JP2010235549A - Gorinsan extract-containing pharmaceutical formulation - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a gorinsan (crude drug preparation) extract-containing pharmaceutical formulation exhibiting excellent action of anti-inflammation of bladders and action of suppressing urinary frequency caused by inflammation of a bladder. <P>SOLUTION: The gorinsan extract-containing pharmaceutical formulation contains a daily dose unit of (A) 75-300 mg of baicalin and (B) 10-75 mg of glycyrrhizinic acid or its salt. <P>COPYRIGHT: (C)2011,JPO&INPIT

Description

  The present invention relates to a Gokansan extract-containing preparation containing baicalin and a predetermined amount of glycyrrhizic acid or a salt thereof.

  Goreisan is an inflammatory disease of the bladder and urethra, and is a herbal medicine prescription that has been suggested to be widely used in less severe cases. More specifically, Goreisan is an inflammatory disease of the bladder and urethra that has an uncomfortable feeling in the bladder, urethra, etc., with which urine becomes closer, the amount of urine is reduced once, urination pain and residual It is used as a therapeutic agent for producing urinary sensation (see, for example, Non-Patent Documents 1 and 2). Goreisan is known to be widely used for various symptoms of inflammatory diseases of the bladder and urethra, but the target is limited to those with mild symptoms, that is, the effect is insufficient. There was a problem.

  In the field of Kampo, there is a provision for the proportion of crude drugs used as raw materials, but there is no clear provision for the amount of each active ingredient contained in the Kampo preparation that is finally obtained. . Therefore, there is a problem that the amount of the active ingredient in the prepared Chinese medicine preparation is not kept constant because the quality of the raw material itself varies depending on the production area, harvest time, etc. of the raw material. In addition, the amount of active ingredients extracted from the raw crude drug varies greatly due to adjustment of the extraction conditions, and these operations are left to the discretion of the formulator. (See, for example, Non-Patent Documents 3 and 4).

  From these backgrounds, it has been demanded to be able to stably provide Goreisan that is excellent in the inflammation suppression effect of the bladder and the like, and Goreisan that can sufficiently exhibit such an effect.

Clinical Application Vol.9, No.5 (1990) 15-17 Monthly Pharmaceutical Affairs Vol. 29, No. 9 (1987) pp. 177-179 Monthly Pharmaceutical Affairs Vol. 27, No. 6 (1985) 1927-1933 Clinical Pharmacology 21, 1, (1990) pp. 305-310

  The main object of the present invention is to provide a Goreisan extract combination preparation having an excellent therapeutic effect on bladder inflammation due to bacterial infection and frequent urination associated with bladder inflammation, and a method for producing the Gokansan extract combination preparation. With a purpose. It is another object of the present invention to provide a quality control method for stably supplying a Gokansan extract-containing preparation capable of producing the above-described effects.

  As a result of intensive studies to solve the above-mentioned problems, the present inventors have found that Gokansan extract combination preparation containing baicalin and glycyrrhizic acid in a specific combination ratio is an inflammatory disease of the bladder caused by bacterial infection It has been found that it has a remarkably excellent therapeutic effect. The present invention has been completed as a result of further studies based on these findings.

The present invention provides the following Gokansan extract blended preparation and a method for producing the same.
Item 1.1 Gokansan extract combination preparation containing (A) baicalin 75 to 300 mg and (B) glycyrrhizic acid or its salt 10 to 75 mg per daily dosage unit.
Item 2. Item 5. The Goreisan extract-containing preparation according to Item 1, which is used for treatment of cystitis.
Item 3. A method for producing a formulation containing Goreisan extract having an action to suppress inflammation of the bladder and an effect of suppressing frequent urination based on inflammation of the bladder, baicalin and glycyrrhizic acid or a salt thereof in the preparation per daily dosage unit But,
(a) Baicalin 75-300 mg,
(b) 10 to 75 mg in terms of glycyrrhizic acid,
The method characterized by adjusting so that it may become.
Item 4. It is a quality control method of Goreisan extract combination preparations having an action of suppressing inflammation of the bladder and an action of suppressing frequent urination based on inflammation of the bladder,
Measure the amount of (A) baicalin and (B) glycyrrhizic acid in the formulation,
Baicalin and glycyrrhizic acid or a salt thereof in the preparation per daily dosage unit,
(a) Baicalin 75-300 mg, and
(b) 10 to 75 mg in terms of glycyrrhizic acid,
As an index,
A method for determining, based on the indices (a) and (b), that the preparation has an action of suppressing inflammation of the bladder and an action of suppressing frequent urination based on inflammation of the bladder.

