JP2002193839A - Cocoa pharmaceutical preparation - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a cocoa pharmaceutical preparation of extemporaneously soluble type, capable of masking unpleasant taste of the medicine and keeping its medicinal quality for a long period. SOLUTION: This cocoa pharmaceutical preparation of extemporaneously soluble type has hardly perceivable unpleasant taste derived from the medicine owing to properly selecting cocoa powder, a sweetener, a powdered milk, a corrigent and a flavor for formulation and controlling each formulating amount thereof; wherein, by using a powdered skim milk as the above powdered milk for the formulation, sufficient stability as a pharmaceutical preparation is secured.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a cocoa flavor which is dissolvable at the time of use, which conceals the taste of a drug having an unpleasant taste when taking it, makes it easy to take, and does not impair the quality for a long time. Related to pharmaceutical preparations.

[0002]

2. Description of the Related Art In recent years, various formulations have been attempted for patients who have difficulty in dropping (swallowing) only ordinary solid preparations, and some of them have been actually used.
For example, a rapidly disintegrating tablet in the mouth that rapidly loses its shape in the mouth, a jelly-like preparation that exhibits a semi-solid or liquid form, and is dissolved in warm water or water when taken while taking conventional tablets or granules to form a liquid preparation Preparations that dissolve before use are one of them. The characteristic of a dissolving preparation at the time of use is that it is changed into a form (liquid) that is easily swallowed artificially by dissolving a solid preparation such as a tablet or granule at the time of use,
It hides the taste of unpleasant drugs and alleviates the pain of the patient when taking it, thereby making it easier to take. As described above, for patients who have difficulty swallowing solid preparations, attempts to improve the compliance (compliance) by alleviating the pain as much as possible (improving ingestibility)
It is one of the current trends in pharmacotherapy and pharmacology,
This is a very important issue.

[0003] As a ready-to-use formulation, "Dolstan" (publisher: Rohto Pharmaceutical Co., Ltd.), "Contac Mediade" (same as Daiichi Pharmaceutical Co., Ltd.), "Arax Cold Effervescent Tablets" and "Arax Cold" Effervescent tablets for children "(Same:
Arax) is sold in Japan. These are refreshing fruit flavors such as lemon flavor and apple flavor, and are easy-to-take preparations that hide the unpleasant taste derived from the cold medicine components. In addition, non-steroidal anti-inflammatory drugs (for example, flurbiprofen, ketoprofen, naproxen, etc.) are mixed with β-cyclodextrin to improve the solubility and to improve the lemon flavor for the purpose of masking unpleasant taste and smell. Patents have been filed with a focus on drinks possessed (Tokuheihei 9-502190).

In the “Pharmacy Newspaper” (March 17, 1999), as a guidance point for taking pediatric drugs, “In the case of bitter drugs, a small amount of sugar, cocoa, etc. may be added to hide the taste. No. " The bitter taste of cocoa, which is familiar to the mouth, the sweetness of sugar, and the flavor of milk are interpreted to be effective in masking the unpleasant taste of the drug. But, for example,
Simply, a commercially available adjusted cocoa (for example, Meiji Seika Co., Ltd., Meiji Milk Cocoa), which is obtained by mixing sugar, milk, etc. into a granule for one dose of a drug generally formulated as a general cold remedy. Only by adding the amount, the original sweetness of the prepared cocoa is remarkably reduced, and the unpleasant taste derived from the drug cannot be sufficiently hidden. In addition, the shelf life of adjusted cocoa as a food is about one year, and it is difficult to secure the stability for three years normally required as a pharmaceutical product by simply applying the adjusted cocoa formulation as it is. In fact, when subjected to a rigorous test (preserved at 60 ° C. for 2 weeks) for predicting the stability of the drug in a short period of time, the adjusted cocoa produced a white suspension which was not observed before the preservation. Therefore, it is necessary to change the formulation so as to endure long-term storage as a pharmaceutical. As described above, when masking the unpleasant taste derived from a drug with cocoa, it has been found that it is difficult to satisfy various requirements required for pharmaceutical preparations simply by adding a predetermined amount of adjusted cocoa to the drug.

