HK1092734B - Oral formulation for twice-daily administration - Google Patents

Abstract

Problem to be solved: To provide an oral preparation containing L-cysteine and ascorbic acid and developing highest therapeutic effect on pigmentation symptoms such as chloasma, freckles, sunburn and eruption. Solution: The oral preparation for twice-daily administration contains L-cysteine or its salt and ascorbic add or its salt and is administered at a single dose of L-cysteine of 90.150mg.

Description

Orally administered medicine preparation of twice daily dosage form

Technical Field

The present invention relates to an oral pharmaceutical preparation containing L-cysteine or a salt thereof and ascorbic acid or a salt thereof, which can exert a maximum therapeutic effect on pigmentation disorders caused by age spots, freckles, suntan, macules, and the like.

Background

L-cysteine (2-Amino-3-mercaptopropionic acid; 2-Amino-3-mercaptopropionicic acid) contains sulfur (S) in its molecule, and is one of sulfur-containing Amino acids having an action as a hydrogen Sulfur (SH) group donor in a living body. The L-cysteine is considered to exhibit a biochemical action of maintaining or activating the activity of various enzymes by SH groups contained in the molecule. L-cysteine is used for treating various skin diseases or leukopenia associated with radiotherapy by normalizing skin metabolism, antiallergic action, detoxifying action, and the like.

In the prior art, L-cysteine preparation is used as a medicine, and is used for treating eczema, urticaria, drug eruption, toxic eruption, common acne and polymorphous exudative erythema by using the preparation with 80 mg of L-cysteine for each time and using the preparation two to three times a day. In addition, for leukopenia caused by radiation disorder, the preparation is administered three times a day, with an L-cysteine dose of 160 mg per dose.

On the other hand, in the field of general pharmaceuticals, preparations containing L-cysteine and ascorbic acid are used for pigmentation disorders caused by spots of the aged, freckles, suntan, macule, etc., or general fatigue, hangover, whelk, eczema, urticaria, macule, drug eruption, etc. It can also be used for the purpose of preventing bleeding such as gum bleeding and epistaxis, and supplying vitamin C during physical fatigue, pregnancy, lactation, and physical weakness after illness, and old age. The administration method of the above preparation is, for example, a preparation in which the L-cysteine is administered in an amount of 80 mg, ascorbic acid is administered in an amount of 100 mg, and calcium pantothenate (calcium pantothenate) is administered in an amount of 8 mg per time when the preparation is used for pigmentation, general fatigue, hangover, whelk, eczema, urticaria, macula, drug eruption, etc. caused by senile plaque, freckle, suntan, macula, etc., and the preparation is administered three times a day. Also, a preparation prepared by blending L-cysteine and ascorbic acid is used for the purpose of bleeding prevention of pigmentation, gum bleeding, epistaxis and the like caused by age spots, freckles, suntan, macula and the like, bleeding prevention of gum bleeding, epistaxis and the like, physical fatigue, physical strength drop during pregnancy, lactation, and illness in the disease, and vitamin C supplement in the old age, and the preparation is prepared by taking 10-80 mg of L-cysteine and 100-500 mg of ascorbic acid per time, and is used by taking the preparation once to three times a day.

However, in order to treat pigmentation disorders caused by age spots, freckles, suntan, macules, and the like, a preparation prepared by blending L-cysteine and ascorbic acid requires a considerable time for skin renewal, and therefore, the effect must be developed for about three months, and the preparation must be continuously administered during this time.

However, in the currently marketed preparation, the maximum dose of L-cysteine, which is 240 mg per day, is divided into three doses, each of which is 80 mg of L-cysteine, and the dose must be taken three times a day. The preparation which must be continuously taken over a long period of three months and which is frequently taken daily is apt to be forgotten to be taken by a patient who lives in normal social life, and thus cannot exert the maximum therapeutic effect of L-cysteine on pigmentation disorders caused by age spots, freckles, suntan, macules, and the like. On the other hand, in a preparation which is administered three times a day, the amount of L-cysteine administered per day is small as compared with a preparation which is administered 80 mg L-cysteine three times a day, and therefore, depending on the patient, the effect thereof may not be sufficiently obtained.

