JP4955287B2 - Paeoniflorin-containing jelly preparation - Google Patents

Description

  The present invention relates to a jelly preparation containing paeoniflorin as an active ingredient, and more particularly to a jelly preparation containing paeoniflorin-containing Hachimi-jio-maru extract as an active ingredient.

Most Chinese herbal medicines are used as powders, granules, tablets, liquids and other preparations. When a traditional Chinese medicine is made into a solid preparation such as a powder, granule, tablet, etc., a dose of several grams per dose is required, which is a considerable burden on the person taking the medicine. In addition, there are problems such as uncomfortable or difficult to take due to bitterness peculiar to traditional Chinese medicine.
There is a liquid preparation as a preparation that reduces the dose of several grams in a solid preparation of Chinese herbal medicine. For example, a liquid preparation of Hachimi-jio-maru extract, which has been awarded as a therapeutic agent for urination disorder, is commercially available as an internal use liquid. Patent Document 1 describes that paeoniflorin is effectively concentrated in this Hachimi-jio-maru extract.

However, when Hachimi-jio-maru extract is used as a liquid, it has the advantage of being easier to take than solid preparations, but not only does the bitterness unique to traditional Chinese medicine spread in the mouth, but it also solubilizes all ingredients. Therefore, it is difficult to reduce the volume of the preparation, it is heavy and bulky, and it is inconvenient to carry. The Hachimi-jio-maru extract is effective for urination disorders, particularly urine leakage and frequent urination, and is often carried around when traveling, so that it is not particularly suitable for carrying.
Japanese Patent Laid-Open No. 11-12185

  Therefore, it has been desired to develop a preparation containing Hachimi-jio-gan extract extract that is small in dose, light and not bulky and convenient for carrying.

  In order to solve the above-mentioned problems, the inventors of the present invention have made extensive researches and as a result, have focused on making Hachimi-jio-maru extract into a jelly formulation. And when pectin is used as the base of the jelly preparation, especially when low methoxyl pectin is used, surprisingly excellent jelly strength is obtained, and further by adjusting the pH to a predetermined range, Hachimi-jio-maru extraction The present invention was completed by finding that paeoniflorin in the extract was stabilized.

  According to the present invention, a jelly preparation containing an extract of Hachimi-jio-maru extract that is lighter and less bulky than a liquid agent and convenient for carrying can be obtained. In this jelly preparation, paeoniflorin, which is an active ingredient in the Hachimi-jio-maru extract, is stabilized, the jelly strength is also stabilized, and the bitterness peculiar to traditional Chinese medicine is masked.

  The paeoniflorin contained in the jelly preparation of the present invention may be chemically synthesized, extracted from herbal medicines such as peony skin, glaze, etc., or Hachimi-jiomaru, Kakkonto It may be extracted from a traditional Chinese medicine such as Keieda-yu. Examples of the form of the extract from the herbal medicine or the herbal medicine include dry powder, extract (eg, dry extract, soft extract, flow extract) and the like.

The case where paeoniflorin contained in the jelly preparation of the present invention is derived from the Hachimi-jio-maru extract will be described below.
Examples of the form of the extract include dry powder and extract extracts such as a dry extract, a soft extract, and a flow extract, with the extract being preferred. As an extract of Hachimi-jio-maru, an extract obtained by heating and extracting Hachimi-jio-maru with water, concentrating the resulting extract, and then extracting the concentrate with ethanol is more preferred.

Such Hachimi-jio-maru extract is, for example, a collection of experienced Chinese medicine prescriptions (Kiichi Hayashi Hen, Nihon Shokudo Co., Ltd.), Kampo prescription commentary (written by Michiaki Yahaji, Somotosha) and Japanese Patent Laid-Open No. 11-12185 Prepared according to the method described in 1.
Specifically, for example, 25 g of ground yolk, 15 g of yam, 15 g of mountain remedy, 15 g of saw potato, 15 g of peony, 15 g of peony skin, 5 g of cinnamon bark and 5 g of eggplant are boiled and extracted with 2200 mL of water (95 ° C., 60 minutes), filtered After that, the filtrate is concentrated. By adding 94 mL of ethanol to the concentrated solution 220 mL thus obtained and leaving it for 16 hours, centrifuging to remove the precipitate, and further concentrating the solution, adding water to the concentrated solution to 55 mL. Hachimi-jio-maru extract (hereinafter also referred to as “extract H”) is produced. A commercially available product can also be used as the Hachimi-jio-maru extract.

