JP2008189626A - Glycyrrhizin-solubilized preparation for oral use and method for producing the same - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a glycyrrhizin-solubilized preparation for oral use exhibiting high enteroabsorbability with a glycerol fatty acid ester and glycyrrhizin existing in a dissolved state, and to provide a method for producing the glycyrrhizin-solubilized preparation for oral use. <P>SOLUTION: The glycyrrhizin-solubilized preparation for oral use comprises glycyrrhizin and/or a pharmaceutically acceptable salt thereof, the glycerol fatty acid ester and such a solvent as to dissolve 2 mass% or more of the glycyrrhizin and/or the pharmaceutically acceptable salt thereof. The method for producing the glycyrrhizin-solubilized preparation for oral use is also provided. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to an oral glycyrrhizin-solubilized preparation in which glycyrrhizin is dissolved and a method for producing the same.

  Glycyrrhizin (hereinafter abbreviated as GL) and salts thereof have a wide range of physiological activities such as antiallergic action, anti-inflammatory action, immunoregulatory action, hepatocellular injury inhibiting action, hepatocyte proliferation promoting action, virus growth inhibiting action, etc. It has been known for a long time as a clinical drug. Currently, it is widely used for liver diseases, skin diseases, various allergies, inflammation and the like alone or as a combination agent with amino acids.

  Existing GL preparations generally include intravenous injections and oral preparations, and intravenous injections are mainly used in clinical settings. However, intravenous injection is highly invasive to patients, and in the treatment of chronic liver disease, long-term intravenous injection causes vascular sclerosis and often makes administration difficult. Furthermore, the current situation of frequent visits for administration has significantly reduced QOL (Quality of Life), especially in elderly patients. For this reason, especially in the treatment of chronic liver diseases, oral preparations that are less invasive to patients are more desirable.

  However, when GL is orally administered, intestinal absorptivity is poor because most of it exists in the intestine in an anionic dissociative form, and a sufficient therapeutic effect is often not obtained. Therefore, many preparations have been made for improving the intestinal absorbability of GL.

For example, the thing which mix | blended glycerol fatty acid ester with GL, and coat | covered with the enteric film is proposed (for example, refer patent document 1). The glycerin fatty acid ester having a surface active action has an effect of increasing the intestinal absorbability of GL.
JP-A-3-255037

  However, since glycerin fatty acid ester has poor solubility of GL, the above oral preparation has only GL dispersed in glycerin fatty acid ester, and GL is not dissolved in the medium. For this reason, even if it fills a capsule, as a result of the disperse | distributing GL sedimenting in a capsule, the reproducible stable high absorbency cannot be expected.

  In order to solubilize a high concentration of GL, an aqueous solvent such as aqueous ammonia, dilute ethanol, polyethylene glycol, or propylene glycol is usually used. However, GL dissolved in an aqueous solvent has poor intestinal absorption. In order to have reproducible and stable absorbability, GL must remain solubilized in the formulation. On the other hand, in order to have high absorbability, it is desirable to include glycerin fatty acid ester and GL having an excellent intestinal absorption promotion effect in the same preparation.

  Therefore, an object of the present invention is to provide an oral GL-solubilized preparation which is present in a state in which glycerin fatty acid ester and GL are dissolved and exhibits high intestinal absorbability.

  As a result of diligent research to solve the above problems, the present inventors have used a small amount of a solvent capable of dissolving GL in an amount of 2% by mass or more, so that GL and glycerin fatty acid ester exist in a dissolved state. The present invention was completed by finding that a preparation can be obtained.

