US2733184A - Inject able penicillin repository prep ar a- - Google Patents

Inject able penicillin repository prep ar a- Download PDF

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US2733184A
US2733184A US2733184DA US2733184A US 2733184 A US2733184 A US 2733184A US 2733184D A US2733184D A US 2733184DA US 2733184 A US2733184 A US 2733184A
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penicillin
oil
aluminum
salt
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    • 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

  • This invention relates to pharmaceutical preparations. More particularly, this invention relates to injectable therapeutic compositions containing penicillin which will prolong the therapeutic blood levels of penicillin, and to a process for the preparation of these compositions.
  • This depot or repository composition when parenterally injected, is capable of holding any desired dose'of the therapeutically active substance, releasing it in the blood stream only gradually over an extended period of time so that large doses may be easily and conveniently administered by this method.
  • the preparation is characterized by a low viscosity at room temperature being highly fluid in nature and thus can be very easily injected parenterally by means of a are maintained over a prolonged period of time, i. e.
  • Another injectable preparation comprising a suspension of finely divided penicillin particles containing peanut oil having a hydrophilic substance such as pectin. dispersed therein, is consideredto obviate some of the disadvantagesof the Romansky formulation discussed supra but has likewise failed to provide the desired repository effect.
  • an injectable substantially anhydrous repository penicillin composition comprising a therapeutically effective salt of penicillin-distr-iituated bra-vehicle composed of an innocuous, now-toxic oil and an aluminum salt of a phosphoric ester of an alcohol, said alcohol being selected from the group consisting of alkyl or arylalkyl alcohols possessing 6 to hypodermic needle.
  • a therapeutically effective salt of penicillin-distr-iituated bra-vehicle composed of an innocuous, now-toxic oil and an aluminum salt of a phosphoric ester of an alcohol, said alcohol being selected from the group consisting of alkyl or arylalkyl alcohols possessing 6 to hypodermic needle.
  • This preparation is further characterized by its excellent stability as it has been held at a temperature of 56 C. for a period of 2 months without any appreciable loss in potency or any physical change in appearance.
  • the formulation is prepared by heating a mixture containing an aluminum salt of a phosphoric ester together with an innocuous, non-toxic oil such as for example sesame oil, at a temperature of about C. until the white color disappears and the mixture becomes somewhat translucent.
  • the product is cooled and to it is added, a therapeutically active salt of'penicillin. This is followed by ball milling the mixture for about sixteen hours and the desired product in its final form is poured into a suitable container or receptacle.
  • the aluminum salts utilizable in the present invention can be represented by the following formula:
  • R is a member selected from the group consisting of an alkyl radical containing from 6 to 18 carbon atoms, an arylalkyl radical, 'an alkyloxyalkyl radical containing from 6 to 18 carbon atoms and an aryloxyalkyl radical.
  • Specific compounds which are included within the purview of this invention include aluminum octadecylphosphate, aluminum cetylphosphate, aluminum hexylphosphate, aluminum 2-ethylhexylphosphate, aluminum lanrylphosphate, aluminum decyl-phosphate, aluminum [3 phenoxyethylphosphate, aluminum '7 phenylpropylphosphate, aluminum butyloxyethyl phosphate, aluminum ethoxybutyl phosphate, aluminum phenethyl phosphate, etc. 1
  • sesame oil which is used in the prep aration of the formulation
  • other injectable oils such as cottonseed, maize, peanut, olive, etc.
  • the oil that is used in the formulation must be highly refined and contain a minimum amount of readily oxidizable material and moisture, the latter in amounts not exceeding 0.05%.
  • the oil must be sterilized, sterilization being effected using any one of the well known conventional methods.
  • the injectable formulation contains the penicillin salt in a finely divided state in which the particle size of the salt is of mixed sizes but wherein substantially all of the. particles of penicillin are between 1 to 200 microns in size and preferably, less than 50 microns in size.
