GB2028655A

GB2028655A - Compositions for rectal administration

Info

Publication number: GB2028655A
Application number: GB7924710A
Authority: GB
Original assignee: Toyama Chemical Co Ltd
Current assignee: Toyama Chemical Co Ltd
Priority date: 1978-07-25
Filing date: 1979-07-16
Publication date: 1980-03-12
Also published as: GB2028655B; IL57846A; IE48602B1; FR2433945B1; GR69652B; AU529031B2; ES482818A1; BE877831A; PH16496A; JPS5517342A; FR2433945A1; IL57846A0; ZA793734B; IT7949844A0; DE2929840C2; PT69969A; IN151264B; LU81546A1; CS516179A2; DK310079A

Abstract

A pharmaceutical composition for rectal administration comprises 7-[D(-)- alpha -(4-ethyl-2,3-dioxo-1- piperazinylcarboxamido)-p- hydroxyphenylacetamido]-3-[5-(1- methyl-1,2,3,4-tetrazolyl)thiomethyl]- DELTA <3>-cephem-4-carboxylic acid or its pharmaceutically acceptable salt, an oily base, and a nonionic surfactant and/or an anionic surfactant and/or a salt of bile acid and is well absorbed in a living body and maintained in a high concentration in blood for a long period of time.

Description

SPECIFICATION Pharmaceutical composition for rectal administration of cephalosporin This invention relates to a pharmaceutical composition of cephalosporin for rectal administration.

The term "cephalosporin" used herein means 7-[D(-)-a-(4-ethyl-2,3-dioxo-1.piperazinylcarboxamido)-p- hydroxyphenylacetamido]-3-[5-( -m ethyl-l ,2,3,4-tetrazolyl)thiomethyl]-A3-cephem-4-carboxyl ic acid represented by the following structural formula and a pharmaceutically acceptable salt thereof which have been developed by Saikawa et al., Saikawa being one of the present inventors (see British Patents 1,508,071 and 1,517,098):

The compound represented by said structural formula is hereinafter referred to as Compound A.Compound A has a broad antibacterial spectrum against gram-positive and gram-negative bacteria and particularly exhibits an effective antibacterial activity against Pseudomonas aeruginosa, Klebsiella pneumoniae and Proteus species which have been known as causes for clinically serious infectious deseases, and are very stable against ss-lactamase produced from bacteria. Thus, Compound A is a very useful therapeutic drug for human infectious diseases.

When Compound A is injected in the form of a pharmaceutically acceptable salt (as intravenous injection, intramuscuiar injection or drip infusion), it is weil absorbed in a living body. However, injections are difficult to use at home and the pain due to injection inspires infants with fear. This is disadvantageous.

On the other hand, oral administration or rectal administration (suppository) are advantageous in that the drug can be used relatively simply without inspiring patients with fear. However, when Compound A or its pharmaceutically acceptable salt is administered orally, it is little absorbed in a living body, and therefore, a high concentration in blood cannot be achieved. Further, the present inventors have found that when Compound A or its pharmaceutically acceptable salt is dispersed in an oily base or a water-soluble base according to the conventionally known method for preparing a pharmaceutical preparation for rectal administration and the preparation thus obtained is administered by rectal route, the compound is little absorbed in a living body and no effect is obtained.

The present inventors, therefore, have conducted extensive research on pharmaceutical compositions to be administered by rectal route which can be well absorbed in a living body and can be maintained in a high concentration in blood for a long period of time, and as a result, have found that when a uniform dispersion of Compound A or its pharmaceutically acceptable salt in a mixture of an oily base and a nonionic surfactant and/or an anionic surfactant and/or a salt of bile acid is administered by rectal route, Compound A is well absorbed in a living body to obtain a high concentration in blood.

An object of this invention is to provide a pharmaceutical composition of a cephalosporin for rectal administration.

A further object of this invention is to provide a pharmaceutical composition of a cephalosporin which can be well absorbed in a living body and can be maintained in a high concentration in blood for a long period of time when administered by rectal route.

Other objects and advantages of this invention will be apparent from the following description.

