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CA1112572A - Injectable chloramphenicol composition - Google Patents

Injectable chloramphenicol composition

Info

Publication number
CA1112572A
CA1112572A CA307,371A CA307371A CA1112572A CA 1112572 A CA1112572 A CA 1112572A CA 307371 A CA307371 A CA 307371A CA 1112572 A CA1112572 A CA 1112572A
Authority
CA
Canada
Prior art keywords
chloramphenicol
composition
pvp
composition according
injectable
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired
Application number
CA307,371A
Other languages
French (fr)
Inventor
Morris E. Stolar
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Abic Ltd
Original Assignee
Abic Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Abic Ltd filed Critical Abic Ltd
Application granted granted Critical
Publication of CA1112572A publication Critical patent/CA1112572A/en
Expired legal-status Critical Current

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/16Amides, e.g. hydroxamic acids
    • A61K31/165Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/22Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/32Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/0019Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Inorganic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Dermatology (AREA)
  • Medicinal Preparation (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

AN INJECTABLE CHLORAMPHENICOL COMPOSITION

ABSTRACT

The present invention relates to a stable injectable chloramphenicol composition having preferably a high content of chloramphenicol. Said composition comprises chloramphenicol, N-methylpyrrolidone, PVP and, if desired, a pharmaceutically acceptable solvent which is miscible with N-methylpyrrolidone.

Description

. . .
`~; The present invention relate~ to a stable injectable .. chloramphenicol composition having a high content oP chlor-amphenicol.

.. ~- Chloramphenicol is utilised at present mainl~ for :,;.
... veteri~ary purpo~e~. It i desired to admin1ster to a large il.,.
animal a compo~ition having a rather high content o~ chlor-amphe~icol~ Said large amount o~ chloramphen1col should e3hib~t oonstant blood level~ and be active for quite a long period o~ time~ So ~ar there ha~ been injected sodlum succinate o~ chloramph~nlcol i~ a concentration of 25% and there are al~o known some ~njectable compositions whioh compri~e up to 25% o~ active compound. Howe~er, these compositions are : .
not Plway~ sati~actory, i.e~ in particular they are unstable ` and ha~e a relatively short shelf life, and it was therefore de~irable to de~elop compoaitions which would have higher concentrations of chloramphenicol and would have the desired properties, i.e~ exhibit con~tant blood levels and have a long : shel~ llie~
It has been ~oud that if chloramphenicol is dissolved .~ in N-methylpyrrolidone there may be prepared composition~
~ having a higher concsntration o~ chloramphenicol(about 50%).
.~ ; Howe~er, these co~po~itions had the following drawbacks:
:
a~ Brratic blcod le~els were obtained~

:~ b~ Pain and ~rritation were cau~ed to the animal treated with : said iniection.

., :
.: ~
:
:,' . ~

..
, ,~ i :-~
2 ~ ~ h~

~ or these reaaon6 said compositions were not applicable~
It has ~ow surprisingly been fo~nd that with the ~ddition of a certain amount o~ polyvinyl pyrrolidone(PVP) to said com-poaltion said drawback~ are overcome~ ~hi~ has been surprl~ing as it could not be e~pected that PVP would cau~e a const~t blood level and in particular that it would dispel the pai~
and irritation~ The shelf life o~ said composition~ iR at lea~t one year.
The pre~ent invention thus con~i~t~ i~ an injectable compo~ition c~mpris~ng chloramphenicol, ~-methylpyrrolidone, PVP and, i~ desired, a pharmaoeutically acceptable ~olvent whiCh is miscible with N-~ethylpyrrolidoneO
~ ompo~itions according to the present invention may compr~es al80~ ii de~ired, only small amount of chloramphe n~col~ ~owever, they ~hould contain preferably at least 30~o of chloramphe~icol and especi~1ly 40-60~o(all percentages are glv9~ herein ~ight/~olume)0 Ccmposition~ according to the pre~ont invention havlng a lower content of chloramphenlcol are also ~uch bett~r than tho~e commercially available a~
they are mu~h more stable.
The ~mount o~ the PVP varles and it should be be~ween 4-20~ pre~6rably between 5 lOYo of the entire composition.
Other solvents, i~ required, are utilised as dilu~t in order to get the required concentration of the composit~cn.
~ suitable solvents one should mention water, ethanol and in particular, certain glycols, or deri~atives thereoft e.g.
propyl~neglycol, glycerol-formal, tertaglycol, polyethylene-,., ~l~col, ~t~

!