On the other hand, as a cocoa-containing preparation, a chocolate preparation “ex-la” sold by Novartis, Inc.
"x" has been known for a long time. Cocoa, sugar, hardened oil,
In the chocolate base consisting of lecithin, skim milk powder, and vanillin, yellow phenolphthalein was initially switched as a drug substance, and since 1997, sennoside has been manufactured and sold. In Japan, there were once several pesticides in the form of chocolate (product name: manufacturer “Source”, Artermin Chocolate: Nakamura Kasei Sangyo “Pharmaceutical products”
1988-99 (Pharmaceutical Timeline), McNin-S: Fujisawa, "Recent New Drugs, 1952, 3rd Collection (Pharmaceutical Timeline)",
Santonin tablets: manufactured and sold by Futaba Pharmaceutical Laboratories, “Recent New Drugs, 1955 Edition, 6th Collection (Yakugyo Jihosha)”
-Lax "as in cocoa powder. However, each of these is a suitable formulation as a chocolate agent, and it is difficult to dissolve them in water or hot water as they are for use as a preparation to be taken.

[0006] Formulations containing cocoa powder include:
Dry syrup containing antibiotics (Farmatsiya (Sofi
a) (1969), 19 (4), 26-9) and chewable tablets (WO9524)
890), but all of them are seasoned with sugar, sorbitol, aspartame, flavors, etc. as a sweetener, but basically the former is in the range of cocoa flavor (for example, 30 g of sugar for 1 g of cocoa). The latter is not conceived as a preparation to be taken as it is dissolved in hot water or hot water.

Further, Japanese Patent Application Laid-Open No. 2000-95710 describes an oral solid preparation comprising a component having an unpleasant taste and cocoa powder, but this patent is an invention relating to an oral solid preparation,
From the description alone, it is still difficult to create a ready-to-use cocoa preparation which has sufficient stability as a pharmaceutical preparation and can sufficiently mask the unpleasant taste derived from the drug.

[0008]

SUMMARY OF THE INVENTION An object of the present invention is to provide a dissolving cocoa preparation which can mask the unpleasant taste of a drug and maintain its quality as a medicine for a long period of time.

[0009]

[Means for Solving the Problems] In general, pediatric syrup, which is a general cold remedy, is seasoned with a strawberry or orange flavor so that it can be easily taken by children who are sensitive to bitterness. There is also a taste, which basically masks the unpleasant taste derived from the drug by the strong sweetness that combines those flavors. Such intense sweetness far exceeds the sweetness of so-called cocoa, and it is difficult to apply it as it is as a dissolving cocoa preparation at the time of use.
On the other hand, the present inventors have thought that cocoa has a unique flavor derived from cacao and may mask the unpleasant taste derived from drugs even if it is not as sweet as a syrup. . As a result, by appropriately selecting the cocoa powder, sweetener and milk powder to be compounded and adjusting the amounts thereof, it is possible to create a ready-to-use cocoa preparation which hardly causes any unpleasant taste derived from the drug. Was. In addition, it has been found that by using skim milk as the compounded milk powder, it is possible to secure sufficient stability as a pharmaceutical.

[0010]

BEST MODE FOR CARRYING OUT THE INVENTION The cocoa preparation of the present invention contains cocoa powder, sweetener and skim milk powder in a weight percentage of 10 to 25, 20 to 70 and 15 respectively.
A suitable result was obtained by blending in a range of ３０30% and further mixing salt and flavor as appropriate.

As the cocoa powder to be used, alkali-treated cocoa powder which is usually used as a beverage, cocoa powder not subjected to an alkali treatment (cocoa powder listed in the standard of pharmaceutical excipients), and a mixture thereof are used as appropriate. Can be. These cocoa powders control the cocoa butter content by squeezing the cocoa bean endosperm after roasting and grinding. In the present invention, the content is not particularly limited, but a grade of about 12 to 26% is preferable in view of ease of drinking. It is preferable that the cocoa powder is blended in an amount of 10 to 25% by weight percentage of the whole cocoa preparation. If the blending ratio is less than this, the unpleasant taste derived from the drug cannot be sufficiently hidden. On the other hand, if it is added beyond this range, the cocoa itself becomes bitter and becomes unsuitable as a beverage.

