JP3658878B2 - Oral solution - Google Patents

Description

【００２４】
試験結果より、生薬、ＰＶＰならびにパラオキシ安息香酸ブチルおよびパラオキシ安息香酸プロピルを配合すると析出物が発生するが、防腐剤としてパラオキシ安息香酸エチルを用いると析出物が発生しないことが解った。[0001]
BACKGROUND OF THE INVENTION
The present invention relates to an internal liquid preparation that does not produce precipitates.
[0002]
[Prior art]
Since herbal medicines have various effects and effects depending on their types, a large number of oral liquid preparations containing herbal medicines are on the market. However, in the case of a herbal medicine mixed solution, prevention of turbidity and precipitation that occurs over time is a major issue to be studied from the viewpoint of commercial properties and effectiveness of the preparation. In general, as a countermeasure for preventing precipitation, a surfactant such as polyoxyethylene hydrogenated castor oil derivative is added to the preparation. However, when a low pH condition is selected due to problems such as stabilization of the compounding components, the surfactant is susceptible to hydrolysis, and precipitates derived from the surfactant are formed over time. Therefore, in order to add a surfactant, it is necessary to set the pH of the preparation higher as an internal solution.
[0003]
Polyvinylpyrrolidone is widely used as a stabilizer, base, binder, coating agent, sugar coating, thickener, excipient, disintegrant, suspending agent, solubilizing agent, etc. in the production of food and pharmaceuticals. ing. In internal use liquids, they are used as stabilizers, thickeners, suspending agents, solubilizing agents, and the like. In particular, when added to a solution containing a herbal extract, it has the effect of preventing turbidity and precipitation that occur over time. Since polyvinylpyrrolidone is stable even at low pH, it can be used even when the pH of the solution is set low due to the stabilization of the compounding components, and is thus useful as a solubilizing agent.
[0004]
Here, when an internal liquid preparation is manufactured, it is necessary to mix | blend antiseptic | preservative for the quality assurance of goods. Benzoic acids (benzoic acid, benzoate, etc.), parabens (propyl paraoxybenzoate, butyl paraoxybenzoate, etc.) and the like are used as preservatives. When parabens are used as preservatives, it is common to use butyl paraoxybenzoate and propyl paraoxybenzoate in combination, since the antiseptic effect is synergistically enhanced as compared to the case where each is used alone.
[0005]
[Problems to be solved by the invention]
However, when propyl paraoxybenzoate and butyl paraoxybenzoate, which are frequently used as preservatives, are added to a solution to which polyvinylpyrrolidone has been added, a white precipitate is produced after preparation of the preparation. Even in such a case, when a surfactant is added to the liquid agent, no precipitate is formed, but it is difficult to use under low pH conditions because of a problem in the stability of the surfactant itself. In addition, if only benzoic acids are used as preservatives, no precipitate is produced, but there is a concern about the antiseptic effect.
[0006]
An object of the present invention is to prevent the formation of precipitates when a solution containing a crude drug is brought to a low pH, and to obtain a solution having a sufficient antiseptic effect.
[0007]
[Means for Solving the Problems]
As a result of investigations to solve the problem, the present inventor used a preservative that has been conventionally used as a preservative in a liquid that contains a crude drug and polyvinylpyrrolidone under low pH conditions. The present invention has been completed by finding that the liquid agent exhibits a preservative effect equivalent to that of the liquid agent and does not cause precipitation.
[0008]
That is, this invention is an internal use liquid agent which mix | blends a crude drug, polyvinylpyrrolidone, and ethyl paraoxybenzoate, and is pH 2.0-4.0.
[0009]
DETAILED DESCRIPTION OF THE INVENTION
In the present invention, herbal medicines are yellow spirit, kudzu, mahuang, cinnamon (branch), saiko, bellflower, licorice, candy, serpentine, senega, ambition, carrot, cheng, cherry bark, ginger, yellow rice, (purple) Soba, ginger, half-summer, spicy, spicy, glaze, peony, ream, apricot, peach, winter, katsuki, tsutsuji, deer horn, muirapuama, shigoka, trash, tochu, kokushi, kaikujin, chorei, nik Herbal powders such as jujube, antelope kaku, rokjou or extracts thereof are listed.
[0010]