Disclosure of Invention

The present invention has been made to solve the above-mentioned problems, and an object of the present invention is to provide a twice-a-day oral pharmaceutical preparation which can maximize the effect of treating pigmentation disorders caused by senile plaques, freckles, suntan, macules, etc., in a preparation containing L-cysteine and ascorbic acid.

The present invention provides a twice-daily oral pharmaceutical preparation comprising L-cysteine or a salt thereof and ascorbic acid or a salt thereof, wherein the amount of L-cysteine or a salt thereof administered at one time is 90 to 150 mg.

The present inventors have produced a preparation containing L-cysteine and ascorbic acid, and have made it possible to exert the maximum therapeutic effect on pigmentation disorders caused by age spots, freckles, suntan, macules, and the like.

As a result, it was found that when L-cysteine was administered twice a day, the above-mentioned therapeutic effect was more excellent when L-cysteine was administered twice a day as compared with when L-cysteine was administered three times a day. Furthermore, when a preparation prepared by blending L-cysteine and ascorbic acid is applied to the treatment of pigmentation disorders caused by age spots, freckles, suntan, macula, and the like, 120 mg of L-cysteine is taken twice a day and has a more excellent therapeutic effect than 80 mg of L-cysteine taken three times a day.

The present invention is less likely to forget to take the preparation, and therefore L-cysteine or a salt thereof can be efficiently taken, as compared with the conventional oral preparation for three times a day.

Therefore, the preparation of the present invention can exert the maximum therapeutic effect on pigmentation disorders caused by age spots, freckles, suntan, macules, and the like.

The invention is described in detail below with reference to the drawings and specific examples, but the invention is not limited thereto.

Detailed Description

L-cysteine or a salt thereof (hereinafter referred to as "L-cysteine compound") used in the preparation of the present invention can be used as any of L-cysteine acid addition salts such as L-cysteine hydrochloride, in addition to L-cysteine. In the present invention, it is preferable that the oral preparation is prepared such that the L-cysteine is administered twice a day in an amount of 90 to 150 mg per dose, more preferably 100 to 130 mg per dose, and particularly preferably 120 mg per dose.

As the other component of the preparation of the present invention, ascorbic acid or a salt thereof (hereinafter referred to as "ascorbic acid compound") may be used, in addition to ascorbic acid, an ascorbic acid salt such as calcium ascorbate or sodium ascorbate. Further, a combination of these may be used. The blending amount of the ascorbic acid in the preparation is the weight ratio of the ascorbic acid to the L-cysteine, and the weight ratio is 2: 1-1: the range of 20 is preferably 1: 1-1: the range of 5 is preferable, and 4: particularly preferably 5.

The preparation of the present invention can be administered twice a day for the treatment and prevention of pigmentation disorders caused by age spots, freckles, suntan, macula, etc., and can be administered twice a day for the treatment and prevention of general fatigue, hangover, whelk, eczema, urticaria, macula, drug eruption, or for the purpose of bleeding prevention such as gum bleeding, epistaxis, etc., physical fatigue, pregnancy, lactation, physical weakness after illness in illness, and vitamin C supplementation in the elderly.

In the present invention, other pharmacologically active ingredients may be formulated in addition to the above-mentioned L-cysteine and ascorbic acid, which are essential ingredients of the preparation. Other pharmacologically active ingredients include pantothenic acid (panthothenac acid), calcium pantothenate, sodium pantothenate, pantothenic acid such as panthenol or salts or derivatives thereof, d- α -tocopherol succinate, d1- α -tocopherol succinate, d1- α -calcium tocopherol succinate, d- α -tocopherol acetate, d1- α -tocopherol acetate, d- α -tocopherol, d1- α -tocopherol or derivatives thereof, thiamine hydrochloride (thiamine hydrochloride), thiamine nitrate, dithianine nitrate, thiamine disulfide (thiamine disulfide), diacetylthiamine sulfate, furathiamine hydrochloride (fursultiamine hydrochloride), thiocyanamide hydrochloride (dicetylamide hydrochloride), hydroxythiamide (nitrosamine sulfate), bisthiamide (bisbenzimide), and salts or derivatives thereof, Vitamin B1 such as benfotiamine (benfotiamine) or its derivatives, vitamin B2 such as riboflavin (riboflavin), riboflavin butyrate, riboflavin phosphate or its derivatives, vitamin B6 such as pyridoxine hydrochloride, pyridoxal phosphate or its derivatives, vitamin B12 such as cyanocobalamin, hydroxycobalamin hydrochloride, hydroxycobalamin acetate, methylcobalamin (mecobalamin) or its derivatives, nicotinic acid such as nicotinic acid, nicotinic acid amide or its derivatives, coix seed, orotic acid, biotin, γ -oryzanol, glucuronolactone, glucuronamide, decene quinone and the like, and 1 or 2 or more thereof can be used. Preferred examples of these include pantothenic acid (pantothenic acid), calcium pantothenate, sodium pantothenate, and panthenol, and salts or derivatives thereof.