  • the penicillin embodied in the preparation' may be a 4 mixtureof-one or more of these specific penicillins such as are commonly obtained in the production of penicillin G, K, or any of the other known penicillins, or it 3 may-be a penicillin which' con'sists mainly or wholly of one-ofwthese.
  • aspecificwpenicillinsw It is .preferable,-however, to use a penicillin which is rich in penicillin G, primarily because of the excellent therapeutic qualities ofthis specific s'alh
  • The-penicillinused may be eitherin" 5 the form of amorphous penicill-iiii' or preferably inthe for m ofia cry'stallihperiicillih.L
  • the protcctivegel is not hydrophilic inF nature'. Since the gel' is insoluble in the oil, it coats the 'particlesin -the oil so that'when thepreparation is brought into contact with th'e aqueous body fluids,- a slow penetration'of the penicillin salt is effected through this insoluble coating.
  • This hot solution was added'with stirringto a hot solution of :45 grams of potassium aluminum sulfate (or 32 grams'of al'u minurn sulfa't'e' hydrate), arid boiled forten minutes .while i the "pH was adjusted to 5.0 to 6.0. The .mixture was thenfilteredjwash'ed with'w'ater and then dried in air.
  • the "products are white'jinfusable powders that burn on'ignition' to? a voltiminous'whiteash.
  • the hydrolysis is preferably efiec'ted I at ti-temperature ranging'btween 20 30 C.,' but temperaturesbetween0 90 C. likewise provide satisfactory 60 rsultsi
  • the formatio'nof the aluminum salt is'preferably accomplished at'a temperature'ranging between" 80 '90" CI -but can proceed satisfactorily j'at' room temperatures oreven atteiiipera'turc's slightly-below. Anyjsolublealib mih'uin 'salt'or' doublesalts"'such"as" alum'sg'm'ay likewise' be used.
  • the volume of solvents used is 'not critical.
  • An intramuscularinjection of-0;25 cceof the formulation .prepared above contain ia g 75,000 units'of penicillinsproducedamaximum blood level of 0.09 unit per cc. of blood 96 hours after injection.
  • Rabbit penicillin blood levels blfumeratonindlcates the number of animals showing-levels, denamw inator'ihdicates Iiurxib'erof 'aulma'ls injected.
  • Theforegein g 'results' indicate that the aetionmf' benM cillin may be: greatlyprolonged-bythe intramusculawid jection of a mixture containing a therapeutic penicillin salt, an" aluminum -salt and'an innocuousnon-toxicoilr"
  • pneumococeio infections are sim'ilzirly sue ce'ptible
  • the injecti'on ofi ithesepreparations "ISKIYCMIJT" acterized by :only. slight-pain. and discomforttogethr the absence ofsoreness. at the :point of injection;
  • ciumi-ianrlamineasalts i. es triethylaminefiidsb and famorphousgform. canulik'ewise' :be mam-.1 ny'mhe ree duo'tion ojcrystalline; particles itouless thantabml microns and preferably.less..than.about fifl-micronsgrtprpq longed blood leveis are obtained when the salts are dis persed in a vehicle composed of an aluminum salt and oil.
  • compositions of penicillin salts in the vehicle composed of an aluminum salt and oil can be prepared containing less than or more than 300,000 units of penicillin.
  • An injectable antibiotic preparation capable of maintaining effective therapeutic blood levels over an extended period of time which comprises a therapeutic salt of penicillin, an innocuous non-toxic oil, and a gel of an innocuous non-toxic oil and a quantity of an aluminum salt ranging from 1 to by weight of the total volume of said oil, said aluminum salt being represented by the following formula:
  • R is a member selected from the class consisting of an alkyl group containing from 6 to 18 carbon atoms, an arylalkyl group containing from 6 to 18 carbon atoms, an alkyloxyalkyl group containing from 6 to 18 carbon atoms and an aryloxyalkyl radical containing from 6 to 18 carbon atoms, the gel being insoluble in the first mentioned innocuous non-toxic oil.
  • An injectable antibiotic preparation capable of maintaining efiective therapeutic blood levels over an extended period of time which comprises procaine penicillin, an innocuous non-toxic oil, and a gel of an innocuous nontoxic oil and aluminum octadecylphosphate.
