JP2007230990A - Therapeutic agent for meniere's disease - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a therapeutic agent for Meniere's diseases comprising sugar alcohols as an active ingredient, easily, simply and sanitarily affording carrying and administration, simultaneously eliminating cathartic actions and thereby ensuring and rapidly expressing reducing effects on endolymphatic hydrops. <P>SOLUTION: The therapeutic agent for the Meniere's diseases comprises the sugar alcohols and sodium alginate in an amount of 0.5-30 wt.% based on the sugar alcohols and calcined gypsum in amount of 0.5-7 wt.% based on the sugar alcohols. The therapeutic agent is prepared by conversion into a hydrous gel formulation. The water content is 30-90 wt.% based on 100 wt.% of the active ingredient. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention is a hydrogel preparation that can be compacted in volume compared to liquids and powders and is easy to carry and take, and monosaccharides, oligosaccharides, or sugar alcohols thereof as active ingredients, The present invention relates to a therapeutic agent for Meniere's disease that can be taken easily, conveniently and hygienically, and at the same time, also eliminates the axillary action, so that the effect of reducing endolymphedema can be realized reliably and rapidly.

It is widely known that the condition of Meniere's disease is endolymphatic edema, and sugar alcohols such as glycerol and mannitol, which are osmotic diuretics, have been tried for the purpose of reducing the burden of endolymphatic edema. Administration does not provide a sufficient therapeutic effect, most of which are not currently administered clinically.
Currently, isosorbitol (1,2: 3,6-dianhydro-D-sorbitol, generic name isosorbide: Niken Chemicals, Inc., isosorbitol content 70%) is clinically applied as a treatment for Meniere's disease. However, this includes 1) a single dose of 30 ml or more, and it is necessary to take 3 times a day, and the dose is large. Furthermore, 2) there is a peculiar bitterness, and the bitter taste is in the oral cavity after taking it. In many cases, the patient feels difficulty taking the medicine because it remains for a long time. Furthermore, because the dosage form is liquid, it is necessary to carry a bottle containing 500 ml and about 750 g (about 11 to 16 doses) due to hygiene problems, and there is an inconvenience that the required number of times cannot be carried. It was.

In the case of sugars other than isosorbitol and sugar alcohols, generally, when an effective amount is taken as a simple powder, the volume of a single dose is 50 cm ³ or more, and about 70 to 120 ml if administered as a saturated aqueous solution. The above distilled water is required, the volume is about 80 to 140 ml, and the weight is about 90 to 140 g. Obviously bulky and heavy, both for internal use and for carrying, is a burden on the patient.

  In addition, glycerol (trisaccharide) exhibits an effect about 2 hours after oral administration (Non-Patent Document 1), whereas conventional isosorbide (6-monosaccharide) solution requires about 6 hours until onset of action. (Non-patent document 2) As the expression of action varies, a therapeutic agent for Meniere's disease that exhibits a certain action early after administration has been expected.

  In patients with Meniere's disease, an increase in arginine vasopressin (hereinafter referred to as AVP), an antidiuretic hormone (ADH), has been reported in the acute phase (Non-patent Document 3), and this AVP1 mu / kg is subcutaneously applied to guinea pigs. As a result, the serum AVP increased several times (almost the same value as the serum AVP in the acute phase of Meniere's disease), and histologically, endolymphatic hydrops occurred (Non-patent Document 4). Therefore, when treating Meniere's disease, special attention must be paid so that AVP does not increase due to stress or dehydration.

  However, as can be inferred from the fact that sugar or sugar alcohol was originally used as an osmotic pressure reducing agent, sugar or sugar alcohol produces an osmotic gradient in the digestive tract when orally administered in large amounts at once, resulting in diarrhea. May cause gastrointestinal symptoms. In the case of severe diarrhea, it has been reported that dehydration continues, and the antidiuretic hormone AVP increases 10 to 15 times (Non-patent Document 5).

