JPH0717495B2 - Method of manufacturing multi-layered suppository - Google Patents

Description

TECHNICAL FIELD The present invention relates to a method for producing a multi-layer suppository, and more specifically, by continuously filling each layer of a multi-layer suppository in which a plurality of layers are laminated horizontally. It relates to a method of manufacturing.

[Prior Art] Conventionally used suppositories have one or more drugs mixed in a base such as an oily base, a water-soluble base or an emulsion base, and uniformly dispersed and mixed. Single layer suppositories are common. The manufacturing method is, for example, a method in which a drug is uniformly dispersed and mixed in a melted oily base, and a fixed amount of the drug is filled into a suppository molding container and then cooled.

By the way, in recent years, various multilayer suppositories have been devised from the viewpoint of effective use of medicinal components. That is, one of the purposes in a multi-layered suppository is to combine a plurality of medicinal components into a suppository, and to include each medicinal component in the base most suitable for its manifestation of its medicinal properties, thereby producing the effect of each medicinal component. It is intended to make full use of. For this purpose, it is necessary that the layer containing a certain medicinal component and the other layer exist in separate states. The method for producing such a multi-layer suppository is basically the same as that for the above-mentioned single-layer suppository, that is, after filling the suppository molded container with the heated and melted base, it is cooled and solidified. There is known a method of repeating the steps of forming into a shape or a semi-solid state, filling and laminating with a new base material, and further cooling and solidifying (JP-A-56-73017).
issue).

[Problems to be solved by the invention]

However, in the conventional method for producing a multi-layered suppository, a cooling operation is required every time one layer is filled, and the produced suppository has a mixture of the bases laminated depending on the storage temperature and the time, and the medicinal ingredients for other layers. There was a problem such as the migration. Further, such a problem has been an obstacle to development of various functions recently required for suppositories, that is, sustained-release suppositories, suppositories having a lower portion of the rectum, and the like.

[Means for solving problems]

Therefore, the present inventor has conducted various studies to solve such problems, and it is possible to continuously fill the laminate of each layer of the multilayer suppository at a melting temperature or higher by subjecting the oily base to a treatment for increasing the viscosity. It has been found that it is possible to produce a multi-layered suppository having a function according to various uses, and completed the present invention.

That is, in the present invention, in producing a multi-layered suppository in which a plurality of layers are laminated horizontally, a solid oily base that forms each layer is heated and melted at a temperature of 40 degrees for layers other than the final layer.
Adjust the viscosity at ℃ to be 10,000 to 1,000,000 cp,
For the final layer, adjust the viscosity as above, or
Alternatively, without any adjustment, a suppository molding container is continuously filled with the base at a temperature equal to or higher than the melting temperature, and then the whole is cooled and solidified to provide a method for producing a multilayer suppository. is there.

The base used in the present invention is solid at room temperature and oily.
It is not particularly limited as long as it is, for example, cocoa butter, lanolin
Fat, isocaca (Made by Kao), Witepsol (Die
Namitsu Nobel), Saposia (Gatsutte Otsuse
Company), SB (Made by Kanebuchi Chemical Industry), Fuamasol (Japan
For example, an external regulation hard fat such as oil and fat) can be used.

The medicinal components used in the present invention include steroids such as hydrocortisone and hydrocortisone acetate for hemorrhoids; local anesthetics such as dibucaine hydrochloride, procaine hydrochloride and lidocaine; anti-inflammatory agents such as glycyrrhetinic acid, dipotassium glycyrrhizinate and allantoin; Examples include bactericides such as chlorhexidine hydrochloride and cetricid; retinol palmitate and vitamins such as dl-α-tocopherol. Examples of suppositories for antipyretic analgesia and anti-inflammatory include aspirin, sodium salicylate, indomethacin, oxyphenbutazone and the like. , Antibiotics, suppositories for chemotherapy, penicillin G sodium, chloramphenicol, fangizone, sulfadimethoxine, and various sulfa drugs, but it goes without saying that they are not limited to these. Ah .

The treatment for increasing the viscosity in the present invention is basically performed by adding a thickener.

Examples of thickeners used include light anhydrous silicic acid, aluminum salts of stearic acid, calcium salts, barium salts or magnesium salts, 12-hydroxystearic acid, condensates of D-sorbitol and benzaldehyde [eg, Gelol D (Shin Nippon Rika Co., Ltd. Manufactured), dextrin fatty acid ester [for example, Leopard KE (manufactured by Chiba Flour Milling Co.)], styrene-ethylene-butylene-styrene polymer [for example,
SEBS (manufactured by Ciel Chemical Co., Ltd.)], organic bentonite, and the like.

In order to carry out the present invention, first, the necessary medicinal components and a thickening agent are added to a product obtained by heating and melting the above-mentioned oily base and uniformly dispersed. Thickeners vary depending on their type, but 1 to
It is preferable to add it in a range of 50% by weight, particularly 5 to 10% by weight so that the viscosity at 40 ° C. is 10,000 to 1,000,000 cp.

Next, a multi-layered suppository is manufactured by filling the obtained suppository base into a suppository forming container, continuously filling the suppository base, and then cooling and solidifying the whole.

In the method of the present invention, the oily base forming the final layer does not necessarily have to be subjected to a treatment for increasing the viscosity.

〔The invention's effect〕

According to the present invention, it is possible to manufacture a multi-layered suppository in which a plurality of layers are laminated horizontally by continuously filling an oily base at a temperature equal to or higher than the melting temperature. Therefore, in addition to the fact that the operation during manufacturing is extremely easy, the respective layers do not mix even at the melting temperature, and it becomes possible to include a plurality of medicinal components in the base most suitable for exhibiting their medicinal effects. Furthermore, it has recently become possible to provide various functions required for suppositories, such as a sustained release suppository and a lower rectal retention suppository.

〔Example〕

 Next, the present invention will be described in detail with reference to examples.

Example 1 An extra-standard hard fat (Isocacao KD35) was heated and melted at 50 ° C., and 1 to 7% by weight of light silicic anhydride (Aerosil 200, Nippon Aerosil Co., Ltd.) was added thereto and a homomixer was used. Mixed well. 1 g of this was filled in a suppository molding container for filling 2 g (transparent container). Separately, an extra-standard hard fat (Isocacao KD35) was heated and melted at 50 ° C, and 1 g of guaiazulene as a coloring agent was added to the container to prepare 1 g, which was continuously filled and laminated to mix the base materials. Was visually observed.

Evaluation Criteria A: Can be laminated without admixture of base materials.

B: A part of the base is mixed and cannot be stacked horizontally.

C: The whole mixture is uniformly mixed and cannot be laminated.

Example 2 Example 1 except that a thickening agent was added to the oily base of the first filling base, gently dispersed and filled, and then ultrasonication (oscillation frequency 45 KHz, high frequency output 60 W) was performed for 30 minutes. The same operation as above was performed to evaluate the laminated state.

The results are shown in Table 2.

Claims (1)

[Claims] 1. When manufacturing a multi-layer suppository in which a plurality of layers are laminated horizontally, a solid oily base which forms each layer is heated and melted, and the layers other than the final layer are heated at a temperature of 40 ° C. The suppository molding container is adjusted to have a viscosity of 10,000 to 1,000,000 cp, and for the final layer, the viscosity is adjusted in the same manner as above, or is not adjusted, and the base is heated at a melting temperature or higher. A method for producing a multi-layer suppository, which comprises continuously filling and then solidifying by cooling.