That is, the present invention comprises GL and / or a pharmaceutically acceptable salt thereof, a glycerin fatty acid ester, and a solvent in which 2% by mass or more of the GL and / or a pharmaceutically acceptable salt thereof can be dissolved. The present invention provides an oral GL-solubilized preparation characterized by containing.
The present invention also provides an oral GL-solubilized preparation in which the glycerin fatty acid ester is a monoglycerin fatty acid ester.
The present invention also provides an oral GL-solubilized preparation in which the solvent is at least one selected from the group consisting of water, aqueous ammonia, aqueous ammonium salt solution, aqueous alkaline solution, alkaline salt solution, polyethylene glycol, propylene glycol, and glycerin. It is to provide.
The present invention also provides an oral GL-solubilized preparation in which the solvent is aqueous ammonia and / or an aqueous ammonium salt solution.
Further, the present invention provides an oral GL-solubilized preparation wherein the glycerin fatty acid ester is a monoglycerin fatty acid ester, the solvent is aqueous ammonia and / or an aqueous ammonium salt solution, and further contains fats and oils and / or fatty acids. Is to provide.
In the present invention, the content of GL and / or a pharmaceutically acceptable salt thereof is 1 to 40% by mass, the content of the glycerin fatty acid ester is 30 to 90% by mass, and the content of the solvent The present invention provides an oral GL-solubilized preparation having an amount of 0.1 to 100% by mass based on the total content of GL and its pharmaceutically acceptable salt as GL.
The present invention also provides an oral GL solubilized preparation whose dosage form is a capsule.
Further, the present invention comprises mixing GL and / or a pharmaceutically acceptable salt thereof, a glycerin fatty acid ester, and a solvent capable of dissolving 2% by mass or more of the GL and / or a pharmaceutically acceptable salt thereof, The present invention provides a method for producing an oral GL-solubilized preparation characterized by stirring and dissolving the GL and / or a pharmaceutically acceptable salt thereof.

  The oral GL-solubilized preparation of the present invention is a novel oral GL-solubilized preparation that is excellent in both solubility and intestinal absorbability and exhibits reproducible and stable high absorption. By providing the GL preparation of the present invention, that is, an oral preparation having a sufficient therapeutic effect in the same manner as existing GL intravenous injections, improvement of the patient's QOL and reduction of the burden on the medical staff can be expected.

In the oral GL solubilized preparation of the present invention, GL and / or a pharmaceutically acceptable salt thereof, glycerin fatty acid ester, and GL and / or a pharmaceutically acceptable salt thereof are dissolved by 2% by mass or more. An oral GL-solubilized preparation comprising a solvent to be obtained. By using a solvent in which 2% by mass or more of GL or a salt thereof can be used, the amount of solvent for dissolving GL or a salt thereof can be suppressed to a small amount in the presence of glycerin fatty acid ester. Therefore, the glycerin fatty acid ester content can be increased.
That is, by administration of the oral GL solubilized preparation of the present invention, it can be expected that a high concentration of GL in a solubilized state is absorbed into the intestinal tract very effectively by a sufficient amount of glycerin fatty acid ester.

  GL and its pharmaceutically acceptable salt used in the present invention are not particularly limited as long as they have the same pharmacological effects as GL in vivo. For example, there are ammonium salts such as GL ammonium salt, sodium salts, potassium salts and the like currently used in clinical practice.

The glycerin fatty acid ester used in the present invention is not particularly limited. Preferably monoglycerol fatty acid ester, more preferably a monoglycerol fatty acid ester of a C ₆ -C _18. This is because GL has a greater intestinal absorption promotion effect. Monoglycerin fatty acid esters include esters of glycerol with hexanoic acid, octanoic acid, decanoic acid, dodecanoic acid, stearic acid, oleic acid, and the like. One kind of monoglycerin fatty acid ester may be used alone or as a mixture of plural kinds of monoglycerin fatty acid esters. In addition, you may use as a mixture of monoglycerol fatty acid ester, diglycerol fatty acid ester, and triglycerol fatty acid ester. Examples of such commercially available products include “Inviter 742” and “Inviter 988” manufactured by Sasol, “Poem M100”, “Poem M200”, “Poem M300” manufactured by Riken Vitamin Co., Ltd., and Kao Corporation. "Homotex PT" manufactured by the same may be mentioned.

