Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/02—Suppositories; Bougies; Bases therefor; Ovules
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K31/00—Medicinal preparations containing organic active ingredients
  • A61K31/33—Heterocyclic compounds
  • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
  • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
  • A61K31/425—Thiazoles
  • A61K31/429—Thiazoles condensed with heterocyclic ring systems
  • A61K31/43—Compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula, e.g. penicillins, penems

Definitions

• compositions for rectal administration containing an alkali metal disalt of sulbenicillin or carbenicillin, a specified amount of an oily or fatty suppository base and a specified amount of a nonionic surfactant. for example. a polyoxyethylene higher alcohol ether.
• the pharmaceutical preparations of the penicillin compounds can be administered through the rectal tract, which gives no substantial pain, although the injections of penicillin compounds are generally accompanied by a strong pain.
• Another advantage is to make the administration feasible by anyone without resorting to administration by a physician. Needless to state, they all have merits of a pharmaceutical preparation for rectal use and a suppository.
• This invention is concerned with the said pharmaceutical composition for rectal use prepared by dispersing the penicillin compounds (I) in the particular mixture of oily or fatty base of 0.5 to times the weight relative to the said penicillin compounds (I) and at least one species of nonionic surfactants selected from a polyoxyethylene higher alcohol ether, a polyoxyethylcs m ene fatty acid ester and polyoxyethylenc sorbitan fatty acid ester of 0.01 to 0.5 time the weight relative to the said oily or fatty base.
• Hydrophile-Lipophile Balance hereinafter abbreviated as HLB
• HLB Hydrophile-Lipophile Balance
• the oily or fatty base employable in this invention includes any of the bases which are commonly used in the manufacture of ointments, suppositories, etc.
• Such an oily or fatty base is exemplified by sesame oil, olive oil, soybean oil, rapeseed oil, cottonseed oil, linseed oil (from Lim Semen), castor oil, rice bran oil, tsubaki oil (from Camelliajaponica L.), corn oil, arachis oil, coconut oil, poppyseed oil, almond oil, avocado oil, palm oil, palm kernel oil, kaya oil (from Torreya nucifera S and Z) tung oil, kapok oil, kuromoji oil (from Lindera umbellata sasanqua oil (from Camellia sasanqua teaseed oil, perilla oil, cocoa butter, lsocacao MO-S (registered by KAO-SOAP Com.Ltd.: Higher saturated fatty acid trigly
• oily and fatty bases may be employed either singly or as mixtures of two or more.
• Particularly preferred oily and fatty bases are corn oil, cocoa butter, lsocacao MO-S, interesterified fats and oils (e.g., palmitic acid, stearic acid, etc. artificial suppository base (e.g., Witepsol (Dynamit Nobel Aktiengesellschaftz'lriglyceride of saturated vegitable fatty acids with monoglycerides).
• the amount of such oily and fatty bases to be employed is 0.5 to 15 times the weight relative to the penicillin compounds [I] to be dispersed therein, and preferably l to 5 times on the same basis.
• the nonionic surfactants of this invention have an HLB value of 7 to 18, desirably 9 to 14.
• the penicillin compounds [I] are hardly absorbed, while when the amount of nonionic surfactant is more than 0.5 time the weight relative to the oily and fatty bases being used, the penicillin compounds [I] decompose gradually, and, therefore, the amount to be used is 0.01 to 0.5 time the weight relative to the oily and fatty bases, preferably, 0.0l to 0.3 time on the same bases.
• nonionic surfactants may be employed either singly or as a mixture of two or more.
• Particularly preferred surfactants are, for example, POE.higher alcohol ether and the mixture of POE.higher alcohol ether and POE.fatty acid ester.
• the dosage forms which can be adopted in the practice of this invention include suppositories which are solid at room temperature but melt at body temperature, ointments or enema-type preparations. These dosage forms may be achieved by procedures which are commonly followed in the preparation of ointments, suppositories and the like, by melting the oily and fatty bases and surfactant together and evenly dispersing the fine-powdered penicillin compounds [I] in the resulting melt.
• the preferred particle size of the penicillin powder is within the range of 200p. lp..
• the dose unit of penicillin compound [I] in these preparations can be adjusted from 500mg. to 5000mg. potency for human adults and from 50mg. to l500mg. potency for infants including neonates, and these drugs are generally administered once or several times a day.
• test drugs Male, fasted rabbits, weighing about 3 kg. each, were used for examining the rectal absorption and the intramuscular absorption of the test drugs:
• the fonner examination was made by administering a test drug in the form of suppository, namely the test drug was inserted into the rectum and pushed about 3cm deep from the anus with a glass rod, or in the form of ointment or enema type preparation, namely the test drug was inserted about 3cm deep from the anus with a small injection syringe.
• the latter examination was made by in- 25 jecting the test drug intramuscularly at the thigh of the rabbits.
• Dispersions of the penicillin compounds [I] in oily or fatty base of this invention and at least one nonionic surfactant selected from POE.higher alcohol ether, PO- E.fatty acid ester and POE.sorbitan fatty acid ester this invention: Test No. l-IZ
• Dispersions of the penicillin compounds [I] in bases other than the above oily or fatty base control: Test No. l3-l6
• Dispersions of penicillin compounds other than the above penicillin compounds [I] in oily or fatty base of this invention and the above surfactant control: Test N0. l7-l8)
• Solution obtained by adding penicillin compounds [I] to distilled water control: Test No. l9).
• the ointment or enema type preparations (Test No. l,2,5,6 and 10) which are prepared by dispersing the penicillin compounds [I] in the mixture of oily or fatty base and the nonionic surfactant;
• the suppository type preparations (Test No. 3, 4, 7, 8, 9, ll and l2) which are prepared by dispensing evenly the dispersion of the penicillin compounds [l] in the mixture of oily or fatty base and the nonionic surfactant, melted at 4045C, and pouring into the container, and then solidifying with ice-water.
• Table 1 (Continued) of penicillin ccnpounds [I urinary recover1es(%) (dosage: 400mg. /rabbit) It is apparant from Table 1 that compared with the cases (Test No. l3 to 16) in which bases other than the oily or fatty base of this invention were employed, or the cases (Test No. I? and [8) in which penicillin compounds other than the penicillin compounds [l] of this invention were employed, the use of the pharmaceutical preparations of the penicillin compounds for rectal use (Test No.
• l to l2 comprising the penicillin compounds [I], the oily or fatty base and the specific nonionie surfactant in specified proportions achieve extremely high concentrations of the penicillins in blood, at levels which are comparable to those attainable by the intramuscular route (Test No. 19).
• POE monostearate 3 a 17 (mayo, 13) 3.5% 0.4 0.4 1.6 2.2 1.1 0.2 3. 8'5 Ampicillin anhydrate 30.0% 5 o iggcacao PKG-5 64 '7 Oe 1s zgiggigfgf fij 6 a 4.0 9.9 14.5 3.9 2.9 0.9 4.4
• nonionic surfactant is a polyoxyethylene higher alcohol ether having an HLB value of from 9 to l4.
• nonionic surfactant is a mixture of a polyoxyethylene higher alcohol ether and a polyoxyethylene fatty acid ester.
• polyoxyethylene higher alcohol ether is polyoxyethylene lauryl ether having an HLB value of about I L5.
• polyoxyethylene higher alcohol ether is polyoxyethylene lauryl ether having an HLB value of about I30.
• polyoxyethylene higher alcohol ether is polyoxyethylene cetyl ether having an HLB value of about l2.8.
• a pharmaceutical composition as claimed in claim 4 wherein the polyoxyethylene higher alcohol ether is polyoxyethylene oleyl ether having an HLB value of about l0.
• a method of treating a disease subject to treat ment with sulbenicillin or carbenicillin which comprises administering through the rectal tract of a patient afflicted with the disease a composition containing (l) a penicillin compound of the formula S ca CH-CONiitf 3 ica wherein R is -SO -O or COO and M and M are the same or different and each represents an alkali metal, (2) an oily or fatty suppository base in an amount of 0,5 to l5 times the weight relative to the weight of the penicillin compound and (3) at least one nonionic surfactant selected from the group consisting of (a) polyoxyethylene higher alcohol ethers, wherein the average number of polyoxyethylene units is 5-30 and the higher alcohol has 8-18 carbon atoms, (b) polyoxyethylene fatty acid esters, wherein the average number of polyoxyethylene units is 5-30 and the fatty acid has l2-l8 carbon atoms and (c) polyoxyethylene sorbitan fatty acid esters, wherein the average number of poly