The preparation of the present invention is preferably a solid oral preparation such as troche, granule, fine granule, powder, hard capsule, coupling agent, soft capsule, pill, dry syrup, chewable tablet, tablet (trochs), effervescent tablet, drop, oral cavity disintegrating agent, oral liquid, syrup, etc., but may also be an oral preparation such as oral liquid, syrup, etc. Further, although the preparation of the present invention may be prepared by separately preparing L-cysteine or a salt thereof and ascorbic acid or a salt thereof, and packaging the respective preparations in the same packaging bag, it is preferable to prepare L-cysteine or a salt thereof and ascorbic acid or a salt thereof at the same time. In this case, L-cysteine or a salt thereof and ascorbic acid or a salt thereof are preferably prepared in a unit of a dose or an integral fraction thereof.

The preparation of the present invention is prepared by blending L-cysteine and ascorbic acid, and if necessary, other pharmacologically active ingredients, and can be prepared by a conventional method. In this case, conventional additives can be used for each preparation. Examples of the formulation additives include crystalline cellulose, hydroxypropyl methyl cellulose, carboxymethyl cellulose, povidone (povidone), polyvinyl acetal diethylaminoacetate, white sugar, lactose, erythritol (erythitol), reduced maltose, calcium carbonate, calcium lactate, carnauba wax (carnauba wax), stearic acid, magnesium stearate, talc, sucrose fatty acid esters, titanium oxide, corn starch, partially gelatinized starch, pullulan (pulullan), gum arabic, gelatin, polyethylene glycol, polyethylene oxide polypropylene oxide glycol, calcium silicate, dimethylpolysiloxane, fumaric acid, anhydrous silicic acid, synthetic aluminum silicate, sodium lauryl sulfate, and polysorbate 80. These preparations may be added to the present invention as excipients, binders, fluidizing agents, disintegrating agents, lubricants, coating agents, plasticizers, solvents, dissolution aids, emulsifiers, suspending agents, stabilizers, preservatives, coloring agents, sweeteners, flavors, taste modifiers, and the like.

In a preferred embodiment of the preparation of the present invention, a tablet is obtained by obtaining a tablet from L-cysteine or a salt thereof, ascorbic acid or a salt thereof, and a preparation additive, and then coating the tablet once or more with a coating solution. The coating is preferably a sugar coating or a film coating.

In another preferred embodiment of the preparation of the present invention, L-cysteine or a salt thereof, ascorbic acid or a salt thereof, and a preparation additive are mixed to obtain a powder.

In another preferred embodiment of the preparation of the present invention, L-cysteine or a salt thereof, ascorbic acid or a salt thereof, and a preparation additive are granulated to obtain granules.

[ examples ]

The following examples are described in more detail, but the present invention is not limited to these examples.

Example 1

Sugar-coated lozenge preparation:

960 g of L-cysteine, 1200 g of ascorbic acid, 96 g of calcium pantothenate, 688 g of crystalline cellulose, 128 g of partially gelatinized starch, 80 g of hydroxypropyl cellulose, 16 g of light anhydrous silicic acid, 16 g of magnesium stearate and 16 g of talc were weighed out and mixed well. Subsequently, this mixture was pastilled into 200 mg per pastille by a usual method to obtain a plain pastille. Subsequently, the tablet was put into a coating chamber, and coated with a coating liquid (ethanol containing 5 wt% of hydroxypropyl methylcellulose: purified water 1: 1) in such a manner that the weight of the tablet was increased by 10 mg. Further, sugar coating was performed using a coating liquid (containing 2 wt% talc, 2 wt% titanium oxide, 3 wt% calcium carbonate, 1 wt% gum arabic powder, and 60 wt% refined white sugar) so as to increase the weight per tablet by 100 mg. Subsequently, coating was performed using an aqueous solution containing 60% by weight of refined white sugar in such a manner that the weight of each tablet was increased by 100 mg, to obtain a once-taken two-tablet formulation of the present invention containing 120 mg of L-cysteine, 150 mg of ascorbic acid, 12 mg of calcium pantothenate and being in the form of a dragee.

