JPS59212427A - Composition for rectum administration - Google Patents

Abstract

PURPOSE:The titled composition having improved absorption of a drug from the rectum, obtained by blending a base for pharmaceutical preparation of rectum administration with a specific fatty acid and a nonionic surface active agent. CONSTITUTION:A base for pharmaceutical preparation of rectum administration (e.g., cacao butter, polyethylene glycol, etc.) is blended with (A) at least one selected from 8-10C fatty acid and its salt, and (B) at last one selected from nonionic surface active agents. Capric acid and caprylic acid are preferable as the component A. Polyoxyethylene alkyl ether, glycerine fatty acid ester, etc. are used as the component B. Administration of the titled composition together with a drug can raise rectum absorption of the drug. It further enables rectum administration of a drug which is slightly absorbed in the rectum and has not been admistered as medicine heretofore.

Description

[Detailed description of the invention] The present invention relates to compositions for rectal administration.

More specifically, the present invention relates to a composition for rectal administration for improving absorption of drugs from the intestine.

The applicant of the present invention previously discovered that rectal absorption of a drug is significantly improved if the drug is administered rectally together with a fatty acid having 8 to 14 carbon atoms or a salt thereof (Japanese Patent Application Laid-open No. 14920-1982).
9JPj), and as the research progressed further, carbon numbers of 8~
The present inventors have discovered that rectal absorption of a drug can be further improved by rectally administering a combination of a fatty acid salt of No. 10 and a nonionic surfactant together with the drug, leading to the completion of the present invention.

That is, the present invention provides carbon & 8-l in the base for rectal administration preparations.
The present invention relates to a composition for rectal administration comprising at least one selected from O fatty acids and their salts (component A) and at least one selected from nonionic surfactants (component B).

The fatty acid having a carbon number of 8 to 10 used in the present invention is preferably capric acid or caprylic acid, and the salts include alkali metal salts (sodium salts, potassium salts, etc.),
Examples include alkaline earth salts (such as calcium salts) and nucleated amine salts (such as basic amino acid salts such as lysine salts and arginine salts).

Nonionic surfactants usually have an HLB of 5 to 20.
Those with values are used. For example, polyoxyethylene alkyl ether/L/ (for example, N1-KKOL B
L-21 manufactured by NIKKOL TO
-10M), polyethylene glycol fatty acid ester (
For example, NIKKOL MYS-40), glycerin fatty acid ester (for example, NIKKOL-MGK), etc. can be used.

The composition for rectal administration according to the present invention is obtained by uniformly dispersing or dissolving component A and component B in a base conventionally used as a base for preparations for rectal administration.

Examples of bases for rectal administration include those known per se, such as oil-based bases and water-soluble bases; examples of oil-based bases include:
For example, cocoa butter, peanut oil, corn fat, glycerin esters of fatty acids [for example, Witepsol (manufactured by Dynamite Nobel), SB-base (manufactured by Kanegafuchi Chemical Co., Ltd.), 0, D, 0 (manufactured by Nisshin Oil Co., Ltd.), etc. Vegetable oils and fats, petrolatum, paraffin and other mineral oils can be removed. Further, examples of the water-soluble base include polyethylene glycol, fluoropylene gelicol, and glycerin.

The composition of the present invention may contain antioxidants, fillers, basic compounds (eg, sodium carbonate), etc., which are known per se.

If the composition of the present invention is administered rectally together with a drug, it will not only further enhance the rectal absorption of drugs that have conventionally been administered rectally, but also enable the rectal administration of drugs that have not traditionally been administered rectally because rectal absorption is difficult. It is what makes it possible.

Therefore, it is preferable to incorporate a drug into the composition of the present invention to form a preparation for rectal administration. Examples of such preparations include so-called anal layer agents, and soft capsules filled with suspensions or ointments dispersed in a liquid oily base.

For example, for an anal layer agent, components A and B are added to a conventional base material and dispersed uniformly, then the drug is added and dispersed uniformly, and the mixture is filled into a container for layer agent and molded. Prepared by. The order of addition is not necessarily limited to the order described above.

Any drug may be used as long as it is absorbed into the blood and exhibits pharmacological activity, and preferably has a molecular weight of 12,000 or less, particularly 6,000 or less.

