JP2005187362A - Liquid jellylike oral medicine composition - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To obtain a liquid jellylike oral medicine composition having properties of a lower viscosity than those of conventional semisolid jellying agents and gelling agents and high fluidity, in which an elderly person, a patient, or the like, having reduced deglutition function internally takes a medicine readily. <P>SOLUTION: The liquid jellylike oral medicine composition is obtained by formulating a mixed solution of an aqueous dispersing agent, a thickener and/or a gelling agent with a pharmacologically active agent so as to adjust the viscosity of the formulated solution of the pharmacological active agent at 20°C to 5-150 mPa s and to have properties of a lower viscosity and high fluidity. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

  The present invention relates to an oral pharmaceutical composition in the form of a liquid jelly that allows elderly people, patients, and the like to easily take medicines. More specifically, the present invention relates to a liquid jelly-like oral pharmaceutical composition having a low viscosity and a high fluidity so that elderly people, patients and the like who have a lower swallowing function can easily take the medicine.

  In recent years, with the progress of an aging society, the number of elderly people who are difficult to take medicines orally due to impaired food intake function has increased. In addition, from the medical field, improvement of oral pharmaceutical preparations is desired so that patients with reduced swallowing function can easily take medicines.

  Oral administration of conventional preparations such as powders, tablets, capsules and the like is usually difficult for elderly people, patients and the like who have a low swallowing function. In addition, dry syrups, solid jelly preparations, gummi preparations and the like have been developed and marketed for the purpose of improving the dosage of oral pharmaceutical preparations. However, the current number is small. Moreover, in the medical field, for a patient with a lowered swallowing function, a device has been devised such as mixing a solid preparation into yogurt or the like, processing it into a paste, and administering it.

On the other hand, a semi-solid jelly-form oral pharmaceutical composition (Patent Document 1) containing a thickener or gelling agent such as carrageenan or locust bean gum as an additive component, or a gelled component added to an adsorption carrier A taking gel composition has been developed (Patent Document 2).
JP 9-194346 A Table 98/058654

  However, the conventional semi-solid jelly-like composition and gel-like composition described above are still satisfactory in terms of viscosity and fluidity and are easy to take for elderly people and patients with reduced swallowing ability. It is not possible. For this reason, it is said that it is better for the elderly and patients who have a lower swallowing function to have a liquid formulation with lower viscosity and higher fluidity.

  For this reason, development of an oral pharmaceutical composition having low viscosity and high fluidity has been desired so that elderly people, patients and the like who have low swallowing ability can easily take the medicine.

  Therefore, from the viewpoints described above, the present invention can easily take a pharmaceutical orally not only for an elderly person or patient having a reduced swallowing function but also for a normal patient who cannot take a solid preparation such as a tablet orally. Another object of the present invention is to provide a liquid jelly-form oral pharmaceutical composition having a lower viscosity and higher fluidity than conventional semi-solid jelly agents and gelling agents.

  In order to achieve the above-described object, the liquid jelly-form oral pharmaceutical composition of the present invention can be obtained by blending a pharmacologically active agent in a mixed solution of an aqueous dispersion and a thickener and / or a gelling agent. The viscosity at 20 ° C. of the agent mixture is adjusted to be 5 to 150 mPa · s, and its properties are low viscosity and high fluidity.

  In the liquid jelly-like oral pharmaceutical composition of the present invention, the aqueous dispersion is composed of water or a mixture of water and a polyhydric alcohol, and the thickener and / or gelling agent is agar, carrageenan, Xanthan gum, locust bean gum, gum arabic, guar gum, karaya gum, gati gum, tara gum, tamarind gum, gellan gum, azotobacter vineland gum, arabinogalactan, pectin, tragacanth, curdlan, gelatin, starch, starch derivative, mannan, Pullulan, alginic acid or a salt thereof, carmellose, croscarmellose sodium, carmellose sodium, furceleran, propylene glycol alginate, hydroxyethylcellulose, hydroxypropylcellulose, hydroxyethylmethylcellulose Hydroxypropyl methylcellulose, dextran, polyvinyl alcohol, povidone, sodium polyacrylate, the configuration is one or more selected from sodium chondroitin sulfate.

  According to the liquid jelly-like oral pharmaceutical composition of the present invention, the pharmacologically active agent-containing liquid is mixed at 20 ° C. by blending the pharmacologically active agent into the mixed liquid of the aqueous dispersant and the thickener and / or the gelling agent. To obtain a liquid jelly-like composition having lower viscosity and higher fluidity than conventional semi-solid jelly-like compositions and gel-like compositions. it can.