As the sweetener, purified sucrose, glucose, fructose, sugar alcohol, aspartame, stevia, sodium saccharin, sucralose, acesulfame potassium, and any mixture thereof can be used.
Since these sweeteners have different degrees of sweetness and different qualities, they cannot be unconditionally limited.However, in view of use as a pharmaceutical, purified sucrose, sucralose, acesulfame potassium, and the like are particularly preferable, and the amount of the sweetener is the degree of sweetness of the above sweetener. The cocoa preparation is preferably used alone or as appropriate in combination in an amount of 20 to 70%, especially 45 to 65% by weight based on the whole cocoa preparation. Below this range, it is not possible to mask the unpleasant taste derived from the drug, but it is not suitable for drinking as a beverage. On the other hand, if it is added beyond this range, not only is the sweetness too strong, but also the sugar intake may be excessive, which is not preferable.

As the milk powder, skim milk powder was mixed. It is preferable to mix whole milk powder in terms of flavor, but on the other hand, there is a problem in storage stability and stability, and skim milk powder is superior in maintaining quality as a pharmaceutical. It is preferable to mix the cocoa preparation in an amount of 15 to 30% by weight based on the whole cocoa preparation.

It is preferable to mix flavor and salt as other raw materials. Vanillin is generally blended as a cocoa flavor, and milk flavor flavors and the like can also be suitably used for the purpose of enhancing flavor. These fragrances have a very high taste, but their types and quality,
Further, the amount of the salt is not the essence of the present invention together with that of the salt, and thus the amount is not particularly limited.

The dosage form of the cocoa preparation of the present invention is not particularly limited as long as it is a dosage form suitable for dissolving at the time of use. Examples of the dosage form include tablets, powders, granules, fine granules and dry syrups. It can be a solid preparation or a liquid preparation. However, from the viewpoint of storage stability and stability, a solid preparation is preferred.

[0016]

EXAMPLES The present invention will now be described in detail with reference to Examples, Comparative Examples and Test Examples, which are merely examples and do not limit the scope of the present invention.

Example 1 Cocoa powder (Meiji Pure Cocoa, manufactured by Meiji Seika Co., Ltd.)
165 g), purified sucrose (265 g), powdered reduced maltose water candy (331 g), skim milk powder (233 g), salt (3 g)
g), vanillin (1 g), and dl-chlorpheniramine maleate (200 mg) were mixed and pulverized, and the obtained mixed powder was granulated by wet granulation, and further mixed with milk cocoa flavor (1 g). Then, the obtained granules were air-tightly wrapped (aluminum-laminated polybag) in an amount of 20 g each to obtain a ready-to-use antihistamine containing 4 mg of dl-chlorpheniramine maleate in one package.

Example 2 Cocoa powder (Meiji Pure Cocoa: 174 g), purified sucrose (575 g), skim milk powder (246 g), salt (3
g), vanillin (1 g), acetaminophen (14,500
mg), methylephedrine hydrochloride 10 times dispersion (9,670m
g), dihydrocodeine phosphate 100 times dispersion (38,667m
g), d-chlorpheniramine maleate (56.4 mg)
Are mixed and pulverized, and the resulting mixed powder is granulated by wet granulation.
g) and vanilla flavor (0.5 g) were added and mixed, and the resulting granules were air-tightly wrapped (aluminum-laminated plastic bags) in 22 g portions to give acetaminophen (300 mg), methylephedrine hydrochloride in one packet. (20m
g), dihydrocodeine phosphate (8 mg) and d-chlorpheniramine maleate (1.2 mg) were obtained as a ready-to-use solution of a common cold drug.

Example 3 Cocoa powder (Aztec Cocoa N22: 167 g)
Purified sucrose (536 g), skim milk powder (243 g), salt (2.7 g), vanillin (1 g), acetaminophen (14,500 mg), methylephedrine hydrochloride (967 m2)
g), dextromethorphan hydrobromide (773 m
g), d-chlorpheniramine maleate (56.4 mg)
Are mixed and pulverized, and the resulting mixed powder is granulated by wet granulation.
g) and vanilla flavor (0.5 g) were added and mixed, and the obtained granules were air-tightly wrapped (aluminum-laminated plastic bags) by 20 g each to give acetaminophen (300 mg), methylephedrine hydrochloride in one package. (20m
g), dextromethorphan hydrobromide (16 m
g), d-chlorpheniramine maleate (1.2 m
g) containing a cold solution for use at the time of use.