  The present inventor has confirmed by experiment that serious diarrhea is produced when sugar or sugar alcohol is actually orally administered as a simple substance. As described above, since the increase in AVP forms endolymphatic edema, it was histologically proved that the effect of reducing the endolymphatic edema of sugar or sugar alcohol is offset by the increase in AVP due to dehydration associated with diarrhea. (Japanese Patent Application No. 2005-210582). This fact suggests the importance of maintaining fluid balance in the treatment of Meniere's disease, so when sugar or sugar alcohol is used for the treatment of Meniere's disease, so as not to cause digestive symptoms such as diarrhea, Great care must be taken.

  As described above, depending on the type of sugar or sugar alcohol, it may take a long time to develop the action, which means that the passage speed of the biological membrane is slow due to differences in molecular weight and molecular structure (Non-patent Document 2) There may also be a need to consider transient diarrhea observed 2-3 hours after dosing, which may be a cause. For example, in the conventional isosorbide solution (manufactured by Nikken Chemical Co., Ltd.), transient diarrhea is observed 2-3 hours after administration, so that an increase in AVP delays the onset of unloading action. Conceivable.

Therefore, in order to ensure that the action is rapidly manifested, it is also an essential condition to suppress the agitation action by the sugar or sugar alcohol.
Takeda T et al: The bound phenomenon of glycerol-induced changes in the endophymatic space. Acta Otalyngol 119: 341-4 (1999) Kakigi A et al .: Time course of dehydrat ef effects of isosorbideon experimentally inducible endohydrophysics in guinea pigs. ORL J Otorhinolarynol Relat Spec 66: 291-296 (2004) Takeda T et el: Antigenic hormone (ADH) and endormotropic hydr. Acta Otalyngol Suppl 519: 219-22, (1995) Takeda T et al: Endolymphatic hydrops induced by chronic administration of vasopressin. Hair Res. 140: 1-6, (2000) Saffate A et al: Renin-aldosterone system and arginine vasopressin in diarhoeic calves. Br Vet J 147: 533-7, (1991)

  The problem to be solved by the present invention is to reduce the volume of pharmaceutical preparations that are bulky and difficult to take, such as Meniere's disease therapeutic drugs containing sugar or sugar alcohol as an active ingredient. The object is to provide a treatment for Meniere's disease that is easy to take and carry. In addition, it is intended to shorten the time until the effect is manifested by reliably suppressing the armpit action that frequently occurs in the treatment for Meniere's disease.

  As a result of intensive studies to solve the above problems, the present inventor has developed a bulky medicine such as Meniere's disease therapeutic drug containing sugar or sugar alcohol as an active ingredient, sodium alginate or sodium alginate and other polysaccharides. By blending the above and calcined gypsum in a certain range, the volume and weight are processed into a jelly-like solid that is about one third or less of the powder formulation and about one fourth or less for a saturated aqueous solution. The present invention has been completed by finding that it is possible. In addition to reducing the dose at one time, it was possible to carry as much as needed by being able to sachet. Further, when one or more kinds of sodium alginate and other polysaccharides were added, digestive symptoms such as axillary action produced when sugar or sugar alcohol was used as an active ingredient could be surely eliminated. Furthermore, when the sugar or sugar alcohol is isosorbitol, it has also succeeded in reducing the bitterness peculiar to isosorbitol solutions.

That is, the present invention is as follows.
(1) A hydrogel preparation containing 0.5 to 30% by weight of sodium alginate and 0.5 to 10% by weight of calcined gypsum with respect to 100% by weight of the active ingredient.
(2) The hydrogel preparation according to (1), wherein the content of sodium alginate is 1 to 15% by weight.
(3) The hydrogel preparation according to (1) or (2), wherein the content of calcined gypsum is 0.5 to 7% by weight.
(4) The hydrogel preparation according to any one of (1) to (3), further comprising d) a polysaccharide other than sodium alginate.
(5) The water-containing gel preparation according to any one of (1) to (4), wherein the water content is 30 to 90% by weight with respect to 100% by weight of the active ingredient.
(6) The hydrogel preparation according to any one of (1) to (5), wherein the active ingredient is a monosaccharide, an oligosaccharide, or a sugar alcohol thereof.
(7) The hydrogel preparation according to (6), wherein the sugar alcohol is isosorbitol.
(8) The hydrogel preparation according to (6) or (7), which is used for a therapeutic agent for Meniere's disease.
(9) Any of (1) to (8), which comprises mixing monosaccharides, oligosaccharides or sugar alcohols thereof, and sodium alginate together with water, and then kneading by adding a water mixture of calcined gypsum. A method for producing the hydrogel preparation according to claim 1.
(10) Meniere's disease therapeutic agent containing the following components.
a) Monosaccharides, oligosaccharides or sugar alcohols thereof b) 0.5-30% by weight sodium alginate c) 100% by weight of component a) 0.5-10% by weight of baked 0.5% by weight of component a Gypsum (11) Meniere's disease therapeutic drug according to (10), wherein the content of sodium alginate is 1 to 15% by weight.
(12) The Meniere's disease therapeutic drug according to (10) or (11), wherein the content of calcined gypsum is 0.5 to 7% by weight.
(13) The Meniere's disease therapeutic drug according to any one of (10) to (12), wherein the sugar alcohol is isosorbitol.
(14) The therapeutic agent for Meniere's disease according to any one of (10) to (13), further comprising d) a polysaccharide other than sodium alginate.