According to this invention, there is provided a pharmaceutical composition of 7-[D(-)-a-(4-ethyl-2,3-dioxo1 -pi perazinylca rboxamido)-p-hydroxyphenyl acet-amidoj-3-[5-( 1-methyl-i ,2,3,4-tetrazolyl)thiomethyl]-A3cephem-4-carboxylic acid or its pharmaceutically acceptable salt which comprises 7-[D(-)-a-(4-ethyl-2,3dioxo-1 -piperazinylcarboxamido)-p-hydroxyphenylacet-amido]-3-[5-( 1 -methyl-1,2,3,4tetrazolyl)thiomethyl]-A3-cephem-4-carboxylic acid or its pharmaceutically acceptable salt, an oily base, and a nonionic surfactant and/or an anionic surfactant and/or a salt of bile acid.

According to this invention, when a pharmaceutically acceptable salt of Compound A is used, a particularly high concentration in blood can be obtained. As such pharmaceutically acceptable salts of Compound A, there may be exemplified salts with alkali metals such as sodium, potassium and the like; salts with alkaline earth metals such as calcium, magnesium and the like; ammonium salts; salts with organic bases such as procain, dibenzylamine, N-benzyl-ss-phenethylamine, 1-ephenamine, arginine, trishydroxymethylaminomethane and the like.

As the nonionic surfactant used in this invention, there may be exemplified polyoxyethylene fatty alcohols ethers of the polyethylene glycol type (for example, Emulgen 120, Emulgen 220, Emulgen 408 and Emulgen 420, trade names of Kao Sekken, and Nikkol BC-1 5TX, Nikkol BC-20TX and Nikkol BO-20, trade names of Nikko Chemicals); polyoxyethylene alkylaryl ethers (for example, Emulgen 920, trade name of Kao Sekken and Nikkol NP-7.5, trade name of Nikko Chemicals); polyoxypropylenepolyoxyethylene alkyl ethers (for example, Pluronic L62, trade name of Asahi Denka); sugar esters of fatty acid esters type (for example, DK Ester F-140, trade name of Dai-ichi Kogyo Seiyaku) and the like.In general, the nonionic surfactants of the polyethylene glycol type having an HLB of 10 to 14 are preferred to those of the polyhydric alcohol type.

As the anionic surfactant, there may be examplified alkyl sulfates (for example, Emerl 10 powder, trade name of Kao Sekken); di-alkyl sulfosuccinates (for example, Rapizole B-90, trade name of Nippon Oil & Fats Co., Ltd.), and as the salt of bile acid, there may be examplified sodium tauroglycolate, sodium glycolate, sodium taurocholate and the like.

In this invention, at least two of the surfactants mentioned above may be used in admixture.

The total amount of the nonionic surfactant, the anionic surfactant and the salt of bile acid used in this invention may be 1 to 20% by weight based on the weight of the oily base, and an amount of 5 to 10% by weight is particularly preferable.

As the oily base used in this invention, there may be exemplified bases having themselves no pharmaceutical activity as used in the production of conventional ointments, suppositories and the like, for example, fats and oils such as peanut oil, sesame oil, soybean oil, corn oil, rape seed oil, cotton seed oil, caster oil, tubaki oil, coconut oil, olive oil, poppy seed oil, cacao butter, laurin butter, beaftallow, squalene, wool fat and the like; those fats and oils that have been modified by chemical reaction, such as hydrogeneration or the like; mineral oils such as vaselin, paraffin, silicone oil and the like; higher fatty acid esters such as isopropyl myristate, n-butyl myristate, isopropyl linolate, cetyl ricinolate, stearyl ricinolate, diethyl sebacate, diisopropyl adipate, and the like; higher aliphatic alcohols such as cetyl alcohol, stearyl alcohol and the like; waxes such as bleached bees wax, spermaceti, Japan wax and the like; higher fatty acids such as stearic acid, oleic acid, palmitic acid and the like; and mixtures of triglycerides of naturally occurring saturated fatty acids having 12 to 18 carbon atoms in which the whole of the hydroxyl groups have been esterified and triglycerides of said fatty acids in which a part of the hydroxyl groups has been esterified.

Vegetable oils are particularly preferable.

These oily bases may be used alone or in admixture of two or more. The amount of the oily base used is 1 to 20 times the weight of Compound A or its pharmaceutically acceptable salt used, and an amount of 2 to 18 times is preferred.

In the preparation of the composition of this invention, the nonionic surfactant and/or the anionic surfactant and/or the salt of bile acid is first dispersed in the oily base, and the necessary amount of Compound A or its pharmaceutically acceptable salt is added to the resulting dispersion and uniformly dispersed in the latter. However, in this invention, the order of adding the base, the surfactants and the cephalosporin is not limited to the above-mentioned one. The particle size of Compound A and its pharmaceutically acceptable salt is preferably 100 or less.

