JPS58213710A - Suppository composition - Google Patents

Abstract

PURPOSE:A suppository composition useful mainly as an antiphlogistic, analgesic, and antipyretic alleviating unpleasant stimulation occurring immediately after insertion in the intestine, obtained by adding a hydrophilic carboxylic group- containing compound and amorphous alumina fine powder to a fatty acid glyceride as a base. CONSTITUTION:A fatty acid glyceride (natural or semisynthetic) is blended with a hydrophilic carboxyl group-containing compound (e.g., ibuprofen shown by the formula I , ketoprofen, flurbiprofen, naproxen, or aspirin) and 1.0-10.0wt% amorphous alumina powder based on fatty acid glyceride, to give a suppository composition. The addition of the amorphous alumina fine powder alleviates stimulation, prevents the main agent in the suppository from precipitating by its high shaping action caused by its high bulkiness, provides melting by the temperature in the outside, restoring properties from deformation, etc.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention is a base composition for rectal administration containing a hydrophilic compound containing a xyl group, such as ibuprofen, in which fine amorphous alumina powder is mixed into the base fatty acid glyceride. This invention relates to a base composition that relieves local discomfort during use.

Conventionally, pharmaceuticals have been administered to the human body by various methods (administration routes). Taking painkillers as an example, the most common method is through the mouth (oral administration). For example, oral administration in the form of solutions, powders, tablets, etc. is the most common and simple method. Sometimes intramuscular or intravenous injections are used to administer drugs directly into the body. Methods of administration of analgesics [7] In addition to the above, the main drug is administered rectally, and there are almost no other administration methods. However, in the case of analgesics, there are many drugs that often cause bilateral pain when administered orally, so continuous administration is often restricted, and injection is not superior to this in terms of rapid action, but in any case, when injecting Pain is unavoidable, and in this case, at least medical attention is required, and sometimes there are side effects. Therefore, in recent years, instead of the above-mentioned administration methods, there has been a tendency to focus on main agents administered rectally.

Next, the advantages of administering the main agent are as described in the first section: (1) Bilateral damage is less likely to occur; (2) there is no strong aversion to taste or odor; (3) continuous use is possible. It is; .

(4) It can be administered to infants; and (5) It can be administered to postoperative patients who are unable to administer it orally.

Next, the 20 to 30 requirements for the base agent are as follows: (1) The base must be easy to melt or dissolve in the rectum: (
2) The drug contained in the base agent is easily released from the base agent into the rectal fluid; and (3) The outside temperature of the yarn used is If11! ! Even if it melts and collapses due to a change in the form of the main ingredient, it has so-called restorability, meaning it can be used again if it is cooled.

The main ingredient must meet the conditions listed above7! Ij4111
In order to meet this demand, research and development are being conducted to develop better base materials. In actual product production, various materials such as main ingredients and base materials as well as additives (improvers in a narrow sense) are combined. Bases can be broadly divided into oil-based ones and hydrophilic ones such as deliethylene glycol (PEG: macrogol), and the present invention deals with the case where the former is used as the base. Natural oils, particularly vegetable oils, have traditionally been used as the oleaginous base. For example, cacao butter has been the most commonly used base material since ancient times. Recently, semi-synthetic mono-, di-, or triglycerides of fatty acids (e.g. Witepzol: K in Mitsuba Trading) have been introduced due to their excellent physical properties such as melting point and resiliency, as well as good dispersibility in the intestines.
tends to be used more often.

Next, additives for the main ingredient include substances (such as surfactants) that promote the release of the main ingredient from the base and increase its absorbability in the body, and substances that can be cooled even if the temperature exceeds the melting temperature during flow-through summation after shipping. For example, materials that can be converted into a usable form, and materials that have the role of preventing uneven distribution of the main ingredient in a short period of time even when placed in a molten state are being researched.

In this way, the base material is manufactured by making various efforts in selecting additives in addition to the base material, and then mixing it with the base material and molding it into the base material. However, even if the base agent commercialized in this way is a mourning preparation with excellent absorbency and quality,
For example, if the base ingredient itself is locally irritating, further efforts may be made to alleviate the irritation (for example, by coating the surface of the bulk powder with a film agent to reduce the time of contact with the local area, or by using trial and error methods to find appropriate additives). (selective addition, etc.) is necessary.

Ippro 7-ton (hereinafter referred to as IP) is an antipyretic, analgesic, and anti-inflammatory agent.
) is known to have a pungent taste.
For this reason, oral administration of this drug to infants and children was particularly discouraged.

Since the IP is a particularly safe drug, the present inventors investigated changing the route of administration and using it as the main agent, and found that the IP had a concentration of LF in the blood that was comparable to that of the oral preparation. Although it was successful, 1% of patients at the time of administration immediately after rectal insertion.
It was found that the product caused a short-lived irritation (tingling sensation, hereinafter simply referred to as irritation)'&, and it was judged that it would not be practical unless this unpleasant irritation was reduced. Therefore, the present inventors conducted a thorough investigation on various additives, and found that small-ridged aluminum oxide powder (hereinafter referred to as AL2
0s It is a half-open composition with additives added to relieve irritation during use. Specifically, fatty acid glyceride is used as a half-open base containing IP,
This invention relates to an IP skewer composition characterized in that amorphous At203 is mixed therein in advance.