5'7
- 3 -~,.";.
,j .
.~
' .~. .
'. The present invention will now be illustrated with ,` reference to the following examples without being restricted by them.
The composition of the present invention were prepared as follows in all exampleæ:
:
,; . The chloramphenicol wa~ dis~olved in N-methylpyrrolidone.
-~ Therea~ter the PVP was added and finally the additional ~olvent, i~ any, was admi~ed~
The PYP utilised i~ a product of General Aniline and - Fil~ Corporation.The K numbers are derived from viRcosity.
-: Exam~ls 1 Chloramphenicol 50.0 g N-Methylpyrrolidone 40.0 g . ; PVP K30 6.0 g Propyleneglycol enough to make lOOoO ml .. At the end of two years ~torage at room temperature ,, only 3.5% of the chloramphenicol degradedO
; : The volume needed of th~ composition (called ~50%")'',.,', to be in~ected to a ruminant for aohieving a dose level :' - of 50 ~ kg was compared with the ~ollowing composition:
.. Chloramphenicol 20 g ~~ Glycerol~ormsl 80 g Water enough to make 100 ml ~: ~he shelf life of the 20/o composition was leEs than 2 mcnths (the degradation of chloramphenicol was about 40%)~
~he results are given in Table I, which show comparitive . blood le~el~ o~ chloramphenicol af~er parenteral administration ~` of 50 m ~ kg of each of the composition~.
, ~i"

` ~

: `
- 4 -TABLE I

. ~__ . . . . .... .
~'ormulatio~ Calf of ~we of ~ow of ~ow of ::: 50 kg 65 kg 500 kg 650 kg 50% 5 6~5 50 65 .
Si~llar compari ons with composition~ having various concentrations o~ chloramphenicol showed the superiority of the 50% composition.
Moreover, the mean serum chloramphenicol concentrations over a certain period of time ~ollowing a ~ingle intramuscular ;: in~20tion o~ said formulations were compared.
The re~ults are æhown in the accompanying drawings .- in which:
~ igol ~hows the mean serum concentration of c~lves at a dose level oi 50 m ~ kgO
.~ Fig.2 ehow the mean serum concentration at cows ,~ .
: at a do~e level of 30 mg/kg; a~d Fig.~ a~o~s the mean ~erum concentration at ewes at '~ . at a do~e level of 50 mg/kg.

,~ The t~t~ ~ere per~ormed by k~own method~ (3ee, for e~ample, Glazko,(s), Set.al. ArchO Biochem. 23, 411-418,1949 . and Zi~.6. et alO Zbl,Vet.MedO(A) 207801-811,1973).

~' am~le 2 `.- Chloramphenicol 10.0 g .- N-Methylpyrrolidine 3000 g PYP ~15 6~0 g . Propyleneglyool enough to make 100.0 ml .;

.
.'` ', .

` ::
h~Z
. ,, ~` Example 3 :~: Chlor~mphenicol 80.0 g .. PVP K15 6.0 g N-Methylpyrrolidone enough to make 100.0 ml ~ Example 4 m: Chloramphenicol 50.0 g ,.
~, N-Methylpyrrolidone 40.0 g PVP K30 10,0 g : Glycerol~o~mal enough to make 100.() ~1 Example 5 Chloramphenicol 50.0 g N-Methylpyrrolidone 40.0 g PVP K30 1.0 g ; . ..:
.. Tetraglycol enough to make100.0 ml . Example 6 . ~
; - Chloramphenicol 40.0 g : ~ N-Methylpyrrolidone 40.0 g :....
:~ PYP K15 15.0 g ., -: .
. Polyethyleneglycol 300 enough to make 100.0 ml `~ 20 Example 7 . Chloramphenicol 30.0 g ;:- N-Methylpyrrolidone 40.0 g .:
:~. PVP K15 20.0 g Ethanol 95% enough to make100.0 ml Example 8 ' ~
Chloramphenicol 30 g N-Methylpyrrolidone 40 g ~VP K15 20 g ~ater enough to ~ake 100 ml.
: ~ - 5 -::
'

Claims (12)

THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLUSIVE PROPERTY
OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. An injectable composition comprising chloramphenicol, N-methyl-pyrrolidone and PVP.
2. The composition of claim 1, further including a pharmaceutically acceptable solvent which is miscible with N-methylpyrrolidone.
3. A composition according to claim 1 or 2, wherein the amount of chloramphenicol is at least 30%.
4. A composition according to claim 1 or 2, wherein the amount of chloramphenicol is 40-60%.
5. A composition according to claim 1 or 2, wherein the amount of PVP is 4-20%.
6. A composition according to claim 1 or 2, wherein the amount of PVP is 5-10%.
7. A composition according to claim 2, wherein the additional solvent is water.
8. A composition according to claim 2, wherein the additional solvent is ethanol.
9. A composition according to claim 2, wherein the additional solvent is a glycol or a derivative thereof.
10. A composition according to claim 9, wherein the glycol is selected among the group comprising propyleneglycol, glycerolformal, tetraglycol, poly-ethyleneglycol.
11. A method for the preparation of an injectable composition as defined in claim 1, wherein the chloramphenicol is dissolved in the N-methyl-pyrrolidone, and PVP is added to the solution.
12. The method for the preparation of an injectable composition as defined in claim 2, wherein the chloramphenicol is dissolved in the N-methyl-pyrrolidone, the PVP is added to the solution, and the pharmaceutically acceptable solvent is added.
CA307,371A 1977-07-15 1978-07-14 Injectable chloramphenicol composition Expired CA1112572A (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IL52533A IL52533A (en) 1977-07-15 1977-07-15 Injectable chloramphenicol composition
IL52533 1977-07-15

Publications (1)

Publication Number Publication Date
CA1112572A true CA1112572A (en) 1981-11-17

Family

ID=11049656

Family Applications (1)

Application Number Title Priority Date Filing Date
CA307,371A Expired CA1112572A (en) 1977-07-15 1978-07-14 Injectable chloramphenicol composition

Country Status (13)

Country Link
JP (1) JPS5420125A (en)
AT (1) AT360149B (en)
AU (1) AU3752578A (en)
BE (1) BE869001A (en)
CA (1) CA1112572A (en)
DE (1) DE2829408A1 (en)
FR (1) FR2397191A1 (en)
GB (1) GB2000970B (en)
IE (1) IE47126B1 (en)
IL (1) IL52533A (en)
NL (1) NL7807641A (en)
NZ (1) NZ187683A (en)
ZA (1) ZA783671B (en)

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3064250D1 (en) * 1979-07-02 1983-08-25 Pfizer Long acting sulfonamide injectable compositions
NL8002636A (en) * 1980-05-08 1981-12-01 Gist Brocades Nv SOLOATE OF AMOXICILLINE, METHOD FOR PREPARING IT AND METHOD FOR PREPARING INJECTION PREPARATIONS FROM THIS SOLVATE
NL178941C (en) * 1982-06-15 1986-06-16 Aesculaap Bv PROCESS FOR PREPARING AN AQUEOUS OXYTETRACYCLINE PREPARATION.
JPS6031189A (en) * 1983-07-30 1985-02-16 カシオ計算機株式会社 musical tone generator
US4696814A (en) * 1985-08-21 1987-09-29 Warner-Lambert Company Parenteral phenytoin compositions
IT1197481B (en) * 1986-09-15 1988-11-30 Zambon Spa PHARMACEUTICAL PREPARATION FOR VETERINARY USE
US20030068339A1 (en) * 2001-10-02 2003-04-10 Phoenix Scientific, Inc. Veterinary florfenicol formulation that is syringeable under cold weather conditions
JP5017122B2 (en) 2004-12-21 2012-09-05 インターベツト・インターナシヨナル・ベー・ベー Injectable veterinary composition
CN113694018A (en) * 2021-09-08 2021-11-26 海南制药厂有限公司制药二厂 Chloramphenicol injection and preparation method thereof

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1538903A (en) * 1975-04-11 1979-01-24 Nelson Res & Dev Carrier for a topically applied physiologically active agent or cosmetic agent

Also Published As

Publication number Publication date
GB2000970A (en) 1979-01-24
BE869001A (en) 1979-01-15
DE2829408A1 (en) 1979-02-01
ZA783671B (en) 1979-06-27
IL52533A0 (en) 1977-10-31
IE781425L (en) 1979-01-15
NZ187683A (en) 1981-03-16
AU3752578A (en) 1980-01-03
GB2000970B (en) 1982-03-17
ATA511878A (en) 1980-05-15
AT360149B (en) 1980-12-29
JPS5420125A (en) 1979-02-15
IE47126B1 (en) 1983-12-28
IL52533A (en) 1980-01-31
FR2397191B1 (en) 1981-12-31
FR2397191A1 (en) 1979-02-09
NL7807641A (en) 1979-01-17

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