JPS5849310A - Preparation of useful glycyrrhizin solution - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

[Detailed description of the invention]

Honkaku is for 4I in rich m, lycyrrhizin #IW
L'41 - This is about how to wear your knees. The active ingredient crityrrhizin has excellent anti-inflammatory effects and has been used as an anti-allergic agent.

[It has been highly praised. Recently, it has been demonstrated at home and abroad that it has a remarkable medicinal effect in improving liver function in chronic hepatitis diseases, and it has also been used as a 1# promoter of r-interferon. Therefore, there is an increasing demand today to reduce the amount of glycyrrhizin, which is stable. ζ- Let us briefly discuss the hierarchy of glycyrrhizin and its salts. Glycyrrhizin (Glycyrrhizin #l) is the diglucuron al of glycyrrhizin! 1, which is a tribasic acid, has a high melting point and is soluble in dilute ethanol and ether, and is castable even in water. The monosalt of glycyrrhizin, like glycyrrhetinth, exhibits a corrugated appearance, and its surface exhibits an agar-like appearance in water, and it dissolves at room temperature, but the monosalt precipitates in a gel-like form as the volume decreases by 1ml. . However, Ji and TriaK
Then, the water becomes KQT-114. Glycyrrhidene #i decomposes into glycyrrhetinic acid and glucuronide by acid decomposition, and turns yellow when heated with alkali. Add a glycyrrhizin bath solution #14 to the edge of the container at room temperature using 1 m water and 0 glycyrrhizin or its monosalt as a raw material.
# It is difficult to compensate for this.Usually, Gliderritin is used at a concentration of 0.1~2.0113 in water and Henshokura's alkaline solution, stirred and heated, and made isotonic. The reaction between glycyrrhizin and alkali occurs when alkali is added at high temperature or at high temperature. Currently, the raw materials for glycyrrhizin solutions are high purity glycyrrhizin and its mono salts (ammonium, sodium, potassium)6, Alkaline salts are not used medicinally because they are often colored due to the alkali IJM used during production.Also, glycyrrhizin is particularly sensitive to heat, such as glucuronic acid, ascorbyl, or cysteine. If you wish to meet a prefectural wisdom, you must be careful, or you may end up with a sudden sinking or coloring. Change j[4I
:Avoiding the heating process that tends to occur, this method is extremely effective for easily mass-producing glycyrrhizin solution at -Kiritomi temperature.
Sakaki conducted extensive research on the advantageous solubility stabilizer for the main drug. As a result, it was found that urea and sodium benzoate were suitable as bath dissolving agents for glycyrrhizin or its salts◎ In other words, these dissolving agents were used to make a bath solution for KIHI.
Glycyrrhiza/or its salt can be easily added at room temperature.
IC1! As a result, a certain acidic bath solution is obtained. Next, in proper pu #1 grinding, add 1 llliL of pu to 6 to 7 to avoid becoming alkaline, and add water to the specified glycyrrhizic concentration (0,1-2,0 whisper) depending on the cost. [If diluted, the purpose of this Jll method can be coupled. In the book, this one-bath detoxifying agent Fi will be described later, and the violet V of the ubiquitous member! By using (urea 1-3) sodium benzoate 1-3-] glycyrrhizin, equidominance of the bath solution can be obtained, so there is no need to limit the concentration of the additive to 1%. What's more, this ammolytic agent is safe for living organisms, and its lff1It as an excipient for pharmaceuticals is large.Next, the solubility of IJum for glycyrrhizin compounds (approximately) is expressed as follows: Like. It is imperative to carefully monitor the performance of urea in order to reduce the total dissolution of urine IA fluid into the main drug, clityrrhizin. As shown in the table above, there is a large difference between the baths of 50- and 33.3-, which are close to the j1 phase bath liquid. 33.3 - Below @[)4
