JP2006052169A - Sol-like or gel-like administration assistant food - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a sol-like or a gel-like administration assistant food for assisting the administration of a medicament, especially a basic medicament having a bitter taste or an unpleasant taste. <P>SOLUTION: The sol-like or gel-like administration assistant food comprises one or more kinds selected from the group consisting of a magnesium salt, a calcium salt and an amino acid. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention relates to a sol-form or gel-form medication supplement for assisting in taking a medicine, particularly a basic medicine having a bitter or unpleasant taste.

  In recent years, sol-like or gel-like foods (so-called jelly-like drinks) for the purpose of assisting in taking medicines have been actively developed. These foods are mixed with a drug to smooth the passage of the drug through the throat and mask the bitterness of the drug with sweetness and flavor.

  However, in the case of macrolide drugs, which are known to have a particularly strong bitterness among various drugs, if they are mixed with these foods and taken, the bitterness is increased, which may make it difficult to take. This is because foods in the form of sol or gel are usually set in the acidic range of 2.5 to 6.4 in order to avoid bacterial contamination after the manufacturing process or opening. In order to mask bitterness, macrolide drugs are usually coated with an alkaline substance. When these are mixed, a neutralization reaction occurs and the macrolide drug coating is peeled off, resulting in the bitterness of the drug itself. This is due to the release of.

In addition, as a method for masking the bitterness of a drug, various methods have been proposed in addition to coating with an alkaline substance mentioned in relation to a macrolide drug (see Patent Documents 1 and 2). For example, a technique for masking the bitter taste by using an aqueous solution containing a bitter component of the drug, citric acid and an alkali metal citrate (see Patent Document 3), and a technique for masking the bitter taste of the drug by a liquid matrix that gels in the body (See Patent Document 4), but since all of them are taken in the form of a liquid with high fluidity, there is a possibility of reversal or the like in a person with reduced swallowing function. On the other hand, a technique for preparing a pharmaceutical composition containing a gelling agent has been disclosed (see Patent Document 5), but this is to mask the bitter taste by adding water at the time of taking to make a jelly form and wrapping the drug. In addition, it can include the problems found in the above-mentioned conventional sol-like or gel-like foods, and there is no specific example in combination with a macrolide drug.
JP-A-6-206824 JP-A-5-255120 JP-A-60-246325 JP 2004-2320 A JP 2000-10370 A

  The present invention relates to a sol-form or gel-form medication supplement for assisting in taking a medicine, particularly a basic medicine having a bitter or unpleasant taste. In particular, an object of the present invention is to provide a sol-like or gel-like medication supplement that can sufficiently mask bitterness even in combination with a macrolide drug.

  The present invention relates to a sol-form or gel-form medication supplement containing one or more selected from the group consisting of magnesium salts, calcium salts and amino acids.

  The sol-form or gel-form medication supplement of the present invention can assist in taking a medicine, particularly a basic medicine having a bitter or unpleasant taste. The medication supplement of the present invention is excellent in that it masks the bitterness or unpleasant taste of the drug, and can sufficiently mask the bitterness even in combination with a macrolide drug. In particular, even if the medication supplement of the present invention has a pH of 2.5 to 6.4, the dietary supplement has a bitter taste like a conventional sol or gel food having the same level of pH. It makes it easier to take medicine without increasing.

  The medication supplement of the present invention contains one or more selected from the group consisting of magnesium salts, calcium salts and amino acids.

  In the present invention, the magnesium salt refers to a magnesium salt and a hydrate thereof. Specific examples include magnesium chloride, magnesium sulfate, magnesium glutamate, magnesium chloride hexahydrate, magnesium sulfate heptahydrate, and the like. Magnesium salts may be used alone or in combination of two or more.

  In the present invention, calcium salt refers to calcium salt and hydrates thereof. Specific examples include calcium chloride, calcium gluconate, calcium lactate, calcium chloride dihydrate and the like. Calcium salts may be used alone or in combination of two or more.

  In the present invention, amino acids refer to amino acids and salts thereof. Examples of amino acid salts include metal salts of amino acids such as sodium salts and potassium salts, but the amino acid magnesium salts and calcium salts are excluded from the amino acid salts. Specifically, arginine, valine, leucine, isoleucine, histidine, glycine, alanine, threonine, proline, serine, glutamine, glutamic acid, asparagine, aspartic acid, lysine, lysine hydrochloride, phenylalanine, tyrosine, methionine, tryptophan, cystine Among them, arginine, lysine, lysine hydrochloride, histidine, glutamine, proline and serine are preferable.