In preparing a pharmaceutical preparation from the composition thus obtained, the composition may be formed into a conventional anal suppository, or a suspension or an ointment in which the surfactant and the cephalosporin are dispersed in the oily base may be put in a soft capsule, or said dispersion or ointment may be put in a tube, which is infused at the time of use. To the above preparations may be added antioxidants such as tocopherol, BHA, NDGA and the like; synergists such as phosphoric acid, citric acid, ascorbic acid, malonic acid; antiseptics; concealing agents; excipients; and the like.

The effective administration amount of the composition of this invention may be varied depending upon Compound A or its pharmaceutically acceptable salt, and such an amount of the composition may be selected that said compound may be administered in an amount 1/5 to 3 times the effective administration amount in the case of an injection.

This invention is illustrated below with reference to Examples, which are merely by way of illustration and not by way of limitation.

Application Example A dispersion of Compound A or its sodium salt in a mixture of an oily base, and various surfactants and/or a salt of bile acid (the present invention); a dispersion of the sodium salt of Compound A in physiological saiine solution as an injection (control); a dispersion of the sodium salt of Compound A in water (control); a dispersion of the sodium salt of Compound A in an oily base (peanut oil) only (control); and a dispersion of the sodium salt of Compound A in a water-soluble base (propylene glycol) only (control) were administered rectally, orally or by injection, and changes of concentration in blood with the lapse of time were compared.

The method of administration of a sample was as follows: In the case of rectal administration, each sample was administered through anus into the rectum of a male Wister rat (weight: about 350 g), which had been abstained from food for 15 hours, by using a small injector or by inserting a Witepsol suppository obtained by pouring the sample into a mold for suppository and solidifying the same therein. After the administration, the anus was sewed up with surgical seaming thread Nos. 4to 6.

In the case of oral administration, each sample was administered to the above rats by means of a sonde for rat.

The measurement of concentration in blood was conducted as follows: The neck of a rat was operated at a certain interval of time and a small amount of blood was sampled from the jugular vein, and the concentration of the compound therein was quantitatively determined by a conventional bioassay method.

Bacillus subtllis ATCC 6633 was used as an examination bacterium and the culture medium was prepared by adding water to a mixture of 5 g of peptone, 3 g of meat extract and 15 g of agar in such an amount that the total volume became one liter, and adjusting the pH thereof to 6.2. The volume of the seed layer was 8 ml.

In measuring a concentration as low as 2 llg/ml or less, Micrococcus luteus ATCC 9341 was used as the examination bacterium, and the culture medium was prepared by adding water to a mixture of 10 g of peptone, 2.5 g of sodium chloride, 5 g of meat extract and 15 g of agar in such an amount that the total volume became one liter and adjusting the pH thereof to 6.5. The volume of the seed layer was 8 ml.

The serum was separated from the sampled blood by centrifugation at 3000 r.p.m. and cultivated at 37 C for a period of 16 to 20 hours by the paper disc method and then examined. A 1% phosphate buffer solution (pH: 6.0) was used as the solution for calibration curve. The results obtained are shown in Table 1. Table 1 (Amount of Compound A or its sodium salt administered was 100 mg/kg) Sample composition Concentration in blood (meg/ml) Admini- Compound A or Surfactant or Stra- its sodium salt salt of bile tion and base acid 15 30 60 120 240 method min min min min min Name Amount (%) Sodium salt of Rectally Compound A 5% - - < 0.1 < 0.1 < 0.1 < 0.1 < 0.1 < 0.1 Water 95% sodium salt of Rectally Compound A 5% - - 0.2 0.2 0.2 0.2 0.2 0.2 Peanut oil 95% Con- Compound A 5% - - 0.8 0.8 0.8 0.8 0.8 0.8 trol Rectally Peanut oil 95% Orally Compound A 5% - - < 0.1 < 0.1 < 0.1 < 0.1 < 0.1 < 0.1 Water 95% contd.