Therefore, it is unethical for the purpose of the mainstream.
The IJ Kum aqueous solution has a tendency to loosen in the same way as urea, but it does not have a big effect on the difference in firmness as seen with urea.Excluding glycyrrhizin, low I11 degrees can also be used as a fixing agent.'' ◎ This product & j1 is suitable for the above-mentioned establishments.To dissolve glycyrrhizin or its salt, no heating or evaporation is performed, and always use 1 liter of glycyrrhizin bath solution for CN use. The purpose of the present invention, which has been modified to suit this purpose, is to provide glycyrrhizin or a salt thereof at room temperature. Dissolve in a water bath solution of a solubilizing agent such as urea or sodium acetate, 1 then add an acidic solution of the main drug, t4, and then lubricate with pnR1i agent KPMb, 0.
~7.0, and dilute it with the specified concentrated acid to imitate it. The roofing agents include electrified alkali carbonate, alkali carbonate, alkali hydroxide, and sodium citrate. Disodium phosphate, sodium benzate and their water bath solutions are used. Next, we will discuss the main stream specifically l11! Clarify ◎ ~ Method using urea ~ 1jJlilf1 As shown in [1], when 150 mK of water is dissolved in sop volume 151', it becomes almost saturated #I liquid, and sopw whisper 2
It will be 64 inches. From the table above, glycyrrhizin 2 (1
Yes, after taking a bath, it first becomes an acidic urea solution of glycyrrhizin. PM is approximately 3.4. Gradually add one drop of sodium oxide solution as a pH adjustment agent to adjust the pH to 6.5.
Before and after. This makes it possible to prevent deterioration of crude drugs due to direct heating neutralization of glycyrrhizin and alkaline agents. Then diluted with water to give 11 and 216.1t.
LJ and 0.2% glycyrrhizin II solution are obtained. When using glycyrrhizin monoammonium salt as the raw material, approximately 1.02% of glycyrrhizin is used as in Example [1].
Use a certain amount of salt. When the monopotassium salt of glycyrrhizin is used, the monopotassium salt of glycyrrhizin is about 1.046 times as strong as the potassium salt of glycyrrhizin, as shown in Example [i], and the saturated solution of urea is used as shown in [I]. It dissolves in water and forms a vaguely sensitive aqueous solution at room temperature. Later, prepare the pkl using IM water potassium hydrate solution and adjust the pH.
6.5 and diluted with water to make 0.2i0.
5 whispers Glycyrrhizia 114?1i is absorbed in 0-benzoic acid) Method using IJum ~ Using 20t of glycyrrhizia as raw material, 0.2-glycyrrhizin bath solution 10J'! 'j
In the case of am, as shown in Example (n), glycyrrhizin 2 (l is 4 oJy * rest) I) Lamb elution 37
5 Dissolves in wa4 〇-ml As shown in the table, it is easily dissolved to obtain a sodium benzoate bath solution of glycyrrhizic acid. In this case, the liquid properties are adjusted depending on the hostility of the solubilizer and Pi! It becomes 5.4. Next, adjust the pH to 7 with 1M* sodium hydroxide solution once every 6.5 m, dilute with water, and add 1
If you set it to 01, you will have a 0.2% glycyrrhizin soluble enemy. 0.21 as a raw material for clityrrhizin monosodium for a long time
! When 10J of clinaluritin m is used as IIII, 1. L) 26x clityrrhizin monosodium 20.5# use 40
)'v 9. Add 550 liters of concentrated sodium solution to the cellar to obtain a weakly acidic solution (pH 5.8). 1ii Water Sensitivity in the same way as above) pm with IJ Kumu enemy to about 6.
5 @ later! Li1 fireflies and water [about p if diluting is OK]
A 0.2'$ glycyrrhizin solution of H6,6 is obtained. Next, the osmotic pressure ratio of each of the main ingredients of the glycyrrhizin extract obtained in the example, each of the S dispersions, and their solutions to physiological saline is as follows.Example (i) Q-2 Chronic glycyrrhizin, 1.5 cyst urea...Osmolality ratio 0.73m Example [i)
