JP2010265248A - Jelly formulation - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a jelly formulation containing isosorbide as an active component and having reduced bitter taste, which meets the keen desire to effectively mask the strong bitter taste of an isosorbide internal medicine and improve the oral dosage of the medicine. <P>SOLUTION: The jelly formulation having improved oral dosage contains an acidic mucopolysaccharide, a sweetening agent, a flavor, an inorganic salt, an organic acid, an antiseptic agent, isosorbide and water, wherein the acidic mucopolysaccharide is especially κ-carrageenan for mitigating remarkable bitter taste of isosorbide and stably keep the jelly state when held in the mouth. <P>COPYRIGHT: (C)2011,JPO&INPIT

Description

  The present invention relates to a jelly agent which is easy to take orally containing bitter taste significantly reduced or suppressed, containing isosorbide which is a pharmacologically active ingredient.

  Oral osmotic diuresis / Meniere's disease ameliorating effect on brain pressure during brain tumor, brain pressure drop due to increased brain pressure due to head trauma, diuresis during renal / ureteral calculi, glaucoma intraocular pressure drop or Meniere's disease Isosorbide (chemical name: 1,4: 3,6-dianhydro-D-glucitol), which is an effective drug for the treatment of diarrhea, may be taken in the absence of seizures such as dizziness that is a symptom of Meniere's disease is there. So far, jelly preparations using internal preparations, syrups or agar as gelling agents, which are preparations obtained by dissolving this agent in water, have been developed in order to rapidly develop the drug efficacy.

  Isosorbide usually needs to be taken in a large amount of 70 to 140 g daily for adults for the purpose of reducing brain pressure and intraocular pressure, and usually 90 to 120 g for adults for meniere disease ameliorating agent. Therefore, in order to reduce the volume of the liquid medicine that the patient takes at one time, the isosorbide concentration is set as high as 70 w / v% in any of the developed liquid medicine products.

Since isosorbide has a unique strong bitter taste, reducing bitterness in oral preparations is a very important issue. Commercially available preparations such as aspartame, erythritol, sodium chloride, xylitol, citric acid hydrate, sodium L-glutamate, fragrance, sodium saccharin hydrate and lactic acid for oral liquids, sodium saccharin hydrate, D-sorbitol liquid and syrup Bitter taste is reduced by adding lactic acid and jelly agent to agar powder, saccharin Na hydrate, citric acid hydrate, anhydrous monohydrogen phosphate Na, sodium hydroxide, cacao powder and flavoring. However, the bitterness suppressing effect due to the addition of each component is not sufficient because the isosorbide concentration is set as high as 70 w / v% and the bitterness is increased in the aqueous preparation form. Therefore, clinically desired preparations that are easy to take with respect to commercially available products, in which bitterness is significantly reduced or suppressed, are now desired.
14th revised Japanese Pharmacopoeia commentary (2001, Yodogawa Shoten). Information on package inserts for ethical drugs: "Isobaide" (Kowa Pharmaceutical Co., Ltd.), "Isosorbide syrup 70%" (Tayo), "Isosorbide internal solution 70%" (Asuka), / "Isosorbide internal solution 70% packaging “30 mL” (Asuka), “Menilet 70% jelly 20 g and 30 g” (Sanwa Chemical Laboratory).