  In the present invention, only a magnesium salt, only a calcium salt, or only an amino acid may be used, or a combination of a magnesium salt and a calcium salt, a combination of a magnesium salt and an amino acid, or a combination of a calcium salt and an amino acid. It may be used. Moreover, you may combine a magnesium salt, a calcium salt, and an amino acid. In terms of bitterness masking, the combination of magnesium salt and amino acid is particularly preferred, and the drug supplement is in the acidic range of pH 2.5-6.4, for example 2.5-6, especially 2.5-4.6. Even if it exists, the masking effect of outstanding bitterness is exhibited with respect to drugs with strong bitterness, such as a macrolide drug.

  When using only a magnesium salt, from the point of masking of bitterness, the magnesium salt is preferably 0.005 to 1% by weight in terms of magnesium in the total weight of the drug supplement of the present invention, Preferably it is 0.01 to 0.5 weight%, Most preferably, it is 0.02 to 0.2 weight%.

  When only the calcium salt is used, from the viewpoint of bitterness masking, the calcium salt is preferably 0.01 to 2% by weight in terms of calcium in the total weight of the drug supplement of the present invention. Preferably it is 0.03 to 0.5 weight%, Most preferably, it is 0.05 to 0.4 weight%.

  When only amino acids are used, the amount of amino acids in the total weight of the drug supplement of the present invention is preferably 0.1 to 10% by weight, more preferably 0.2 to 10%, in terms of bitterness masking. 5% by weight, particularly preferably 0.3 to 2% by weight.

  When using a combination of a magnesium salt and a calcium salt, the magnesium equivalent amount of the magnesium salt is 0.001 to 0.5% by weight in the total weight of the drug supplement of the present invention from the viewpoint of bitterness masking. More preferably, the content is 0.01 to 0.1% by weight, and the calcium equivalent amount of the calcium salt is preferably 0.005 to 1% by weight, and more preferably 0.02 to 0%. .3% by weight.

  When using a combination of a magnesium salt and an amino acid, the magnesium equivalent amount of the magnesium salt is 0.001 to 0.5% by weight in the total weight of the drug supplement of the present invention from the viewpoint of bitterness masking. It is preferably 0.01 to 0.1% by weight, and the amino acid is preferably 0.1 to 5% by weight, more preferably 0.2 to 1% by weight.

  When using a combination of calcium salt and amino acid, from the viewpoint of bitterness masking, the calcium equivalent amount of the calcium salt may be 0.005 to 1% by weight in the total weight of the drug supplement of the present invention. Preferably, it is 0.02 to 0.3% by weight, and the amino acid is preferably 0.1 to 5% by weight, more preferably 0.2 to 1% by weight.

  Among these, a combination of a magnesium salt and an amino acid is preferable because it can effectively mask a wide range of drugs.

  In the case of using a combination of magnesium salt, calcium salt and amino acid, from the viewpoint of bitterness masking, the magnesium equivalent amount of the magnesium salt is 0.001 to 0.5 weight in the total weight of the drug supplement of the present invention. %, More preferably 0.01 to 0.1% by weight, and the calcium equivalent of the calcium salt is preferably 0.005 to 1% by weight, more preferably 0.02 to It is 0.3% by weight, and the amino acid is preferably 0.1 to 5% by weight, more preferably 0.2 to 1% by weight.

The medication supplement of the present invention is sol or gel at normal temperature (15 to 25 ° C.). Specifically, in the case of a sol from the viewpoint of ease of swallowing, the viscosity at 20 ° C. is preferably 1000 to 20000 cP, and in the case of a gel, the jelly strength at 20 ° C. is 10 to 100 g / it is preferable that the cm ^2. The viscosity of the drug supplement is 20 ° C., and the viscosity is No. Using a 4-rotor, the rotation speed is 12 rpm, and a value calculated by multiplying the reading after 5 minutes by a multiplier. In addition, the jelly strength is set at a temperature of the medication supplement of 20 ° C., filled in a container with a bottom diameter of 40 mm at a height of 15 mm, a plunger with a diameter of 20 mm at a compression speed of 10 mm / sec, and a clearance of 5 mm. Measure the maximum strength load and divide the maximum load by the plunger area to obtain the calculated value.

  The medication supplement of the present invention can be made into a sol or gel form by blending a gelling agent and water. The gelling agent is not particularly limited, and specifically, agar, gelatin, carrageenan, sodium alginate, xanthan gum, gellan gum, guar gum, locust bean gum, tara gum, pectin, modified starch (eg, pregelatinized starch), carboxymethylcellulose Sodium etc. are mentioned. Although water will not be specifically limited if it is water suitable for a drink, Tap water, various ion-exchange water, purified water, etc. are mentioned.

