JP2001114696A - Jerry state chinese medicine composition - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a jerry state Chinese medicine composition excellent in medicine level preservation stability. SOLUTION: This jerry state Chinese medicine composition as a base agent for an oral Chinese medicine composition containing the Chinese stock medicine is obtained by blending preferably 0.05-1.0 wt.% carageenan, 0.01-1.0 wt.% locust bean gum, 0.01-1.0 wt.% xanthan gum and 0.1-1.0 wt.% phosphate buffer based on the total amount of the Chinese medicine composition to form a jerry state.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a pharmaceutical composition of Kampo jelly, and more particularly, to an oral pharmaceutical composition having a powdery or granular preparation of Kampo preparation which is easy to take for patients who are difficult to take, especially syneresis. The present invention relates to a Kampo jelly pharmaceutical composition that is hard to take, has good appearance, maintains pH, dispersibility of active ingredients, and maintains storage stability at a pharmaceutical level, and has a hardness that is easy to take and can be taken well.

[0002]

2. Description of the Related Art Pharmaceuticals in the form of Kampo preparations are often in the form of powders or granules, and general pharmaceuticals include tablets and liquids in addition to powders and granules. Since the dosage of herbal medicines contains several hundred milligrams to several thousand milligrams per dose, the dosage form is made into powders or granules, but it is difficult to take, spread in the mouth, or spread in the mouth. The bitterness peculiar to Chinese medicine remained, and it was easy for uncomfortable feeling to remain in the mouth after taking. In addition, since a large amount of a tablet or the like is taken at a time, a plurality of small tablets are taken. In addition, in the case of liquid medicine, in order to soften the taste peculiar to Chinese medicine, a single dose is 20m.
Although a dose of L or more is set, portability is inconvenient because it is contained in a glass bottle, and thus a formulation technique capable of solving the problem of taking a Kampo formulation has been desired.

[0003] As a jelly preparation of a Kampo preparation, a preparation obtained by converting a Kampo drug substance into a jelly preparation using gelatin is known (Japanese Patent Publication No. 7-116049 (easy-to-take Kampo preparation composition)). This jelly preparation has low storage stability due to the use of gelatin, and must be stored in a cool place (about 4 ° C. in a refrigerator). In addition, long-term stability test (room temperature 3 years) or accelerated stability test (40 ° C, 75
% RH, 6 months).
In other words, gelatin is a gelling agent with low physicochemical stability, and jelly for confectionery using it has set a shelf life within a short storage period in a cold place for these reasons. include. Therefore, considering the distribution of pharmaceuticals, jelly using gelatin has a problem in the stability at the pharmaceutical level.

[0004]

DISCLOSURE OF THE INVENTION The present inventors have concluded that the present invention relates to a jelly oral pharmaceutical composition containing carrageenan, locust bean gum, and polyacrylic acid or a partially neutralized product or salt thereof, and having an accelerated stability ( 40 ° C., 75% RH,
(6 months) and a long-term stability (room temperature for 3 years) are being developed (OP487, JP-A-8-4).
288, JP-A-8-4289). The present inventors have conducted research on applying the technology relating to this jelly-shaped oral pharmaceutical composition to a Chinese herbal drug substance. As a result, due to the specific properties of the Chinese herbal drug substance (for example, high Brix), In order to make jelly, it was necessary to reduce the content of Chinese herbal medicines, and it was found that a single dose became 15 g or more. Also, problems arise in the form of compact packaging and the quality as a pharmaceutical product, necessitating the development of new technology for the preparation of jelly formulations suitable for Chinese herbal medicines.

The present invention has been made in view of the above, and is a jelly pharmaceutical composition suitable for Chinese herbal medicine, which has excellent storage stability at a pharmaceutical level, and preferably maintains appearance, pH, and content of active ingredients. And the dispersibility of the active ingredient is 3
An object of the present invention is to provide a Kampo jelly pharmaceutical composition that can withstand an annual or 6-month accelerated test at 40 ° C. and 75% RH, and that is easy to take and has good throat.