The content of paeoniflorin contained in the jelly preparation of the present invention is not particularly limited, but is 0.001 to 1%, preferably 0.03 to 0.1% by weight with respect to the jelly preparation.
When the paeoniflorin-containing component blended in the jelly preparation of the present invention is an extract from a herbal medicine or a traditional Chinese medicine, the content is not particularly limited, but it is 5 to 90% by weight with respect to the jelly preparation, preferably 10 to 80%. %. When the paeoniflorin-containing component is Hachimi-jio-maru extract (including Extract H), the content is usually 5 to 85% by weight with respect to the jelly preparation, preferably 10 to 80%. .

In the jelly preparation of the present invention, a jelly preparation having excellent storage stability can be obtained by using pectin as the base.
Pectin is a polysaccharide extracted from citrus fruits, apples, etc., in which galacturonic acid is linearly linked by α-1,4 glucoside bonds. The carboxyl group of galacturonic acid is partially methyl esterified, and those having a methoxyl group content of more than 7% are called high methoxyl (HM) pectin and those having 7% or less are called low methoxyl (LM) pectin. Both high methoxyl pectin and low methoxyl pectin are commercially available.

The pectin in the present invention is not particularly limited as long as it can be jellyd, and may be either high methoxyl pectin or low methoxyl pectin. From the viewpoint of the stability of paeoniflorin, which is an active ingredient, low methoxyl pectin is more preferable. preferable.
The content of pectin is not particularly limited, but in the case of high methoxyl pectin, it is usually 0.5 to 6%, preferably 2 to 5% by weight with respect to the jelly preparation, and in the case of low methoxyl pectin, usually the jelly preparation. The weight ratio is 0.5 to 4%, preferably 1.8 to 2.8%.

  In the jelly preparation of the present invention, the divalent metal ion is adjusted so as to be 0.015 to 0.05 parts by weight, more preferably 0.020 to 0.035 parts by weight in terms of metal with respect to 1 part by weight of low methoxyl pectin. A more stable jelly preparation is obtained. Here, the divalent metal ion may be any one that releases a divalent cation in the jelly preparation, and examples thereof include calcium ion and magnesium ion, and calcium ion is preferable.

When adjusting the metal ion concentration of a herbal extract or herbal extract-containing jelly preparation, the herbal extract or herbal extract may generally contain a small amount of metal ions. It is necessary to adjust the metal ion concentration in the jelly preparation in consideration of the amount of metal ions inherent in the extract. That is, when adjusting the divalent metal ion concentration in the jelly preparation, the divalent metal ion concentration in the jelly preparation is measured, and when the desired divalent metal ion concentration is insufficient, the divalent metal ion concentration is measured. Can be adjusted to a desired divalent metal ion concentration.
As a method for measuring the divalent metal ion concentration in the jelly preparation, generally known methods can be used. For example, it can be measured by using liquid chromatography.

  When a divalent metal ion is added to a jelly preparation, it can be added in the form of a metal salt, such as purified calcium chloride, calcium citrate, calcium gluconate, calcium lactate, calcium sulfate, calcium phosphate, etc. , Magnesium salts such as magnesium chloride, magnesium citrate, magnesium gluconate, magnesium lactate, magnesium sulfate, magnesium phosphate and the like, preferably calcium salt, particularly calcium lactate. When these metal salts are added, they are added so that the metal ion concentration in the jelly preparation is a desired metal ion concentration in terms of metal.

In addition, when producing a jelly preparation having a desired divalent metal ion concentration without directly measuring the divalent metal ion concentration in the jelly preparation, from the amount of low methoxyl pectin blended in the jelly preparation, Based on the weight ratio of the low methoxyl pectin and the metal equivalent of the divalent metal ion, the metal equivalent of the divalent metal ion that should be in the jelly preparation is calculated, and from there, the crude drug extract or the Chinese medicine extract By subtracting the metal equivalent amount of the contained metal ion, the metal equivalent amount of the divalent metal ion to be newly added can be calculated.
Furthermore, when high methoxyl pectin is used as the pectin, a jelly preparation having better storage stability can be obtained without adding a divalent metal ion.