The solvent used in the present invention is capable of dissolving 2% by mass or more of GL and / or a pharmaceutically acceptable salt thereof, and precipitates and precipitates other components of the oral GL-solubilized preparation. It is not particularly limited as long as it does not occur, that is, as long as the solubilized state can be maintained.
In the present invention, “dissolved” means that the solution becomes transparent enough to read letters written on paper through a transparent test tube containing the solution.

  The solvent may be an aqueous solvent, an inorganic salt solution, or the like. Examples of the aqueous solvent include water, ethanol, dilute ethanol, aqueous alkaline solution such as aqueous ammonia, polyethylene glycol, propylene glycol, glycerin and the like. Examples of the inorganic salt solution include an aqueous ammonium salt solution and an aqueous solution of sodium chloride, potassium chloride, calcium chloride, magnesium chloride, and the like. Examples of the aqueous ammonium salt solution include aqueous solutions of ammonium carbonate, ammonium chloride, and ammonium acetate. Further, it may be a solution of amino acids such as glycine, methionine, cysteine, arginine, cellulose derivatives, organic substances such as sodium decanoate, soybean lecithin, egg yolk lecithin, and other surfactants.

  Further, by using an alkaline aqueous solution or an alkaline salt solution, the chemical reaction between GL and other components contained in the preparation can be suppressed, and the chemical stability of GL can be improved. Examples of the alkaline aqueous solution or alkaline salt solution include aqueous ammonia and aqueous ammonium salt solutions, sodium hydroxide, potassium hydroxide, disodium hydrogen phosphate, dipotassium hydrogen phosphate, disodium hydrogen carbonate, dipotassium hydrogen carbonate, sodium carbonate, carbonic acid. Examples of the aqueous solution include potassium, sodium tripolyphosphate, and sodium acetate.

  The solvent may be one type of solution or a mixed solution of a plurality of types. By using a wide variety of solutions as appropriate solvents, precipitation and sedimentation of GL or other components in oral GL-solubilized preparations can be prevented under various storage conditions, and GL concentration and oral use can be prevented. The viscosity of the GL solubilized preparation can be freely adjusted.

  The solvent is preferably at least one selected from the group consisting of water, aqueous ammonia, aqueous ammonium salt solution, aqueous alkaline solution, alkaline salt solution, polyethylene glycol, propylene glycol, and glycerin. This is because the solubility of GL is high. More preferred is aqueous ammonia and / or an aqueous ammonium salt solution. This is because when the GL ammonium salt is used, the chemical stability of the GL can be improved and the ammonium salt of the GL can be maintained.

  The chemical stability of GL can be improved by adding an alkaline aqueous solution or alkali salt to the oral GL-solubilized preparation of the present invention.

  It is also preferred that the oral GL-solubilized preparation of the present invention further contains an oil and / or a fatty acid. This is because the viscosity of the oral GL-solubilized preparation can be freely adjusted with oils and fats. The viscosity of the oral preparation is an important factor in the preparation, and it is desired that the oral preparation has an appropriate viscosity as an oral preparation. Normally, a high-concentration GL solution tends to have a high viscosity, but the addition of oils or the like can reduce the viscosity of an oral GL-solubilized preparation to the extent that it can be filled in a capsule or the like. Examples of the fat or fatty acid include soybean oil, sesame oil, coconut oil, palm kernel oil, olive oil, sunflower oil, safflower oil, perilla oil, triglycerin medium chain fatty acid ester, oleic acid, safflower oil fatty acid and the like.