Comparative example 1

Comparative dragee formulations:

600 g of L-cysteine, 750 g of ascorbic acid, 60 g of calcium pantothenate, 1240 g of crystalline cellulose, 230 g of partially gelatinized starch, 75 g of hydroxypropyl cellulose, 15 g of light anhydrous silicic acid, 15 g of magnesium stearate and 15 g of talc were weighed out and mixed well. Subsequently, this mixture was pastilled into 200 mg per pastille by a usual method to obtain a plain pastille. Subsequently, the tablet was put into a coating chamber, and coated with a coating solution (ethanol containing 5 wt% of hydroxypropyl methylcellulose: purified water 1: 1) in an amount of 10 mg per tablet. Further, sugar coating was performed using a coating liquid (containing 2 wt% talc, 2 wt% titanium oxide, 3 wt% calcium carbonate, 1 wt% gum arabic powder, and 60 wt% refined white sugar) so as to increase the weight per tablet by 100 mg. Subsequently, coating was performed using an aqueous solution containing 60% by weight of refined white sugar in a manner of adding 100 mg by weight per tablet to obtain a dragee preparation for oral administration three times a day of the present invention containing 80 mg of L-cysteine, 100 mg of ascorbic acid, 8 mg of calcium pantothenate in one-dose two tablets and in the form of dragee.

Test example 1

Effect on pigmentation disorders:

the dragee preparations obtained in example 1 and comparative example 1 were administered to 11 adults suffering from pigmentation disorders caused by age spots, freckles, suntan, macules, and the like over a period of 12 weeks. The number of administrations was two tablets once per day (morning, evening) for the formulation of example 1, and three times per day (morning, noon, evening) for the formulation of comparative example 1. The degree of improvement of pigmentation disorders caused by age spots, freckles, suntan, macules, etc. was examined 12 weeks after the start of administration, and was classified into marked improvement, moderate improvement, mild improvement, and no improvement, and the results are shown in table 1. It was confirmed that the degree of improvement of pigmentation disorders caused by age spots, freckles, suntan, macule, etc. was higher than that of the case of comparative example 1 in the case of example 1, and that no discernible side effect was observed in any of the cases.

[ Table 1]

	Is remarkably improved	Moderate improvement	Slight improvement
				Example 1	18.2％	63.6％	81.8％
Comparative example 1	9.1％	45.5％	81.8％

Example 2

Powder preparation (1):

200 g of L-cysteine, 250 g of ascorbic acid, 20 g of calcium pantothenate, 180 g of corn starch, 340 g of lactose, and 10 g of magnesium stearate are mixed homogeneously. The resulting mixed powder was divided into 600 mg per pack, and 120 mg of L-cysteine, 150 mg of ascorbic acid, 12 mg of calcium pantothenate were contained in one pack for one dose, and the one-day-two-dose powder preparation of the present invention was in the form of divided powder.

Example 3

Powder preparation (2):

150 grams of L-cysteine, 250 grams of ascorbic acid, 20 grams of calcium pantothenate, 180 grams of corn starch, 390 grams of lactose, and 10 grams of magnesium stearate were mixed uniformly. The resulting mixed powder was divided into 600 mg per pack, and the one-dose one pack contained 90 mg of L-cysteine, 150 mg of ascorbic acid, 12 mg of calcium pantothenate and was a one-day two-dose powder preparation of the present invention in the form of divided powder.

Example 4

Powder preparation (3):

250 grams of L-cysteine, 250 grams of ascorbic acid, 20 grams of calcium pantothenate, 180 grams of corn starch, 290 grams of lactose, and 10 grams of magnesium stearate were mixed uniformly. The resulting mixed powder was divided into 600 mg per pack, and 150 mg of L-cysteine, 150 mg of ascorbic acid, 12 mg of calcium pantothenate were contained in one pack for one dose, and the once-daily-twice-administration type powder preparation of the present invention was in the form of divided powder.