The water-containing gel preparation of the present invention can remarkably reduce the volume and weight compared to a liquid preparation or a powder preparation by blending sodium alginate and calcined gypsum in a certain range. For example, a jelly-like solid substance by blending a certain amount of sodium alginate and calcined gypsum into monosaccharides, oligosaccharides which are treatments for Meniere's disease, or sugar alcohols thereof (hereinafter referred to as “sugar alcohols”). As a result, the volume and weight are reduced to about one-third or less compared to a sugar alcohol simple powder formulation, and to about one-fourth or less for a saturated aqueous solution of sugar alcohols. Can be packaged, and can be stored, carried and taken very easily. Further, this jelly-like solid has less water separation even after time has passed as compared to the case where agar or jelly is used as a gelling agent. In addition, agar and jelly dissolve completely at 40-80 ° C, but this solid matter hardly dissolves even at 80 ° C, so there is no need for cold storage during carrying in the summer, making carrying much easier. .
It is also possible to add one or more polysaccharides other than sodium alginate to the formulation, which, together with the effects of sodium alginate, eliminates gastrointestinal symptoms such as axillary action, and reduces the effect of sugar alcohols on reducing endolymphedema We have succeeded in ensuring the expression and promoting it at the same time. There was no rebound phenomenon. In addition, it has succeeded in reducing unpleasant flavors such as the unique bitterness that causes pain to patients when taking the medicine by using a gel preparation.

Sodium alginate in the present invention is a main component of agar and is used as food, and is highly safe. The blending amount of sodium alginate with respect to 100% by weight of the active ingredient is 0.5 to 30% by weight, preferably 1 to 15% by weight, particularly preferably 1 to 10% by weight.
In addition, calcined gypsum is a neutral food additive and is highly safe. The amount of calcined gypsum is 0.5 to 10% by weight, preferably 1 to 7% by weight, based on 100% by weight of the active ingredient.
When the blending amount of sodium alginate and / or calcined gypsum is out of the above range, it tends to be difficult to form a solid having a suitable hardness.
Any active ingredient may be used, but the present invention is particularly effective for those which have a large dose per dose and become bulky when used as a liquid or powder preparation. Examples include sugar alcohols that are treatments for Meniere's disease, and examples include monosaccharides or oligosaccharide alcohols such as erythritol, xylitol, xylose, glucose, sorbitol, isosorbitol, maltitol, and lactitol. In the case of isosorbitol having a crystal-like shape, it shows a significant volume reduction effect.

In addition, the therapeutic agent for Meniere's disease of the present invention may contain a polysaccharide other than sodium alginate as the d component. Examples thereof include sodium and hydroxypropylcellulose. These may be used alone or in combination.
The blending amount of the polysaccharide is 0.5 to 30% by weight, preferably 0.5 to 20% by weight, based on the sugar alcohol.

The therapeutic agent for Meniere's disease of the present invention can be made into a gel preparation by adding an appropriate amount of purified water as the e component to the a to d components.
The amount of water is not uniform depending on the types and blending amounts of the components a to d, but is generally about 30 to 90% by weight, preferably about 30 to 80% by weight, based on the sugar alcohol.
When the amount of water exceeds this range, it is difficult to produce a good gel as a jelly-like solid having an appropriate hardness.