Specific examples of drugs include β-lactam JJj
Antibacterial agents (for example, penicillins, β-lactam antibiotics such as cephalosporins, clapranic acid, chenamycin, etc.) This is a concept that also includes atoms replaced with oxygen atoms.)
, amine glycoside antibiotics, polysaccharide drugs, pepquid derivatives, nucleic acid drugs, etc.

Examples of penicillins include ampicillin, cyclacillin, cloquinacillin, benzilbenicillin, carbenicillin, piperagillin, mesocillin, virpenicillin, and tinflucillin.

Examples of cephalosborias include cephalothin, cefoxyti/, cefazolin, cephalolicin, cefacedryl, cefothiam, ceforanide, cefanone, cefaclor, cefadroxil, cefatridine, cefradi/, cephaloglyci/, ceftriquinone, cefotecno, cefothiam, latamoxef, cefvilamite. , cefuchelane, cefmetuxime, cefmetuxime, cefodazidine, cefmetuxime and the like.

Examples of aminoglycosides include streptomycin,
Kanamaycin/, cladiomycin, paromomycin, bekanamycin, ribostamycin, gentamicin, tofilamycin, dipekacin, peptide drugs such as insulin, angiotensin, ACT
H, TRI and sonoanalok, engufarin, L) 1
-RH, Pef.

Examples include tide antibiotics (eg, polymyxin B1 colimethi/, gramicidin, bacitracin, etc.). Furthermore, examples of nucleic acid drugs include citicoline.

The amount of component A and component B blended in the composition of the present invention is an amount sufficient to promote rectal absorption of the drug to be incorporated later, although it varies depending on the type of base, the type of drug intended to promote absorption, etc. , 0.05 to 20% by weight as the total amount of component A and component B.

Preferably 0.1-15% by weight, more preferably 0.1-15% by weight.
2~1O Judo Chi.

The blending ratio of component A and component B is usually 1 to 300 parts by weight, preferably 10 parts by weight of component B to 100 parts by weight of component A.
When a drug is blended into the composition of the present invention in an amount of ~200 parts by weight, the amount of the drug may be sufficient as long as it has a medicinal effect, and it varies depending on the type of drug, the subject to be administered, the symptoms, etc. It may be determined by a person skilled in the art on a case-by-case basis. For example, in the case of antibiotics, an amount corresponding to a one-time dose of 10 to 500η may be added.

Example 1 Uitebuzol H-5 (manufactured by Dynamite Nobel) 2
After melting 2.4f and NIKKOL MYS-40 (1,1) at about 60 to 70°C, 0.84f of sodium caprate was added at about 50"F or below and uniformly dispersed to obtain a composition. Dibekacin sulfate 8.159 was added to the thus obtained composition and uniformly dispersed.This was filled into a container for layering agent with 1251 and molded to obtain a layering agent of dibekacin sulfate.

Example 1 Anal layer preparations having the compositions shown in Tables 1 and 2 were obtained in the same manner as in Example 1, and administered through the anus of dogs or rabbits that had been fasted for 24 hours. Blood or urine was collected over time after administration, and the active concentration was determined using a biological assay to measure the blood concentration or urinary excretion rate of the drug, and the results are shown in Tables 1 to 2.
It was shown to.

The test bacteria used is Bacillus subtilis ATCC.
66BB was used.

Table 1 in the margin below Blood concentration of aminoglycoside antibiotics (dogs) Table 2
Urinary excretion rate of amine glycoside antibiotics (rabbit) Procedural amendment exporter January 1982? Mr. Z Japan Patent Office Commissioner 1. Indication of the case Patent Application No. 10960 of 1982 2. Name of the invention Rectal administration set RwJ 3. Person making the amendment Relationship to the case Patent applicant's name (name) Kyoto Pharmaceutical Co., Ltd. Company 4, Agent ■541 Address 406 New Life Hirano-cho, 4-53-3 Hirano-cho, Higashi-ku, Osaka Telephone: (06) 227-1156 6. Number of inventions increased by amendment 7. Column 8 of ``Detailed Explanation of the Invention Section 1'', Contents of Amendment (1) Specification, page 10, Table 2, corrector 〇〇〇〇,〇

Claims (1)

[Claims] A composition for rectal administration, comprising a base for a preparation for rectal administration, and at least one selected from fatty acids having 8 to 10 carbon atoms and their salts, and at least one selected from nonionic surfactants. thing.