In general, a method is known in which sugars, sugar alcohols, high-intensity sweeteners, fragrances, and the like are blended to improve unpleasant tastes such as bitterness and irritation of drugs. However, the components that can exert a masking effect are different for each drug, and it is difficult to find an optimal combination. Many attempts have been made to improve the taste of a liquid preparation containing a drug exhibiting a bitter taste so far, but none of them has sufficiently suppressed the bitter taste and has good dosage.
JP, 2001-226293, A dosage adjuvant containing lecithin, a milk flavoring agent, ascorbic acid, and trisodium citrate, using κ carrageenan, locust bean gum, and xanthan gum as a gelling agent. JP, 2003-171314, A 0.5-35 mg / ml of organic acid and alkali metal salt of organic acid, a physiologically active ingredient which has a bitter taste, a sweetener, and a fruit flavor, JP, 2004-292360, A aqueous pharmaceutical composition containing isosorbide, acesulfame salt, an organic acid, and saccharin and / or a fragrance Republished 06-1344 Sweetener In addition to the general methods such as adding jelly, isosorbide solution that is bitter and difficult to swallow is surprisingly easy to dissolve from jelly preparations, just like solution, by using agar as a gelling agent. And found that the ingestion is improved. JP, 2006-131625, A An isosorbide formulation with improved taste quality, comprising a high-intensity sweetener and a fragrance selected from aspartame and / or acesulfame potassium. JP 2006-193514 A Isosorbide, aspartame as a first sweetener, and at least one second sweetener selected from saccharin or a salt thereof, acesulfame or a salt thereof, glycyrrhizic acid or a salt thereof, and stevia An oral pharmaceutical composition containing an unpleasant taste containing a basic drug having an unpleasant taste and an anionic polymer substance. JP, 2000-290199, A Pharmaceutical composition for oral use containing a pharmaceutical active ingredient which has an unpleasant taste, two or more kinds of high sweeteners (sweetness 150 or more), and a substance which shows acidity. JP, 2001-106641, A Buccal medicine containing an active ingredient having a bitter taste, a sugar alcohol, a refreshing agent and an oleaginous base. JP, 2000-290199, A Active pharmaceutical ingredient having an unpleasant taste, two or more kinds of high sweeteners (such as stevia, aspartame, saccharin or a salt thereof) having a sweetness of 150 or more, and sour agents (citric acid, malic acid, etc.) Oral pharmaceutical composition containing JP-A-2008-106048 An oral preparation containing an acidic mucopolysaccharide, a refreshing agent and a sweetener such as saccharin, aspartame, acesulfame, sucrose, lactose and reduced maltose water candy, and a surfactant (in addition, a bitter taste is suppressed).

  As described above, it has been strongly desired to effectively mask the strong bitterness of the internal use of isosorbide and improve the dosage. Therefore, an object of the present invention is to provide a jelly agent that contains isosorbide as an active ingredient, has a reduced bitter taste, and is easy to take.

The present inventors diligently studied to solve the above problems.
First, an aqueous gel-forming polymer listed as a pharmaceutical additive was picked up and added to a 70 w / v% aqueous solution of isosorbide to examine the possibility of gelation. As a result, agar (used in Republished 06-1344) and κ-type carrageenan are the best aqueous gel-forming polymers that form stable gels, and other aqueous gel-forming polymers are Although gel is formed, water separation is remarkable when left as it is, or when it is contained in the oral cavity, it quickly liquefies, and further has a disadvantage such as coloring by blending, so that a practical jelly agent cannot be prepared. It was. After all, among the aqueous gel-forming polymers listed as pharmaceutical additives, only kappa carrageenan formed a stable aqueous gel in the presence of isosorbide except for agar. Furthermore, as a result of confirming it in the mouth, surprisingly, kappa carrageenan was found to relieve the bitterness of isosorbide.
Based on the above observations, the jelly agent of the present invention uses κ-type carrageenan as a gelling agent, and in order to further reinforce the bitter taste suppressing effect of κ-type carrageenan, κ-type carrageenan, various sweeteners and flavoring agents, The bitterness masking effect of the combination was investigated. As a result, saccharin sodium and acesulfame potassium, particularly sweeteners, showed a more pronounced mitigating effect on bitterness than other sweeteners.
In general, the addition of flavors derived from plant essential oils, sugars, and beans is attempted with the expectation of a mitigating effect on bitterness. In the present invention, various scent components were added to investigate their effects. As a result, the bitterness alleviated by the coexistence of isosorbide, κ-type carrageenan, saccharin sodium and acesulfame potassium was hardly alleviated by the addition of a flavor derived from plant essential oil. In contrast, the addition of sugars and beans-derived flavors such as coffee flavors, chocolate flavors, tea flavors, caramel flavors, caramel and cacao unexpectedly made the jelly taste even better. In general, the persistence of sweetness is said to be enhanced by saltiness or sourness. In the present invention, addition of salty or sourness was attempted. As a result, when the sweetness is increased by adding a large amount of saccharin sodium and acesulfame potassium, the sweet taste of these sweeteners themselves is expressed. These sweeteners need to be used in an appropriate blending amount, but this sweetness has become more mellow by the addition of salty and sour agents.
Furthermore, κ-type carrageenan is used for the purpose of stably maintaining the gel state when an oral gel containing isosorbide, κ-type carrageenan, sodium saccharin and acesulfame potassium, flavours derived from sugars and beans, salting agents and sour agents is contained in the oral cavity. The addition effect of acidic mucopolysaccharides, water-soluble polymers, polyhydric alcohols and saccharides other than those was investigated. All of these components became larger or smaller by the addition thereof, and a tendency to increase the retention of the gel state when contained in the oral cavity of the aqueous gel was observed. In particular, the effect was remarkable in the coexistence of sorbitol and glycerin.