[0006]

Means for Solving the Problems The present inventors have conducted intensive studies in order to solve the above-mentioned problems, and as a result, a Chinese medicine composition has been prepared by using carrageenan, locust bean gum, xanthan gum and phosphate as base materials. By blending a buffer, it was found that a Kampo jelly oral pharmaceutical composition having excellent storage stability was obtained, and the present invention was completed. The oral pharmaceutical composition of a preferred form of the present invention is less likely to synerise, and can maintain the storage stability of a pharmaceutical level with respect to appearance, maintenance of pH, dispersibility of active ingredient, and maintenance of content. It has an easy hardness and is good for throat.

That is, the present invention is as follows. (1) A jelly-like oral pharmaceutical composition containing a Chinese herb drug substance, comprising a carrageenan, locust bean gum, xanthan gum and a phosphate buffer. (2) The pharmaceutical composition according to (1), wherein the carrageenan is both κ-carrageenan and i-carrageenan. (3) The oral pharmaceutical composition according to (1) or (2), further comprising a molten solid component. (4) The molten solid component is one or more selected from sugar, sugar alcohol and polyhydric alcohol (3).
Oral pharmaceutical composition of (5) Carrageenan is added to 0.05 of the total amount of the pharmaceutical composition.
The oral pharmaceutical composition according to any one of the above (1) to (4), which comprises 1.0 to 1.0% by weight. (6) The oral pharmaceutical composition according to any one of (1) to (5), which contains 0.01% to 1.0% by weight of locust bean gum based on the total amount of the pharmaceutical composition. (7) Xanthan gum is added in an amount of 0.0
The oral pharmaceutical composition according to any one of (1) to (6), which contains 1 to 1.0% by weight. (5) A phosphate buffer is added in an amount of 0.1 to the total amount of the pharmaceutical composition.
The oral pharmaceutical composition according to any one of (1) to (7), containing 1 to 2.5% by weight. (9) The oral pharmaceutical composition according to any one of (1) to (8), which is subdivided into single dose units.

[0008] The pharmaceutical composition of the present invention is not particularly limited as long as it does not deviate from the present invention. The jelly composition usually has a structure in which a dispersion medium of a base is held in a solid-phase skeleton gap composed of the base.In the Kampo jelly pharmaceutical composition of the present invention, the Chinese medicine bulk drug is contained in the dispersion medium. In the form of dissolved, dispersed, suspended, etc.

[0009]

BEST MODE FOR CARRYING OUT THE INVENTION As the base used in the pharmaceutical composition of the Chinese medicine jelly of the present invention, carrageenan, locust bean gum, xanthan gum and phosphate buffers are used.

In the present invention, carrageenan used as a base of a Kampo jelly pharmaceutical composition is a base already known as a base of jelly. Carrageenan includes κ (kappa), ι (iota) and λ (lambda) types, all of which are already known, but those used in the present invention are preferably κ (kappa) type and ι (iota) type. . These may be used alone or as a mixture, but it is particularly preferable to use κ carrageenan and ι carrageenan in combination. The content of carrageenan in the jelly oral pharmaceutical composition of the present invention is preferably 0.05 to 1.0% by weight, more preferably the total amount of carrageenan, based on the total weight of the pharmaceutical composition. It is 0.05 to 0.7% by weight, more preferably 0.08 to 0.5% by weight.

[0011] In the present invention, locust bean gum used as a base of a Kampo jelly pharmaceutical composition is a base already known as a base of jelly. The content of the locust bean gum in the jelly-shaped oral pharmaceutical composition of the present invention is, specifically, 0.01% to 1.0% by weight based on the total weight of the pharmaceutical composition. It is preferably from 0.05 to 0.7% by weight, more preferably from 0.08 to 0.5% by weight.

In the present invention, the xanthan gum used as the base of the Kampo jelly-like pharmaceutical composition is already known. The content of xanthan gum in the jelly-shaped oral pharmaceutical composition of the present invention, specifically, xanthan gum is preferably 0.01 to 1.0% by weight based on the total weight of the pharmaceutical composition, more preferably Is 0.05-
It is 0.7% by weight, more preferably 0.08 to 0.5% by weight.