  When the paeoniflorin-containing component as an active ingredient is Extract H, when the pH of the jelly preparation is 3.0 to 4.5, the paeoniflorin contained in the preparation is stable over a long period of time, and more stable when the pH is 3.5 to 4.0 is there.

  As a pH adjuster for adjusting the pH of the jelly preparation of the present invention to the above range, citric acid, malic acid, tartaric acid, fumaric acid, phthalic acid, lactic acid, adipic acid, succinic acid, maleic acid, ascorbic acid, Organic acids such as erythorbic acid, gluconic acid, glycerophosphoric acid, salicylic acid, aminoethylsulfonic acid and their salts (for example, alkali metal salts or alkaline earth metal salts), and inorganic acids such as hydrochloric acid, phosphoric acid, acetic acid, carbonic acid and Its salts, amino acids such as glycine, alanine, aspartic acid, essential amino acids and their salts (for example, alkali metal salts or alkaline earth metal salts), or alkaline agents such as sodium hydroxide, potassium hydroxide, triethanolamine, ammonia And a salt thereof, and two or more of these pH adjusters may be used in combination.

The jelly preparation of the present invention includes sweeteners, preservatives, fragrances, flavoring agents, emulsifiers, dispersants, solubilizers, as long as the stability of paeoniflorin as an active ingredient and the stability of the jelly preparation itself are not reduced. You may add an antioxidant, a coloring agent, etc. suitably.
Examples of the sweetener include erythritol, xylitol, acesulfame potassium, sugar, mannitol, maltitol, sucralose, aspartame, saccharin, saccharin sodium, stevia, sorbitol, reduced maltose varicella and the like. You may use together.
Examples of the preservative include potassium sorbate, sorbic acid, methyl paraoxybenzoate, ethyl paraoxybenzoate, propyl paraoxybenzoate, butyl paraoxybenzoate, and the like, and these preservatives are used in combination of two or more. Also good.
Examples of the fragrances include cola flavor, brown sugar flavor, apple flavor, lemon flavor, strawberry flavor, and menthol, and these fragrances can be used in combination of two or more.

The jelly preparation of the present invention can be produced by a usual method for producing a jelly preparation. Specifically, for example, first, a jelly base, a paeoniflorin-containing extract and an arbitrary component are dispersed, dissolved or suspended by adding a suitable amount of warm water as a dispersion medium and stirring, or the jelly base, paeoniflorin An appropriate amount of water as a dispersion medium is added to the extract and optional components at room temperature and heated while stirring to disperse, dissolve or suspend the mixture, and then the dispersion, solution or suspension is cooled. By doing so, a jelly preparation can be obtained. When a component that is not preferable to be exposed to high temperature is blended, after allowing the dispersion, solution or suspension obtained above to reach an appropriate temperature, the component is added, and the mixture is further cooled to be a jelly preparation. Alternatively, a jelly preparation may be obtained by adding a component that is not preferable to be exposed to high temperature immediately before cooling.
The packaging form of the jelly preparation thus obtained is not particularly limited, but it is particularly convenient to carry if a single dose of the active ingredient is filled in one stick.
Filling and sticking the jelly preparation to the stick is performed by a conventional method.

  Hereinafter, the present invention will be described in more detail with reference to production examples, examples, comparative examples, and test examples. However, the scope of the present invention is not limited to these examples.