  The Goreisan extract-containing preparation of the present invention contains a specific amount of baicalin and glycyrrhizic acid, and is an excellent preparation for suppressing inflammation of the bladder due to bacterial infection and frequent urination associated with inflammation of the bladder. In addition, the preparation of the present invention is also excellent in the action of improving symptoms such as residual urine sensation and urination pain associated with inflammation of the bladder due to bacterial infection. Therefore, the Gokansan extract combination preparation of the present invention has a remarkably excellent therapeutic effect even for cystitis, which has not been expected to improve the symptoms sufficiently. In addition, the preparation of the present invention does not affect the amount of urination and can be safely applied.

  Furthermore, according to the method for producing a Gokansan extract blended preparation of the present invention, a Gokansan extract blended preparation exhibiting the above excellent effects can be easily prepared.

  In addition, according to the quality control method of the Gokansan extract blended preparation of the present invention, it is possible to stably supply the Gokansan extract blended preparation that exhibits the above-mentioned excellent effects using the contents of baicalin and glycyrrhizic acid as indices. is there.

1. Gokansan extract combination preparation The Gokansan extract combination preparation of the present invention contains Gokansan extract, and (A) component: baicalin and (B) component: glycyrrhizic acid or a salt thereof in the final preparation have a predetermined compounding amount. It is characterized by being satisfied. Hereinafter, each component will be described in detail.

Component (A): Baikalin Baikalin is a flavone derivative contained in the root of the cutworm family Scutellaria baicalensis Georgi (Ogon), and is known to have a gallant, diuretic and anti-inflammatory action.

Component (B): Glycyrrhizic acid Glycyrrhizic acid is a component contained in licorice (scientific name: Glycyrrhiza) and is known to have an anti-inflammatory effect. In the present invention, a pharmaceutically acceptable salt of glycyrrhizic acid can also be used as the component (B). Examples of such salts include dipotassium glycyrrhizinate, ammonium glycyrrhizinate, and sodium glycyrrhizinate. In licorice, glycyrrhizic acid exists in both free acid and salt forms. The content when a salt of glycyrrhizic acid is used as the component (B) of the present invention is converted as glycyrrhizic acid.

Plant material five淋散extract five淋散extract, Scutellaria root, licorice, peony, Takusha, Bukuryou, pottery, Sanshin, rehmannia, Mokutsuu, a talc and Shazenshi.

These plant materials have specified use sites according to the Japanese Pharmacopoeia. The preparation of Gojosan that can be used in the present invention is described in "Guide to General Kampo Prescription" (supervised by the Pharmaceutical Affairs Bureau of the Ministry of Health and Welfare, edited by the National Pharmacopoeia Specialist Committee, published by Yakuho Hokpo (published April 1, 1975) )).

  For example, according to the “Guide to General Kampo Prescription”, the ingredients and the amount (dry weight) are as follows: Bukuryu 5-6, Toki 3, Ogon 3, Ganzo 3, Peonies 2, Sanshishi 2, Diou 3, Takusha 3, Mokutsu 3, Kaseki 3 and Shazenshi 3 are extracted with 10 times the weight of hot water, then concentrated to 1/2 volume and the solids removed (extract) Used.

  In addition, there are some components and component ratios that are slightly different and production methods that are slightly different, such as not containing ziou, mokutsu, kasseki, and chazenshi, but these differences are particularly significant in the Gokansan extract used in the present invention. Without limitation, any are included.