In the present invention, the phosphate buffer used as the pH buffer of the Kampo jelly pharmaceutical composition is already known. The content of the pH buffer in the jelly-shaped oral pharmaceutical composition of the present invention depends on the individual Chinese herbal drug, but specifically, the phosphate buffer is 0% based on the total weight of the pharmaceutical composition. It is preferably 0.1 to 2.5% by weight, more preferably 0.2 to 2.0% by weight, and even more preferably 0.3 to 1.5% by weight. As the phosphate buffer, known phosphate buffers such as disodium hydrogen phosphate, sodium dihydrogen phosphate, dipotassium hydrogen phosphate, and potassium dihydrogen phosphate can be used. pH
The pH range maintained by the buffer is preferably from 4 to 8, more preferably from 4.5 to 7, and even more preferably from 5 to 6.

[0014] The Kampo jelly pharmaceutical composition of the present invention may further contain a molten solid component. What is a molten solid component?
It refers to a solid substance that melts in a pharmaceutical composition by itself. Specific examples of the molten solid component include sugar, sugar alcohol or polyhydric alcohol, and more specifically, sucrose, fructose, sorbitol, xylitol, lactitol, propylene glycol, glycerin and the like. The content of the molten solid component in the jelly-like oral pharmaceutical composition of the present invention is, specifically, 0.1 to 50% by weight based on the total weight of the pharmaceutical composition with the phosphate buffer. Is more preferable, more preferably 1 to 45% by weight, and still more preferably 5 to 40% by weight. The molten solid component can be used alone or as an arbitrary mixture.

Further, the Kampo jelly pharmaceutical composition of the present invention may contain, in addition to the above-mentioned components, substances conventionally known as a base for the jelly composition. In addition, as a dispersion medium of the base contained in the Chinese medicine jelly pharmaceutical composition of the present invention in a form held in the gap of the solid phase skeleton composed of the base, the base can be dispersed at an appropriate temperature. Usually, it is possible to use a liquid that is acceptable as an additive for pharmaceuticals and that can be administered orally. As such a liquid, purified water such as distilled water or deionized water is usually used. In the dispersion medium held in the gap between the solid-phase frameworks of the base material, it is possible to contain any components other than the above-described Chinese herbal drug in a dissolved, dispersed, suspended, or the like state.

The Kampo jelly pharmaceutical composition of the present invention can be prepared, for example, according to a conventionally known method for preparing a Kampo medicinal composition or a method similar to a jelly-like pharmaceutical composition, except that the above components are blended to form a jelly. It can be prepared by dispersing the base of the jelly composition in a dispersion medium at an appropriate temperature, dissolving, dispersing or suspending the Chinese herbal drug in the temperature while adjusting the temperature, and then cooling and gelling. It is possible. The apparatus used for the preparation is not particularly limited as long as it can be heated with a stirrer or a vacuum stirrer. The optional component can be added at any time before the Kampo jelly pharmaceutical composition of the present invention is gelled, for example, when the Kampo drug substance is dispersed in the base or when the Chinese medicine bulk drug is added to the dispersion. In addition, when the Kampo jelly pharmaceutical composition is gelled, it is convenient to take it if it is divided into individual doses and gelled.

The Chinese herbal drug component of the pharmaceutical composition of the present invention is not particularly limited. Ordinarily known powder extracts, soft extracts and fluid extracts can be used. In the present invention, even a herbal drug having a large dose and a high Brix can be used. In addition, the content of the Chinese herb drug substance component is determined by the form of each drug substance and the like, and is not particularly limited.
0.1 to 50% by weight, more preferably 0.5 to 25% by weight, even more preferably 1 to 50% by weight of the total weight of the Kampo jelly pharmaceutical composition.
-20% by weight.

The filling amount of the Chinese medicine jelly pharmaceutical composition of the present invention is not particularly limited. For example, a stick or a cup which is easy to take is filled with 1 to 15 g per packet, and the same amount as a single dose is taken. By filling and enclosing, the user can take the medicine correctly without making a mistake in a single dose.

The jelly-like pharmaceutical composition of the present invention desirably contains, for example, stabilizers, sweeteners, emulsifiers, fragrances, preservatives, etc., which are acceptable for oral administration and are orally acceptable to pharmaceutical additives. Can be added, but is not particularly limited. Examples of the stabilizer include ascorbic acid and tocopherol. Sweetening agents include stevia, saccharin sodium and the like. As an emulsifier, polysorbate 8
0, polyvinyl alcohol, sodium lauryl sulfate and the like. Examples of the fragrance include a flavor type and an essence type which can be added to pharmaceuticals. Examples of the dispersant include water-soluble polymers such as carboxymethylcellulose, sodium alginate, hydroxypropylcellulose, and hydroxyethylcellulose. Examples of preservatives include sodium benzoate, ethyl paraoxybenzoate, propyl paraoxybenzoate and the like.