In the formulation, pharmaceutically acceptable carriers, excipients, diluents, binders, preservatives, stabilizers, flavoring / coloring agents and the like can be blended as necessary.
In addition, as long as the purpose of the present invention is not impaired, other medicinal components other than sugar alcohols, such as dry aluminum hydroxide gel, natural aluminum silicate, precipitated calcium carbonate, etc. Sympathetic β agonists, vasodilators or cerebral circulation improving drugs as drugs that improve circulation, diuretics as drugs that reduce maze edema, sedatives and autonomic nerve regulators as drugs that reduce sedation or antiemetic It is also possible to mix.

For the hydrogel preparation of the present invention, for example, a wet mixture (liquid I) prepared by preheating warm active ingredients such as sugar alcohols and sodium alginate together with water in a hot water bath, and a water mixture of calcined gypsum (liquid II) are prepared. The liquid I and liquid II can be mixed and stirred.
The amount of water added at the time of preparing the liquid I is about 10 to about 70% by weight, preferably about 25 to about 60% by weight, based on the mixture of sugar alcohols and sodium alginate. Is 1 to 7 times, preferably 1 to 5 times the weight of calcined gypsum.

  Further, if necessary, the addition of a preliminarily prepared gelation accelerator further accelerates the curing and is sure. Each gelation accelerator is prepared by pulverizing an appropriate amount of calcined gypsum and distilled water. In some cases, gelation can be delayed by changing the number of times of stirring. In addition, in order to surely delay the gelation, in addition to adding calcium carbonate dihydrate, calcium carbonate and other insoluble calcium salts such as calcium sulfate 5-95% by weight of calcined gypsum, It is also possible to add sodium carbonate, sodium hydrogen carbonate, sodium phosphate, sodium hydrogen phosphate or the like as an agent. Thereby, gelation is delayed for several minutes to 10 hours or more.

  The use of calcium chloride as a source of calcium ions (Prescription Example 3 [Comparative Example 2]) is due to the deliquescence phenomenon, resulting in about 30-40 volume% water separation of the gel part after 10 hours. Certain sugar alcohols dissolve in large quantities, which is inappropriate.

The dose of sugar alcohols depends on the pathology, but is 0.5 to 3.0 g / kg, preferably 0.8 to 1.5 g / kg per day for adults. This is divided into 1 to several doses. To do.
Hereinafter, the present invention will be described in detail with reference to Examples and Comparative Examples, but the present invention is not limited thereto.

Formulation Example 1 [Comparative Example 1] (isosorbitol 1 in [Table 1])
Isosorbitol 21g
Pectin 3g
Agar 1g
30ml distilled water

Formulation Example 2 (isosorbitol 2 in [Table 1])
Isosorbitol 21g
Sodium alginate 0.8g
0.75g of calcined gypsum
13ml distilled water

Formulation Example 3 [Comparative Example 2] (isosorbitol 3 in [Table 2])
Isosorbitol 21g
Sodium alginate 0.8g
0.75g calcium chloride
13ml distilled water

Formulation Example 4 [Comparative Example 3] (isosorbitol 4 in [Table 2])
Isosorbitol 21g
Sodium alginate 0.8g
0.75g calcium sulfate dihydrate
13ml distilled water

When agar is selected as the gelling agent (Formulation Example 1 [Comparative Example 1]), a large amount of water is required to obtain a solid substance, so that the single dose is about 55 g and 40 ml. Although it is possible to carry the necessary number of times, it is impossible to expect sufficient weight reduction and volume reduction. In addition, since it takes a long time to solidify, the concentration of the components was uneven depending on the location. After gelation, water separation occurs over time, and a large amount of sugar is dissolved in the water separation solution and has a high concentration. Therefore, the liquid has an extremely rich flavor. In addition, agar is completely dissolved at 80 ° C. and becomes liquid after solidifying. Even at 80 ° C. or lower, agar softens as the ambient temperature rises, so softening and water separation progress during the summer, making it difficult to take and carry.
For example, in the case of an isosorbitol solution, a particularly high concentration of isosorbitol is dissolved in the water separated from the gel formulation, and the unique bitter taste spreads in the oral cavity and remains for a long time of 30 to 40 minutes. The merit of being able to take well through the throat, realized by gelling, disappears due to water separation.