  The Gokansan extract used in the present invention is described in the Kampo-related letters that are currently in common use, as defined in the “Basic Handling Policy of Kampo Preparations” established by the Kampo Medicine Research Committee. Chinese herbal prescriptions (herbal medicine blends) and extracts and extract powders obtained from these Chinese herbal prescriptions are included. That is, in the present invention, Gokansan extract may use the extract (extract form) obtained by the above preparation method, or use the so-called extract powder (extract powder form) in which the extract is formulated by a conventional method. Also good. Usually, the extract powder form of Gojosan is used for convenience. As a method for preparing Gokansan extract powder, for example, the extract obtained by the above-described method is concentrated under reduced pressure, and dried extract is obtained by a spray drying method. For example, silicic anhydride, starch, etc.) may be added to obtain an adsorption powder.

  The Gokansan extract contains (A): baicalin derived from Ogon, and (B) derived from licorice: glycyrrhizic acid or a salt thereof. The preparation of the present invention comprises (A) component: 75 to 300 mg, preferably 80 to 250 mg, more preferably 80 to 150 mg per unit daily dosage of the formulation containing baicalin and Gokansan extract; and (B) component: glycyrrhizic acid Is prepared so as to contain 10 to 75 mg, preferably 10 to 40 mg, per daily dosage unit of the Gokansan extract combination preparation. By defining the contents of (A) baicalin and (B) glycyrrhizic acid within this range in Goreisan, it is effective in suppressing bladder inflammation due to bacterial infection, and is effective in suppressing frequent urination associated with bladder inflammation. Since it is also excellent in improving symptoms such as urinary sensation and micturition pain, it can be made into an excellent preparation for treating cystitis.

  The content ratio of the component (A) and the component (B) in the preparation of the present invention is not particularly limited as long as the effect of the present invention is exhibited, but the content ratio of the component (A) and the component (B) in the preparation is ( The amount of component (B) is 0.03 to 1 part by weight, preferably 0.04 to 0.5 part by weight, based on 1 part by weight of component A).

  The contents of the component (A) and the component (B) in the Gokansan extract-containing preparation of the present invention can be measured and confirmed by a conventionally known method such as HPLC. Specifically, baicalin follows the 15th revision of the Japanese Pharmacopoeia Manual (herbal medicine, etc.) D-71-D-76 “Ougon” quantitative method, and glycyrrhizic acid or its salt is the 15th revision. It can be measured in accordance with the quantitative method described in the Japanese Pharmacopoeia Manual (herbal medicines, etc.) D-142-D-151, “Palliform”.

  The preparation of the present invention contains 75 to 300 mg of (A) baicalin and 10 to 75 mg of (B) glycyrrhizic acid per daily dosage unit, and the blending ratio of component (B) to 1 part by weight of component (A) is 0.03. It is preferable that the ratio of (A) baicalin is 80 to 250 mg and (B) glycyrrhizic acid is 10 to 40 mg, and the blending ratio of component (B) to 1 part by weight of component (A) is preferable. Is more preferably 0.04 to 0.5. By satisfying such a blending ratio, the effect of the present invention is further remarkably exhibited.

  As long as the preparation method of Gokansan extract is as described above, the (A) component and the (B) component may be used as long as the (A) component and the (B) component satisfy the above contents and content ratios. Each condition may be adjusted in order to keep the content and content ratio in the range. Specifically, adjust the shearing method of Ogon and licorice (cut finely or roughly), select the production area and harvest time of Ogon and licorice, adjust the extraction solvent, adjust the extraction temperature, adjust the extraction time Examples of the method include increasing / decreasing the number of extractions, selecting a concentration method and a drying method, and mixing the Gokansan extract with a thick component (A) and the component (B) with a thin Gokansan extract. The preparation of the present invention is prepared by adjusting the yield and content of the component (A) and the component (B) by these methods, and confirming the contents of both components in the obtained Gokansan extract. Can do. In addition, for example, pure baicalin or glycyrrhizic acid (or a salt thereof) that is commercially available from Wako Pure Chemical Industries, Ltd. so that the components (A) and (B) have the above contents and content ratios. Products may be externally added.