Table 1 (Cont'd) Compound A 5% Nikkol Rectally Peanut oil 90% BC-20 TX 5 31.0 39.0 8.7 1.7 0.5 Compound A 10% Emulgen Rectally Com oil 85% 408 5 8.4 8.3 5.3 2.2 0.7 Compound A 10% Ractally Witespol Mikkol 10 20.0 30.0 20.0 7.2 1.7 H.1580% BC-20 TX Compound A 20% Rectally Witepsol Emulgen 10 18.0 30.0 33.0 14.0 6.4 Present H-15 70% 408 invention Sodlum salt of Rectally Compound A 5% Emerl 10 10.5 2.8 1.2 0.2 < 0.1 Peanut oil 90% powder 5 Sodium salt of Rectally Compound A 5% Nikkol 5 36.0 32.0 10.0 1.5 0.3 Bc-20 TX Sodium salt of Rectally Compound A 10% Emulgen 10 11.5 12.8 7.2 1.6 0.3 Com oil 80% 408 Sodium salt of Rectally Compound A 10% Nikkol 10 13.0 16.7 15.4 8.0 3.4 Soybean oil 80% MP 7.5 Table 1 (Cont'd) Sodium salt of Rectally Compound A 20% Emulgen 10 21.5 27.0 12.2 1.2 < 0.1 Peanut oil 70% 408 Sodium salt of Rectally Compound A 10% DK Ester 10 12.4 8.3 2.3 0.9 0.4 Miglyol 812 80% F-140 Sodium salt of Compound A 20% Emulgen 10 18.0 30.0 33.0 14.0 6.4 Present Rectally Witepsol 408 inven- H-1570% tion Sodium salt of Sodium Rectally Compound A 5% tauro- 5 12.0 6.4 1.5 0.3 < 0.1 Peanut oil 90% cholate Arginine salt of Rectally Compound A 50% Mikkol 5 6.4 3.3 0.7 Peanut oil 90% BC-20 TX < 0.1 < 0.1 Arginine salt of Rectally Compound A 10% Pluronic 10 5.3 4.8 1.9 0.7 0.3 Soybean oil 80% L-62 As is clear from Table 1, when the sample of this invention was rectally administered, a much higher concentration in blood was obtained than when the control samples were administered orally and rectally.

Production Example 1 in 85 g of corn oil was dispersed 5 g of a nonionic surfactant polyoxyethylene oleyl alcohol ether (Emulgen 408) and thereafter 10 of 7-[D(-)-a-(4-ethyl-2,3-dioxo-1 -piperazinylcarboxamido)-p-hydroxyphenyl acetamido]-3-[5-( 1 -methyl-1 ,2,3,4-tetrazolyl)thiomethyl]-A3-cephem-4-carboxylic acid was added to the dispersion, after which the resulting mixture was stirred to disperse the carboxylic acid uniformly in the dispersion. A gelatine soft capsule was filled with the resulting dispersion in an amount of 1.25 g per capsule to prepare a soft capsule suppository.

Production Example 2 On a water bath at 38 to 45"C, 80 g of a triglyceride of a higher fatty acid (Witepsol H-1 5, trade name of Dynamite Nobel) was melted, and thereto was dissolved 10 g of a nonionic surfactant polyoxyethylene oleyl alcohol ether (Nikkol BC - 20 TX), after which 10 g of 7-[D(-)-a-(4-ethyl-2,3-dioxo-1-piperazinylcarboxamido) p-hydroxyphenylacetamido] -3-[5-(1 -methyl-l ,2,3,4-tetrazolyl (thiom ethyl [-A3-cephem-4-carboxylic acid was added to the resulting solution. The resulting mixture was stirred to form a uniform dispersion, which was then cooled to a temperature near the freezing point and thereafter poured into a mould for rectal suppository to prepare a solid suppository.

Production Example 3 To 80 g of soybean oil was added 10 g of a nonionic surfactant polyoxyethylene nonylphenyl ether (Nikkol NP 7.5), and the latter was dispersed in the former, after which 10 g of sodium 7-[D(-)-a-(4-ethyl-2,3-dioxo-1- piperazinylcarboxamido)-p-hydroxyphenyacetamido]-3-[5-(1 -methyl-1 ,2,3,4-tetrazolyl)thiomethyl]-A3- cephem-4-carboxylate was added to the resulting dispersion. The resulting mixture was then stirred to form a uniform dispersion. In the same manner as in Production Example 1, a soft capsule suppository was prepared.

Production Example 4 To 80 g of corn oil were added 10 g of a nonionic surfactant (Emulgen 408) and then 10 g of sodium 7-[D(-)-a-(4-ethyl-2,3-dioxo-1 -piperazinylca rboxamido)-p-hydroxyphenylacetamido]-3-[5-(1 -methyl-1,2,3,4 tetrazolyl)thiomethyl]-A3-cephem-4-carboxylate, and the resulting mixture was stirred to form a uniform dispersion. In the same manner as in Production Example 1, a soft capsule suppository was subsequently prepared.