The polyvinylpyrrolidone in the present invention is a linear polymer of 1-vinyl-2pyrrolidone and means a compound having a K value of 15 to 21, 26 to 35, 50 to 62, or 80 to 100. There is another name for polyvidone or povidone, abbreviated as PVP. For example, it is called PVP K15, PVP K29 / 32, PVP K30, PVP K60, PVP K90, and the like. Of these, those having an average molecular weight of 40,000 to 1,200,000 are particularly preferred. The concentration of polyvinyl pyrrolidone is most preferably 0.5% to 2% (w / v) of the internal solution. When the concentration of polyvinyl pyrrolidone is less than 0.5%, the effect as a solubilizing agent is weak, and it is not necessary to blend polyvinyl pyrrolidone in excess of 2% as a solubilizing agent.
[0011]
The blending amount of ethyl paraoxybenzoate used in the present invention is preferably 0.001% to 0.03% (w / v) from the viewpoint of antiseptic effect. If the blending amount is less than 0.001%, the antiseptic effect is not sufficient, and if it exceeds 0.03%, the safety of ethyl paraoxybenzoate may become a problem.
[0012]
The present invention is preferably carried out in the pH range of 2.0 to 4.0, particularly in the range of pH 2.5 to 3.5, where it is difficult to use the surfactant. When the pH exceeds 4.0, the preservative effect of ethyl paraoxybenzoate is weakened, and when the pH is less than 2.0, it is not preferable for an internal use liquid in terms of flavor. Hydrochloric acid, phosphoric acid, sodium hydroxide, etc. can be used as the pH adjuster at that time, but organic substances such as citric acid, malic acid, tartaric acid and succinic acid are used from the viewpoint of masking the bitterness and flavor of the blended ingredients. It is preferable to use an acid or a salt thereof.
[0013]
The liquid preparation of the present invention can be used in combination with other preservatives (benzoic acid, benzoate, etc.) that do not produce precipitates even at low pH.
[0014]
When producing an internal solution, a water-soluble or fat-soluble vitamin can be added to the liquid of the present invention. Examples of the water-soluble vitamin used include vitamin B1, B2, B6 or B12 and salts, esters or derivatives thereof, or nicotinamide. Examples of fat-soluble vitamins include vitamins A, D, E, and K.
[0015]
The liquid agent of this invention can be manufactured by the normal method of manufacturing a liquid agent. In addition, components that are usually used in internal liquids such as various amino acids, caffeine, sweeteners, and fragrances can be blended as long as the effects of the present invention are not impaired.
[0016]
【The invention's effect】
According to the present invention, it is possible to provide an internal liquid preparation that does not produce a precipitate even at a low pH.
[0017]
【Example】
Hereinafter, the present invention will be described in more detail with reference to examples and test examples. In the examples, PVP is polyvinyl pyrrolidone.
[0018]
Example 1
Vitamin B1 4mg
Vitamin B2 4mg
Vitamin B6 4mg
Taurine 800mg
Nicotinamide 15mg
Calcium gluconate 200mg
Magnesium aspartate 100mg
Shigoka dry extract drug substance 400mg
Garbage extract crude drug 200mg
Eucommia extract active ingredient 200mg
PVP K29 / 32 500mg
Sodium benzoate 30mg
Ethyl paraoxybenzoate 6mg
Citric acid appropriate amount sugar 8000mg
Fragrance Trace purified water 50ml (pH3.0)
The above components were mixed and dissolved, and then filtered to obtain an internal solution.
[0019]
Example 2
The amount of PVP added in Example 1 was 250 mg (0.5% (W / V)) to obtain an internal solution by the same operation.
[0020]
Comparative Example 1
A comparative solution was obtained by changing the ethyl paraoxybenzoate of Example 1 to 3.3 mg of butyl paraoxybenzoate and 3.3 mg of propyl paraoxybenzoate.
[0021]
Comparative Example 2
A comparative liquid preparation was obtained by setting the amount of PVP added in Comparative Example 1 to 250 mg (PVP concentration 0.5% (W / V)).
[0022]
Test Example The presence or absence of precipitates immediately after the preparation of the liquid preparations obtained in the above Examples and Comparative Examples was observed. The results are shown in Table 1.
[0023]
[Table 1]

[0024]
From the test results, it was found that when crude drug, PVP, butyl paraoxybenzoate and propyl paraoxybenzoate were added, a precipitate was generated, but when ethyl paraoxybenzoate was used as a preservative, no precipitate was generated.

Claims (1)

A liquid preparation containing a crude drug, polyvinylpyrrolidone and ethyl paraoxybenzoate, and having a pH of 2.0 to 4.0.