  • An injectable antibiotic preparation capable of maintaining efiective therapeutic blood levels over an extended period of time which comprises procaine penicillin, an innocuous non-toxic oil, and agel of an innocuous non- 5 toxic oil and aluminum laurylphosphate;
  • An injectable antibiotic preparation capable of maintaining effective therapeutic blood levels over an extended period of time which comprises procaine penicillin, an innocuous non-toxic oil, and a gel of an innocuous nontoxic oil and aluminum decylphosphate.
  • An injectable antibiotic preparation capable of maintaining effective therapeutic blood levels over an extended period of time which comprises procaine penicillin, an innocuous non-toxic oil, and a gel of an innocuous nontoxic oil and aluminum octylphosphate.
  • An injectable antibiotic preparation capable of maintaining effective therapeutic blood levels over an extended period of time which comprises procaine penicillin, an innocuous non-toxic oil, and a gel of an innocuous nontoxic oil and an aluminum salt represented by the following formula:
  • R is a member selected from the class consisting of an alkyl group containing from 6 to 18 carbon atoms, an arylalkyl group containing from 6 to 18 carbon atoms, an alkyloxyalkyl group containing from 6 to 18 carbon atoms and an aryloxyalkyl radical containing from 6 to 18 carbon atoms, the gel being insoluble in the first mentioned innocuous non-toxic oil.
  • An injectable antibiotic preparation capable of maintaining effective therapeutic blood levels over an extended period of time which comprises an innocuous non-toxic oil having dispersed therein particles of a therapeutic salt of penicillin G coated with a gel of innocuous non-toxic oil and aluminum cetylphosphate, the amount of aluminum cetylphosphate present in the gel ranging from 1% to 15% by weight of the total amount of non-toxic oil present in the preparation.

Description

INJECTAI ILE PENICILLIN REPOSITORY PREPARA- TION CONTAINING OIL AND GELLED OIL William M. Ziegler, Clementon, N. J., assignor, by mesne assignments, to American Cyanamid Company, New York, N. Y., a corporation of Maine No Drawing. Application August 7, 1951,
Serial No. 240,796
7 Claims. (Cl. 167-65) This invention relates to pharmaceutical preparations. More particularly, this invention relates to injectable therapeutic compositions containing penicillin which will prolong the therapeutic blood levels of penicillin, and to a process for the preparation of these compositions.
In the past, a common method for the administration of penicillin involved the introduction of penicillin in physiologic saline or water through the intramuscular route. This method was highly unsatisfactory in that the penicillin had a tendency to decompose or was rapid- 1y absorbed in the body fluids and then eliminated in the urine. As a result, high levels of pencillin endured in the blood for only brief periods of time. To effect a high blood level of penicillin, it was necessary to give frequent injections of the antibiotic. In view of the fact that satisfactory results in the therapeutic use of penicillin are secured only when effective blood levels 18 carbon atoms, alkoxyalkyl alcohols possessing from 6 to 18 carbons and aryloxyalkyl alcohols.
This depot or repository composition, when parenterally injected, is capable of holding any desired dose'of the therapeutically active substance, releasing it in the blood stream only gradually over an extended period of time so that large doses may be easily and conveniently administered by this method.
The preparation is characterized by a low viscosity at room temperature being highly fluid in nature and thus can be very easily injected parenterally by means of a are maintained over a prolonged period of time, i. e.
several days, the inconvenience and obvious disadvantages of this method precluded its widespread acceptance and use. Further disadvantages included the poor stability of penicillin in physiologic saline and also the loss in potency of the antiobiotic material in this medium, particularly at elevated temperatures.
