JP2962682B2 - Antitussive - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to an antitussive containing dextromethorphan phenolphthalate as an active ingredient.

[0002]

2. Description of the Related Art In general, an antitussive (also referred to as an antitussive) suppresses coughing, depletes physical strength, disturbs sleep,
Dextromethorphan phenolphthalate is used as an active ingredient of non-narcotic antitussives that suppress cough center
It is known by Japanese Pharmacopoeia and other pharmaceutical ingredient standards.

[0003] This phenol dextromethorphan phthalate has no bitterness, is effective and has no habitual action when taken orally. Therefore, it can be used as a preparation such as a drop (candy or candy) or a syrup. It is suitable as a form of antitussive and has high utility value.

[0004]

However, dextromethorphan phenol phthalate is difficult to uniformly disperse when preparing a drop or syrup because it is hardly soluble in water and ethanol. There is a point.

As a more specific problem, dextromethorphan phenol phthalate, which is hardly soluble in water and ethanol and has a lower specific gravity than saccharides, separates into an upper layer when kneaded with saccharides as a main component of the dropping agent. In the case of dropping agents, it is necessary to continue kneading by hand or using a kneader until just before molding, which makes the operation complicated, and bubbles are easily mixed at the time of kneading. Cannot be manufactured.

[0006] In addition, a liquid syrup mixed with dextromethorphan phenol phthalate has a problem that it is separated with the elapse of time after mixing and the state of uniform dispersion is not stable.

Therefore, the present invention solves the above-mentioned problems and improves the dispersion stability of the active ingredient in an antitussive containing dextromethorphan phenol phthalate as an active ingredient. It is to stabilize the state. Another object of the present invention is to provide an antitussive syrup having a stable quality with less air bubbles mixed therein and a stable antitussive syrup for a long time.

[0008]

In order to solve the above-mentioned problems, the present invention relates to an antitussive containing a saccharide as a main component and dextromethorphan phenolphthalate as an active ingredient. The sucrose fatty acid ester was added.

In the above-mentioned antitussive, the compounding ratio of the sucrose fatty acid ester is 0.1 to 2.0% by weight. Drops or syrups are suitable as preparations for the above-mentioned antitussives.

The antitussive of the present invention is characterized in that sucrose fatty acid esters having a large amount of hydrophilic acid groups and also having a lipophilic fatty acid group are particularly effective for dispersing dextromethorphan phenol phthalate. After being mixed with saccharides, the dispersing state becomes very good and a stable antitussive is obtained.

Further, the addition of sucrose fatty acid ester improves the emulsification stability of dextromethorphan phenol phthalate, so that the time required for kneading is short and a stable antitussive dropping agent with no air bubbles is obtained. Or an antitussive syrup that remains in a uniformly dispersed state for a long time.

[0012]

BEST MODE FOR CARRYING OUT THE INVENTION As a saccharide which is a main component of an antitussive in the present invention, a well-known saccharide applicable to a general antitussive drop or syrup can be used.
Such sugars include, for example, starch syrup, maltose, sugar,
Reduced maltose, D-sorbitol, reduced lactose, and the like. In the case of a syrup, a sweetener is further added. Incidentally, the saccharide is usually the main component which accounts for 80 to 99% by weight of the dropping agent or 20 to 70% by weight of the syrup.

The dextromethorphan phenol phthalate used in the present invention is described in the Japanese Pharmacopoeia Standard for Pharmaceutical Ingredients and is one of the well-known dextromethorphan-based antitussive active ingredients. As phenolphthalic acid dextromethorphan, a commercially available product manufactured by Shionogi & Co., Ltd. can be used.

According to the antitussive expectoration standard of the OTC drug manufacturing (import) approval standard, the maximum daily dose for an adult is 90 mg (preferably 4 mg).
The maximum dose per dose is 30 mg, and the concentration in the antitussive may be adjusted within this range. For example, one grain
Assuming that 8 to 12 drops of 5 g are taken per day, 0.25 to 100 parts by weight of sugar in the drop
It is suitable to add 0.75 parts by weight of dextromethorphan phenol phthalate.

Next, the sucrose fatty acid ester used in the present invention is obtained by esterifying with a fatty acid while partially leaving a hydroxyl group (OH group) of sucrose which is a disaccharide.
Monoesters, diesters, triesters, polyesters, and mixtures of two or more thereof can be used. In addition, any sucrose fatty acid ester can be used as an emulsifier for a drug as long as it conforms to the Pharmaceutical Ingredients Standard outside the Japanese Pharmacopoeia. Specific examples of fatty acids constituting such sucrose fatty acid esters include stearic acid, palmitic acid, oleic acid, lauric acid and the like.

The mixing ratio of the above-mentioned sucrose fatty acid ester is suitably 2 to 200 parts by weight based on 100 parts by weight of dextromethorphan phenol phthalate.
Usually, the mixing ratio of the sucrose fatty acid ester in all the components is preferably 0.1 to 2.0% by weight. When the sucrose fatty acid ester is in a small amount less than the above-mentioned predetermined range, dextromethorphan phenol phthalate in the mixture at the time of production is separated before the end of molding, or immediately separated in a syrup and is not usable. . Further, even if the amount is more than the above-mentioned predetermined range, the dispersion stability is not further improved, and practicality is rather lost.

To produce the antitussive of the present invention in the form of a drop, first, the selected saccharide is used as it is or dissolved in an appropriate amount of water at a water content of 15 to 40% and a water content of 100 to 115 ° C. Prepare an aqueous solution of the drop substrate.