  The amount of the gelling agent and water can be appropriately selected according to the type of the gelling agent, the viscosity of the medication supplement, and the jelly strength. For example, the gelling agent in the total weight of the medication supplement of the present invention The amount of water can be selected so that the amount of water is 0.5 to 2% by weight, but is not limited to this range. From the viewpoint of obtaining preferable viscosity and jelly strength, the amount of water in the total weight of the drug supplement of the present invention is preferably 70 to 85% by weight.

  A proton donating substance can be added to the medication supplement of the present invention. The proton donating substance is a substance that becomes an acidic region when dissolved in water among substances used as foods, food additives, or pharmaceutical additives. Here, amino acids are excluded from the proton donating substance. Specific examples include citric acid, lactic acid, succinic acid, adipic acid, malic acid, tartaric acid, gluconic acid, fumaric acid, carbonic acid, phosphoric acid, ascorbic acid and the like, preferably citric acid, carbonic acid and phosphoric acid. is there.

  The proton donating substance is preferably 0.01 to 5% by weight, more preferably 0.05 to 3% by weight, particularly preferably 0.1 to 0.3% by weight based on the total weight of the drug supplement of the present invention. 5% by weight. Since the drug supplement of the present invention exerts a bitter taste masking effect even in the acidic region, the proton donating substance should be formulated so that the pH of the drug supplement is in the acidic region of 2.5 to 6.4. Can do. By setting the pH within this range, effects such as avoiding bacterial contamination in the manufacturing process of the medication supplement and improving the storage stability of the product can be expected. In particular, in relation to these effects, it is preferable to blend so that the pH is 2.5 to 4.6. In addition, for strongly basic substances such as arginine, the pH can be adjusted to an acidic range of 2.5 to 6.4 depending on the amount of proton donating substance and the type of magnesium salt to be combined, and the bitter taste masking effect. Is obtained.

  The medication supplement of the present invention can contain a sweetener, specifically, sugar alcohols such as erythritol, xylitol, sorbitol, mannitol, palatinit, maltitol, lactitol, reduced starch syrup, glucose, galactose, mannose , Monosaccharides such as fructose, xylose, sucrose, maltose, isomaltose, lactose, lactulose, palatinose sugar disaccharide, fructooligosaccharide, galactooligosaccharide, xylooligosaccharide, lactosucrose, soybean oligosaccharide, isomaltoligosaccharide, xylooligosaccharide, Examples include oligosaccharides such as raffinose, starch syrup, trehalose, isomerized sugar, coupling sugar, aspartame, stevia, saccharin, acesulfame potassium, sucralose, etc., preferably sucrose, fructose Vinegar, erythritol, xylitol, maltitol, aspartame, stevia.

  The sweetener can be, for example, 5 to 25% by weight, preferably 10 to 20% by weight, based on the total weight of the drug supplement of the present invention.

  Other additives can be added to the medication supplement of the present invention as long as the effects of the present invention are not impaired. Examples include pH adjusters such as sodium citrate, strawberry flavor, banana flavor, and chocolate flavor. Flavoring agents, proteins such as skim milk powder, shelf-life improving agents such as catechins, water-soluble vitamins, coloring agents, flavoring agents such as cocoa powder, dextrin, sodium chloride, potassium chloride and the like.

  The manufacturing method of the medication supplement of this invention is not specifically limited, A well-known method can be used as a manufacturing method of what is called a jelly-like drink. For example, one or more selected from the group consisting of magnesium salts, calcium salts and amino acids, a gelling agent, and optionally a protic donor, an additive, etc. are added to an appropriate amount of water and heated to 60-90 ° C. And after melt | dissolving uniformly, it can be adjusted so that it may become a desired viscosity or jelly intensity | strength by adding water depending on the case and cooling. After heating to 60 to 90 ° C. and uniformly dissolving, if necessary, sterilization at 90 to 98 ° C. can be continued.

  The medication supplement of the present invention can be taken together with various drugs. The method of taking is not particularly limited, and for example, the medicine can be mixed with the medication supplement of the present invention.