  On the other hand, according to Formulation Example 2 of the present invention in which sodium alginate and calcined gypsum are blended, a konjac-like gel preparation with a small volume and no water separation is obtained. No water separation occurred even after 2 months storage at room temperature. Moreover, even if it heats at 80 degreeC or more for 10 minutes, melt | dissolution does not occur, only a very small amount of water separation is recognized by the surface layer, and it does not return to a liquid state. Isosorbitol is a sugar alcohol that is relatively simple but has a relatively low armpit action, and sodium alginate itself is a polysaccharide, so that it can provide antipruritic action. In addition, it requires other polysaccharides as an antipruritic agent. It is also possible to add.

  [Preparation of Gel Preparation of Formulation Example 2]: Mix 10 ml of distilled water with isosorbitol and sodium alginate, boil in hot water, remove rough heat to make liquid I. If sodium alginate is preliminarily mixed with a small amount of distilled water, it can be easily mixed with the isosorbitol solution. When calcined gypsum is mixed with 3 ml of distilled water (liquid II), liquid I is added all at once and the whole is stirred at an appropriate speed, a konjac-like gel preparation is obtained in an average of several seconds to several minutes. Since it gels in a short time, the component concentration becomes uniform. Moreover, a more preferable gel formulation can be obtained by storing at low temperature for several hours. The volume of the obtained gel preparation is half or less than that when using agar (Formulation Example 1), which is very convenient for carrying. In addition, water separation is not observed even after a long time has passed since the preparation, but the unique taste can be completely shielded by coating the surface layer.

  In Formulation Example 2, isosorbitol was replaced with other sugar alcohols in the same manner to obtain a gel preparation. When 21 g of these sugar alcohols are dissolved in distilled water to form a saturated aqueous solution, 70 to 120 ml of distilled water is required, and the volume of the saturated aqueous solution is 80 to 140 ml. All of the obtained gel preparations were about 1/4 or less of the saturated aqueous solution and 1/6 or less of xylitol. The results are shown in Table 1.

As shown in Formulation Example 3, the same weight as that of calcium chloride is used instead of calcined gypsum as the calcium ion supply agent, and adjustment is performed in the same manner as in Formulation Example 2. Curing starts within a few minutes after kneading, but water separation due to deliquescence occurs immediately after that, and after 10 hours, 4 ml of a bitter solution of isosorbitol is separated from the volume of the gel part of 14 cm ³ , and conventional isosorbide It is extremely difficult to take more than the solution and is not suitable for the purpose of the present invention.

In the prescription example 4, it adjusts by the method similar to the prescription example 2 using calcium sulfate dihydrate of the same weight instead of calcined gypsum as a calcium ion supply agent. The volume of the gel preparation is 20 cm ³ and does not become bulky compared with the prescription 2, but it takes 10 hours or more to complete the gelation, and there is a part where gelation does not occur, Hardness was uneven and a complete gel preparation could not be obtained.

Furthermore, calcium sulfate dihydrate and a set retarder were added to calcined gypsum in various proportions and adjusted in the same manner as in Formulation Example 2 to obtain a gel preparation. All of the obtained gel preparations were about one-fourth or less of the volume of the saturated aqueous solution containing 21 g of isosorbitol, which was about 80 ml. The results are shown in Table 2.
Neither isosorbitol 5, 6 or 7 with calcined gypsum produced water separation at room temperature, but only slight water separation was observed even after heating at 80 ° C. for 10 minutes. Easy.

Comparison with conventional preparations The effect of this drug was compared with the solution of isosorbitol (manufactured by Nikken Chemical Co., Ltd .: generic name isosorbide, isosorbitol content 70%) currently used in Japan.
Endolymphatic sac closure was performed only on the left side of 50 guinea pigs weighing 280-320 mg, and after 1 month, 10 animals were divided into 5 groups as shown in Table 3 and confirmed to have normal stool Above, only the distilled water was administered to the control group, the isosorbide preparation (hereinafter referred to as IB conventional product) was administered to the second group and the third group, and the fourth group and the fifth group were adjusted by the method of Formulation Example 2. Administration of a gel formulation (isosorbitol 2.8 g / kg) was performed. Observation of gastrointestinal symptoms and endolymph reduction effect is continued until 6 hours after administration (Non-Patent Document 2), where the effect of IB conventional products is maximized, and at 3 hours and 6 hours after administration. The perfusion was fixed, and the tissue was collected and observed.
All groups were prepared so that a single dose was 4 ml / kg. Procedures such as closure and tissue preparation, and measurement were performed in the same manner as in the non-patent paper (Takeda T: Hair Res. 183: 9-18, (2003)).