The content ratio of each constituent component of the oral GL solubilized preparation of the present invention is as long as the GL or other constituents in the oral GL solubilized preparation can maintain the solubilized state without causing precipitation or sedimentation. Although not particularly limited, the content of GL and / or a salt thereof is 1 to 40% by mass, the content of glycerin fatty acid ester is 30 to 90% by mass, and the content of the solvent is GL. It is preferable that it is 0.1-100 mass% with respect to the total content as GL of the salt.
If the content of GL and / or a salt thereof is less than 1% by mass, sufficient GL drug efficacy cannot be expected. On the other hand, if it exceeds 40% by mass, the viscosity of the oral GL-solubilized formulation becomes too high, which is preferable in terms of formulation. Absent. If the content of the glycerin fatty acid ester is less than 30% by mass, a sufficient intestinal absorption promotion effect cannot be expected, whereas if it exceeds 90% by mass, it is difficult to keep the GL solubilized. If the content of the solvent is less than 0.1% by mass with respect to the total content of GL and its salt as GL, it is difficult to keep the GL solubilized and the viscosity becomes too high, If it exceeds 100% by mass, the content of the solvent in the whole oral GL-solubilized preparation becomes too high, and the effects of the present invention may not be sufficiently exhibited.

  When the solvent is an aqueous ammonium salt solution or the like, the content of the ammonium salt or water can be arbitrarily changed as long as GL maintains solubilization in the preparation. For example, in gelatin capsules and the like, it is known that the water content of the filler or the content of the aqueous base affects the success or failure of the encapsulation. The oral GL-solubilized preparation of the present invention enables formulation design based on the premise of encapsulation, and can provide a product with a higher degree of completion as a capsule preparation.

  The dosage form of the oral GL solubilized preparation of the present invention is not particularly limited as long as it is a medically acceptable dosage form as an oral preparation, but is preferably a capsule. Examples of the capsule include a soft capsule using gelatin or the like, a hard capsule, or a seamless capsule.

When the oral GL-solubilized preparation of the present invention is affected by gastric acid degradation or gelation under low pH in the stomach, the absorption of GL may be significantly hindered. For this reason, capsules having the property of passing through the stomach and disintegrating in the small intestine, that is, soft capsules, hard capsules, or seamless capsules that have been previously provided with enteric or acid resistance are more preferable.
Further, an enteric coat can be further applied to the oral GL-solubilized preparation of the present invention which is a capsule. Examples of the pharmaceutically acceptable enteric coating agent include cellulose acetate phthalate, hydroxypropylmethylcellulose phthalate, hydroxypropylmethylcellulose acetate succinate, acrylic acid copolymer, and methacrylic acid copolymer.

  The oral GL-solubilized preparation of the present invention is prepared by the production method of the present invention, that is, a solvent in which GL and / or a salt thereof, glycerin fatty acid ester, and the GL and / or a salt thereof can be dissolved by 2% by mass or more. Can be produced by a method for producing an oral GL-solubilized preparation, wherein the GL and / or salt thereof is dissolved. The order of mixing, stirring conditions, etc. are in accordance with conventional methods.

  The oral GL solubilized preparation of the present invention may contain a pharmaceutically acceptable optional component in addition to the essential components as long as the effects of the present invention are not hindered. Examples of the optional component include a stabilizer and a preservative.

  The oral GL solubilized preparation of the present invention comprises acute and chronic liver dysfunction caused by drug or virus infection, eczema, dermatitis, hives, drug eruption, poisoning eruption, cutaneous pruritus, acne and other skin diseases, pneumonia , Pancreatitis, nephritis, stomatitis, mastitis and other inflammation, allergic diseases, various immune diseases, various viral diseases, sepsis, ischemia-reperfusion injury, chronic obstructive pulmonary disease (COPD) . Compared to existing injection preparations, the burden on the patient is small and it can be used easily, so it is particularly effective as a therapeutic agent for chronic diseases such as chronic liver diseases that require long-term medication.

  The oral GL solubilized preparation of the present invention is appropriately prescribed by a clinician according to the symptoms, body weight, age, etc. of the patient to be administered. The GL content in the oral GL solubilized preparation of the present invention is not particularly limited as long as it is an amount that exhibits a medicinal effect. As a volume, for example, per day, oral administration can be performed once to several times a day, with an upper limit of 500 mg as GL.

  EXAMPLES Next, although an Example is shown and this invention is demonstrated further in detail, this invention is not limited to a following example.