A mixture of dextromethorphan phenolphthalate and sucrose fatty acid ester 100
An aqueous solution to which 160 to 250 parts by weight of water is added is added to the prepared aqueous solution of the drop substrate while being added little by little to each other, and mixed and uniformly dispersed. At this time, other medicinal components are added as needed.

Then, the mixture is concentrated by heating or concentrated by heating under vacuum to reduce the water content to 3% or less. If necessary, a fragrance, a dye and the like are added and kneaded, and then molded.

As a molding method, a certain amount of the raw material is poured into a mold and then cooled and solidified, a method using a stamping machine including a punch and a die, or cooled and solidified after passing between two rollers having a circumferential groove. For example, a method of cutting a rope-shaped one to a certain size, and the like.

The heating and vacuum concentration methods include:
A method of performing concentration under normal pressure or vacuum in a batch system,
Although there is a method of performing continuous vacuum concentration, any method may be adopted.

In order to produce the antitussive of the present invention in the form of a syrup, the selected saccharide may be used as it is or dissolved in an appropriate amount of water to obtain a syrup having a water content of 40 to 95% and a water content of 60 to 95%.
Prepare a syrup base in an aqueous solution at 100 ° C.

Thereafter, a mixture of dextromethorphan phenolphthalate and sucrose fatty acid ester is uniformly dispersed in the same manner as the dropping agent, and if necessary, water is added to make a syrup (liquid). .

[0024]

[Example 1] 6 g of dextromethorphan phenolphthalate and 2.7 g of sucrose fatty acid ester
(Equivalent to 0.15% by weight of the total amount), and then an appropriate amount of water or hot water was added to form a soft paste. Further, according to the above-described embodiment, a drop substrate (equivalent to 1794 g as a solid content) is prepared, and this is heated to about 100 ° C. to dissolve the paste. After cooling to a suitable temperature (60 to 90 ° C.), the mixture was cooled by molding and solidified to obtain a molded dropping agent. The above operation is performed under a vacuum condition (500 to
The pressure was reduced to about 700 mmHg.

Example 2 The same operation as in Example 1 was performed by a continuous vacuum method (under reduced pressure of about 500 to 700 mmHg).
A drop agent was produced in exactly the same manner as described above. In Example 1 and Example 2, it was confirmed that the dropping agent was in a homogeneous state even when stirring was stopped in the mixing step and the dissolving step of the production process, and that the active ingredient and the like were not separated.

Example 3 1.8 g of dextromethorphan phenolphthalate and sucrose fatty acid ester 1.
After mixing well 8 g (corresponding to 0.15% by weight of the total amount),
An appropriate amount of water or hot water was added to form a soft paste. Also, a syrup base was prepared according to the above embodiment, and 480 g of water was added to 720 g of the syrup base, and about 10
The mixture was heated and dissolved at 0 ° C, and the paste was mixed with the mixture by stirring to obtain a syrup. In Example 3, it was confirmed that the dropping agent was in a homogeneous state even when stirring was stopped in the mixing step and the dissolving step of the manufacturing process, and that the active ingredient and the like were not separated.

Comparative Example 1 A drop was formed in exactly the same manner as in Example 1 except that sucrose fatty acid ester was not added to dextromethorphan phenol phthalate.

Comparative Example 2 A dropping agent was produced in exactly the same manner as in Comparative Example 1, except that the same operation was performed in a continuous vacuum system. In Comparative Examples 1 and 2, when stirring was stopped in the mixing step and the dissolving step of the production process, dextromethorphan phenol phthalate did not dissolve and floated on the surface of the composition and did not become uniform. I needed to continue.

Comparative Example 3 A syrup was obtained in exactly the same manner as in Example 3 except that sucrose fatty acid ester was not added to dextromethorphan phenolphthalate.

In Comparative Example 4, when stirring was stopped in the mixing step and the dissolving step of the production process, dextromethorphan phenol phthalate did not dissolve, and did not float uniformly on the surface of the composition. In addition, it was necessary to continue stirring at all times.

The dispersing state of the dropping agents of Examples 1 and 2 obtained as described above and the dropping agents of Comparative Examples 1 and 2 was compared with the naked eye, or the syrup of Example 3 and Comparative Example 3 were compared. When the dispersion state of the syrup preparation (after standing for 12 hours) was compared with the naked eye, in each case, the examples were more excellent in uniformity than the comparative examples, and in the examples, there was no air bubble mixing, and the examples were remarkable. There was a significant difference. Therefore, a quantitative test of dextromethorphan phenolphthalate was carried out, and the results were compared, and it was found that there was a clear significant difference.

[0032]

As described above, the present invention provides an antitussive containing saccharide as a main component, dextromethorphan phenol phthalate as an active ingredient, and a sucrose fatty acid ester as a dispersant. There is an advantage that the dispersed state after mixing with the above becomes a stable antitussive.

The addition of sucrose fatty acid ester improves the emulsification stability of dextromethorphan phenol phthalate, so that it can be produced as an antitussive drop which can be produced even if the time required for kneading is reduced, or is uniform. There is an advantage that it becomes a cough syrup having a stable dispersion state for a long time.

Continued on the front page (58) Fields surveyed (Int. Cl. ⁶ , DB name) A61K 31/485 A61K 9/08 A61K 9/20 A61K 47/26 CA (STN)

Claims (3)

(57) [Claims] 1. An antitussive comprising a saccharide as a main component and dextromethorphan phenolphthalate as an active ingredient, wherein a sucrose fatty acid ester is added as a dispersant for the active ingredient. 2. The compounding ratio of the sucrose fatty acid ester is as follows:
The antitussive according to claim 1, which is 0.1 to 2.0% by weight. 3. The antitussive according to claim 1, wherein the preparation is a drop or a syrup.