Numerous attempts have been made to overcome the disadvantages of the foregoing method, but none of them has been highly satisfactory. For example, the advantages of prolonged therapeutic blood levels of penicillin following a single injection has been established by the use of a composition containing penicillin in suspension in a mixture of oil and beeswax (Romansky U. S; 2,443,778). However, the inclusion of wax inthis vehicle was found to be disagreeable to the patient and was proved to-be the apparent cause of a number of unfavorable local reactions such as sensitization of the patient together with the resulting allergic reactions. Numerous cases of fibrosis were likewise reported. Further, the residual beeswax was dissolved with great difiicul ty, requiring some to days for complete assimilation, and in extreme cases, necessitating removal'by surgery.
Another injectable preparation, disclosed in U. S. 2,518,510, comprising a suspension of finely divided penicillin particles containing peanut oil having a hydrophilic substance such as pectin. dispersed therein, is consideredto obviate some of the disadvantagesof the Romansky formulation discussed supra but has likewise failed to provide the desired repository effect.
It has now been discovered that effective therapeutic blood levels of penicillin can be obtained for prolonged periods of time by the administration of an injectable substantially anhydrous repository penicillin composition comprising a therapeutically effective salt of penicillin-distr-ibuted bra-vehicle composed of an innocuous, now-toxic oil and an aluminum salt of a phosphoric ester of an alcohol, said alcohol being selected from the group consisting of alkyl or arylalkyl alcohols possessing 6 to hypodermic needle. By limiting the particle size of the peniciilin to a pre-determined range, the antibiotic remains in suspension and does not settle out. Injections of the aforedescribed composition containing 75,000 units of penicillin in animals have provided blood levels in excess of 0.03 unit per cc. of blood for periods of time in excess of 96 hours.
This preparation is further characterized by its excellent stability as it has been held at a temperature of 56 C. for a period of 2 months without any appreciable loss in potency or any physical change in appearance.
The formulation is prepared by heating a mixture containing an aluminum salt of a phosphoric ester together with an innocuous, non-toxic oil such as for example sesame oil, at a temperature of about C. until the white color disappears and the mixture becomes somewhat translucent. The product is cooled and to it is added, a therapeutically active salt of'penicillin. This is followed by ball milling the mixture for about sixteen hours and the desired product in its final form is poured into a suitable container or receptacle.
The aluminum salts utilizable in the present invention can be represented by the following formula:
wherein R is a member selected from the group consisting of an alkyl radical containing from 6 to 18 carbon atoms, an arylalkyl radical, 'an alkyloxyalkyl radical containing from 6 to 18 carbon atoms and an aryloxyalkyl radical. Specific compounds which are included within the purview of this invention include aluminum octadecylphosphate, aluminum cetylphosphate, aluminum hexylphosphate, aluminum 2-ethylhexylphosphate, aluminum lanrylphosphate, aluminum decyl-phosphate, aluminum [3 phenoxyethylphosphate, aluminum '7 phenylpropylphosphate, aluminum butyloxyethyl phosphate, aluminum ethoxybutyl phosphate, aluminum phenethyl phosphate, etc. 1
In addition to the sesame oil which is used in the prep aration of the formulation, it has been found in practice that other injectable oils such as cottonseed, maize, peanut, olive, etc., may be similarly employed with highly satisfactory results. The oil that is used in the formulation must be highly refined and contain a minimum amount of readily oxidizable material and moisture, the latter in amounts not exceeding 0.05%. Before compounding, the oil must be sterilized, sterilization being effected using any one of the well known conventional methods.
The injectable formulation contains the penicillin salt in a finely divided state in which the particle size of the salt is of mixed sizes but wherein substantially all of the. particles of penicillin are between 1 to 200 microns in size and preferably, less than 50 microns in size.
