JPH01207229A - Suppository - Google Patents

Abstract

PURPOSE:To obtain a suppository which shows clear boundaries between individual layers, when a multi-layered suppository is produced to facilitate the quality control, by dispersing a pigment insoluble in the base material in the oily base material. CONSTITUTION:An oily base material which is solid at room temperature is combined with a pigment insoluble in the base (preferably less than 50 microns, especially less than 10 micron average particle size) by 0.001-1.0wt.%, preferably 0.001-0.01wt.% and the pigment is dispersed homogeneously. The use of the base material enables the suppository to be uniformly colored and the quality control becomes easy, when multi-layered suppositories are produced.

Description

[Detailed Description of the Invention] [Industrial Application Field] The present invention provides suppositories, and more specifically, when made into multilayer suppositories, the boundaries between each layer are clear and quality control can be easily performed. It concerns suppositories.

[Conventional technology]

Suppositories that have been widely used in the past are generally single-layer suppositories, which are made by blending one or more medicinal ingredients into an oily base that is solid at room temperature and whose main ingredient is fatty acid triglyceride. It is.

Incidentally, in recent years, various multilayer suppositories have been devised from the concept of drug delivery systems. That is, by using base materials with different melting points in a multilayer suppository, the release of the drug from the suppository over time can be sustained, or by adding various thickeners to a certain layer, only the drug in that layer can be used. Efforts have also been made to delay the release sound of the drug, and to add absorption enhancers such as sodium cassilonate and sodium salicylate only to certain layers to increase the absorption of the drug only in that layer.

[Problem to be solved by the invention]

However, there have been several problems with conventional suppositories, particularly multilayer suppositories. That is, multilayer suppositories generally have
The heated and melted first base is poured into a suppository molding container, cooled to solidify or semi-solidified, and then heated and melted again.
It is manufactured by repeatedly injecting base gold and cooling it, but in multilayer suppositories manufactured in this way, the boundaries between each layer and other layers are unclear, making manufacturing control difficult. It often doesn't make it all the way. For example, the injection of each layer does not proceed smoothly, resulting in uneven products, or the interfaces are mixed, resulting in defective products. However, since each layer of a multilayer suppository generally uses the same base material, it is difficult to distinguish them in terms of appearance, and therefore, there is insufficient control to prevent the occurrence of such defective products.

Additionally, suppositories are generally white and bullet-shaped, making them difficult to distinguish visually, and there is a risk of misuse when handling two or more types of suppositories.

As a means to solve these problems, it has been proposed to color suppositories like other preparations such as tablets. As the coloring agent, for example, azulene, which is a bluish-purple anti-inflammatory agent, and yellow lecithin are used. Since these colorants are oil-soluble, they can uniformly color the oil-based base, but in multilayer suppositories, migration from one specific layer to another occurs during storage, resulting in insufficient effect. I was unable to demonstrate my potential.

Therefore, there has been a desire to develop colored suppositories that have clear boundaries between layers, can be easily controlled for quality, and are stable over a long period of time.

[Means to solve the problem]

Therefore, the present inventors conducted extensive research to overcome all the drawbacks of conventional suppositories, and as a result, a suppository using a base in which pigments that are insoluble in an oil-based base are uniformly dispersed in an oil-based base has been developed. They discovered that not only can coloring be uniform, but also that in the case of multilayer suppositories, there is no movement of pigment between the layers, making it easier to control quality during filling and prevent misuse of pigments. The invention is complete.

That is, the present invention provides a suppository made of an oleaginous base, characterized in that an insoluble pigment is uniformly dispersed in the oleaginous base.

The base used in the present invention is not particularly limited as long as it is solid at room temperature and oily. ? Shea ■ (Gattefosse), SB ■ (manufactured by Kanebuchi Chemical Industry Co., Ltd.), Fur-Sol ■ (
Examples include non-regular hard fats such as Nippon Oil & Fats.

In the present invention, "insoluble in an oleaginous base" means that it is not compatible with the oleaginous base, whether the oleaginous base is in a solid state or in a molten state.

Preferred examples of such dyes include tar-based dyes, specifically red 2°3.102.104.
105.106, 201.202.203.204.2
05, 206, 207, 208, 213, 214. 2
15.218. 219. 220. 221. 22
3.225, 226. 227. 228.230゜231.232, yellow 4.5.201.202.20
No. 3.204.205, green 3.201.202.20
4,2Q5, orange 201.203.204,2
No. 05.206.207, Blue 1.2, 201, 202
゜203.204,205, brown color 201, purple 2
Gold such as No. 01 can be mentioned.

These tar-based pigments are approved for use as coloring agents in pharmaceuticals in Japan, and are usually used as colorants for oil-based bases.
．． 001~LO weight.

Preferably, the weight ratio of 0001 to 001 is added. The dye used in the present invention preferably has an average particle size of 50 μm or less, particularly 10 μm or less. If the particle size is large, the coloring will be uneven, which is not preferable.

