JPS5916595B2 - Manufacturing method for suppository base - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention provides a raw material made from lauric acid fat that melts at body temperature, has an elevated melting point of 37°C or less, has a sufficient hardness of 0°C at room temperature, and has good drug absorption from the rectum. This invention relates to a method for producing fats and oils suitable for medicinal bases.

The lauric acid oils and fats referred to herein refer to natural oils and fats with a lauric acid content of 40 to 50%, such as coconut oil and palm cedar oil.
These fats and oils generally have an elevated melting point of 24-28'5°C, an iodine value of 8-20, and a saponification value of 240-260. The obvious difference from other natural fats and oils is its unique lauric acid content and low iodine value. Therefore, at low temperatures, it has a high hardness but a low melting point, so it is not suitable as a j0 base for crude drugs. Conventionally, cacao butter has been widely used as a base for crude drugs.

Cocoa butter melts easily at body temperature, has sufficient hardness at room temperature, is harmless and easily available, but has an iodine value of around 34 and is susceptible to oxidation during long-term storage, which may deactivate drugs. In addition, they have drawbacks such as poor emulsifying properties, insufficient emulsification with body fluids, and poor drug absorption. Therefore, synthetic oils and fats have been developed to replace drugs with systemic effects. Such synthetic oils and fats are produced by hydrogenating lauric acid oil and fractionating the hydrolyzed fatty acids.
A mixture of saturated fatty acids (containing a large amount of lauric acid) having 12 to 18 carbon atoms and a polyhydric alcohol such as glycerin, excluding the fatty acid portion of ~10, has a partial glyceride of ~20 to
Esterification reactions conducted under 35 conditions that yield a yield of 40% have come to be widely used. These synthetic fats and oils do not contain unsaturated acids, are stable against oxidation, have appropriate hardness, have a hydroxyl value of 30 to 50, and have better emulsifying properties with body fluids than cacao butter.

However, the production of these synthetic oils and fats requires the addition of heavy metal catalysts such as zinc dust, zinc oxide, tin chloride, and titanium compounds during esterification under reduced pressure or in a nitrogen atmosphere, and the reaction takes place for a long time at high temperatures of 200°C or higher. There are problems such as.

That is, ((a)) Reaction for a long time at a high temperature of 200° C. or higher promotes deterioration such as polymerization, and the presence of a metal catalyst promotes coloration due to the reaction between hydroxyl groups and heavy metals. These reactants are difficult to remove even by conventional purification operations, and satisfactory decolorization cannot be achieved.
In particular, the deodorizing operation after bleaching will cause the coloring to occur again. or,
There are problems in terms of time and work. (b) The heavy metal catalyst added during esterification may remain in the product to a considerable extent, which is not preferred as a base for suppositories.
The present invention solves these problems, and includes a step of hydrogenating lauric acid oil to an iodine value of 5 or less without hydrolyzing the raw material oil into fatty acids, and a process of adding glycerin to the obtained hydrogenated oil to an oil value of 10. A step of adding ~15% by weight and performing a glycerolysis reaction, a step of removing most monoglycerides and low molecular weight glycerides from the reaction product by molecular distillation to obtain a residual oil with a hydroxyl value of 30 to 50, and a step of removing the residual oil. The gist of the present invention is to provide a method for producing a suppository base having a melting point of 37° C. or less and an SFI value of 60 or more at 20° C. and having good drug absorption properties, which comprises a step of random transesterification.

Each step will be explained in detail below. First step.

Anneal oil has about 5-8% oleic acid, and palm kernel oil has about 13% oleic acid.
This is a necessary step to increase the oxidation stability of the product and give it a desirable hardness by converting it into stearic acid by hydrogenation. It is desirable to do so. This hydrogenation can be carried out by conventional methods for hydrogenated oil production.

Second process.

This step is often carried out using only hydrogenated lauric acid oil, but if a higher melting point is required, a small amount of another extremely hardened oil may be added. Hydrogenated palm oil and the like are suitable fats and oils for this purpose. This step is a so-called glycylolysis reaction in which glycerin is added to hydrogenated lauric acid oil and fat and reacted in the presence of a catalyst to produce partial glyceride. Partial glycerides refer to monoglycerides and diglycerides, in which a certain amount of hydroxyl groups are produced. Add an alkali metal hydroxide such as caustic soda as a catalyst, and add glycerin of 10 to 15% to oil at 150 to 200℃.
React for 30 to 60 minutes. It is best to carry out the process in an inert gas stream without contacting with air (oxygen). After the reaction is completed, the catalyst is deactivated with an inorganic or organic acid such as phosphoric acid, and the catalyst is removed by adsorption and decolorized with activated clay. Third step.