  As described above, the present invention includes acidic mucopolysaccharides, sweeteners, flavoring agents, inorganic salts, organic acids, preservatives, isosorbide and water, and particularly by using κ-type carrageenan as acidic mucopolysaccharides, It was possible to provide a jelly agent with good dosing property in which the bitterness was alleviated and the gel state was stably maintained when contained in the mouth.

  The production method of the jelly preparation of the present invention is as follows, for example, but the order of addition of each component is not particularly limited.

  Acid mucopolysaccharides, sweeteners, flavorings, inorganic salts, organic acids, preservatives, isosorbide (about 10 to 85% depending on the choice of formulation) Dissolve in water under heating and stirring at 95 ° C., seal the resulting aqueous solution in a sachet with heat, cool to room temperature, and make a jelly preparation.

Hereinafter, the jelly agent of the present invention will be described in more detail.
The formulation volume for currently marketed syrup, internal solution and jelly is set to 20 or 30 mL, and the concentration of isosorbide is set to 70 w / w%. Accordingly, the concentration of isosorbide in the present invention is basically 70 w / w%. The allowable concentration range is 95 to 105%, that is, 66.5 to 73.5 w / w% with a median of 70 w / w%.

  As the acidic mucopolysaccharide used in the present invention, κ-type carrageenan is used as a gelling agent. The addition amount in the jelly preparation is 0.2 to 0.5 w / w%, more preferably 0.25 to 0.35 w / w%, still more preferably 0.3 to 0.4 w / w%. When the addition amount is less than 0.1 w / w%, the gel is hardly formed and the bitterness reducing effect due to gelation disappears. In addition, if the amount added is too large, the gel will not collapse in the mouth and digestive tract, elution of isosorbide will be slow, the feeling of taking will be worse, and the viscosity of the heated mixed solution will be high, making it difficult to fill the packaging container. There are disadvantages such as

  Examples of acidic mucopolysaccharides used in combination with κ-type carrageenan for the purpose of stably maintaining the gel state when contained in the oral cavity of an aqueous gel include ι and λ-type carrageenan, sodium alginate, plant-derived acidic polymer tragacanth gum and Examples include fucoidan, microorganism-derived acidic polymer xanthan gum, gellan gum, and glycosaminoglycan chondroitchondroitin, chondroitin sulfate, sodium chondroitin sulfate, hyaluronic acid, keratan sulfate, heparan sulfate, heparin, dermatan sulfate and dextran sulfate. The addition amount to the whole of these jelly preparations is 0.1 to 10 w / w%, more preferably 0.3 to 7 w / w%, still more preferably 0.5 to 5 w / w%.

  As a sweetener used in combination with κ-type carrageenan, saccharin sodium and acesulfame potassium are each used alone, or both are used in combination. The addition amount to the whole of these jelly agents is 0.1 to 0.4 w / w%, more preferably 0.2 to 0.3 w / w% when saccharin sodium is used alone, and 0 when acesulfame potassium is used alone. 0.04 to 0.1 w / w%, more preferably 0.02 to 0.05 w / w%, and in the case of combination, 0.05 to 0.35 w / w% of a 4: 1 weight mixture of sodium saccharin and acesulfame potassium, More preferably, it is about 0.1-0.25 w / w%.

  Water-soluble polymers used in combination with κ-type carrageenan for the purpose of stably maintaining the gel state when contained in the oral cavity of aqueous gel include cellulose ethers such as methylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxy Examples include methylcellulose, polysaccharide pectin, locust bean gum, gum arabic, tragacanth gum, xanthan gum, synthetic polymer sodium polyacrylate and carboxyvinyl polymer. Other examples include polyvinyl alcohol, polyvinyl pyrrolidone, polyethylene glycol, and methacrylic acid copolymer. The addition amount to the whole of these jelly agents is about 0.1 to 10% by weight, more preferably about 0.2 to 7 w / w%, and still more preferably about 0.5 to 5 w / w%.