The penicillin embodied in the preparation'may be a 4 mixtureof-one or more of these specific penicillins such as are commonly obtained in the production of penicillin G, K, or any of the other known penicillins, or it 3 may-be a penicillin which' con'sists mainly or wholly of one-ofwthese. aspecificwpenicillinsw It, is .preferable,-however, to use a penicillin which is rich in penicillin G, primarily because of the excellent therapeutic qualities ofthis specific s'alh The-penicillinused may be eitherin" 5 the form of amorphous penicill-iiii' or preferably inthe for m ofia cry'stallihperiicillih.L
This preparation" difl'ers -markedlyfrom that disclosed in= U. 'S. 2,507193' wherein'pe'nicillin 'isnsuspended in an oil that ha's been gelled with aluminum stearate; in that th aluminu'm phosphate saItUs'ed in this.invention does not dissolve in the oil to produce a gel but instead, the oil"- dissolvesin ith alum inum' salt l forming an insoiuble gel-like materi'al thzit-apparently coatsthe penicil lin parti'clesi Likewiseythis new 'and highly'limpro'ved preparation is distinguishablei iromihat disclose'd in U. S.. 2,5'1 8,510 in -that: the protcctivegel is not hydrophilic inF nature'." Since the gel' is insoluble in the oil, it coats the 'particlesin -the oil so that'when thepreparation is brought into contact with th'e aqueous body fluids,- a slow penetration'of the penicillin salt is effected through this insoluble coating.
Additional ladvantages 'and' features of thisnew and highly improved preparati'onare set forth in-the following examplewhich' discloses the principleof the invention and the preferred embodiment of applying that principle." It-ise understood, however; that the example isfimerely illustrative :and not limitative in nature, being capable I of-various other-modifications:v 0
EXAMPLE The preparation of atypical gelling agent such as for example aluminum cetylphosphate is illustrated as fol lows-:-
To a solution of-24 grams of cetyl'alcohol in 20 cc. of benzene chilled in. anice bath was added 10 cc. of phosphorus 'oxychloride." The -resulting solution was allowed to stand until the-evolution of fumes of hydrogen chloride almost ceased and then the solution was heated to 70 C. for a few minutes. After cooling, the solution was poured onto 200 grams "of ice, and a 5% solution of sodium hydroxide was added from time to time to keep the pH between 3.0 and 8.0 while hydrolysis occurred. The'tinal solution was adjusted to a pH of 6.8 arid then heated to expel'the benzene. This hot solution was added'with stirringto a hot solution of :45 grams of potassium aluminum sulfate (or 32 grams'of al'u minurn sulfa't'e' hydrate), arid boiled forten minutes .while i the "pH was adjusted to 5.0 to 6.0. The .mixture was thenfilteredjwash'ed with'w'ater and then dried in air.
One-tenth mol quantities of "alcohols such. as .octadecyl, lauryl,'decyl,"octyl,"etc. can likewise be treated in the same fashion to secure corresponding aluminum salts.
The "products are white'jinfusable powders that burn on'ignition' to? a voltiminous'whiteash.
The alkylphosphoryl chloride can be prepared within temperatureeran tng trem 0 *cj but preferably between=25-'30 C. The hydrolysis is preferably efiec'ted I at ti-temperature ranging'btween 20 30 C.,' but temperaturesbetween0 90 C. likewise provide satisfactory 60 rsultsi The formatio'nof the aluminum salt is'preferably accomplished at'a temperature'ranging between" 80 '90" CI -but can proceed satisfactorily j'at' room temperatures oreven atteiiipera'turc's slightly-below. Anyjsolublealib mih'uin 'salt'or' doublesalts"'such"as" alum'sg'm'ay likewise' be used. The volume of solvents used is 'not critical.
FORMULATION 4 L grams of procaine penicillin. The mixture was then ball milled for. sixteen hours andtheniilledin It should be mentioned that the heating temperatures of the mixture containing the oil and aluminum phosphate salt are limited only by the cracking point of the various oils used.
The quantity of alumin'umsaltis preferably about 8% by weighfi: pf: volu'n'ie =of-' the oil iused sazisfaemry rema having 'likewise 'been obfained when "quantities ranging from 1 to l5% were used. An intramuscularinjection of-0;25 cceof the formulation .prepared above contain ia g 75,000 units'of penicillinsproducedamaximum blood level of 0.09 unit per cc. of blood 96 hours after injection.
