General
- Ciclosporin,
cyclosporine or cyclosporin, is an immunosuppressant drug widely used
post-allogeneic organ transplant to reduce the activity of the
patient's immune system and so the risk of organ rejection. It has
been studied in transplants of skin, heart, kidney, lung, pancreas,
bone marrow and small intestine. Ciclosporin is a cyclic nonribosomal
peptide of 11 amino acids (an undecapeptide) produced by the fungus
Tolypocladium inflatum Gams, initially isolated from a Norwegian soil
sample.
- Cyclosporine
is a potent immunosuppressant medication that is considered a disease
modifying antirheumatic drug (DMARD) because it not only decreases the
pain and swelling of arthritis but it may also prevent joint damage
and reduce the risk of long term disability.
Function
- Ciclosporin is
thought to bind to the cytosolic protein cyclophilin (immunophilin) of
immunocompetent lymphocytes, especially T-lymphocytes. This complex of
ciclosporin and cyclophylin inhibits calcineurin, which under normal
circumstances is responsible for activating the transcription of
interleukin-2. It also inhibits lymphokine production and interleukin
release and therefore leads to a reduced function of effector T-cells.
It does not affect cytostatic activity. It has also an effect on
mitochondria. Ciclosporin A prevents the mitochondrial PT pore from
opening and inhibits thus cytochrome c release, a potent apoptotic
stimulation factor. However, this is not the primary mode of action
for clinical use but rather an important effect for research on
apoptosis.
Production
-
The
production of a nanosuspension is the transformation of a macrosized
powder into a mostly aqueous nanosized suspension. Therefore the first
step is the wetting of the dry powder with a solution of the
stabiliser of the suspension. Nanosuspensions can be prepared with
concenentrations of up to 40% (w/w). High pressure homogenisation is a
high energy process and stresses the coumpound. In order to minimise
the stress for the drug, as well as to minimise the friction of the
homogenisation material (e.g. valve, valve seat) some
prehomogenisation steps are performed.
-
A
macrosuspension containing 4% (w/w) of cyclosporine and 0.5% of
Poloxamer 188 as stabiliser was produced. The temperature of the
nanosuspension during the production was varied in order to
investigate the influences on the quality and the stability of the
resulting nanosuspensions.
Technology
-
Industrial
interests focussed on high sales drugs (e. g. cyclosporine) to be
formulated with SLN. Pharmatec (Milan/Italy) developed a cyclosporine
SLN formulation for oral administration as competitive product to
Sandimmun Neoral.
-
Cyclosporine
has been a key drug in the prevention of rejection in patients
undergoing transplants for 20 years, and to date is approved for use
in kidney, heart and liver transplant patients. Chiron's application
for Pulminiq is aiming to get approval for the use of the drug,
alongside standard immunosuppressive therapy, to improve survival and
cut rejection in lung transplant patients.
Market
-
The
biotechnology arm of an Enterprises in Kolkata, plans to market
Cyclosporin, used in kidney transplantation, in the U.S. global
generic drug market. To this effect the company also plans a joint
venture with an U.S. based company at Puerto Rico. Initially this
company will supply the bulk drug to the JV to produce the drug
locally. The demand for Cyclosporin in the U.S. market is estimated at
$450 million.
-
Eons'
generic cyclosporine is expected to produce a significant impact on
the market for the softgel capsule, which currently exceeds $300
million annually. Transplant recipients must take daily doses of the
drug to prevent organ rejection, at an annual cost of more than $6000
for the brand.
Entrepreneur
who want the informations on Production
and Processing, Technology, Applications, Patent, Consultants, Company Profiles,
Reports, Market can Email as to
informer@eth.net,
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