  Examples of the polyhydric alcohol used in combination with the κ-type carrageenan for the purpose of stably maintaining the gel state when contained in the oral cavity of an aqueous gel include glycerin or propylene glycol. The addition amount to the whole of these jelly agents is 1-15 w / w%, More preferably, it is about 2-10 w / w%, More preferably, it is about 3-5 w / w%.

        Examples of the flavoring agent used in the present invention include coffee flavoring, chocolate flavoring, tea flavoring, caramel flavoring, caramel and cacao, and one kind selected from these is used alone, or two or more kinds are used in combination. The addition amount in these jelly agents is 0.05-0.5 w / w%, More preferably, it is 0.1-0.2 w / w%, More preferably, it is 0.2-0.3 w / w%.

  Examples of the inorganic salts used in the present invention include sodium chloride, potassium chloride, potassium monophosphate, and sodium dihydrogen phosphate. One kind selected from these may be used alone, or two or more kinds may be used in combination. . The amount of addition in these jelly agents is 0.05 to 0.5 w / w%, more preferably 0.1 to 0.4 w / w%, still more preferably 0.2 to 0.3 w / w%.

Examples of the organic acid used in the present invention include succinic acid, fumaric acid, malic acid, tartaric acid, citric acid, glutamic acid, ascorbic acid, inosinic acid, and gluconic acid. Or use 2 or more types together. The addition amount in these jelly agents is 0.05 to 0.5 w / w%, more preferably 0.1 to 0.4 w / w%, and still more preferably 0.2 to 0.3 w / w%.

  Examples of the saccharide used in the present invention include sucrose, reduced maltose water candy, and sorbitol. One kind selected from these may be used alone, or two or more kinds may be used in combination. The addition amount in these jelly preparations is 0.5 to 10 w / w%, more preferably 1 to 7 w / w%, still more preferably 2 to 5 w / w%. In addition, mannitol, erythritol, xylitol, reduced palatinose, maltitol, lactitol, glucose, fructose, lactose, brown sugar, honey, trehalose, xylose, mannose, raffinose, galactose, fructose, rhamnose, high fructose syrup or palatinose Etc. may be used.

  Preservatives or preservatives such as sodium benzoate, methyl paraben, propyl paraben, butyl paraben and other alkyl esters of paraoxybenzoic acid, antioxidants, metal chelating agents and the like are blended with the jelly agent of the present invention as necessary. .

  When the jelly agent of the present invention is filled in a subdividable packaging form (disposable container, stick container), it can be swallowed once and can also be provided with portability.

Hereinafter, the content of the present invention will be described in more detail by way of examples. However, the present invention is not limited to these examples.

Example 1
κ-type carrageenan 0.2g, ι-type carrageenan 0.5g, λ-type carrageenan 0.1g, saccharin sodium 0.15g, acesulfame potassium 0.05g, chocolate flavor 0.1g, caramel flavor 0.1g, anhydrous sodium hydrogen phosphate Dissolve in 0.3g, tartaric acid 0.2g, methyl parahydroxybenzoate 0.1g, propyl paraoxybenzoate 0.01g, water 28.19g with heating and stirring at 85-90 ° C, and gradually dissolve isosorbide 70g with stirring. In addition, 20 or 30 g of the aqueous solution obtained was dissolved and sealed in a packaging container while hot, and cooled to room temperature to obtain a jelly agent.

Example 2
κ-type carrageenan 0.3 g, ι-type carrageenan 0.2 g, λ-type carrageenan 0.2, saccharin sodium 0.1 g, acesulfame potassium 0.1 g, chocolate flavor 0.2 g, cacao 0.2 g, anhydrous potassium monohydrogen phosphate 0 0.2, 0.1 g of malic acid, 5 g of glycerin, 0.1 g of methyl paraoxybenzoate, 0.01 g of propyl paraoxybenzoate, 2 g of sorbitol, 0.5 g of reduced maltose starch syrup in 25.49 g of water at 85 to 90 ° C. Further, 70 g of isosorbide was gradually added and dissolved while stirring, and 20 or 30 g of the obtained aqueous solution was sealed in a sachet with heat and cooled to room temperature to obtain a jelly agent.