Molecular distillation is performed to remove the majority of the monoglycerides and low molecular weight fat fraction from the glycerolysis product. Molecular distillation is distillation carried out under a high vacuum of 10-2 to 10-3 mmHg, and there are centrifugal and thin film flow methods, and either type may be used in the present invention. Usually 150
By distilling at ~180°C and removing about 40-60% of the low molecular weight portion, it has a hydroxyl value of 30-50 and a melting point of 40.
Obtain residual oil at ~44°C. Fourth step.

The residual oil obtained in the third step has a high melting point and insufficient hardness, but by random transesterification to unify the distribution of glycerade, it melts at body temperature (i.e., melting point is below 37°C). ) and obtain a product with sufficient hardness. Random transesterification is carried out using an alkali metal hydroxide such as caustic soda or an alkali metal alcoholade such as sodium methylate as a catalyst, and at 60 to 200°C and 30 to 60°C in the presence of an inert gas or under reduced pressure.
react for minutes. After the reaction is completed, the catalyst is deactivated with an inorganic or organic acid, and the product is further purified by a conventional method. Next, in order for the oil and fat thus obtained to have properties as a high-quality suppository base especially for systemic effects, it must generally satisfy the following conditions.

(1) The rising melting point is below body temperature.

(2) Solidify quickly during molding.

(3) Must have sufficient hardness at room temperature.

(4) Having a hydroxyl value of 30 to 50.

Whether or not the above items are satisfied depends on the rising melting point, crystallization rate, hydroxyl value, SFI (SOlid Fat Index),
Test 1 The solidification time and load required to deform the molded product will be measured using a suppository mold.

The presence or absence of cracks in the molded product is also a necessary judgment item for practical purposes. If the crystallization rate is greater than 0.15 m1n-1, it can be said that solidification occurs rapidly. Also, if the SFI value is as follows, the product has hardness suitable for practical use and melts at body temperature. Example Hydrogenating palm kernel oil at 140°C using a nickel catalyst,
A hardened oil with a melting point of 41.0°C and an iodine value of 0.40 was obtained.

This is subjected to a glycerolysis reaction using 12% glycerin to oil and 0.1% caustic soda as a catalyst at a temperature of 150 to 170° C. for 60 minutes under a nitrogen gas flow. After the reaction is complete, the catalyst is deactivated and purified using activated clay. This refined oil has an acid value of 1.
5. It has an analytical value of hydroxyl value of 170.5 and melting point of 30.5°C, but it was distilled to a temperature of 180°C using a thin film falling molecular distillation apparatus.
Molecular distillation was carried out under soil conditions of 5°C. A residual oil was obtained with a yield of 42.5%.

The residual oil has an analytical value of hydroxyl value of 43.5 and melting point of 41.5°C. The obtained residual oil was mixed with 0.15% caustic soda as a catalyst.
% using 160-170℃, 5111LHg under reduced pressure 6
Perform random transesterification for 0 minutes. After the reaction is complete,
After deactivating the catalyst, it was purified in a conventional manner to obtain an oil or fat having the following analytical values. Crystallization rate {Deman: Milchwis
enschaftl8, 67-70 (1963)}0.
16-1, when poured into a suppository mold controlled at 10°C, it solidifies within 7 minutes, and the molded product can withstand a load of 3.01<g at 20°C.

Claims (1)

[Scope of Claims] 1. A step of hydrogenating a lauric acid oil to an iodine value of 5 or less, a step of adding 10 to 15% by weight of glycerin to the oil to the obtained hydrogenated oil to perform a glycerolysis reaction, and a step of performing a glycerolysis reaction from the reaction product. A process of removing monoglycerides and low molecular weight glycerides by molecular distillation to obtain a residual oil with a hydroxyl value of 30 to 50, and a process of subjecting the residual oil to random transesterification. A method for producing a suppository base with good drug absorption of 60 or more at 20°C. 2. The method for producing a suppository base according to claim 1, wherein a small amount of another extremely hardened oil is added to the lauric acid-based hydrogenated oil to carry out a glycerolysis reaction. 3. Production of a suppository base according to claim 1 or 2, in which an alkali metal hydroxide is used as a catalyst during the glycerolysis reaction and the random transesterification reaction, and the reaction is carried out at 200°C or lower in an inert gas stream. Method. 4 Using an alkali metal alcoholate as a catalyst for the random transesterification reaction, in an inert gas stream of 5
Claim 1 or 2 in which the reaction is carried out at ~70°C
2. Method for producing a suppository base as described in Section 1.