  As described above, since the liquid jelly-like oral pharmaceutical composition of the present invention has low viscosity and high fluidity, it is difficult to take a solid drug as well as elderly people and patients whose swallowing function is lowered. Even a normal patient can easily take a pharmacologically active agent orally. Therefore, it is expected to greatly contribute to improving the compliance of elderly people and patients.

  Next, the best mode for carrying out the liquid jelly-form oral pharmaceutical composition of the present invention will be described.

  The liquid jelly-form oral pharmaceutical composition of the present invention is prepared by blending a pharmacologically active agent in a mixture of an aqueous dispersion and a thickener and / or a gelling agent, thereby allowing the viscosity of this pharmacologically active agent-containing liquid at 20 ° C. Is a liquid jelly-like composition adjusted so as to be 5 to 150 mPa · s.

  That is, by adjusting the pharmacologically active agent blending liquid so that its viscosity at 20 ° C. is 5 to 150 mPa · s, it has a low-viscosity and high-flowing property that is lower in viscosity than the conventional semi-solid jelly-like composition. It can be set as the liquid jelly-like composition which has. Since this liquid jelly-like composition is a low-viscosity and high-fluidity liquid whose viscosity is lower than that of conventional semi-solid jelly preparations, it can be easily taken orally even by elderly people and patients with reduced swallowing function. It is possible.

  When the viscosity of the pharmacologically active agent combination liquid is less than 5 mPa · s at 20 ° C., aspiration is likely to occur during swallowing of elderly people, patients, and the like whose swallowing function has deteriorated. Further, if the viscosity exceeds 150 mPa · s at 20 ° C., the fluidity is lowered due to the high viscosity, and it is not preferable because it is difficult for the elderly or patients who have a swallowing function to fall orally.

  Examples of the pharmacologically active agent component in the liquid jelly-like oral pharmaceutical composition of the present invention include, for example, a stomach medicine, a cold medicine, a vitamin agent, and the like, and the case where two or more kinds of the ingredients are included. Since this pharmacologically active agent varies in type and amount depending on the symptoms of the elderly, patients, etc., the viscosity of the oral pharmaceutical composition of the present invention varies depending on the type and amount of pharmacologically active agent to be blended. Arise.

  In order to adjust the viscosity in the liquid jelly-form oral pharmaceutical composition of the present invention so that the viscosity at 20 ° C. of the pharmacologically active agent combination liquid is 5 to 150 mPa · s, the kind and amount of the pharmacologically active agent to be mixed are adjusted. Accordingly, it is necessary to adjust the blending amount of the mixture of the aqueous dispersant and the thickener and / or the gelling agent and measure the viscosity individually.

  As the aqueous dispersant in the liquid jelly-like oral pharmaceutical composition of the present invention, water or a mixed solution of water and a polyhydric alcohol can be used.

  Examples of the polyhydric alcohol include glycerin and propylene glycol. Glycerin, propylene glycol, and the like are widely used as solvents and solubilizing agents for oral preparations, and include pharmacologically active ingredients that are difficult to disperse and dissolve with water alone, for example, pharmacologically active agents such as fat-soluble vitamins. In particular, it is useful for improving the dispersibility and solubility and obtaining a good preparation.

  As the thickener and / or gelling agent in the liquid jelly-like oral pharmaceutical composition of the present invention, the following substances can be selected and used. That is, agar, carrageenan, xanthan gum, locust bean gum, gum arabic, guar gum, karaya gum, gati gum, tara gum, tamarind gum, gellan gum, azotobacter vinegar gum, arabinogalactan, pectin, tragacanth, curdlan, gelatin, starch , Starch derivatives, mannan, pullulan, alginic acid or salts thereof, carmellose, croscarmellose sodium, carmellose sodium, furceleran, alginate propylene glycol ester, hydroxyethylcellulose, hydroxypropylcellulose, hydroxyethylmethylcellulose, hydroxypropylmethylcellulose, dextran, polyvinyl alcohol , Povidone, sodium polyacrylate, chondroitin sulfate Thorium is one or more of. The reason why the two agents are listed as the thickener and / or the gelling agent is that it may be difficult to distinguish the thickener from the gelling agent.