Comparative Example 1 Cocoa powder (Meiji Pure Cocoa: 116 g), purified sucrose (383 g), skim milk powder (164 g), salt (2
g) and vanillin (0.7 g) were mixed and pulverized, and the obtained mixed powder was subjected to wet granulation to obtain granules. Further, milk cocoa flavor (0.33 g) and vanilla flavor (0.33 g) were added. Mix and mix the resulting granules in 1
Adjusted cocoa (cocoa base) that does not contain drugs by applying airtight packaging (aluminum-laminated plastic bags) in 3.8g increments
I got

Comparative Example 2 Cocoa powder (Meiji Pure Cocoa: 116 g), purified sucrose (383 g), skim milk powder (164 g), salt (2 g)
g), vanillin (0.7 g), acetaminophen (1
4,500mg), 10 times dispersal of methylephedrine hydrochloride (9,670mg)
mg), dihydrocodeine phosphate 100 times dispersion (38,667m
g), d-chlorpheniramine maleate (56.4 mg)
Are mixed and pulverized, and the obtained mixed powder is subjected to wet granulation to obtain granules, and further, milk cocoa flavor (0.33
g) and vanilla flavor (0.33 g) were added and mixed, and 15.1 g of the obtained granules were air-tightly wrapped (aluminum-laminated plastic bag) to give acetaminophen (300 mg), hydrochloric acid in one package. Methylephedrine (2
0 mg), dihydrocodeine phosphate (8 mg), and chlorpheniramine d-maleate (1.2 mg) were obtained as a ready-to-use total cold drug.

Test Example 1 Change in melt state after storage under severe conditions (60 ° C., 2 weeks) Examples 1 to 3 airtightly packed in an aluminum laminated plastic bag
, And for comparison, Meiji milk cocoa (adjusted cocoa) was stored in a thermostat at 60 ° C. for 2 weeks, respectively.
Each was dissolved in 100 mL of hot water. In the preparations of Examples, no significant change was observed in the dissolution state before and after the storage. On the other hand, the adjusted cocoa as a control gave a white suspended solid which was insoluble in hot water after the same storage.

Test Example 2 Change in Content after Storage under Severe Conditions (Stored at 60 ° C. for 2 Weeks) The preparation of Example 2 airtightly packed in an aluminum-laminated plastic bag was stored in a thermostat at 60 ° C. for 2 weeks. The content of each drug substance contained in the preparation was compared before and after storage. Assuming that each drug substance content before storage (that is, at the time of manufacture) is 100%, acetaminophen: 99.6%, methylephedrine hydrochloride: 95.9%, dihydrocodeine phosphate:
99.3%, chlorpheniramine d-maleate
1%.

Test Example 3 Sensory Evaluation For Examples 2, 3, Comparative Examples 1 and 2,
One packet was suspended in 100 mL of hot water, and their ingestibility was compared. Among several evaluation items, depending on the formulation, there may be a case where the sweetness is hardly felt or a taste other than cocoa (an unpleasant taste derived from the drug) is felt.
Compared by name. Sweetness is enough (4 points),
Slightly missing (2 points), missing (0 points), tastes other than cocoa are not bothersome (4 points), slightly anxious (2 points), very anxious (0 points), overall (4 points), difficult to take a little (2
Points), difficult to take (0 points) as a guide, and compared by dividing the total points by the number of people. Table 1 shows the obtained results.

[0025]

[Table 1]

As shown in Test Example 1, a change in the solution state was found in the commercially available cocoa before and after storage under the harsh condition of 60 ° C. for 2 weeks, whereas the preparations of Examples 1 to 3 did not. No remarkable change in dissolution was observed. This condition is
It is often used to easily predict the stability of a drug. Since the commercially available adjusted cocoa originally has a shelf life of usually one year, it cannot be concluded from this result that the commercially available adjusted cocoa is unstable.
However, it shows that the preparation according to the compounding method of the present invention is more stable than a commercially available cocoa preparation.

In Test Example 2, the chemical stability of the drug in the preparation was examined. As a result, it was confirmed that the stability of each drug was ensured in the present preparation even in the case of a composite preparation called a general cold medicine.