Production Example 5 To 80 g of corn oil were added 10 g of a nonionic surfactant (Emulgen 408) and then 10 g of sodium 7-[D(-)-a-(4-ethyl-2,3-dioxo-1 -piperazinylcarboxamido)-p-hydroxyphenylacetamido]-3-[5-(1 -methyl-1,2,3,4 tetrazolyl)thiomethyl]-A3-cephem-4-carboxylate, and the resulting mixture was stirred to form a uniform dispersion. This dispersion was put in a suppository tube.

Production Example 6 To 90 g of peanut oil were added 5 g of an anionic surfactant sodium laurylsulfate (Emerl 10 powder), and then 10 g of sodium 7-[D(-)-o-(4-ethyl-2,3-dioxo-1 -piperazinylcarboxamido)-p-hydroxyphenylacetamido]-3- [5-(1 -methyl-1 ,2,3,4-tetrazolyl )thiomethyl]-A3-cephem-4-carboxylate, and the resulting mixture was stirred to form a uniform dispersion, which was then put in a suppository tube.

Production Example 7 On a water bath at 38 to 45"C, 70 g of a triglyceride of a higher saturated fatty acid (Witepsol H - 15) was melted, and therein was dissolved in 10 g of a nonionic surfactant polyoxyethylene oleyl alcohol ether (Emulgen 408). To the resulting solution was added 20 g of sodium 7-[D(-)-a-(4-ethyl-2,3-dioxo-1 - piperazinylca rboxa mido)-p-hydroxyphenylacetam ido]-3-]5-(1 -methyl-1 2,3,4-tetrazolyl )thiomethyl]-A3- cephem-4-carboxylate, and the resulting mixture was stirred to form a uniform dispersion. In the same manner as in Production Example 2, a solid suppository was prepared.

Production Example 8 In 80 g of peanut oil were dispersed 8 g of polyoxyethylene oleyl alcohol ether (Emulgen 408) and 2 g of sodium taurocholate, after which 10 g of sodium 7-[D(-)-a-(4-ethyl-2,3-dioxo-1 -piperazinylcarboxamido)-p- hydroxyphenylacetamido]-3-[5-(1 -methyl-1 ,2,3,4-tetrazolyl)thiomethyl]-A3-cephem-4-carboxylate, and the resulting mixture was stirred to form a uniform dispersion. A suppository tube was filled with this dispersion.

Production Example 9 On a water bath at 38 to 45"C, 80 g of a triglyceride of a higher saturated fatty acid (Witepsol H-15) was melted, and therein were dissolved 7 g of a nonionic surfactant polyoxyethylene oleyl alcohol ether (Nikkol BC - 20 TX) and 3 g of sodium laury sulfate (Emeryl 10 powder). To the resulting solution was added 10 g of sodium 7-[D(-)-a-(4-ethyl-2,3-dioxo- 1 -piperazinylca rboxamido)-p-hydroxyphenylacetamido]-3-[5-(1 -methyl- 1 ,2,3,4-tetrazolyl)thiomethyl]-A3-cephem-4-carboxylate, and the resulting mixture was stirred to form a uniform dispersion. In the same manner as in Production Example 2, a solid suppository was prepared.

Claims

1. A pharmaceutical composition for rectal administration which comprises 7-[D(-)-a-(4-ethyl-2,3-dioxo 1 -piperazinylcarboxam ido)-p-hydroxyphenylacetamido]-3-[5-(1 -methyl-1 2,3,4-tetrazolyl )thiomethyl]-A3- cephem-4-carboxylic acid or its pharmaceutically acceptable salt, an oily base, and a nonionic surfactant and/or an anionic surfactant and/or a salt of bile acid.

2. A pharmaceutical composition for rectal administration according to claim 1, which consists essentially of 7-[D(-)-a-(4-ethyl-2,3-dioxo-1 -piperazinylcarboxam ido)-p-hydroxyphenylacetamido]-3-[5-( 1 methyl-1,2,3,4-tetrazolyl)thiomethyl]-A3-cephem-4-carboxylic acid or its pharmaceutically acceptable salt, an oily base and a nonionic surfactant.