The following table showsan' average of the animals indicating penicillin-blood 'levels..of--0.03 unit per cc. or above at the indicated hour after an intramuscular injection of 0.25 cc. of a formulation containing varying amounts 'of alum'inum*salt" and 751000 units-bf peni cillin; Consequentbloodsamples'were takenat the"i1f-" tervalsindicated.- Blood levels were "determined byfa -microbiol'ogical plate assay -method *usin'g' S. 'luteli: A-
control was also drawn before injection;
Rabbit penicillin blood levels blfumeratonindlcates the number of animals showing-levels, denamw inator'ihdicates Iiurxib'erof 'aulma'ls injected.
Theforegein g 'results' indicate that the aetionmf' benM cillin may be: greatlyprolonged-bythe intramusculawid jection of a mixture containing a therapeutic penicillin salt, an" aluminum -salt and'an innocuousnon-toxicoilr" The preparations: herein= described are effective'agairist= many grampositive organisms; bothaerobic and anaero bic, .as. iwell as against gonococokand-t meningococcii Likewiseg. pneumococeio infections are sim'ilzirly sue ce'ptible The injecti'on ofi ithesepreparations "ISKIYCMIJT" acterized by :only. slight-pain. and discomforttogethr the absence ofsoreness. at the :point of injection;
While I the present invention has tbeen tdes'cribed -withh particular reference to .the use of ifcrystals iof procailreif penicillin,'fit is. understood that. other comm'erciallyiavail? able fisaltsliof penicillin such sassodium; we
ciumi-ianrlamineasalts i. es triethylaminefiidsb and famorphousgform. canulik'ewise' :be mam-.1 ny'mhe ree duo'tion ojcrystalline; particles itouless thantabml microns and preferably.less..than.about fifl-micronsgrtprpq longed blood leveis are obtained when the salts are dis persed in a vehicle composed of an aluminum salt and oil.
It should likewise be mentioned that therapeutic salts of penicillin of any desired potency may be employed. However, to produce satisfactory penicillin blood levels for extended periods of time, it is preferred to use highly potent products. Compositions of penicillin salts in the vehicle composed of an aluminum salt and oil can be prepared containing less than or more than 300,000 units of penicillin.
It is understood that the data and example herein given are intended to be exemplary only in character, the invention being directed essentially to the incorporation of an available penicillin salt in a vehicle comprising the nontoxic innocuous oil and aluminum salt disclosed herein.
It will be apparent, therefore, that the invention is capable of being employed with varying constituents such as for example, different salts of penicillin, diiferent alnminum phosphate salts and different oil vehicles. It is obvious from the foregoing that the invention is capable of various modifications and that, therefore, it is intended and desired to embrace within the scope of this invention such modifications and changes that are necessary to adapt it to varying conditions and uses, as defined by the scope of the appended claims.
I claim:
1. An injectable antibiotic preparation capable of maintaining effective therapeutic blood levels over an extended period of time which comprises a therapeutic salt of penicillin, an innocuous non-toxic oil, and a gel of an innocuous non-toxic oil and a quantity of an aluminum salt ranging from 1 to by weight of the total volume of said oil, said aluminum salt being represented by the following formula:
wherein R is a member selected from the class consisting of an alkyl group containing from 6 to 18 carbon atoms, an arylalkyl group containing from 6 to 18 carbon atoms, an alkyloxyalkyl group containing from 6 to 18 carbon atoms and an aryloxyalkyl radical containing from 6 to 18 carbon atoms, the gel being insoluble in the first mentioned innocuous non-toxic oil.
2. An injectable antibiotic preparation capable of maintaining efiective therapeutic blood levels over an extended period of time which comprises procaine penicillin, an innocuous non-toxic oil, and a gel of an innocuous nontoxic oil and aluminum octadecylphosphate.
AIOH
3. An injectable antibiotic preparation capable of maintaining efiective therapeutic blood levels over an extended period of time which comprises procaine penicillin, an innocuous non-toxic oil, and agel of an innocuous non- 5 toxic oil and aluminum laurylphosphate;
4. An injectable antibiotic preparation capable of maintaining effective therapeutic blood levels over an extended period of time which comprises procaine penicillin, an innocuous non-toxic oil, and a gel of an innocuous nontoxic oil and aluminum decylphosphate.