(1-2) Other components The preparation of the present invention can be prepared into various dosage forms according to conventionally known methods in addition to the above-mentioned Goreisan extract, together with pharmaceutically acceptable excipients, carriers and the like. it can. Examples of the dosage form include liquid preparations (including suspensions) such as liquids (including syrups), tablets, pills, powders, fine granules, granules, capsules (including soft capsules), etc. An oral preparation in the form of a solid preparation can be mentioned.

  When the preparation of the present invention is a liquid preparation, it can be stored frozen, or it may be stored after removing water by lyophilization or the like. Freeze-dried preparations, dry syrups and the like are used by adding sterilized water and dissolving them again at the time of use.

  When the preparation of the present invention is prepared as a solid agent, for example, in the case of a tablet, a carrier conventionally known in this field can be widely used. Examples of such carriers include excipients such as lactose, sucrose, sodium chloride, glucose, urea, starch, calcium carbonate, kaolin, silicic acid; water, ethanol, propanol, simple syrup, glucose solution, starch solution, gelatin Binders such as solution, carboxymethylcellulose, shellac, methylcellulose, potassium phosphate, polyvinylpyrrolidone, crystalline cellulose, hydroxypropylcellulose, hypromellose, carmellose calcium, sodium alginate; dry starch, agar powder, laminaran powder, sodium bicarbonate, poly Disintegrating agents such as oxyethylene sorbitan fatty acid esters, sodium lauryl sulfate, stearic acid monoglyceride, starch, crospovidone, povidone, low-substituted hydroxypropylcellulose; Disintegration inhibitors such as allin, cocoa butter and hydrogenated oil; absorption accelerators such as quaternary ammonium salts and sodium lauryl sulfate; humectants such as glycerin; adsorbents such as starch, lactose, kaolin, bentonite and colloidal silicic acid A lubricant such as purified talc, stearate, boric acid powder and polyethylene glycol can be used. Further, the tablets can be made into tablets with ordinary coatings as necessary, for example, sugar-coated tablets, gelatin-encapsulated tablets, enteric-coated tablets, film-coated tablets, double tablets, and multilayer tablets. Further, the above-mentioned Gokansan extract can be filled into a conventionally known capsule made of gelatin, pullulan, starch, gum arabic, hydroxypropylmethylcellulose (HPMC) or the like as a raw material to form a capsule.

  Moreover, when preparing in the form of a pill, a conventionally well-known thing can be widely used as a support | carrier in this field | area. Examples thereof include excipients such as glucose, lactose, starch, cacao butter, hydrogenated vegetable oil, kaolin and talc, binders such as gum arabic powder, tragacanth powder, gelatin and ethanol, and disintegrants such as laminaran and agar. Can be used.

  In addition to the above, for example, surfactants, absorption promoters, adsorbents, fillers, preservatives, stabilizers, emulsifiers, solubilizers, salts that regulate osmotic pressure, dosage units of the preparations obtained It can be appropriately selected and used according to the form.

  Moreover, you may contain other active ingredients, such as an amino acid, vitamins, and inorganic salts. Examples of other active ingredients include valine, leucine, isoleucine, threonine, methionine, phenylalanine, tryptophan, lysine, glycine, alanine, asparagine, glutamine, serine, cysteine, cystine, tyrosine, proline, hydroxyproline, aspartic acid, glutamic acid Amino acids such as hydroxy lysine, arginine, ornithine and histidine; vitamins such as vitamin A1, vitamin A2, carotene, lycopene (provitamin A), vitamin B6, vitamin B1, vitamin B2, ascorbic acid, nicotinamide and biotin; Examples thereof include alkali metal salts such as sodium chloride and potassium chloride, and inorganic salts such as citrate, acetate and phosphate.

  The preparation of the present invention can be prepared in various forms such as powders, fine granules, granules, tablets, pills, capsules and the like using conventional methods in the art. It can be obtained by tableting after adding appropriately the excipients and the like necessary for obtaining Goreisan extract and other tablets with adjusted content of component and component (B), mixing and dispersing well. In addition, when preparing a powder, the additives necessary for obtaining Gokansan extract and other powders prepared by adjusting the components (A) and (B) are appropriately added, and powdered by a suitable method. Can be obtained.