Example 3
κ-type carrageenan 0.3 g, ι-type carrageenan 0.4 g, λ-type carrageenan 0.5 g, acesulfame potassium 0.3 g, cacao 0.1 g, caramel 0.2 g, anhydrous sodium dihydrogen phosphate 0.3 g, tartaric acid 0. 2 g, 0.1 g of xanthan gum, 0.1 g of methyl paraoxybenzoate and 0.01 g of propyl paraoxybenzoate were dissolved in 27.39 g of water with heating and stirring at 85 to 90 ° C., and 70 g of isosorbide was gradually added while stirring. After dissolving, 20 or 30 g of the obtained aqueous solution was filled and sealed in a packaging container while hot, and cooled to room temperature to obtain a jelly agent.

Example 4
κ-type carrageenan 0.4 g, ι-type carrageenan 0.4 g, sodium saccharin 0.2 g, acesulfame potassium 0.1 g, coffee flavor 0.1 g, cacao 0.2 g, sodium chloride 0.1 g, anhydrous disodium hydrogen phosphate 1 g, 0.2 g of citric acid, 0.1 g of methyl paraoxybenzoate and 0.01 g of propyl paraoxybenzoate were dissolved in 28.09 g of water with heating and stirring at 85 to 90 ° C., and 70 g of isosorbide was gradually added while stirring. 20 or 30 g of the aqueous solution obtained was dissolved in a packaging container while hot, and cooled to room temperature to obtain a jelly agent.

Example 5
κ-type carrageenan 0.5 g, ι-type carrageenan 0.5, λ-type carrageenan 0.25, saccharin sodium 0.3 g, caramel flavor 0.1 g, caramel 0.2 g and cacao 0.1 g, anhydrous monobasic hydrogen phosphate 3g, 0.2g of sodium chloride, 0.2g of tartaric acid, 0.1g of sodium polyacrylate, 0.1g of methyl paraoxybenzoate, 0.01g of propyl paraoxybenzoate in 27.64g of water under heating and stirring at 85-90 ° C. Then, 70 g of isosorbide was gradually added and dissolved while stirring, and 20 or 30 g of the obtained aqueous solution was sealed in a packaging container with heat, cooled to room temperature, and used as a jelly agent.

Example 6
κ-type carrageenan 0.3 g, ι-type carrageenan 0.25, acesulfame potassium 0.15 g, tea flavoring 0.1 g, caramel 0.2 g and cacao 0.1 g, anhydrous sodium dihydrogen phosphate 0.3 g, sodium chloride 0. 2g, apple 0.2g, sorbitol 2g, glycerin 3g, hydroxypropylmethylcellulose 400 type 0.1g, methyl paraoxybenzoate 0.1g, paraoxybenzoic acid 0.01g under water heating at 85-90 ° C with stirring at 85-90 ° C. Further, 70 g of isosorbide was gradually added and dissolved while stirring, and 20 or 30 g of the obtained aqueous solution was sealed in a sachet with heat and cooled to room temperature to obtain a jelly agent.

Example 7
κ-type carrageenan 0.4 g, λ-type carrageenan 0.1 g, saccharin sodium 0.2 g, black tea flavor 0.1 g, caramel flavor 0.1 g, caramel 0.1 g, anhydrous disodium hydrogen phosphate 0.3 g, citric acid 0. 2 g, 5 g of glycerin, 0.1 g of methyl parahydroxybenzoate and 0.01 g of propyl paraoxybenzoate were dissolved in 23.39 g of water under heating and stirring at 85 to 90 ° C., and 70 g of isosorbide was gradually added with stirring to dissolve. Then, 20 or 30 g of the obtained aqueous solution was filled in a packaging container with heat and sealed, and cooled to room temperature to obtain a jelly agent.