The half-open bottle containing the IP according to the present invention consists of the following set bν: Ibuprofen in one suppository 50-40011L9A Z20
s 40-200 m9 fatty acid daliceride 800-15001! Weight of 1 piece 900
~2000 ■ The main ingredient is IP, but At 20 s is fine amorphous At
20s (preferably Aluminum Oxide-C manufactured by Nippon Aerosil Co., Ltd.) is blended into the preparation from 4 to 10 times, and as the fatty acid glyceride, Witepsol, which is most commonly used as a semi-open base, is used. In addition, Uitedezol, At2
Additives other than 0s, such as preservatives and other substances known for use in half-open compositions, may optionally be included. +p (Structural Formula I), which is the crude drug of the composition in the present invention, has a molecular structure of [-tecal] having a xyl group, and it is presumed that this hydrophilic functional group is responsible for the above-mentioned irritation. .

The mechanism of action of A120g is unclear, but according to experiments, I
The irritating properties of P are as follows when IP is in a crystalline state.

It is weak and becomes strong when it is in a dissolved state, so that the IP partially dissolved in the base during half-open manufacturing becomes ^β2o3 when cooled.
This is thought to be due to the presence of 6205, which causes it to precipitate as fine crystals on the surface of 6205. Furthermore, since ^1320B is a structurally amphoteric substance with strong adsorptive properties, it is presumed that the xyl group of the terminal free cal of IP is protected.

What can be said from these estimates is that, like IP, many anti-inflammatory agents, antipyretics, and analgesics have hydrophilic functional groups in their molecules, such as sil groups in their molecules, and aspirin is one example. It is known that aspirin's main drug also has the same irritating properties as IP immediately after rectal insertion.

Base formulation IC to which the present inventors have added Ag2O3 in advance,
Kneading aspirin (411m) ・In experiments conducted on aspirin's main ingredient, ^β203 showed an effect of alleviating irritation, so AJ203 commonly exhibits an effect of alleviating irritation with these compounds. considered to be a thing.

Therefore, the hydrophilic cal-xyl group-containing compounds targeted by the present invention include the following substances, all of which are primarily used as analgesics.

rToprofen (Structural stratification) Nazoloxene (Structural Formula W) Flurbizolofen (Structural Formula V) Next, the base fatty acid glyceride used in the present invention is a natural or semi-synthetic fatty acid glyceride (a mixture of mono-, di- or triglycerides). body). Preferred is the commercial product Quitedezol, which is manufactured so as to reliably melt at body temperature (melting point 33-36C), and is said to have good dispersibility even in the intestines. Next, the amount of ^/1203 mixed in the half-open mixture of the present invention is 1.0 to 10.0% by weight based on the amount of fatty acid glycerol in the base. According to the present invention, if the amount is less than 1%, there is no effect of reducing irritation, and the amount to eliminate irritation during insertion is preferably 2 or more. On the other hand, 〇205 is a fine and bulky powder that has a stronger effect than fc, and this effect is good for preventing the main compound from settling +b% during sitting cutting.It is also convenient for imparting the above-mentioned restorability, and this effect is more than 5. Addition of 4-7
− was sufficient. In other words, the addition of ^8z05 can kill two birds with one stone since it not only reduces irritation but also has many other effects. As a result of testing the skewering composition of the present invention in which 1zos was mixed with the present inventor on a large number of human bodies, it was found that irritation during use was eliminated.

Half-open with the above composition is mixed lol! It is molded into a bullet shape using a temporary method and weighs 0.9 to 1.32 for children and 1.3 for adults.
It is said to be a product with a size of 5 to 2 degrees.

The IP-containing zakushi according to the present invention does not easily lose its shape even when stored outdoors during the hot season, and even if it softens, it can be cooled for a while in the refrigerator before use. It is a half-open product that can be used for a long period of time because it has excellent storage stability and does not cause any irritation during use. The following is a first embodiment of the present invention.

Example 1 1 P 11] Op fatty acid glycetoid.

Uitep V-le W-55900f ^this 3 [I P
Mix it in the above ratio and put it in a mixer 1ζ, about 50'
The creamy mixture obtained by heating the mixture and kneading it until the whole was uniform was placed in a skewer filling machine and formed into half-open pieces of 1030 cm in size to form a product.

1 circle! ! L flood l P 5009 fatty acid glycerides.

Huitedezol H-15150051 Porinupate ao 21^g203
100) In the same process as in Example 1, each sample was molded into a half-open piece of 1920 cm to obtain a product. Examples 1 and 2 Half-open products made from +C were used for clinical trials at many clinical facilities, and as mentioned above, no patients complained of irritation or local discomfort during use.

Example 5 , , 511 fatty acid glyceride 960P^e20,40'i The same steps as in Example 1 were followed to obtain a 1050 cm antipyretic skewer product for infants.

Example 4 Getoderofen 5 fatty acid glyceride 25i^rhos
``By preparing according to the process of Example 1 and IWJ, one 1,240-inch analgesic skewer product was obtained.

Example 5 Aspirin 100v Fatty acid glyceride 400LtAe2Q312v A half-open product for antipyretic and analgesic use was prepared in the same manner as in Example 1, weighing 1,280 square meters.

Claims (7)

[Claims] (1) A skewer composition characterized in that a hydrophilic carboxylic group-containing compound and amorphous alumina fine powder are contained in fatty acid glyceride, which is a skewer base. (2) Claim 1, characterized in that the amorphous alumina fine powder is mixed with the fatty acid glyceride of the base so as to have a weight of 1.0 to 10.0 weight ii. The skewer composition described in . (3) The skewer composition according to claim 1, wherein the hydrophilic compound containing a xyl group is ibuprofen. (4) The skewering composition according to claim 11, wherein the hydrophilic compound containing a xyl group is ketoprofen. (5) The skewer composition according to claim 1, wherein the hydrophilic calζ xyl group-containing compound is flurbiprofen. (6) The skewering composition according to claim 1, wherein the hydrophilic carboxyl group-containing compound is nazoloxene. (7) The skewering composition according to claim 1, wherein the hydrophilic carcinyl group-containing compound is aspirin.