  The daily dose when the Gosangsan extract formulation of the present invention is prepared into various dosage forms can be appropriately changed according to the patient's condition and the degree of symptoms, but for each adult, it is converted to the amount of baicalin. 75 to 300 mg and 10 to 75 mg in terms of the amount of glycyrrhizic acid. The preparation of the present invention is usually used in the form of oral administration divided into 1 to 3 times a day. The dose time is not particularly limited, but is preferably before or between meals.

  The Goreisan extract combination preparation of the present invention characterized by containing the components (A) and (B) in a predetermined amount is a remarkably excellent effect of suppressing bacterial inflammation of the bacterial bladder, and accompanying frequent urination Demonstrate the effect. Furthermore, since the preparation of the present invention suppresses bacterial bladder inflammation, it can also improve symptoms such as residual urine sensation and micturition pain associated with bacterial bladder inflammation. Based on these actions, the preparation of the present invention exhibits a particularly excellent effect particularly in the treatment of cystitis.

2. Method for Producing Gogosan Extract Combination Preparation The method for producing Gokansan extract combination preparation of the present invention is a method for easily preparing the above-mentioned Gokansan extract combination preparation (may be abbreviated as “production method of the present invention”). is there).

That is, the present invention relates to a method for producing a Goreisan extract combination preparation having an action of suppressing inflammation of the bladder and an action of suppressing frequent urination based on inflammation of the bladder, and baicalin in the preparation per daily dosage unit. And glycyrrhizic acid or a salt thereof,
(a) Baicalin 75-300 mg,
(b) 10 to 75 mg in terms of glycyrrhizic acid,
A method characterized by adjusting to be provided.

  The content of each component in the Gokansan extract combination preparation obtained by the production method of the present invention can be measured and confirmed according to the method described in the Japanese Pharmacopoeia as described above.

  As a result of the measurement, when the content and content ratio of the component (A) and the component (B) in the preparation are out of the above range, for example, a concentrated Gokansan extract exceeding the predetermined content, and the predetermined content You may adjust so that it may become the content of this invention by mixing the thin Gojosan extract which is less than quantity.

  Other components such as Gosansan, baicalin, glycyrrhizic acid and carrier are as described above.

3. The present invention relates to a method for controlling the quality of Goreisan extract, which is capable of stably providing a Gosansan extract-containing preparation having an action of suppressing inflammation of the bladder and a function of suppressing frequent urination based on inflammation of the bladder. Provided is a quality control method for the combined preparation (hereinafter sometimes abbreviated as “quality control method of the present invention”).

In the quality control method of the present invention, (A) baicalin and (B) glycyrrhizic acid or a salt thereof in the Gokansan extract combination preparation are measured by the method described in the above Japanese Pharmacopoeia, and the above-mentioned per day dosage unit. Baicalin and glycyrrhizic acid or a salt thereof in the preparation are
(a) Baicalin 75-300 mg, and
(b) 10 to 75 mg in terms of glycyrrhizic acid,
As an index,
This is a method for determining, based on the indicators (a) and (b), that the preparation has an action of suppressing inflammation of the bladder and an action of suppressing frequent urination based on inflammation of the bladder.

  That is, if the measured content of baicalin and glycyrrhizic acid is within the ranges of the indicators (a) and (b), the Gosansan extract combination preparation is based on excellent bladder inflammation suppression effect and bladder inflammation It has an action to suppress frequent urination, and the preparation can be judged as a compatible product. On the other hand, when the contents of baicalin and glycyrrhizic acid are out of the ranges of the indicators (a) and (b), the preparation is determined to be incompatible. If it is determined to be incompatible, for example, externally adding the component (A) and / or the component (B), etc. It can be.

  By the quality control method of the present invention, it is possible to stably supply to the market a Goreisan extract combination preparation having an action of suppressing inflammation of the bladder and an action of suppressing frequent urination based on inflammation of the bladder.