Production Example 1
Add 25g of ground yellow, 15g of yam, 15g of mountain remedy, 15g of potato, 15g of cocoon, 15g of peony skin, 5g of cinnamon bark and 5g of adduct to 2200mL of water and heat at 95 ° C for 60 minutes. The mixture is filtered, the filtrate is concentrated to 220 mL, and 94 mL of ethanol is added to the resulting concentrate and left for 16 hours. This was centrifuged to concentrate the liquid from which the precipitate was removed, and water was added to the concentrate to make 55 mL, whereby extract H was produced.
In addition, the calcium concentration of Extract H is determined according to the Japanese Pharmacopoeia General Test Method Liquid Chromatograph Method, high performance liquid chromatography apparatus LC-10ADVP (manufactured by Shimadzu Corporation), electrical conductivity detector CDD-10AvP (manufactured by Shimadzu Corporation) and It was 0.092% (W / V) when it measured using column TSKgel IC-Cation I / IIHR 4.6mmIDx10cmL (made by Tosoh Corporation).

Example 1
A jelly preparation (pH 3.8) was prepared using the following ingredients, filled in an aluminum stick, and packaged (1 bag 14 g).
Ingredient name Prescription amount in 2 packets (g)
Extract H 12.320
LM pectin 0.644
Erythritol 2.800
Xylitol 2.800
Acesulfame potassium 0.050
Citric acid 0.028
Na citrate 0.026
Calcium lactate 0.042
Potassium sorbate 0.014
Brown sugar flavor 0.028
Purified water 9.248
Total 28.000

Example 2
A jelly preparation (pH 3.0) was prepared using the following components, which were filled in an aluminum stick and packaged (1 package 14 g).
Ingredient name Prescription amount in 2 packets (g)
Extract H 22.400
HM pectin 0.560
Refined white sugar 4.500
Acesulfame potassium 0.050
Citric acid 0.040
Na citrate 0.020
Calcium lactate 0.057
Potassium sorbate 0.014
Brown sugar flavor 0.028
Purified water 0.331
Total 28.000

Example 3
A jelly preparation (pH 3.8) was prepared using the following ingredients, filled in an aluminum stick, and packaged (1 bag 14 g).
Ingredient name Prescription amount in 2 packets (g)
Extract H 19.600
LM pectin 0.780
Erythritol 3.000
Xylitol 2.000
Citric acid 0.028
Na citrate 0.026
Calcium lactate 0.041
Potassium sorbate 0.014
Corra flavor 0.028
Purified water 2.483
Total 28.000

Example 4
A jelly preparation (pH 3.8) was prepared using the following ingredients, filled in an aluminum stick, and packaged (1 bag 14 g).
Ingredient name Prescription amount in 2 packets (g)
Extract H 5.600
LM pectin 0.500
Erythritol 2.000
Xylitol 3.000
Citric acid 0.028
Na citrate 0.026
Calcium lactate 0.018
Potassium sorbate 0.014
Chocolate flavor 0.028
Purified water 16.786
Total 28.000

Example 5
A jelly preparation (pH 3.0) was prepared using the following components, which were filled in an aluminum stick and packaged (1 package 14 g).
Ingredient name Prescription amount in 2 packets (g)
Extract H 2.800
HM pectin 1.120
Erythritol 2.000
Xylitol 3.000
Refined white sugar 10.000
Citric acid 0.040
Na citrate 0.020
Calcium lactate 0.023
Potassium sorbate 0.014
Chocolate flavor 0.028
Purified water 8.955
Total 28.000

Example 6
A jelly preparation (pH 3.0) was prepared using the following components, which were filled in an aluminum stick and packaged (1 package 14 g).
Ingredient name Prescription amount in 2 packets (g)
Extract H 4.300
HM pectin 0.140
Erythritol 4.500
Xylitol 4.500
Refined white sugar 10.000
Citric acid 0.040
Na citrate 0.020
Calcium lactate 0.023
Potassium sorbate 0.014
Chocolate flavor 0.028
Purified water 4.435
Total 28.000

Comparative Example 1
A jelly preparation (pH 4.5) was prepared using the following ingredients, filled in an aluminum stick, and packaged (14 g per package).
Ingredient name Prescription amount in 2 packets (g)
Extract H 12.210
Carrageenan 0.036
Locust bean gum 0.036
Potassium sorbate 0.014
Xylitol 2.800
Erythritol 2.800
Acesulfame potassium 0.050
Sodium citrate 0.336
Potassium chloride 0.014
Brown sugar flavor 0.028
Purified water 9.675
Total 28.000

Comparative Example 2
A jelly preparation (pH 4.5) was prepared using the following ingredients, filled in an aluminum stick, and packaged (14 g per package).
Ingredient name Prescription amount in 2 packets (g)
Extract H 12.210
Kanteng powder 0.182
Potassium sorbate 0.014
Xylitol 2.800
Erythritol 2.800
Acesulfame potassium 0.050
Sodium citrate 0.336
Corra flavor 0.028
Purified water 9.580
Total 28.000

Test example 1
After the extract H produced in Production Example 1 was stored at 70 ° C. for 1 week, the paeoniflorin content was measured by HPLC, and the ratio (%) of the residual amount to the value at the start is shown in Table 1.

