for productivity of dry granulation process and powder properties of granules according to component ratio of microcrystalline cellulose

[0110] The evaluation was performed in the same manner as in Test Example 1 with regard to compositions of Examples 4 to 6 and Comparative Examples 5 to 8. The results thereof are shown in table 6 below.

[0111] [Table 6]

[0112]

[0113] As can be confirmed from the above results, in the case of Examples 4 to 6, it was found that the dry granulation process is smoothly performed, and the powder properties of the obtained granules are also suitable for capsule filling. It was also found that the individual mass deviation of the filled capsules is 5.0% or less, which is appropriate, making it possible to reproducibly fill the capsules with each target amount of 410 mg, 430 mg and 450 mg.

[0114] In contrary, in the case of Comparative Examples 5 and 6, it was found that a proportion of small particle sizes in the granules increases (the proportion of particles passing through 80 mesh exceeds 40%), resulting in poor flowability of powder, which increases powder dustability during the capsule filling process, and the individual mass deviation of the filled capsules also exceeds 5.0%, which is inappropriate, making it impossible to reproducibly fill the capsules with each target amount of 400 mg and 403 mg.

[0115] In addition, in the case of Comparative Examples 7 and 8, it was found that as a total amount increases, a filling amount increases relative to a capsule volume and the individual mass deviation exceeds 5.0%, which is inappropriate, making it impossible to reproducibly fill the capsules with each target amount of 475 mg and 500 mg.

[0116] Thus, it can be confirmed that the pharmaceutical preparation according to the present invention exhibits excellent productivity and uniformity. While the present invention has been described in detail above, it is apparent to those skilled in the art that such detailed descriptions are set forth to illustrate exemplary embodiments only, but are not construed to limit the scope of the present invention. Thus, it should be understood that the substantial scope of the present invention is defined by the accompanying claims and equivalents thereto.

Claims

Claims

1. A pharmaceutical preparation comprising dry granules comprising: cyproheptadine orotate hydrate; DL-carnitine hydrochloride; L-lysine hydrochloride; and cyanocobalamin as active ingredients, and microcrystalline cellulose; anhydrous calcium hydrogen phosphate; and magnesium aluminometasilicate as additives, wherein a weight ratio of a total weight of the active ingredients to anhydrous calcium hydrogen phosphate in the dry granules is 1:0.082 to 1:0.199, and a weight ratio of a total weight of the active ingredients to magnesium aluminometasilicate in the dry granules is 1:0.099 to 1:0.215.

2. The pharmaceutical preparation of claim 1, wherein the weight ratio of the total weight of the active ingredients to microcrystalline cellulose in the dry granules is 1:0.016 to 1:0.232.

3. The pharmaceutical preparation of claim 1, wherein cyproheptadine orotate hydrate is comprised in an amount of 1 mg to 3 mg,DL-camitine hydrochloride is comprised in an amount of 100 mg to 200 mg,L-lysine hydrochloride is comprised in an amount of 100 mg to 200 mg, and cyanocobalamin is comprised in an amount of 0.5 mg to 2 mg.

4. The pharmaceutical preparation of claim 1, whereinmicrocrystalline cellulose is comprised in an amount of 5 mg to 70 mg, anhydrous calcium hydrogen phosphate is comprised in an amount of 25 mg to 60 mg, and magnesium aluminometasilicate is comprised in an amount of 30 mg to 65 mg.

5. The pharmaceutical preparation of claim 1, wherein the weight ratio of the total weight of the active ingredients to anhydrous calcium hydrogen phosphate in the dry granules is 1 :0.099 to 1 :0.166, and the weight ratio of the total weight of the active ingredients to magnesium aluminometasilicate in the dry granules is 1 :0.132 to 1 :0.199.

6. The pharmaceutical preparation of claim 1, wherein the weight ratio of the total weight of the active ingredients to microcrystalline cellulose in the dry granules is 1 :0.033 to 1 :0.166.

7. The pharmaceutical preparation of claim 1, further comprising at least one selected from the group consisting of silicon dioxide, light anhydrous silicic acid, magnesium stearate and talc as additives.

8. The pharmaceutical preparation of claim 1, wherein the pharmaceutical preparation is formulated into one type selected from the group consistinig of tablets, powders, granules, pills and capsules.

9. The pharmaceutical preparation of claim 1, wherein the pharmaceutical preparation is for preventing or treating anorexia.

10. A method for preparing a pharmaceutical preparation, the method comprising: mixing cyproheptadine orotate hydrate; DL-carnitine hydrochloride; L-lysine hydrochloride; and cyanocobalamin as active ingredients, and microcrystalline cellulose; anhydrous calcium hydrogen phosphate; and magnesium aluminometasilicate as additives, and preparing the resulting mixed composition into dry granules, wherein a weight ratio of a total weight of the active ingredients to anhydrous calcium hydrogen phosphate in the dry granules is 1 :0.082 to 1 :0.199, and a weight ratio of a total weight of the active ingredients to magnesium aluminometasilicate in the dry granules is 1 :0.099 to 1 :0.215.

11. The method of claim 10, wherein the weight ratio of the total weight of the active ingredients to microcrystalline cellulose in the dry granules is 1 :0.016 to 1 :0.232.

12. The method of claim 10, wherein at least one selected from the group consisting of silicon dioxide, light anhydrous silicic acid, magnesium stearate and talc is further mixed as additives.

13. The method of claim 10, further comprising: formulating the prepared dry granules into a dosage form.

14. A method for preventing or treating anorexia, comprising administering to a subject in need thereof the pharmaceutical preparation according to claim 1.

15. A use of the pharmaceutical preparation according to claim 1 for preventing or treating anorexia.

16. A use of the pharmaceutical preparation according to claim 1 for preparing a medication for preventing or treating anorexia.

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