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• Pharmacology & Pharmacy (AREA)
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• Life Sciences & Earth Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• General Health & Medical Sciences (AREA)
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• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

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• 1972
  • 1972-03-06 JP JP47023279A patent/JPS4891218A/ja active Pending
• 1973
  • 1973-03-02 US US337476A patent/US3881012A/en not_active Expired - Lifetime
  • 1973-03-03 DE DE19732310770 patent/DE2310770A1/de active Pending
  • 1973-03-05 SE SE7303026A patent/SE408132B/sv unknown
  • 1973-03-05 ES ES412341A patent/ES412341A1/es not_active Expired
  • 1973-03-05 DK DK119273AA patent/DK138975B/da unknown
  • 1973-03-05 CA CA165,216A patent/CA1016458A/en not_active Expired
  • 1973-03-05 AU AU52912/73A patent/AU466461B2/en not_active Expired
  • 1973-03-05 BE BE128365A patent/BE796270A/xx not_active IP Right Cessation
  • 1973-03-06 NL NL7303167A patent/NL7303167A/xx not_active Application Discontinuation
  • 1973-03-06 GB GB1072973A patent/GB1376283A/en not_active Expired
  • 1973-03-06 CH CH327873A patent/CH583034A5/xx not_active IP Right Cessation
  • 1973-03-06 FR FR7307995A patent/FR2183677B1/fr not_active Expired

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