Hereinafter, although a test example etc. are shown and this invention is demonstrated in detail, this invention is not limited to these.
<Production and evaluation test of cystitis model animal>
(1) Cyclophosphamide (CP) 200 mg / kg was intravenously injected into test animals (rabbit (JW, female) 7 weeks old) for 3 days.
(2) At the second CP injection, 1 mL of E. coli 10 ⁶ / mL E. coli solution was injected into the bladder to prepare cystitis model rabbits (n = 5 / group).
(3) From the 3rd day of CP treatment, the following preparations were orally administered twice a day (morning and evening).
(4) The above administration was continued for 6 days.
(5) On the last administration day, frequent urination suppression and urine volume were measured based on the following indices.
(6) Necropsy was performed on the day after the final administration day, the properties of the bladder mucosa were observed, and the degree of inflammation suppression was scored.

  In addition, the animal group which has not performed any treatment was made into the normal group (n = 5), and the animal group which administers only a physiological saline with respect to a cystitis model animal was made into the negative control group (n = 5).

  Each formulation was administered as described in Tables 3 and 4. Specifically, the values shown in Tables 3 and 4 are the daily dose (Xmg / kg / day) per body weight (kg) of the test animal. The daily dose was divided into two equal parts and orally administered twice a day (morning and evening).

  In addition, when converting to human doses, considering species differences between pharmacological effects and pharmacokinetics, whole animals (gerbils) based on the CRC textbook Training Guidelines for CRC Certified by the Japanese Clinical Pharmacological Society Dose Xmg / kg / day was converted to human dose Xmg / body / day.

<Preparation of dosage formulation>
In Examples 1 to 17 and Comparative Examples 1 to 6, herbal medicines shown in Table 1 were cut, extracted and dried to obtain extract powders. The obtained extract powder was suspended in 30 mL of distilled water to prepare an administration preparation.

  A specific preparation method is to extract 1 part by weight of a mixture of herbal medicines shown in Table 1 at about 95 ° C. for 1 hour using 10 parts by weight of Japanese Pharmacopoeia “Normal Water” and centrifuge to obtain an extract. , “Gokansan extract”, which was concentrated under reduced pressure and dried using spray drying (drying with a spray dryer was performed by dropping the extract into an atomizer with a rotational speed of 10,000 rpm and supplying hot air at 150 ° C. Used).

  The method for confirming the contents of the component (A) and the component (B) in the Gokansan extract obtained is as follows.

(A) Component quantification method After thoroughly extracting 2.0 g of Gokansan extract with methanol, follow the quantification method described in the 15th revised Japanese Pharmacopoeia (Drugs, etc.) D-71-D-76 “Ougon” Quantified.

  The column was COSMOSIL “5C18-MS-II” (inner diameter 4.6 × 150 mm) (manufactured by Nacalai Tesque), the column temperature was 40 ° C., and the mobile phase was diluted 146 times with distilled water (sum) Absorbance at 277 nm was measured with an ultraviolet absorptiometer (manufactured by Shimadzu Corporation) using a mixed solution in which 18: 7 was used by Kojun Pure Chemical Industries, Ltd. and acetonitrile (manufactured by Wako Pure Chemical Industries, Ltd.).

(B) Component quantification method After thoroughly extracting 0.5 g of Gokansan extract with dilute ethanol, the 15th revised Japanese Pharmacopoeia Manual (herbal medicine, etc.) D-142-D-151 pages “Kanzo” quantification method Quantified according to

  The column was COSMOSIL “5C18-MS-II” (inner diameter 4.6 × 150 mm) (manufactured by Nacalai Tesque), the column temperature was 20 degrees, and the mobile phase was diluted 15 times with distilled water to acetic acid (Wako Pure) Absorbance at 254 nm was measured with an ultraviolet absorptiometer (manufactured by Shimadzu Corporation) using a mixture of 3: 2 from Yakuhin Co., Ltd. and acetonitrile (manufactured by Wako Pure Chemical Industries, Ltd.).

Adjustment of the content of component (A) and component (B) After quantifying component (A) and component (B) in the obtained extract, if the extraction amount is small, finely chop and the amount of extraction is large In some cases, an extract having a desired content was obtained by roughly chopping. When the extract does not have the desired content, the pure product of the component (A) and / or the component (B) ((A) component: “dipotassium glycyrrhizinate”, (B) component: “ "Baicalin" (both manufactured by Wako Pure Chemical Industries, Ltd.)) was added for adjustment.