  An oral GL-solubilized preparation was prepared with the components and contents (mass / mass%) shown in Table 1. The main component of Poem M100 (manufactured by Riken Vitamin Co., Ltd.) is glycerin monocaprylate. Specifically, each component was weighed so as to have the indicated content, and these were mixed and stirred under non-heating to dissolve the GL monoammonium salt. The prepared oral GL solubilized preparation had the properties shown in the table.

  An oral GL solubilized preparation was prepared in the same manner as in Example 1 with the components and contents shown in Table 2. JP (Japan Pharmacopoeia) ammonia water has an ammonia content of 9.5 to 10.5 mass / volume%.

  An oral GL solubilized preparation was prepared in the same manner as in Example 1 with the components and contents shown in Table 3.

  An oral GL solubilized preparation was prepared in the same manner as in Example 1 with the components and contents shown in Table 4.

  An oral GL solubilized preparation was prepared in the same manner as in Example 1 with the components and contents shown in Table 5.

  An oral GL solubilized preparation was prepared in the same manner as in Example 1 with the components and contents shown in Table 6.

  An oral GL solubilized preparation was prepared in the same manner as in Example 1 with the components and contents shown in Table 7. Note that SDS in the table is sodium dodecyl sulfate.

  An oral GL-solubilized preparation was prepared in the same manner as in Example 1 with the components and contents shown in Table 8. The main component of Miglyol 812 (manufactured by Sasol) is a triglycerin fatty acid ester having a fatty acid composition of 50 to 65% octanoic acid and 30 to 45% decanoic acid.

(Comparative Example 1)
In the same manner as in Example 1, with the components and contents shown in Table 9, each component is weighed so as to have the indicated content, and these are mixed and stirred to obtain an oral GL-solubilized preparation. Prepared.

(Comparative Example 2)
An oral GL solubilized preparation was prepared in the same manner as in Comparative Example 1 with the components and contents shown in Table 10. In addition, the main component of Inviator 742 (made by Sasol) is a mixture of monoglycerin fatty acid ester, diglycerin fatty acid ester, and triglycerin fatty acid ester of octanoic acid and decanoic acid.

(Reference Example 1)
An oral GL solubilized preparation was prepared in the same manner as in Example 1 with the components and contents shown in Table 11.

(Reference Example 2)
An oral GL solubilized preparation was prepared in the same manner as in Example 1 with the components and contents shown in Table 12.

From the results of Examples 1 to 8, oral GL is a clear solution in which GL is solubilized by mixing and stirring GL of 40% by mass or less, a glycerin fatty acid ester, and a solvent. It is clear that solubilized preparations can be produced.
In particular, it is clear from the results of Examples 1 and 2 that the use of aqueous ammonia as a solvent facilitates solubilization of GL and reduces the content of the solvent in solubilization.

From the results of Examples 2 and 4, the fatty acid constituting the glycerin fatty acid ester used in the present invention may be a saturated fatty acid, an unsaturated fatty acid, a medium chain fatty acid, or a long chain fatty acid. It is clear.
Furthermore, from the results of Examples 5 and 6, the solvent used in the present invention is not limited to ammonia water, but may be an aqueous ammonium salt solution. From the results of Example 7, the solvent used in the present invention is ammonia water or the like. The solvent used in the present invention may further contain a mixture of triglycerin medium chain fatty acid esters based on the results of Example 8 and may be a combination of ethanol, organic substances, and surfactants. It is clear that each can also.

  On the other hand, as apparent from the results of Example 2 and Comparative Example 1, GL is solubilized if there is no solvent, that is, a solvent capable of dissolving 2% by mass or more of GL and / or a pharmaceutically acceptable salt thereof. Not forming a white precipitate. Even when glycerol fatty acid ester was a mixture of monoglycerol fatty acid ester, diglycerol fatty acid ester, and triglycerol fatty acid ester, GL could not be solubilized.