比較例１および２（pH4.5）では、ゼリー強度の低下が認められたが、実施例１（pH3.8）では、ゼリー強度の低下が認められなかった。 Test example 2
For the jelly preparations obtained in Example 1, Comparative Example 1 and Comparative Example 2, the jelly strength after 3 months at 40 ° C. was measured. The jelly strength (N / m ² ) was measured by Yamaden RHEONER RE-3305 using a cylindrical plunger with a diameter of 16 mm at a compression speed of 1 mm / s and a clearance of 5%. Table 2 shows the jelly strength and the ratio (%) of the jelly strength to the jelly strength at the start (0 time).

In Comparative Examples 1 and 2 (pH 4.5), a decrease in jelly strength was observed, but in Example 1 (pH 3.8), a decrease in jelly strength was not observed.

40℃で6ヶ月経過後のペオニフロリン残存量は90％以上であり、ゼリーの強度に低下は認められなかった。 Test example 3
According to the formulation of Example 1, three lots of jelly preparation (pH 3.8) were prepared, packaged in an aluminum stick (1 package 14 g), and the paeoniflorin content and jelly strength after 6 months at 40 ° C. were measured.

The remaining amount of paeoniflorin after 6 months at 40 ° C. was 90% or more, and no decrease in the strength of the jelly was observed.

Claims (15)

  A jelly preparation characterized by containing paeoniflorin as an active ingredient and using pectin as a jelly base.   The jelly preparation according to claim 1, wherein paeoniflorin is contained in a herbal medicine or a herbal medicine extract.   The jelly preparation according to claim 2, wherein the herbal medicine extract is an Hachimi-jio-maru extract.   The jelly preparation according to claim 3, wherein the Hachimi-jio-maru extract is obtained by heating and extracting the Hachimi-jio-maru with water, concentrating the extract, and then extracting the concentrate with ethanol.   A jelly preparation comprising the Hachimi-jio-gan extract according to any one of claims 3 or 4 in a weight ratio of 5 to 85% with respect to the jelly preparation.   The jelly preparation according to any one of claims 1 to 5, comprising pectin in a weight ratio of 0.5 to 6% with respect to the jelly preparation.   The jelly preparation according to any one of claims 1 to 6, wherein the pectin is a high methoxyl pectin.   The jelly preparation according to any one of claims 1 to 6, wherein the pectin is a low methoxyl pectin.   The jelly preparation according to claim 8, comprising 0.015 to 0.05 part by weight of a divalent metal ion in terms of metal with respect to 1 part by weight of low methoxyl pectin.   The jelly preparation according to claim 9, wherein the divalent metal ion is a calcium ion.   The jelly preparation according to any one of claims 1 to 10, which has a pH of 3.0 to 4.5.   The jelly preparation according to any one of claims 1 to 11, which is packaged in a stick.   2 to 1 part by weight of low methoxyl pectin in a jelly preparation containing 5 to 85% by weight of Hachimi-jio-maru extract in a weight ratio of 0.5 to 6% by weight of jelly preparation and low methoxyl pectin A method for stabilizing a paeoniflorin-containing jelly preparation, characterized in that the content of a valent metal ion is adjusted to 0.015 to 0.05 parts by weight in terms of metal.   The stabilization method according to claim 13, wherein the Hachimi-jio-maru extract is one obtained by heating and extracting the Hachimi-jio-maru with water, concentrating the extract, and then extracting the concentrate with ethanol.   The stabilization method according to any one of claims 13 and 14, comprising adjusting the pH to 3.0 to 4.5.