Note: Descriptions are shown in the official language in which they were submitted.
. . .
`~; 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.
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~ 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~
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'. 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~.
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TABLE I
. ~__ . . . . .... .
~'ormulatio~ Calf of ~we of ~ow of ~ow of
::: 50 kg 65 kg 500 kg 650 kg
1205 16025 125 16205
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
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~` 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.
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