  In the present invention, the viscosity of the pharmacologically active agent combination liquid is substantially adjusted by mixing the thickener and / or the gelling agent with the aqueous dispersant. As described above, since the liquid jelly-form oral pharmaceutical composition of the present invention differs in the type and amount of the pharmacologically active agent to be blended, it is a mixture of an aqueous dispersant and a thickener and / or a gelling agent. The amount is not uniquely determined. Therefore, it is necessary to estimate the viscosity in advance according to the type and blending amount of the pharmacologically active agent to be blended.

  The mixing of the aqueous dispersant with the thickener and / or the gelling agent is carried out, for example, by heating with respect to the thickener and / or the gelling agent in order to obtain a uniform gel-state mixture. It is preferable to use an order in which the aqueous dispersant having a temperature of 0 ° C. or higher is mixed. The order of mixing the aqueous dispersion with the thickener and / or the gelling agent is not particularly problematic. This is because it is sufficient if it is possible to obtain a mixed solution in a uniform gel state.

  The liquid jelly-like oral pharmaceutical composition of the present invention is adjusted to pH 3.8 to 8.0 by adding a pH adjuster as necessary from the viewpoint of maintaining a good gelled state. Is preferred. Examples of the pH adjuster include calcium lactate, sodium citrate, sodium hydrogen phosphate, sodium hydrogen carbonate and the like that are allowed to be used as pharmaceutical additives.

  In addition to the components described above, the following optional components can be added to the liquid jelly-form oral pharmaceutical composition of the present invention. That is, sweeteners such as sucrose, saccan sodium, xylitol, D-sorbitol, D-mannitol, stabilizers such as ascorbic acid, sodium edetate, sodium lauryl sulfate, sucrose fatty acid, which can be taken as pharmaceuticals Emulsifiers such as esters, polyoxyethylene sorbitan monolaurate, preservatives such as ethyl paraoxybenzoate and methyl paraoxybenzoate, corrigents such as erythritol, citric acid, and lemon oil, colorants, and fragrances include l-menthol, Perfumes such as flavors such as fruit juice.

  These optional components can be appropriately added within a range that does not impair the effects of low viscosity and high fluidity in the present invention. The preferred amounts of these optional ingredients are usually 0.05 to 40% by weight for sweeteners, 0.001 to 0.5% by weight for stabilizers, 0.1 to 1% by weight for emulsifiers, antiseptics 0.01 to 0.1% by weight for the agent, 0.005 to 5% by weight for the flavoring agent, and 0.01 to 0.1% by weight for the fragrance.

  Preparation of the liquid jelly-form oral pharmaceutical composition of this invention can be performed by the method similar to the preparation method of a conventionally well-known semi-solid jelly agent.

Next, the liquid jelly-form oral pharmaceutical composition of this invention is demonstrated concretely based on an Example.
(Examples 1 and 2)

表１に示した配合量で、寒天、キサンタンガム、エリスリトールおよび精製白糖を秤取し、これらを粗混合した。この混合剤に加熱により約９０℃以上の温度とした精製水５０ｍＬを加えて混合溶液とした。次いで、この混合溶液を加熱状態で掻き混ぜて各成分を均一に溶解させた後、さらにｐＨ調整剤としての乳酸カルシウムと、矯味剤としてのクエン酸とを添加し溶解させた。さらに、この混合溶液を６０〜７０℃に保ち、表１に示す量の数種の薬理活性成分を加えて掻き混ぜ、各成分を均一に溶解させた。さらに、上記溶解溶液に約６０℃の精製水を加えて全量を９０ｍＬとした後、常温になるまで放冷して、実施例１および２の液体ゼリー状経口医薬組成物を得た。
（実施例３、４）

Agar, xanthan gum, erythritol and purified sucrose were weighed out in the blending amounts shown in Table 1, and these were roughly mixed. 50 mL of purified water that was heated to about 90 ° C. or higher by heating was added to the mixture to prepare a mixed solution. Next, the mixed solution was stirred in a heated state to uniformly dissolve each component, and then calcium lactate as a pH adjuster and citric acid as a corrigent were added and dissolved. Further, this mixed solution was kept at 60 to 70 ° C., and several kinds of pharmacologically active ingredients in amounts shown in Table 1 were added and stirred to dissolve each component uniformly. Further, purified water at about 60 ° C. was added to the dissolved solution to make a total volume of 90 mL, and the mixture was allowed to cool to room temperature to obtain liquid jelly-form oral pharmaceutical compositions of Examples 1 and 2.
(Examples 3 and 4)