  Using the oral GL-solubilized preparation prepared in Example 1 and Example 2, the GL chemical stability was evaluated by measuring the residual amount of GL after storage at room temperature and 60 ° C. for 12 days. . Specifically, when the residual amount of GL contained in the oral GL solubilized preparation after storage at room temperature for 12 days is defined as 100%, the residual amount of GL after storage at 60 ° C. for 12 days is calculated. did. GL was detected using HPLC (CLASS-VP, manufactured by Shimadzu Corporation). Table 13 shows the detection results. From the detection results, it is clear that the chemical stability of GL is improved by using aqueous ammonia as a solvent.

  The viscosity of the oral GL solubilized preparations prepared in Examples 1, 2, 3, and 8 was measured using a Brookfield digital viscometer. Table 14 shows the measurement results. From the viscosity values of the oral GL-solubilized preparations of Examples 1, 2, and 3, it was found that the viscosity of the oral GL-solubilized preparation increased by decreasing the amount of solvent or increasing the GL content. On the other hand, the viscosity of the oral GL solubilized preparation was reduced by adding Miglyol 812 to the oral GL solubilized preparation. In other words, it is clear from the measurement results that the viscosity of the oral GL-solubilized preparation can be reduced by adding fats and oils, that is, it can be arbitrarily adjusted to a viscosity suitable for encapsulation. It is.

  The oral GL-solubilized preparation prepared in Example 2 was filled into gelatin-coated soft capsules to attempt preparation. Molded with No. 4 oval mold by a general rotary die method. The form at the time of molding was good, and no adhesion failure of the film, liquid leakage, deformation, etc. were confirmed, and a sufficient yield as a product was obtained. In addition, the shape was maintained for 12 months or longer under room temperature storage in a desiccator, and no turbidity, softening, deformation, adhesion or the like of the film was observed in any capsule. Further, neither clouding of the filler nor precipitation of GL was confirmed, and the oral GL solubilized preparation maintained a solubilized state for a long time even when encapsulated. On the other hand, when a dissolution test was conducted, the oral GL-solubilized preparation had good disintegration and dissolution properties, and maintained the performance of a normal soft capsule. Therefore, it is clear that the oral GL solubilized preparation of the present invention can sufficiently cope with the existing encapsulation technology.

  The oral GL-solubilized preparation prepared in Example 2 was filled into a hard capsule made of gelatin, and preparation was attempted. Using a commercially available No. 1 hard capsule, the fitting part was adhered with gelatin and dried. The shape was maintained for 5 months under room temperature storage in a sealed container, and no liquid leakage, deformation, white turbidity of the filler, GL deposition, etc. were observed. Therefore, it is clear that the oral GL-solubilized preparation of the present invention can be liquid-filled into normal hard capsules.

(Test Example 1)
Using an oral GL-solubilized preparation prepared with a GL content of 14%, a glycerin fatty acid ester of Poem M100, and a solvent of purified water or purified water and ammonium carbonate, ammonia salt and water in GL solubilization The content ratio was examined. As shown in FIG. 1, while preparing the total amount with an appropriate amount of Poem M100, oral GL-solubilized preparations having different ratios of ammonium carbonate and purified water were prepared, and the solubility of each GL was examined. It was. FIG. 1 is a plot of the prepared oral GL-solubilized preparation with the vertical axis representing ammonium carbonate content (%) and the horizontal axis representing purified water content (%). In the figure, ○ indicates a solubilized formulation, and ■ indicates an insoluble formulation. The curve in the figure shows an approximate curve of the solubilized formulation (◯) plotted. In the preparation prepared at the ratio of the upper part of the curve, it is presumed that GL is solubilized. When only purified water was used as the solvent, a large amount of solvent was required. However, when 2% ammonium carbonate was contained, the GL was sufficiently high even if the purified water content was about 1%. Solubilized. That is, it was found that the water content can be reduced as the ammonium carbonate content increases. Therefore, when an ammonium salt and water are used as the solvent, the oral GL solubilized preparation of the present invention is suitable for encapsulation of the water content in the preparation by appropriately selecting the content ratio of the ammonium salt and water. It is clear that it can be adjusted arbitrarily.