Example 8
κ-type carrageenan 0.3 g, ι-type carrageenan 0.1 g, acesulfame potassium 0.35 g, chocolate flavoring 0.2 g, caramel flavoring 0.1 g, caramel 0.1 g, anhydrous sodium hydrogenphosphate 0.3 g, tartaric acid 0. 2 g, locust bean gum 0.1 g, glycerin 6 g, methyl paraoxybenzoate 0.1 g, propyl paraoxybenzoate 0.01 g were dissolved in 28.59 g of water at 85-90 ° C. with heating and stirring, and 70 g of isosorbide was further stirred. While gradually adding and dissolving, 20 or 30 g of the obtained aqueous solution was filled and sealed in a packaging container while hot, and cooled to room temperature to obtain a jelly agent.

Comparative Example 1
κ-type carrageenan 0.1 g, ι-type carrageenan 0.05 g, λ-type carrageenan 0.5 g, anhydrous disodium hydrogenphosphate 0.3 g, citric acid 0.2 g, methyl paraoxybenzoate 0.1 g, propyl paraoxybenzoate 0 .01 g was dissolved in 28.74 g of water under heating and stirring at 85 to 90 ° C., and 70 g of isosorbide was gradually added with stirring to dissolve, and 20 or 30 g of the resulting aqueous solution was sealed in a packaging container while hot. And cooled to room temperature to obtain a jelly agent.

Comparative Example 2
κ-type carrageenan 0.05g, ι-type carrageenan 0.6g, λ-type carrageenan 0.3g, sodium saccharin 0.2g, disodium hydrogen phosphate 0.2g, tartaric acid 0.2g, methyl paraoxybenzoate 0.1g, paraoxy 0.01 g of propyl benzoate is dissolved in 28.24 g of water under heating and stirring at 85 to 90 ° C., and 70 g of isosorbide is gradually added with stirring to dissolve, and 20 or 30 g of the resulting aqueous solution is placed in a packaging container. It was filled with heat and sealed, and cooled to room temperature to obtain a jelly agent.

Comparative Example 3
κ-type carrageenan 0.6 g, ι-type carrageenan 0.4 g, λ-type carrageenan 0.1 g, saccharin sodium 0.15 g, acesulfame potassium 0.05 g, chocolate flavor 0.1 g, cacao 0.1 g, anhydrous disodium hydrogen phosphate 0 .3 g, 0.2 g of tartaric acid, 0.1 g of methyl paraoxybenzoate and 0.01 g of propyl paraoxybenzoate were dissolved in 28.39 g of water with heating and stirring at 85 to 90 ° C., and 70 g of isosorbide was gradually added with stirring. 20 or 30 g of the aqueous solution obtained was dissolved in a packaging container while hot, and cooled to room temperature to obtain a jelly agent.

Comparative Example 4
κ-type carrageenan 0.7g, ι-type carrageenan 0.75, λ-type carrageenan 0.1g, sodium saccharin 0.2g, disodium hydrogen phosphate 0.3g, tartaric acid 0.2g, methyl paraoxybenzoate 0.1g, paraoxy 0.01 g of propyl benzoate is dissolved in 28.19 g of water under heating and stirring at 85 to 90 ° C., 70 g of isosorbide is gradually added with stirring and dissolved, and 20 or 30 g of the obtained aqueous solution is placed in a packaging container. It was filled with heat and sealed, and cooled to room temperature to obtain a jelly agent.

[Experimental example]

考 察：
容器からの排出し易さ及び口中におけるゼリー剤の状態はκ型カラギーナンの添加量及び多価アルコールの存在によって影響され、κ型カラギーナンの至適な添加量は０．２〜０．７ｗ／ｗ％である。 1. Ease of discharge from container and state of jelly agent in mouth By five subjects, the jelly preparations of Examples 1 to 8 and Comparative Examples 1 to 4 were easily discharged from the container and jelly in the mouth (non-chewing) The state of the agent was observed. The results are shown in Table 1.

Discussion:
Ease of discharge from the container and the state of the jelly agent in the mouth are affected by the amount of κ-type carrageenan added and the presence of polyhydric alcohol, and the optimum amount of κ-type carrageenan added is 0.2 to 0.7 w / w. %.