A) Examination of gastrointestinal symptoms Tables 4 and 5 show the criteria for observing the firmness and shape of stool.

  In the IB conventional product administration group, the stool began to soften after 2 hours, and after 3 hours (Group 2), the diarrhea symptoms were worst, 2 out of 10 normal stools, 3 loose stools, 3 loose stools, mud 2 stools. After 6 hours (Group 3), there were 4 normal stool animals, 3 slightly loose stools, 2 loose stools and 1 mud stool, and diarrhea symptoms were somewhat improved compared to 3 hours after administration. However, there was no significant difference between the second group and the third group. The length of the formed stool was 60.2 ± 15.8 after 6 hours, but 8 out of 10 stool intervals were scattered and some 20-40 cm intervals were also found in some places. From this, it is speculated that considerable gastrointestinal symptoms appeared. When the stool firmness and interval after 6 hours were compared with the control group, significant differences were observed in the observation results of stool stiffness and stool interval (P <0.01, P <0.05, Mann, respectively) -Whitney test), it can be seen that the armpit action appeared although it was moderate. This fact is consistent with gastrointestinal symptoms such as diarrhea, bloating, and groovy feeling that patients occasionally complain after administration of IB conventional products.

  On the other hand, in this developed product, the stool hardness after 3 hours (Group 4) is slightly soft stools, the other 8 are normal stools, stool intervals are irregular, Since there were few compared with the IB conventional product, it is estimated that the antipruritic action was significantly superior (P <0.05) and the digestive symptom was light compared with the IB conventional product (Group 2) (P < 0.01, Mann-Whitney test). After 6 hours (Group 5), all animals had normal stool, the interval was constant at 6 animals, and digestive symptoms were significantly lighter than those of the IB conventional product (Group 3). It was found (stool firmness, interval, P <0.01, P <0.01, Mann-Whitney test).

B) Endolymphatic edema reduction effect Relationship between the extension of the membrane and the increase of the area on the operation side Measures the extension of the Lysnel membrane and the volume change of the endolymphatic space at each rotation, and integrates the result in the same way as the following formula Then, the extension rate of the membrane and the increase rate of the area of the endolymphatic sac were obtained for each cochlea, and the effect of reducing endolymphedema was evaluated from the volume change.

    Table 7 shows the mean ± standard deviation of the stretch rate (IR-L) and the area increase rate (IR-S) of the membrane on the operation side.

On the operation side, the degree of formation of experimental edema due to closure is large, ranging from several percent to hundreds of tens of percent. Compared with the average ± standard deviation of membrane extension rate and area increase rate, the effect of the administered drug, It is difficult to examine such changes over time.
In FIG. 1, the horizontal axis represents the membrane extension rate, and the vertical axis represents the area increase rate. A scatter diagram of two variables on the operation side and a regression line are shown for each animal group. When endolymphatic edema occurs, the volume of the endolymphatic space increases and the Lysnel membrane extends. From FIG. 1, in the 1st group (control group) which administered distilled water, it is estimated that a primary correlation exists statistically between both. When edema is reduced by drug administration, the area of the endolymphatic space is reduced despite the extension of the membrane, and the regression line moves downward.

  In FIG. 1, the regression line of the second group (3 hours after the IB conventional product) and the third group (6 hours after the IB conventional product) move downward compared to the regression line of the first group (control group). , There were significant differences (P <0.01, P <0.001, ANCOVA, respectively).