  As is clear from the above results, GL and / or a pharmaceutically acceptable salt thereof, a glycerin fatty acid ester, and a solvent in which 2% by mass or more of the GL and / or a pharmaceutically acceptable salt thereof can be dissolved. Are mixed and stirred to obtain an oral GL-solubilized preparation in a clear liquid form in which a high concentration of GL and a salt thereof are dissolved.

  As is clear from the results of Reference Examples 1 and 2, the GL trialkali salt can be dissolved in the monoglycerin fatty acid ester without using a solvent.

Existing GL preparations have been used in clinical settings in Japan for over 60 years and have been highly evaluated. However, in order to provide better medical care in the current advanced medical treatment and aging society, further improvement of the existing GL preparation is required.
The present invention is provided as a novel oral GL-solubilized preparation having a therapeutic effect equivalent to the intravenous GL preparation currently used. If an oral preparation with a high therapeutic effect can be prescribed, injections and hospital visits can be minimized, and improvement in patient QOL can be expected. In addition, the burden on the medical staff who has injected the patient is reduced, which is medically effective. Furthermore, compared with the treatment using interferon (IFN) which is a biological product currently used in the treatment of viral chronic liver disease, the oral GL solubilized preparation of the present invention is inexpensive because it is easy to produce. It is possible to reduce the medical expenses that the country and individuals bear, and it is also economically beneficial. Therefore, the present invention is judged to be a technology that can satisfy many social needs.

In Test Example 1, the GL-solubilized preparation for oral use in which the solubility of GL was examined was plotted with ◯ as the solubilized formulation and as ■ as the insoluble formulation. The vertical axis represents ammonium carbonate content (%), and the horizontal axis represents purified water content (%). The curve in the figure shows an approximate curve of the solubilized formulation (◯) plotted.

Claims (8)

  It contains glycyrrhizin and / or a pharmaceutically acceptable salt thereof, a glycerin fatty acid ester, and a solvent in which 2% by mass or more of the glycyrrhizin and / or a pharmaceutically acceptable salt thereof can be dissolved. Oral glycyrrhizin solubilized preparation.   The oral glycyrrhizin-solubilized preparation according to claim 1, wherein the glycerin fatty acid ester is a monoglycerin fatty acid ester.   The solubilized oral glycyrrhizin according to claim 1 or 2, wherein the solvent is at least one selected from the group consisting of water, aqueous ammonia, aqueous ammonium salt solution, aqueous alkaline solution, alkaline salt solution, polyethylene glycol, propylene glycol, and glycerin. Formulation.   The oral glycyrrhizin-solubilized preparation according to any one of claims 1 to 3, wherein the solvent is aqueous ammonia and / or an aqueous ammonium salt solution.   The oral glycyrrhizin-solubilized preparation according to claim 1, wherein the glycerin fatty acid ester is a monoglycerin fatty acid ester, the solvent is aqueous ammonia and / or an aqueous ammonium salt solution, and further contains fats and oils and / or fatty acids. .   The content of the glycyrrhizin and / or pharmaceutically acceptable salt thereof is 1 to 40% by mass, the content of the glycerin fatty acid ester is 30 to 90% by mass, and the content of the solvent is the glycyrrhizin. The glycyrrhizin solubilized preparation for oral use according to any one of claims 1 to 5, wherein the glycyrrhizin is a glycyrrhizin content of 0.1 to 100% by mass with respect to the total content of glycyrrhizin and pharmaceutically acceptable salts thereof.   The oral glycyrrhizin-solubilized preparation according to any one of claims 1 to 6, wherein the dosage form is a capsule.   Glycyrrhizin and / or a pharmaceutically acceptable salt thereof, a glycerin fatty acid ester, and a solvent capable of dissolving 2% by mass or more of the glycyrrhizin and / or a pharmaceutically acceptable salt thereof are mixed and stirred, and the glycyrrhizin and A method for producing an oral glycyrrhizin-solubilized preparation characterized by dissolving a pharmaceutically acceptable salt thereof.

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