(Formulation)
The extractability of the obtained extract powder was evaluated from its properties.
◎: Not sticky ○: Slightly sticky △: Slightly sticky ×: Sticky

<Evaluation indicators and results>
(Inhibition of inflammation)
Bleeding mucosa-like bleeding and edema were compared with the normal group and scored to calculate the average score.
(bleeding)
0 points: no bleeding (normal group)
1 point: Very mild bleeding (recognized or scattered)
2 points: clear bleeding site 3 points: moderate to severe bleeding 4 points: crimson intense bleeding spots, mild ulcers (injuries deep)

(edema)
0 point: No edema (normal group)
1 point: Very mild edema (appreciated only)
2 points: Clear edema (can be clearly distinguished from surroundings)
3 points: moderate edema (swells about 1 mm)
4 points: Strong edema (swells over 1 mm, spreads around)

  As a result of the above evaluation, the evaluation results (average score) of bleeding and edema in the group of animals administered with Examples 1 to 17 were all reduced by 1.5 or more compared to the negative control group. On the other hand, the average score of the group administered with Comparative Example 10 (levofloxacin hydrate) remained at a decrease of 1.4 relative to the negative control group. That is, it was shown that the product of the present invention has a higher effect in suppressing inflammation of the bladder than the antibiotic (levofloxacin hydrate) that has been conventionally used as a therapeutic agent for cystitis.

(Inhibition of frequent urination)
The number of urination was measured from 10:00 am to 6:00 pm on the last administration day.

  The number of urinations was 1.5 in the normal group and 2.5 in the negative control group. From this result, in order to obtain a normal range, the number of urinations was required to be reduced once (2.5 times−1.5 times = 1 time) relative to the negative control group.

  From the measurement results, the average number of urinations in each group to which the preparations of Examples 1 to 17 were administered decreased 1.5 times compared to the negative control group. A similar decrease in the number of urinations was also observed in the group administered with Comparative Example 10 (levofloxacin hydrate). In addition, when the average number of urinations decreased more than once compared with the negative control group, it was determined as ◯, and when the average number of urinations increased or decreased less than once compared with the negative control group, it was determined as x. The determination results are shown in Tables 3 and 4.

(Urine volume)
The urine volume may be changed due to the adverse effect of the drug whose urination volume was measured from 10:00 am to 6:00 pm on the last administration day, and such a preparation was inferior in safety. In any animal group, there was no change in urine output in urine volume (no significant difference between two groups (p <0.05)).

(safety)
The condition of the test animals during the test period was observed, and safety was evaluated according to the following criteria.
○: No physical condition was found and the patient was healthy. △: The body weight was decreased.

(Comprehensive evaluation)
A comprehensive evaluation was performed according to the following indices, combining the results of (1) preparation, (2) inflammation suppression effect, and (3) other evaluations.

  In addition, if the result of the said comprehensive evaluation is other than x, it is a range which is satisfactory practically.

  The results obtained by the above evaluation are shown in Tables 3 and 4 below. Here, regarding inflammation suppression, the average score of bleeding and edema in the negative control group was “3.8”.

  From Tables 3 and 4, the Goreisan extract combination preparations (Examples 1 to 17) containing 75 to 300 mg baicalin and 10 to 75 mg glycyrrhizic acid are effective in bladder inflammation and frequent urination, which are typical symptoms of cystitis. On the other hand, it was shown that there was an excellent improvement effect. Moreover, the Gokansan extract combination preparation (Examples 4-17) containing 80-300 mg of baicalin and 10-75 mg of glycyrrhizic acid showed an excellent anti-inflammatory effect. Furthermore, the Gokansan extract preparations (Examples 4 to 14) containing 80 to 250 mg baicalin and 10 to 40 mg glycyrrhizic acid were able to reduce the burden on patients at the time of taking and were excellent in preparation properties. In particular, the Gokansan extract combination preparations (Examples 4 to 12) containing 80 to 150 mg baicalin and 10 to 40 mg glycyrrhizic acid had sufficient safety and more desirable formulation. In addition, regarding the amount of urination, any of the preparations of Examples was not different from the normal group, and it was shown that the preparations do not affect the urine volume and do not deteriorate the QOL.