  The drug that can be taken with the medication supplement of the present invention is not particularly limited, and is useful in combination with a basic drug having a bitter or unpleasant taste, especially in combination with a macrolide drug having a strong bitter taste. Also useful. For macrolides, the medication supplement of the present invention can exert a masking effect regardless of its pH. That is, in the neutral to alkaline region, as well as in an acidic region (for example, pH 2.5 to 6.4, especially pH 2.5 to 6, particularly pH 2.5 to 4.6) that increases bitterness in conventional jelly-like beverages. Even if there is, the bitterness can be masked. Specific examples of macrolide drugs include clarithromycin, azithromycin, erythromycin and the like.

  From the viewpoint of masking the bitter taste of the macrolide drug, a combination of a magnesium salt and an amino acid is preferable. The magnesium salt is preferably magnesium chloride hexahydrate or magnesium sulfate heptahydrate, magnesium chloride hexahydrate or magnesium sulfate heptahydrate alone, or magnesium chloride hexahydrate and magnesium sulfate heptahydrate. Or combinations of these with other magnesium salts. The amino acid is preferably arginine, and examples thereof include arginine alone or a combination of arginine and another amino acid. The other amino acid is preferably at least one selected from lysine hydrochloride, proline and glutamine.

  When the macrolide is clarithromycin, a combination of magnesium sulfate heptahydrate and an amino acid containing arginine is preferable. In this case, the amino acid is arginine alone or selected from lysine hydrochloride, proline and glutamine. It is preferable to use a combination of at least seeds and arginine. When the macrolide is azithromycin, a combination of magnesium hydrochloride hexahydrate and an amino acid containing arginine is preferable. In this case, the amino acid is arginine alone or at least one selected from lysine hydrochloride, proline and glutamine. And arginine are preferably used in combination.

  The medication supplement of the present invention is also useful for other basic drugs having an unpleasant taste. Specific examples of such basic drugs include cefditoren pivoxil, cefpodoxime proxetil, cefteram pivoxil, cefdinir, cefcapene pivoxil hydrochloride, cefaclor, faropenem sodium, theophylline, chloramphenicol , Cefotiam hexetyl hydrochloride, Cefcanel daloxate hydrochloride, lenampicillin hydrochloride, bacampicillin hydrochloride, tarampicillin hydrochloride, berberine chloride, digitoxin, sulpyrine, azelastine hydrochloride, ethiephrine hydrochloride, diltiazem hydrochloride, propranolol hydrochloride, promethazine hydrochloride, pipaverine hydrochloride, ticlopidin hydrochloride, Examples include aminophylline, phenobarbital, calcium pantothenate, donevezil hydrochloride, aminoguanidine hydrochloride, and the like.

  The form of the drug is not particularly limited, and examples thereof include tablets, capsules, fine granules, powders, and dry syrups.

  Hereinafter, the present invention will be described in more detail with reference to Examples and Comparative Examples. The present invention is not limited by these examples.

Examples 1 to 3, Comparative Example 1: Medication supplement containing magnesium salt / calcium salt In the formulation shown in Table 1, ingredients other than purified water were mixed, and half of purified water was added to this, and the mixture was heated to 70 ° C. After heating and dissolving uniformly, the remaining purified water was added and cooled to obtain a gel-like medication supplement.

Measurement of the pH of the medication supplement The pH of the medication supplement was measured using a pH meter F-8 (manufactured by Horiba, Ltd.).

Measurement of the bitterness masking effect of the drug supplement The measurement of the bitterness masking effect of the drug supplement was performed as follows.
Ten subjects (adults) eat a mixture of 10g each of supplementary supplements and 0.5g of Zithromac for children (Pfizer Pharmaceutical Co., Ltd .: azithromycin hydrate preparation). 1 to 5 points, and the average score was calculated.
1 point: Strong bitterness, very difficult to drink 2 points: Bitterness, difficult to drink 3 points: Slightly bitter, slightly difficult to drink 4 points: Slightly bitter but easy to drink 5 points: No bitterness Very easy to drink

  Comparative Example 1 corresponding to a conventional product was poor in bitterness masking effect and had an evaluation of less than 2 points, whereas it was an example of a gel-like medication supplement of the present invention containing magnesium salt and / or calcium salt 1-3 show that it is excellent in the bitterness masking effect.

Examples 4-17, Comparative Example 2: Medication supplements containing amino acids With the formulation shown in Table 2, gel-like supplements were obtained in the same manner as in Example 1, and the pH and bitterness masking effects were measured. .

  Comparative Example 2 corresponding to the conventional product was poor in bitterness masking effect and was evaluated with less than 2 points, whereas Examples 4 to 17 which are gelled medication supplements of the present invention containing amino acids had bitterness. It can be seen that the masking effect is excellent.