The medicinal ingredients to be incorporated into the suppositories of the present invention are not particularly limited as long as they are those conventionally used in suppositories, but for hemorrhoid suppositories steroids such as hydrocortisone acetate and zolednisolone acetate; , local anesthetics such as zobucaine; bactericidal agents such as cetricide and chlorhexicine hydrochloride; vitamins such as vitamin E; hemostatic agents such as zinc oxide; allantoin and its derivatives. In addition, examples of medicinal ingredients of suppositories other than those for hemorrhoids include nonsteroidal antipyretic, analgesic, and antiinflammatory agents such as indomethacin and aspirin; hypnotic sedatives such as phenoparbital sodium; antiemetics such as tonpelitone; and ptylscobromide? Examples include antispasmodics such as lamin; laxatives such as glycerin; antitussive expectorants such as zozolophyllin; and anti-malignant tumor agents such as tegafur.

Although the suppositories of the present invention include both single-layer suppositories and multi-layer suppositories, multi-layer suppositories are particularly preferred. Multilayer suppositories include 2-layer suppositories, 3-layer suppositories, 4-layer suppositories...
The weight of one suppository is approximately 1.5 to 2.
．． Considering that it is about OP, two-layer suppositories are the easiest to manufacture. For this reason, especially in two-layer suppositories, if either the tip or the base of the suppository is colored with the above-mentioned oil-based base-insoluble dye, especially a tar-based dye, the boundary between the tip and the base can be clearly indicated. Can be done. According to this idea, it is possible to color each layer of a multilayer suppository with three or more layers using various dye tones, but it is fine as long as it is possible to distinguish each layer, and it is preferable to use the same dye. It is possible to distinguish the boundaries of each layer by coloring every other layer, or it is also possible to color every other layer using a plurality of different pigments.

The suppositories of the present invention, particularly the multilayer suppositories, are prepared by adding the pigment to a heated and melted oil-based base, mixing and stirring until homogeneous, pouring into a suppository molding container, cooling, and performing the same operation. 2
It can be manufactured by pressing all the layers and sequentially performing all the same operations.

[Effect]

The pigment used in the suppository of the present invention is not compatible with the oily base. Therefore, the suppository of the present invention is colored by dispersing fine particles of the pigment in an oily base. Therefore, in the oily base, the pigment particles are fixed to the solidified oily base and do not move, especially in the case of multilayer suppositories.
It seems that no migration occurs from one particular layer to another.

〔Effect of the invention〕

The suppository of the present invention has a pigment insoluble in the oily base uniformly dispersed in the oily base.
In the case of multilayer suppositories, the boundaries between each layer are clear, which increases the accuracy and ease of quality control during manufacturing. Furthermore, since this dye is insoluble in the oil-based base, it does not migrate to other 1- molecules and is stable for a long period of time.

〔Example〕

EXAMPLES Next, the present invention will be described in detail with reference to Examples, but the present invention is not limited thereto.

Example 1 Oil-based base Incacao [Kao ■, melting point 37''C) 9Q9
Heat and melt 95 weight i%, red No. 102 1QOO5 weight i
% addition, 1.7% in a silastic container after mixing.
The mixture was filled in two batches to obtain a pale red single-layer suppository.

Example 2 The suppository base prepared in Example 1 was filled into a Silastic container with Q5F and cooled. After that, heated and melted Inca Cao'i 1.29 was further filled and cooled, so that the tip became light red and the base became pale red. A white two-layer suppository was obtained.

Example 3 Oil-based base Incacao [Kao ■ Melting point 37°C] 99, 99
7wt% by weight was melted by heating, and 3wt% of Blue No. 2 000 was added and mixed. The suppository base 052 prepared in Example 1 was poured into a Silasnac container, and after being cooled and solidified, only Incacao 052, which had been heated and melted, was poured and solidified. Then the suppository base f 0 prepared above
．． 7F was injected and filled to obtain a multilayer suppository consisting of three colors: pale red, white, and pale blue.

Example 4 Incacao (melting point 37°C) 98997 wt% was dissolved by heating, blue No. 2 0.0 O3 wt%, zopcaine hydrochloride 1
Add i% by weight, mix and stir, pour into a plastic container at 0.5F, and cool and solidify. Next, 86.9% by weight of incacao (melting point 37°C) was melted by heating, and 1% by weight of zoletnisone acetate, 1% by weight of allantoin, and 1% by weight of zoletnisone acetate were added. Oi amount, α-tocopherol acetate 2.0ffif%, zinc oxide xaoi! %, mix and stir, and pour 1.2f more into the Shirasunak container that was poured earlier.
The mixture was cooled and solidified to obtain a two-layer suppository.

Experiment 1 Poly/8 suppositories produced in Example 2 and Example 3 were heated at 35°C.
The samples were stored in a constant temperature room at 20° C., and changes in coloration were observed over time. As a control, a multilayer suppository containing guaiazulene kumquat as an oil-soluble pigment instead of the water-soluble pigment of Example 2 was used.

The results are shown in Table 1. The product of the present invention showed no migration of the dye and was stable compared to the control product. Table 1 Judgment Criteria m: No migration of the dye +: Movement of the dye was within 5 mna from the interface; Movement is within l OInrn from the boundary surface +++ Movement of two dyes is at least l Onum from the boundary surface

Claims (1)

[Claims] 1. A suppository made of an oleaginous base, characterized in that an insoluble pigment is uniformly dispersed in the oleaginous base.