The product of the present invention is a dosage form in which the problems in taking Chinese herbal preparations are taken into consideration as a maximum, and is made into a jelly form that is easy to take without being stuck in the throat, and can greatly contribute to improvement of compliance. A formulation can be provided.

[0021]

EXAMPLES The present invention will be described below with reference to Examples, Comparative Examples and Comparative Examples, but the present invention is by no means limited to Examples.

[0022]

Examples 1 and 2 and Comparative Examples 1 and 2 Hachimi-jiogan jelly The component B in Table 1 was weighed and dissolved by heating at 80 ° C.
The components were added to form a suspension. This was heat-sterilized at 80 to 90 ° C. for 1 hour, and then filled into containers at 5 g while keeping the temperature at 70 to 60 ° C.

[0023]

[Table 1] Table 1 配合 Compounding amount (% by weight) Component ── ─────────────────── Example 1 Example 2 Comparative Example 1 Comparative Example 2 ─────────────────── Ａ A Hachimi-jiogan dried extract 15.4 19.3 15.4 19.3 ──────────────────────── Ι Bι-Carrageenan 0.4 0.4 0.4 0.4 κ-Carrageenan 0.1 0.1 0.1 0.1 Locust bean gum 0.4 0.5 0.4 0.5 Xanthan gum 0.3 0.3 − − Sodium citrate 0.5 0.4 0.5 0.4 Sodium hydroxide − − − 0.5 Disodium hydrogen phosphate 0.6 0.6 − − D-sorbitol 7.0 5.0 7.0 5.0 Propyl paraben 0.02 0.02 0.02 0.02 ──────────────────────────── ─と す る Add purified water to make 100g ──────────────────────────────────

[0024]

Example 3 and Comparative Example 3 Kakkonto jelly The components B in Table 2 were weighed, heated and dissolved at 80 ° C.
The components were added to form a suspension. This was heat-sterilized at 80 to 90 ° C. for 1 hour, and then filled into containers at 5 g while keeping the temperature at 70 to 60 ° C.

[0025]

[Table 2]

[0026]

Example 4 and Comparative Example 4 Kakkonto jelly The component B in Table 2 was weighed, heated and dissolved at 80 ° C.
The components were added to form a suspension. This was heat-sterilized at 80 to 90 ° C. for 1 hour, and then filled into containers at 5 g while keeping the temperature at 70 to 60 ° C.

[0027]

[Table 3]

[0028]

Example 5 and Comparative Example 5 Goreisan jelly The component B in Table 2 was weighed and dissolved by heating at 80 ° C.
The components were added to form a suspension. This was heat-sterilized at 80 to 90 ° C. for 1 hour, and then filled into containers at 5 g while keeping the temperature at 70 to 60 ° C.

[0029]

[Table 4]

[0030]

Reference Examples 1 and 2 Blank jelly (jelly excluding Chinese herbal medicine) The component B in Table 2 was weighed out and dissolved by heating at 80 ° C. This was heat-sterilized at 80 to 90 ° C. for 1 hour, and then filled into containers at 5 g while keeping the temperature at 70 to 60 ° C.

[0031]

[Table 5]

<Evaluation of Kampo Jelly Pharmaceutical Composition of the Present Invention>
The Chinese medicine jelly pharmaceutical compositions obtained in the above Examples, Comparative Examples and Reference Examples were tested for heat stability and storage stability.

(1) Heat Stability Test The jelly strength at 80 ° C. over time was tested for various jellies produced in Examples 1 to 5, Comparative Examples 1 to 5 and Reference Examples 1 and 2. Examples include various Chinese herbal ingredients and are formulations according to the present invention. The comparative example is a formulation in which xanthan gum and phosphate buffer were removed or replaced with another one in order to see the effect of the present invention. The reference example is a so-called blank prescription, excluding the Chinese herbal component of the example.

The jelly strength of the test sample thus obtained was measured. The test method was Rheometer CR200D
Using a (San Kagaku Co., Ltd.), place the heated specimen over time on a measuring table, measure the maximum load up to the point where the pressure-sensitive shaft for jelly strength test has penetrated 20 mm from the jelly surface, and judge the maximum load value. Strength.