In Test Example 3, cocoa powder, sweetener,
The difference in the ingestibility due to the difference in the mixing ratio between the skim milk powder and the drug was compared with a typical combination as a general cold remedy. Comparative Example 1 is a composition in which the drug was removed from Comparative Example 2, and the amount was adjusted to be suitable when the beverage was dissolved in 100 mL of hot water. In Examples 2 and 3, the mixing ratio of cocoa powder, sweetener and skim milk powder to the drug was higher than that of Comparative Example 2. As shown in Table 1, Comparative Example 1 in which cocoa powder, a sweetener and skim milk powder were added in suitable amounts as a beverage.
In Comparative Example 2 in which the drug was simply added to the compound, particularly, the sweetness disappeared and the unpleasant taste derived from the drug could not be hidden. On the other hand, as in Examples 2 and 3, cocoa powder, a sweetener, skim milk powder and by adjusting the mixing ratio with the drug appropriately, to have a sufficient sweetness as a cocoa and mask the unpleasant taste derived from the drug, It is possible to obtain a preparation with high ingestibility comprehensively.

[0029]

Industrial Applicability According to the present invention, there is provided a cocoa preparation which is dissolvable at the time of use, which conceals the taste of a drug having an unpleasant taste upon taking it, facilitates its use, and does not impair the quality for a long time. It became possible. As a result, the patient's pain at the time of taking the drug was further reduced (improvement of the taking of the drug), and the compliance of the drug was improved.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) A61K 31/165 A61K 31/165 31/196 31/196 31/4402 31/4402 31/4741 31/4741 31 / 4748 31/4748 31/485 31/485 35/78 35/78 C 47/10 47/10 47/22 47/22 47/26 47/26 47/42 47/42 A61P 11/08 A61P 11/08 11/10 11/10 11/14 11/14 29/00 29/00 43/00 113 43/00 113 (72) Inventor Kuniko Shoji 760, Shioka-cho, Kohoku-ku, Yokohama-shi, Kanagawa-ken Meiji Seika Co., Ltd. Institution (72) Inventor Yoshiharu Kimura 5-3-1 Chiyoda, Sakado-shi, Saitama F-term in Meiji Seika Co., Ltd. Food Research Institute (reference) 4C076 AA29 AA31 BB01 CC04 CC15 DD23 DD40 DD59 DD67T EE41T EE57 EE58T FF52 4C086 AA01 BC17 CB22 CB23 GA13 MA03 MA05 MA41 MA43 MA52 NA09 ZA07 ZA08 ZA61 ZA62 ZA63 ZC13 4C088 AB30 AB81 AC01 C A01 MA41 MA43 MA52 NA09 ZA07 ZA08 ZA61 ZA62 ZA63 ZC13 4C206 AA02 CA34 FA03 FA05 FA33 GA02 GA31 KA01 KA08 KA14 KA15 MA03 MA05 MA61 MA63 MA72 NA09 ZA07 ZA08 ZA61 ZA62 ZA63 ZC13

Claims (11)

[Claims] 1. A ready-to-use cocoa preparation containing cocoa powder, a sweetener, skim milk powder and a drug. 2. The compounding ratio of cocoa powder, sweetener and skim milk powder is 1% by weight in the whole preparation, respectively.
The cocoa preparation according to claim 1, which is 0 to 25, 20 to 70, and 15 to 30%. 3. The cocoa preparation according to claim 1, wherein the cocoa powder is cocoa powder not subjected to an alkali treatment. 4. The cocoa preparation according to claim 1, wherein the sweetener is selected from one or more of purified sucrose, glucose, fructose, sugar alcohol, aspartame, stevia, saccharin sodium, sucralose, and acesulfame potassium. 5. A comprehensive cold medicine comprising a drug alone or a combination of these pharmaceutically active ingredients, such as antipyretic analgesics, antitussives, bronchodilators, antihistamines, expectorants, and crude drug components. The cocoa preparation according to claim 1, which is formulated. 6. The cocoa preparation according to claim 5, wherein the antipyretic analgesic is one or more selected from acetaminophen and mefenamic acid. 7. The cocoa preparation according to claim 5, wherein the antitussive is one or more selected from codeine phosphate, dihydrocodeine phosphate, noscapine, and dextromethorphan hydrobromide. 8. The cocoa preparation according to claim 5, wherein the bronchodilator is methylephedrine hydrochloride. 9. The cocoa preparation according to claim 5, wherein the antihistamine is selected from one or more of diphenhydramine and chlorpheniramine maleate. 10. The cocoa preparation according to claim 5, wherein the expectorant is guaifenesin. 11. The cocoa preparation according to claim 5, wherein the crude drug component is one or more selected from powdered ginger powder and powdered ginger powder.