  The regression lines of Group 4 (3 hours after the development product) and Group 5 (6 hours after the development product) moved further downward, and there was a significant difference compared to the first group (control group) ( (P <0.001, P <0.001, ANCOVA), it was found that the effect of reducing the load was greater. Comparing the effects of the newly developed product and the conventional product, the effect of reducing the load 3 hours after administration (Group 4) is significantly greater than that of the IB conventional product (Group 2) (P <0.01, ANCOVA). On the other hand, there was no significant difference in the 5th group after 6 hours from the administration compared to the conventional IB product (the 3rd group) (ANCOVA).

From these facts, the unloading effect of the newly developed product appeared surely 3 hours after administration (P <0.001), and the effect persisted even after 6 hours (P <0.001). ). Even when compared with the conventional product, the effect at 3 hours after administration was significantly greater than that of the conventional product (P <0.01), and it was found that the onset of action was rapid.
Although there is no significant difference after 6 hours, the regression line has moved downward compared to the conventional product, and it is clear from the properties of the stool that the gastrointestinal symptoms were successfully improved, including the swallowing action. Therefore, it is expected that a sufficient therapeutic effect can be expected without burdening the digestive organs.

  Based on the above, the newly developed product is a Meniere's disease therapeutic agent that is easy to carry and take, is simple, and has an excellent effect on reducing endolymphedema.

ＩＲ−Ｌ、×：第３群（ＩＢ従来品６時間後）のＩＲ−Ｓ ｖｓ ＩＲ−Ｌ、●：第４群（本開発品３時

Example 2: In order to see the difference in the effect of reducing the load between the developed product and the conventional product on the operation side, the relationship between the film extension rate and the area change rate was shown. The second group (3 hours after IB conventional product administration) and the third group (6 hours later) move downward immediately before the regression, but the significant difference is small after 3 hours (after 3 hours: P <0.01, After 6 hours: P <0.001, ANCOVA). In this developed product, there was a significant downward movement at 3 hours (Group 4) and 6 hours (Group 5), and there was a clear significant difference (P <0.001, P <0. 001, ANCOVA). When the effects after 3 hours were compared, the fourth group was lower than the second group, and there was a significant difference (P <0.01, ANCOVA).

IR-L, x: IR-S vs IR-L of the third group (after 6 hours of the IB conventional product), ●: Fourth group (3 hours of the newly developed product)

Claims (14)

A hydrogel preparation containing 0.5 to 30% by weight of sodium alginate and 0.5 to 5% by weight of calcined gypsum with respect to 100% by weight of the active ingredient. The hydrogel preparation according to claim 1, wherein the content of sodium alginate is 1 to 15% by weight. The hydrogel preparation according to claim 1 or 2, wherein the content of calcined gypsum is 0.5 to 7% by weight. Furthermore, d) The hydrogel formulation of any one of Claims 1-3 containing polysaccharides other than sodium alginate. The water-containing gel preparation according to any one of claims 1 to 4, wherein the water content is 30 to 90% by weight with respect to 100% by weight of the active ingredient. The hydrogel preparation according to any one of claims 1 to 5, wherein the active ingredient is a monosaccharide, an oligosaccharide, or a sugar alcohol thereof. The hydrogel preparation according to claim 6, wherein the sugar alcohol is isosorbitol. The hydrogel preparation according to claim 6 or 7, which is used for a therapeutic agent for Meniere's disease. The monosaccharide, oligosaccharide, or sugar alcohol thereof, and sodium alginate are mixed with water, and then kneaded with a water mixture of calcined gypsum and kneaded. A method for producing a hydrogel formulation of Meniere's disease drug containing the following ingredients.
a) Monosaccharides, oligosaccharides or sugar alcohols thereof b) 0.5-30% by weight sodium alginate c) 100% by weight of component a) 0.5-10% by weight of baked 0.5% by weight of component a plaster The therapeutic agent for Meniere's disease according to claim 10, wherein the content of sodium alginate is 1 to 15% by weight. The therapeutic agent for Meniere's disease according to claim 10 or 11, wherein the content of calcined gypsum is 0.5 to 7% by weight. The therapeutic agent for Meniere's disease according to any one of claims 10 to 12, wherein the sugar alcohol is isosorbitol. Furthermore, d) Any one of Claims 10-13 containing polysaccharides other than sodium alginate, The Meniere's disease therapeutic agent of Claim 1.

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