Table 6 shows the test results. In the examples, none of them was affected by heat and showed a stable jelly strength. In each of the comparative examples, the jelly strength tended to decrease due to the influence of heating. Further, in the reference examples, none of them was thermally affected.

From these results, it is clear that the Kampo drug substance decreases the jelly strength with heating over time, but any of the formulations containing carrageenan, locust bean gum, xanthan gum and a phosphate buffer in the Examples It is clear that the stability of the jelly strength is very good, and it is clear that the present invention is a stable Kampo jelly pharmaceutical composition which is not affected by the Kampo drug substance.

[0037]

[Table 6] Table 6 {80 ° C heating time} {1 hr 3 hr 5 hr} Example 1 71 g 72 g 70 g Example 2 65 g 65 g 64 g Example 3 92 g 88 g 96 g Example 4 99 g 99 g 90 g Example 5 83 g 84 g 80 g 比較 Comparative example 1 60 g 50g 31g Comparative Example 2 50g 42g 31g Comparative Example 3 60g 57g 25g Comparative Example 4 53g 49g 40g Comparative Example 5 70g 49g 34g Reference Example 1 99g 98g 99g Reference Example 2 94g 94g 93g ───────────────

(2) Stability Test of Kampo Jelly Pharmaceutical Composition The samples obtained in Examples 1 to 5 were subjected to 40 ° C., 75%
It was left for 6 months under RH conditions. Thereafter, these samples were examined for changes in appearance (shape and syneresis). As a result, no change in shape or syneresis was observed in the samples of Examples 1 to 5.

From these results, it can be seen that the Kampo jelly pharmaceutical composition of the present invention in which the base is made to have a specific composition is not affected by the Kampo drug substance and that the storage stability is ensured in a pharmaceutical level test. Understand.

[0040]

EFFECT OF THE INVENTION The Kampo jelly pharmaceutical composition of the present invention can be used to take a traditional Chinese medicine preparation which has been difficult to take, because it can be provided as a jelly preparation having excellent storage stability at a pharmaceutical level and a good throat. Improvement of compliance of patients can be expected very much.

 ────────────────────────────────────────────────── ─── Continuing from the front page (72) Inventor Mitsugu Togashi 51, Sanjo-cho, Omiya-shi, Saitama Ota Pharmaceutical Co., Ltd. 72) Inventor Koji Matsuura 233, Shiratori-cho, Okawa-gun, Kagawa Prefecture 11F term (reference) 4C076 AA09 BB01 DD26Z DD30Z DD38A DD38F DD43Z DD45R DD67A DD67F EE30A EE58A FF63 4C088 AA04 AB04 AB12 AB26 AB32 AB33 AB37 AB58 AB59 AC05 AC06 AC11 AC12 AC13 AC18 BA08 MA07 MA28 NA03

Claims (9)

[Claims] 1. A jelly-like oral pharmaceutical composition containing a Chinese herb drug substance, comprising a carrageenan, locust bean gum, xanthan gum and a phosphate buffer. 2. Carrageenan is κ carrageenan and ι.
The pharmaceutical composition according to claim 1, which is both carrageenan. 3. The oral pharmaceutical composition according to claim 1, further comprising a molten solid component. 4. The oral pharmaceutical composition according to claim 3, wherein the molten solid component is one or more selected from sugar, sugar alcohol and polyhydric alcohol. 5. The oral pharmaceutical composition according to claim 1, wherein carrageenan is contained in an amount of 0.05 to 1.0% by weight based on the total amount of the pharmaceutical composition. 6. The pharmaceutical composition according to claim 1, wherein the locust bean gum is contained in an amount of 0.01 to 1.0% by weight based on the total amount of the pharmaceutical composition.
The oral pharmaceutical composition according to any one of the above. 7. The oral pharmaceutical composition according to claim 1, wherein xanthan gum is contained in an amount of 0.01 to 1.0% by weight based on the total amount of the pharmaceutical composition. 8. The oral pharmaceutical composition according to claim 1, comprising a phosphate buffer in an amount of 0.1 to 2.5% by weight based on the total amount of the pharmaceutical composition. 9. The oral pharmaceutical composition according to claim 1, wherein the composition is subdivided into single dose units.