表２に示す配合量で、カラギーナン、キサンタンガム、エリスリトールおよび精製白糖を秤取し、これらを粗混合した。この混合剤に加熱により液温を約９０℃以上とした精製水５０ｍＬを加えて混合溶液とした。次いで、この混合溶液を加熱状態で掻き混ぜて各成分を均一に溶解した後、さらにｐＨ調整剤としての乳酸カルシウムと矯味剤としてのクエン酸とを添加し溶解させた。さらに、この混合溶液を６０〜７０℃に保ち、表２に示す量の数種の薬理活性成分を加えて攪拌し、各成分を均一に溶解させた。さらに、上記溶解溶液に約６０℃の精製水を加えて全量を９０ｍＬとした後、常温になるまで放冷して、実施例３および４の液体ゼリー状経口医薬組成物を得た。
（実施例５、６）

Carrageenan, xanthan gum, erythritol and purified sucrose were weighed out in the amounts shown in Table 2, and these were roughly mixed. To this mixture was added 50 mL of purified water having a liquid temperature of about 90 ° C. or higher by heating to obtain a mixed solution. Next, this mixed solution was stirred in a heated state to uniformly dissolve each component, and then calcium lactate as a pH adjuster and citric acid as a corrigent were added and dissolved. Further, this mixed solution was kept at 60 to 70 ° C., and several kinds of pharmacologically active components in the amounts shown in Table 2 were added and stirred to dissolve each component uniformly. Further, purified water at about 60 ° C. was added to the dissolved solution to make a total volume of 90 mL, and the mixture was allowed to cool to room temperature to obtain liquid jelly-form oral pharmaceutical compositions of Examples 3 and 4.
(Examples 5 and 6)

表３に示す配合量で、カラギーナン、キサンタンガム、エリスリトールおよび精製白糖を秤取し、これらを粗混合した。この混合剤に加熱により約９０℃以上の温度とした精製水５０ｍＬを加えた混合溶液とした。次いで、この混合溶液を加熱状態で掻き混ぜて各成分を均一に溶解した後、さらにｐＨ調整剤としてのクエン酸ナトリウムと矯味剤としてのクエン酸とを添加し溶解させた。さらに、この混合溶液を６０〜７０℃に保ち、表３に示す量の数種の薬理活性成分を加えて掻き混ぜて各成分を均一に溶解させた。さらに、上記溶解溶液に約６０℃の精製水を加えて全量を９０ｍＬとした後、常温になるまで放冷して、実施例５および６の液体ゼリー状経口医薬組成物を得た。

Carrageenan, xanthan gum, erythritol and purified sucrose were weighed out in the amounts shown in Table 3, and these were roughly mixed. A mixed solution was obtained by adding 50 mL of purified water to a temperature of about 90 ° C. or higher by heating to this mixture. Next, the mixed solution was stirred in a heated state to uniformly dissolve each component, and then sodium citrate as a pH adjuster and citric acid as a taste-masking agent were added and dissolved. Furthermore, this mixed solution was kept at 60 to 70 ° C., and several kinds of pharmacologically active components in the amounts shown in Table 3 were added and stirred to dissolve each component uniformly. Further, purified water at about 60 ° C. was added to the dissolved solution to make a total volume of 90 mL, and then the mixture was allowed to cool to room temperature to obtain liquid jelly-form oral pharmaceutical compositions of Examples 5 and 6.

  The liquid jelly-form oral pharmaceutical compositions of Examples 1 to 6 are all liquid jelly-like properties having low viscosity and good fluidity. For this reason, it was a composition which was excellent in throat strain and very easy to take.

  About each sample of Examples 1-6 and the comparative example 1 of a commercially available semi-solid jelly-form agent, the viscosity (mPa * s) in 20 degreeC was measured, and the result was shown in Table 4. The viscosity was measured using an A & D SV type viscometer (SV-10). About each sample of Examples 1-6, pH was also measured and the result was shown in Table 4.