3. A pharmaceutical composition for rectal administration according to claim 1, which consists essentially of 7-[D(-)-a-(4-ethyl-2,3-dioxo-1 -piperazinylcarboxamido)-p-hyd roxyphenylacetamido]-3-[5-(1 methyl-1 ,2,3,4-tetrazolyl)thiomethyl]-A3-cephem-4-carboxylic acid or its pharmaceutically acceptable salt, an oily base and an anionic surfactant.

4. A pharmaceutical composition for rectal administration according to claim 1, which consists essentially of 7-[D(-)-a-(4-ethyl-2,3-dioxo-1 -piperazinylcarboxamido)-p-hydroxyphenylacetamido]-3-[5-(1 - methyl-1 ,2,3,4-tetrazolyl)thiomethyl]-A3-cephem-4-carboxylic acid or its pharmaceutically acceptable salt, an oily base and a salt of bile acid.

5. A pharmaceutical composition for rectal administration according to any one of claims 1 to 4, wherein the oily base is at least one member selected from the group consisting of fats and oils; hydrogenated fats and oils; mineral oils; higher aliphatic alcohols; higher fatty acid esters; higher fatty acids; waxes; and triglycerides of naturally occurring saturated fatty acids having 12 to 18 carbon atoms.

6. A pharmaceutical composition for rectal administration according to any one of claims 1 to 4, wherein the oily base is at least one vegetable oil.

7. A pharmaceutical composition for rectal administration according to claim 5, wherein the oily base is at least one member selected from the group consisting of peanut oil, sesame oil, soybean oil, corn oil, rape seed oil, cotton seed oil, castor oil, tubaki oil, coconut oil, olive oil, poppy seed oil, cacao butter, laurin butter, beef tallow, squalene, wool fat, vaselin, paraffin, silicone oil, isopropyl myristate, n-butyl myristate, isopropyl linolate, cetyl ricinolate, stearyl ricinolate, diethyl sebacate, diisopropyl adipate, cetyl alcohol, stearyl alcohol, bleached bees wax, spermaceti, Japan Wax, stearic acid, oleic acid, palmitic acid and a mixture of triglyceride of a naturally occurring higher saturated fatty acid having 12 to 18 carbon atoms in which the whole of the hydroxyl groups have been esterified and a triglyceride of a naturally occurring higher saturated fatty acid having 12 to 18 carbon atoms in which a part of the hydroxyl groups have been esterified.

8. A pharmaceutical composition for rectal administration according to claim 5, wherein the base oil is peanut oil, corn oil, a triglyceride of a higher fatty acid, or soybean oil.

9. A pharmaceutical composition for rectal administration according to claim 1 or 2, wherein the nonionic surfactant is a polyoxyethylene higher alcohol ether, a polyoxyethylene alkylaryl ether, a polyoxypropylene-polyoxyethylene alkyl ether or a fatty acid ester of sucrose.

10. A pharmaceutical composition for rectal administration according to claim 1 or 2, wherein the nonionic surfactant is a polyethylene glycol type one having an HLB of 10 to 14.

11. A pharmaceutical composition for rectal administration according to claim 1 or 3, wherein the anionic surfactant is an alkyl sulfate of a di-alkyl sulfosuccinate.

12. A pharmaceutical composition for rectal administration according to claim 1 or 4, wherein the salt of bile acid is sodium tauroglycolate, sodium glycolate or sodium taurocholate.

13. A pharmaceutical composition for rectal administration according to claim 1, wherein the amount of the oily base is 1 to 20 times the weight of the cephalosporanic acid or its salt and the total amount of the nonionic surfactant, the anionic surfactant and the salt of bile acid is 1 to 20% by weight based on the weight of the oily base.

14. A pharmaceutical composition for rectal administration according to claim 13, wherein the amount of the oily base is 2 to 18 times the weight of the cephalosporanic acid or its salt and the total amount of the nonionic surfactant, the anionic surfactant and the salt of bile acid is 5 to 10% by weight of the weight of the oily base.

15. A pharmaceutical composition for rectal administration according to claim 1, 2, 3 or 4, wherein the salt of cephalosporanic acid is an alkali metal salt, an alkaline earth metal salt, an ammonium salt, or a salt with an organic base.

16. A pharmaceutical composition for rectal administration according to claim 1, 2, 3 or 4, wherein the salt of cephalosporanic acid is a sodium, potassium, calcium, magnesium, ammonium, procain, dibenzylamine, N-benzyl-ss-phenethylamine,1 -ephenamine, arginine or trishydroxymethylamine salt.