  As shown in Table 4, among the components (A) and (B), the preparation containing only (A) component: baicalin (Comparative Example 1) has an insufficient inflammation-inhibiting effect, and the component (B): glycyrrhizin In the preparation containing only acid (Comparative Example 2), the frequent urination inhibitory effect was insufficient.

  Moreover, even if it is a formulation containing both (A) component and (B) component, the formulation (comparative examples 3-8) in which the content of each component is outside the predetermined range is a formulation, safety, It has been shown that sufficient effects cannot be obtained in at least one of suppression of inflammation or frequent urination. In Comparative Examples 7 and 8, the extract powder was sticky, and thus could not be formulated.

  Furthermore, it was shown that the symptoms were not sufficiently improved even when walnut extract (Comparative Example 9) or levofloxacin hydrate (Comparative Example 10), which has been conventionally used as a therapeutic agent for cystitis, was used. .

  In summary, when taking a large amount of the active ingredient, there is a tendency that the effect on the disease state becomes remarkable, but according to the Goreisan extract combination preparation of the present invention, the content of the active ingredient is not increased. , By containing a specific amount of baicalin and glycyrrhizic acid, it is excellent in formulation and safety, and for various symptoms of cystitis (senile urination, residual urinary sensation, etc.) for which treatment effects have not been obtained sufficiently in the past It was also shown that the treatment effect can be remarkably improved.

[Prescription example]
Table 5 below shows Formulation Examples 1-9. Manufacture of the Gokansan extract combination preparation in each formulation example is as follows.

A Gokansan extract powder having the following contents of the component (A) and the component (B) was obtained. The obtained extracts (a) to (h) were used according to Formulation Examples 1 to 9. According to a conventional method, Formulation Examples 1 to 6 were tablets, and Formulation Examples 7 to 9 were powders.
(a) Component (A): 30.0 mg / g Component (B): 4.0 mg / g
(b) Component (A): 20.0 mg / g Component (B): 20.0 mg / g
(c) Component (A): 30.0 mg / g Component (B): 16.0 mg / g
(d) Component (A): 32.0 mg / g Component (B): 4.0 mg / g
(e) Component (A): 32.0 mg / g Component (B): 8.0 mg / g
(f) (A) component: 32.0mg / g (B) component: 16.0mg / g
(g) Component (A): 83.3mg / g Component (B): 3.3mg / g
(h) Component (A): 83.3mg / g Component (B): 12.3mg / g

Claims (4)

A Gokansan extract formulation containing (A) baicalin 75 to 300 mg, (B) glycyrrhizic acid or its salt 10 to 75 mg per daily dosage unit. 5. The Goreisan extract-containing preparation according to claim 1, which is used for treatment of cystitis. A method for producing a formulation containing Goreisan extract having an action to suppress inflammation of the bladder and an effect of suppressing frequent urination based on inflammation of the bladder, baicalin and glycyrrhizic acid or a salt thereof in the preparation per daily dosage unit But,
(a) Baicalin 75-300 mg,
(b) 10 to 75 mg in terms of glycyrrhizic acid,
The method characterized by adjusting so that it may become. It is a quality control method of Goreisan extract combination preparations having an action of suppressing inflammation of the bladder and an action of suppressing frequent urination based on inflammation of the bladder,
Measure the amount of (A) baicalin and (B) glycyrrhizic acid in the formulation,
Baicalin and glycyrrhizic acid or a salt thereof in the preparation per daily dosage unit,
(a) Baicalin 75-300 mg, and
(b) 10 to 75 mg in terms of glycyrrhizic acid,
As an index,
A method for determining, based on the indices (a) and (b), that the preparation has an action of suppressing inflammation of the bladder and an action of suppressing frequent urination based on inflammation of the bladder.