Example 5

Granule preparation:

granules were prepared by granulating 240 g of L-cysteine, 300 g of ascorbic acid, 24 g of calcium pantothenate, 6 g of pyridoxine hydrochloride, 160 g of carboxymethyl cellulose, 937 g of mannitol, 247 g of corn starch, 60 g of tartaric acid, 12 g of aspartame (aspartame), 12 g of potassium acesulfame potassium (acesulfame potassium), and 2 g of perfume. The resulting granules were divided into 1000 mg per pack to obtain a once-taken one-daily two-dose granule preparation of the present invention containing 120 mg of L-cysteine, 150 mg of ascorbic acid, 12 mg of calcium pantothenate, and 3 mg of pyridoxine hydrochloride in one dose pack and in the form of granules.

Example 6

Coating film ingot preparation (1):

720 g of L-cysteine, 900 g of ascorbic acid, 72 g of calcium pantothenate, 150 g of d-alpha-tocopherol acetate, 36 g of riboflavin, 840 g of crystalline cellulose, 66 g of lactose, 60 g of light anhydrous silicic acid, 18 g of magnesium stearate and 18 g of talc were weighed out and mixed well. Subsequently, this mixture was pastilled to a weight of 240 mg per pastille by a usual method to obtain a plain pastille. Subsequently, the tablet was put into a coating room, and a film was coated with a coating liquid (ethanol containing 5% by weight of hydroxypropylmethylcellulose: purified water 1: 1) in an amount of 10 mg per tablet to obtain a one-day two-time oral coated film tablet preparation of the present invention containing 120 mg of L-cysteine, 150 mg of ascorbic acid, 12 mg of calcium pantothenate, 25 mg of d- α -tocopherol acetate, and 6 mg of riboflavin in one-time dose of the tablet, and being in the form of a coated film tablet.

Example 7

Coating film ingot preparation (2):

720 g of L-cysteine, 900 g of ascorbic acid, 72 g of calcium pantothenate, 60 g of d-alpha-tocopherol acetate, 150 g of pyridoxine hydrochloride, 840 g of crystalline cellulose, 72 g of lactose, 30 g of light anhydrous silicic acid, 18 g of magnesium stearate and 18 g of talc were weighed out and mixed well. Subsequently, this mixture was pastilled to a weight of 240 mg per pastille by a usual method to obtain a plain pastille. Subsequently, the tablet was put into a coating chamber, and a film was coated with a coating liquid (ethanol containing 5% by weight of hydroxypropylmethylcellulose: purified water 1: 1) in an amount of 10 mg per tablet to obtain a once-taken two-times-daily-oral-use coated tablet preparation of the present invention containing 120 mg of L-cysteine, 150 mg of ascorbic acid, 12 mg of calcium pantothenate, 10 mg of d- α -tocopherol acetate, and 25 mg of pyridoxine hydrochloride in the form of a coated tablet.

[ possibility of Industrial use ]

The oral preparation for twice daily intake of the present invention can effectively take in L-cysteine, and therefore, can be suitably used for treating pigmentation disorders caused by age spots, freckles, suntan, macule, etc.

The present invention may be embodied in other specific forms without departing from the spirit or essential attributes thereof, and it should be understood that various changes and modifications can be effected therein by one skilled in the art without departing from the spirit and scope of the invention as defined in the appended claims.

Claims (13)

1. A twice-daily oral pharmaceutical preparation comprising L-cysteine or a salt thereof; and ascorbic acid or salt thereof, wherein the content of the L-cysteine or salt thereof is 120 mg, and the weight ratio of the L-cysteine or salt thereof to the ascorbic acid or salt thereof is 2: 1-1: 20.

2. A twice-daily oral pharmaceutical preparation according to claim 1, wherein the ratio of L-cysteine or a salt thereof to ascorbic acid or a salt thereof is 4: 5 by weight.

3. A twice-daily oral pharmaceutical preparation according to claim 1, wherein the ascorbic acid or a salt thereof is 1 or 2 or more selected from ascorbic acid, calcium ascorbate and sodium ascorbate.

4. A twice daily oral pharmaceutical formulation according to claim 1, which is in the form of a lozenge, granule, fine granule, powder, hard capsule, bonded capsule, soft capsule, pill, oral liquid, syrup, dry syrup, chewable tablet, effervescent tablet, drop, orally disintegrating tablet.