Examples 18 to 23: Medication supplements using magnesium salt and amino acids in combination With the formulation shown in Table 3, gel-like supplements were obtained in the same manner as in Example 1, and the pH and bitterness masking effect were measured.
However, regarding bitterness masking effect, in addition to the implementation for children with Zithromac fine granules as in Example 1, 10 g of supplementary food supplement and 0.5 g of Claris children's dry syrup (made by Taisho Pharmaceutical Co., Ltd .: Clarithromycin formulation) It was also carried out on the mixture of.

  Furthermore, for Example 20, the jelly strength was calculated as follows. Using a Leona-RE-3305 type creep meter (manufactured by Yamaden Co., Ltd.), the medication supplement of Example 20 (20 ° C.) was filled into a sample container having a bottom diameter of 40 mm to a height of 15 mm, The maximum load of breaking strength was measured using a 20 mm plunger with a compression speed of 10 mm / sec and a clearance of 5 mm, and the maximum load was divided by the plunger area to calculate the jelly strength.

  It turns out that all of Examples 18-20 which are the gelatinous medication supplement of this invention are excellent in the bitterness masking effect with respect to Zithromax and Claris. Especially, it turns out that Example 20 which used together a magnesium salt and an amino acid is excellent in the bitterness masking effect compared with Example 18 and 19 each used independently.

  Moreover, it carried out similarly to Example 1 by the mixing | blending shown in Table 4, and obtained the gelatinous medication supplement, and measured pH. About the bitterness masking effect, it implemented similarly to Examples 18-20.

  From Examples 21-22 which are the gel-like medication supplement of this invention, it turns out that the combination of a several amino acid and the combination of a different magnesium salt are also excellent in the bitterness masking effect with respect to a Zithromax and Claris. Moreover, from Example 23, it turns out that the bitterness masking effect outstandingly excellent by using together these magnesium salts and an amino acid is acquired.

Example 24: Sol-form supplementary foods Sol-form supplements were obtained in the same manner as in Example 1 with the formulation shown in Table 5, and the pH was measured. About the bitterness masking effect, it implemented similarly to Examples 18-20. The viscosity was measured as follows. The temperature of the medication supplement of Example 24 was set to 20 ° C., and No. 1 was measured with a B-type rotational viscometer (manufactured by Tokyo Keiki Co., Ltd.). Using a 4-rotor, the rotation speed is 12 rpm, and a value calculated by multiplying the reading after 5 minutes by a multiplier of 500.

  It turns out that Example 24 which is a sol-formation supplement of this invention is excellent in the bitterness masking effect with respect to a Zithromax and Claris.

  The present invention provides a sol-form or gel-form supplementary food that can assist in taking a medicine, particularly a basic medicine having a bitter or unpleasant taste. The medication supplement of the present invention is excellent in that it masks the bitterness or unpleasant taste of the drug, and can sufficiently mask the bitterness even in combination with a macrolide drug. In particular, even if the medication supplement of the present invention has a pH of 2.5 to 6.4, the dietary supplement has a bitter taste like a conventional sol or gel food having the same level of pH. It is easy to take medicine without increasing, and it is extremely useful in industry.

Claims (9)

  A sol-form or gel-form supplement comprising at least one selected from the group consisting of magnesium salts, calcium salts and amino acids.   The medication supplement according to claim 1, wherein the magnesium salt is selected from magnesium chloride, magnesium sulfate, magnesium glutamate, magnesium chloride hexahydrate and magnesium sulfate heptahydrate.   The medicinal supplement according to claim 1 or 2, wherein the calcium salt is selected from calcium chloride, calcium gluconate, calcium lactate and calcium chloride dihydrate.   The amino acid is selected from arginine, valine, leucine, isoleucine, histidine, glycine, alanine, threonine, proline, serine, glutamine, glutamic acid, asparagine, aspartic acid, lysine, lysine hydrochloride, phenylalanine, tyrosine, methionine, tryptophan and cystine The medication supplement according to any one of claims 1 to 3.   The medication supplement according to any one of claims 1 to 4, comprising one or more of magnesium salts and one or more of amino acids. The drug supplement according to any one of claims 1 to 5, further comprising a proton donating substance.   The medication supplement according to any one of claims 1 to 6, wherein the pH is 2.5 to 6.4.   The medication supplement according to any one of claims 1 to 7, which assists in taking a basic drug having a bitter or unpleasant taste.   The medication supplement according to claim 8, wherein the basic drug is a macrolide drug.