0.2-glycyrrhizin, 2-urea...Osmotic pressure ratio LO4s example [厘]υ, 5-dominant glycyrrhizin, 2q
II Urinary volume...Osmotic pressure ratio 1 to 5; Example (ff)
0.2 Glycyrrhizin, 1.5 Glycyrrhizin
Um...-Osmolar pressure ratio...-0.64a Example (V) 0.2 s Gritti Luritin, 2.2 s Sodium benzoate 1 Noum...& Osmolality ratio 1.08u Isoshin of glycyrrhizin used (3,1-2,01
1, a wide range of baths other than the above are taken once.夾′l#A? 41C ■] [■] [V] When a bath solution such as
The osmotic pressure ratio is over 1.0, and the port decomposition agent is not an isotonic agent.
・The effect of being attended to by the main bed is as follows. iI6ali1wt with glycyrrhizin or its salt
It is possible to make a small batch of products in a small scale.
As an industrial method, the heating process is reduced, so there is no loss of quality, and the uniformity of the product is maintained. This is especially useful when combining other drugs that are sensitive to heat. The urea or sodium benzoate that causes #I dissolution by this bed not only serves as a solubilizing agent but also as an isotonic agent, ensuring product safety.Example (1) Dissolve 15 liters of urea in 150 liters of water and add to this at room temperature.
Add a little glycyrrhizin 205Ft'. After a while, it became clear and exposed (1) H3, 4
) is obtained. Gradually add about 70 wbt 4 to make mP't' around 6.5, dilute it with water, make 10 bottles, add 2 capsules of Grinaritin (1) In practice, 200jF of urea is dissolved in 200ml of water, and 20.1ml of glycyrrhizin monosodium is gradually added at a temperature in the troughs to obtain a clear acidic solution (PH 4.23).Next, ammonia Carefully add a sample to bring the pH to 6.
51iJ41t, diluted with water to make 11, then 2S solution, further 1O] to make 0.2glycyrrhizia bathi [('Dki 6,83 km Le. Example [厘] Urea 160 ft' Water 160 It melts in the liquid, and when you add 41.8 ff4 of Krychirurin Monokali 9M to it at room temperature, it becomes fjt's silky, smooth taste (
pH'4.5) is superior. ' Add about 90 liters of 1m potassium hydroxide solution to make Pklk' around 6.5, dilute with water to make 8I3, then the pH will be 0.51 of 8! /! Jf Ruriten's enemy is served. Example (y) When 40 W/y% sodium chloride solution (m number 375) was removed, 20 ft of glycyrrhizin was gradually added to the solution, and a clear bath liquid (pH 5.43) was obtained. to I
Add # to M2 and add sodium solution approximately 50wIm4 *m L
p'klwo 6S Maetoshi and then #i diversion with water I
If OA is 0.2 whisper glycyrrhizin solution (1) H6,
63 will be attended. To carry out, take 550 inches of 40 Vv benzoin de-sodium solution,
Add this to glycyrrhizin monosodium 20.5 at room temperature.
When t is added, d becomes d [Nataru H5, 8). Then about 46 inches of IM water hydroxide was added,
If Pi16.5 is used and diluted with water to 1°J, 0.2 (glycyrrhizin (PM&Ji)) will be obtained.

Claims (1)

[Scope of Claims] (1) Glycyrrhizin or its salt, an active ingredient of Glycyrrhiza M, contains urine bulk or #i sodium zoate and PBmll at room temperature.
A useful glycyrrhizin solution [111116] (2) Glycyrrhizin or its salt is dissolved in an oxygen bath solution at room temperature, and the resulting wave-rich bath liquid is used as a p11ilIIIllll11 agent. The useful glycyrrhizin described in item 1 (1) of the hour hand-required range is characterized in that it is made into an approximately neutral solution and diluted with water to a predetermined amount! 1'ftL method, 1 (3) Add glycyrrhizin or its salt to a thick solution of benzoic acid, add glycyrrhizin or its salt at room temperature, and apply the liquid using a PFI brush. A list of useful glinalritin solutions as described in item 1), where the % value is an approximately neutral solution and dilution at a given amount of kK*.