5. A twice-daily oral pharmaceutical preparation comprising L-cysteine or a salt thereof; ascorbic acid or a salt thereof; and 1 or more than 2 selected from pantothenic acid or its salt or its derivative, vitamin B1 or its derivative, vitamin B2 or its derivative, vitamin B6 or its derivative, vitamin B12 or its derivative, nicotinic acid or its derivative, semen Coicis, orotic acid, biotin, gamma-oryzanol, glucuronolactone, glucuronamide and decenequinone, wherein the content of L-cysteine or its salt is 120 mg, and the weight ratio of L-cysteine or its salt to ascorbic acid or its salt is 2: 1-1: 20.

6. A twice-daily oral pharmaceutical preparation comprising L-cysteine or a salt thereof; ascorbic acid or a salt thereof; and a preparation additive, wherein the content of the L-cysteine or the salt thereof is 120 mg, the mixing ratio of the L-cysteine or the salt thereof to the ascorbic acid or the salt thereof is 2: 1-1: 20, and the preparation is in the form of pastille, wherein the pastille is obtained by obtaining the pastille from the L-cysteine or the salt thereof, the ascorbic acid or the salt thereof and the preparation additive, and then coating the pastille more than once by using the coating liquid.

7. A twice-daily oral pharmaceutical preparation comprising L-cysteine or a salt thereof; ascorbic acid or a salt thereof; and a preparation additive, wherein the content of the L-cysteine or the salt thereof is 120 mg, the mixing ratio of the L-cysteine or the salt thereof to the ascorbic acid or the salt thereof is 2: 1-1: 20 by weight, and the preparation is in the form of powder, wherein the powder is obtained by mixing the L-cysteine or the salt thereof, the ascorbic acid or the salt thereof and the preparation additive.

8. A twice-daily oral pharmaceutical preparation comprising L-cysteine or a salt thereof; ascorbic acid or a salt thereof; and a preparation additive, wherein the content of the L-cysteine or the salt thereof is 120 mg, the mixing ratio of the L-cysteine or the salt thereof to the ascorbic acid or the salt thereof is 2: 1-1: 20, and the preparation is in the form of granules, wherein the granules are obtained by granulating the L-cysteine or the salt thereof, the ascorbic acid or the salt thereof and the preparation additive.

9. A twice-daily oral pharmaceutical preparation comprising 120 mg of L-cysteine or a salt thereof; 150 mg ascorbic acid or a salt thereof; and 12 mg of calcium pantothenate, crystalline cellulose, partially gelatinized starch, hydroxypropyl cellulose, light anhydrous silicic acid, magnesium stearate, talc, hydroxypropyl methylcellulose, titanium oxide, calcium carbonate, gum arabic powder, and refined white sugar, wherein the dosage form is dragee.

10. A twice-daily oral pharmaceutical preparation comprising 120 mg of L-cysteine or a salt thereof; 150 mg ascorbic acid or a salt thereof; and 12 mg of calcium pantothenate, corn starch, lactose, and magnesium stearate, wherein the dosage form is powder.

11. A twice-daily oral pharmaceutical preparation comprising 120 mg of L-cysteine or a salt thereof; 150 mg ascorbic acid or a salt thereof; and 12 mg of calcium pantothenate, 3 mg of pyridoxine hydrochloride, carboxymethyl cellulose, mannitol, corn starch, tartaric acid, aspartame, acesulfame potassium, and spice, wherein the dosage form is granule.

12. A twice-daily oral pharmaceutical preparation comprising 120 mg of L-cysteine or a salt thereof; 150 mg ascorbic acid or a salt thereof; and 12 mg of calcium pantothenate, 25 mg of d-alpha-tocopherol acetate, 6 mg of riboflavin, crystalline cellulose, lactose, light anhydrous silicic acid, magnesium stearate, talc, and hydroxypropyl methylcellulose, wherein the dosage form is a coating film tablet.

13. A twice-daily oral pharmaceutical preparation comprising 120 mg of L-cysteine or a salt thereof; 150 mg ascorbic acid or a salt thereof; and 12 mg of calcium pantothenate, 10 mg of d-alpha-tocopherol acetate, 25 mg of pyridoxine hydrochloride, crystalline cellulose, lactose, light anhydrous silicic acid, magnesium stearate, talc powder, and hydroxypropyl methylcellulose, wherein the dosage form is a coating film tablet.