5. An injectable antibiotic preparation capable of maintaining effective therapeutic blood levels over an extended period of time which comprises procaine penicillin, an innocuous non-toxic oil, and a gel of an innocuous nontoxic oil and aluminum octylphosphate.
6. An injectable antibiotic preparation capable of maintaining effective therapeutic blood levels over an extended period of time which comprises procaine penicillin, an innocuous non-toxic oil, and a gel of an innocuous nontoxic oil and an aluminum salt represented by the following formula:
wherein R is a member selected from the class consisting of an alkyl group containing from 6 to 18 carbon atoms, an arylalkyl group containing from 6 to 18 carbon atoms, an alkyloxyalkyl group containing from 6 to 18 carbon atoms and an aryloxyalkyl radical containing from 6 to 18 carbon atoms, the gel being insoluble in the first mentioned innocuous non-toxic oil.
7. An injectable antibiotic preparation capable of maintaining effective therapeutic blood levels over an extended period of time which comprises an innocuous non-toxic oil having dispersed therein particles of a therapeutic salt of penicillin G coated with a gel of innocuous non-toxic oil and aluminum cetylphosphate, the amount of aluminum cetylphosphate present in the gel ranging from 1% to 15% by weight of the total amount of non-toxic oil present in the preparation.
References Cited in the file of this patent UNITED STATES PATENTS

Claims (1)

1. AN INJECTABLE ANTIBIOTIC PREPARATION CAPABLE OF MAINTAINING EFFECTIVE THERAPEUTIC BLOOD LEVELS OVER AN EXTENDED PERIOD OF TIME WHICH COMPRISES A THERAPEUTIC SALT OF PENICILLIN, AN INNOCUOUS NON-TOXIC OIL, AND A GEL OF AN INNOCUOUS NON-TOXIC OIL AND A QUANTITY OF AN ALUMINUM SALT RANGING FROM 1 TO 15% BY WEIGHT OF THE TOTAL VOLUME OF SAID OIL, SAID ALUMINUM SALT BEING REPRESENTED BY THE FOLLOWING FORMULA:
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Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2964448A (en) * 1959-01-27 1960-12-13 Anschel Joachim Relaxin composition and process for preparing same
US3016330A (en) * 1955-11-10 1962-01-09 Novo Terapeutisk Labor As Therapeutical antibiotic composition
US3105793A (en) * 1956-11-28 1963-10-01 Lobel Mervyn Joseph Injectable medicinal composition
US3242464A (en) * 1961-07-31 1966-03-22 Rca Corp Data processing system
US3494949A (en) * 1967-01-03 1970-02-10 Dow Chemical Co Aluminum salts of alkyl orthophosphates

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2340331A (en) * 1935-04-02 1944-02-01 Lubri Zol Corp Lubrication
US2416985A (en) * 1938-10-04 1947-03-04 California Research Corp Compounded mineral oil
US2507193A (en) * 1949-05-17 1950-05-09 Bristol Lab Inc Penicillin product

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2340331A (en) * 1935-04-02 1944-02-01 Lubri Zol Corp Lubrication
US2416985A (en) * 1938-10-04 1947-03-04 California Research Corp Compounded mineral oil
US2507193A (en) * 1949-05-17 1950-05-09 Bristol Lab Inc Penicillin product

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3016330A (en) * 1955-11-10 1962-01-09 Novo Terapeutisk Labor As Therapeutical antibiotic composition
US3105793A (en) * 1956-11-28 1963-10-01 Lobel Mervyn Joseph Injectable medicinal composition
US2964448A (en) * 1959-01-27 1960-12-13 Anschel Joachim Relaxin composition and process for preparing same
US3242464A (en) * 1961-07-31 1966-03-22 Rca Corp Data processing system
US3494949A (en) * 1967-01-03 1970-02-10 Dow Chemical Co Aluminum salts of alkyl orthophosphates

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