考 察：
本発明・実施例のゼリー剤においては、イソソルビドの苦みが顕著に改善され、風味も良好で食感が良く、服用し易い結果が示された。 2. Observation of bitterness, flavor, texture and ease of taking,
The five subjects examined the jelly preparations of Examples 1-8 and Comparative Examples 1-4 for bitterness, flavor, texture, and ease of taking.
Evaluation criteria: 5-level evaluation
Bitterness [I don't feel 1, feel a little 2, feel 3, feel strongly 4, feel very strong 5]
Flavor [Very good 5, good 4, slightly good 3, defective 2, defective 1]
Texture [very good 5, good 4, slightly good 3, bad 2, bad 1]
Ease of taking [very good 5, good 4, slightly good 3, bad 2, bad 1]
If there are 5 cases, it was decided that it was difficult to take 5 doses. The results are shown in Table 2.

Discussion:
In the jelly preparations of the present invention and examples, the bitterness of isosorbide was remarkably improved, the flavor was good, the texture was good, and the results were easy to take.

考 察：
本発明実施例１〜５において、投入１５分後のゼリー剤からのイソソルビドの溶出率は約８０〜９８％近辺であり、速やかな溶出性を示した。このことから本発明のゼリー剤は、服用後に、遅滞なく薬効の発現が期待される。一方、本発明実施例７〜８は実施例１〜５よりも若干溶出率が低いが薬効発現には支障がない値を示している。一方、比較例３〜４は顕著に溶出率が低く、速やかな薬効の発言は期待できない。 3. Solubility of sorbitol from water from jelly preparations Solubility of isosorbide from the jelly preparations of the present invention, Examples 1 to 8 and Comparative Examples 1 to 4 was determined by a paddle method based on Japanese Pharmacopoeia XIV. Measured by the method. In this case, water, 900 mL of Japanese Pharmacopoeia Disintegration Test Method 1st solution and 2nd solution were used as the test solution, and the paddle rotation speed was set to 50 rpm for measurement. The isosorbide concentration was determined by the liquid chromatograph C method. Table 3 shows the measured values of the elution rate 15 minutes and 30 minutes after the jelly agent was added to the test solution.

Discussion:
In Inventive Examples 1 to 5, the elution rate of isosorbide from the jelly agent after 15 minutes from the introduction was about 80 to 98%, indicating a quick elution. For this reason, the jelly agent of the present invention is expected to exhibit drug efficacy without delay after taking. On the other hand, Examples 7 to 8 of the present invention have values that are slightly lower than those of Examples 1 to 5 but do not hinder the development of drug efficacy. On the other hand, Comparative Examples 3 to 4 have a remarkably low elution rate, and prompt remarks on drug efficacy cannot be expected.

Claims (10)

A jelly agent comprising acidic mucopolysaccharide, sweetener, flavoring agent, inorganic salt, organic acid, preservative, isosorbide and water. 2. The jelly agent according to claim 1, wherein the acidic mucopolysaccharide is κ-type carrageenan and the amount added is 0.2 to 0.5 w / w%. The jelly preparation according to claim 1, wherein the sweetener used in combination with the kappa carrageenan is saccharin sodium and acesulfame potassium, each of which is used alone or in combination of both. Acid mucopolysaccharides used in combination with κ-type carrageenan are ι and λ-type carrageenans, sodium alginate, plant-derived acidic polymers, microbial-derived acidic polymers, and glycosaminoglycans, one of these alone or in combination of two or more The jelly agent according to claim 1. 2. The water-soluble polymer used in combination with κ-type carrageenan is pectin, cellulose ethers, locust bean gum, xanthan gum, sodium polyacrylate and carboxyvinyl polymer, which are one kind or a combination of two or more kinds. Jelly agent. The jelly agent according to claim 1, wherein the polyhydric alcohol used in combination with the κ-type carrageenan is glycerin or propylene glycol, and the addition amount thereof is 2 to 10 w / w%. The jelly agent according to claim 1, wherein the flavoring agent is one type of use selected from coffee flavoring, chocolate flavoring, tea flavoring, caramel flavoring, caramel and cacao, or a combination of two or more. The jelly agent according to claim 1, wherein the inorganic salt is one type of use selected from sodium chloride, potassium chloride, potassium monobasic phosphate and sodium dihydrogen phosphate, or a combination of two or more types. The jelly agent according to claim 1, wherein the organic acid is one type or a combination of two or more types selected from succinic acid, fumaric acid, malic acid, tartaric acid, citric acid, glutamic acid, ascorbic acid, inosinic acid, and gluconic acid. 2. The jelly agent according to 1, containing each of saccharides sucrose, reduced maltose water candy and sorbitol alone or in combination.