表４の結果から、比較例１の市販の半固形ゼリー剤の２０℃における粘度が７８８．３ｍＰａ・ｓと高いのに対し、実施例１〜６の試料は、いずれも２０℃におけるｐＨが３．８〜４．５であるとき、その２０℃における粘度が１０〜１５ｍＰａ・ｓと極めて低く、低粘性かつ高流動性の性状を有する液体ゼリー状組成物であることが分かる。
［官能試験］
実施例１〜６の組成物を試料として、各試料に対する服用し易さの度合を５名のパネラーによる官能試験を行い、その試験を評価しその結果を表５に示した。

From the results in Table 4, the viscosity of the commercially available semi-solid jelly preparation of Comparative Example 1 at 20 ° C. is as high as 788.3 mPa · s, whereas all of the samples of Examples 1 to 6 have a pH of 3 at 20 ° C. When the viscosity is from 0.8 to 4.5, the viscosity at 20 ° C. is as low as 10 to 15 mPa · s, and it is found to be a liquid jelly-like composition having low viscosity and high fluidity.
[Sensory test]
Using the compositions of Examples 1 to 6 as samples, the degree of ease of taking each sample was subjected to a sensory test with five panelists, the test was evaluated, and the results are shown in Table 5.

なお、評価結果を対比するため、比較例１の試料と共に、実施例１の試料における薬理活性成分を１包１ｇ中に重量換算で１／３量を通常使用される賦形剤で顆粒状とした製剤を比較例２の試料とした。

In addition, in order to compare the evaluation results, together with the sample of Comparative Example 1, the pharmacologically active ingredient in the sample of Example 1 is 1/3 of the pharmacologically active ingredient in a sachet in a granular form with a commonly used excipient. The prepared preparation was used as a sample of Comparative Example 2.

  In this sensory test, the dose of each sample was 30 mL for the samples of Examples 1 to 6 and the commercial product for the sample of Comparative Example 1 so that the compounding amount of the pharmacologically active ingredient would be a normal single dose. 1 dose, and for the sample of Comparative Example 2, one packet was taken as a dose.

  The method of sensory test is a method in which each panelist swallows the sample of Examples 1 to 6 and the sample of Comparative Example 1 directly in the mouth, and takes the sample of Comparative Example 2 with 100 mL of water. A test was conducted. The result of the sensory test was determined based on the following evaluation criteria.

The criteria for evaluation by each panel are as follows. Very easy to drink: 3, easy to drink: 2, slightly difficult to drink: 1, difficult to drink: 0
From the results of Table 5, the samples of Examples 1 to 6 all have low viscosity and fluidity, and show good dosing properties. That is, in the samples of Examples 1 to 6, it was evaluated that 4 out of 5 panelists were very easy to drink, whereas the sample of Comparative Example 1 was evaluated to be very easy to drink as well. Since only 2 out of 5 people did, the sensory difference between the samples of Examples 1 to 6 and the sample of Comparative Example 1 is presumed to be more than the result represented by the score. Moreover, about the sample of the comparative example 2, most panelists evaluated that it was hard to drink, and it turns out that the oral administration is difficult.

  Therefore, the liquid jelly-form oral pharmaceutical composition of the present invention is easily pharmacologically active not only for elderly people and patients whose swallowing function has decreased, but also for normal patients who are difficult to take solid compositions. It can be seen that the agent can be taken easily.

Claims (3)

  By blending a pharmacologically active agent in a mixed liquid of an aqueous dispersant and a thickener and / or a gelling agent, the viscosity at 20 ° C. of this pharmacologically active agent blended liquid is adjusted to be 5 to 150 mPa · s. A liquid jelly-like oral pharmaceutical composition characterized by having low viscosity and high fluidity.   The liquid jelly-like oral pharmaceutical composition according to claim 1, wherein the aqueous dispersant is water or a mixed solution of water and a polyhydric alcohol.   The thickener and / or gelling agent is agar, carrageenan, xanthan gum, locust bean gum, gum arabic, guar gum, karaya gum, gati gum, tara gum, tamarind gum, gellan gum, azotobacter vinegar gum, arabinogalactan, Pectin, tragacanth, curdlan, gelatin, starch, starch derivatives, mannan, pullulan, alginic acid or salts thereof, carmellose, croscarmellose sodium, carmellose sodium, furceleran, propylene glycol alginate, hydroxyethylcellulose, hydroxypropylcellulose, hydroxyethyl Methylcellulose, hydroxypropylmethylcellulose, dextran, polyvinyl alcohol, povidone, sodium polyacrylate , One or two or more at which claim 1 or a liquid jellied oral pharmaceutical composition described in 2 is selected from sodium chondroitin sulfate.