IMMUNOFAN - new high effective immunostimulant (Description)

Igor M. Maltcev root at amtis.kaluga.su
Mon Jul 4 04:09:13 EST 1994


       INFORMATION ON EXPERIMENTAL AND CLINICAL TRIAL OF IMMUNOFAN
                           RUSSIA  1989-94

  IMMUNOFAN is a preparation, containing synthetic hexapeptide as
an acting substance. Molecular mass 836 D.
  The preparation is a white powder without smell. It is easily
dissolved in water or in sodium chloride isotonic solution, or in 95%
alcohol.

                    Experimental data on IMMUNOFAN
                    1.Pharmacological properties.
  1.1. IMMUNOFAN has a powerful immunoregulating activity in
respect of restoration of disturbed indicators of the cellular and
humeral immunity.
  1.2. The drug stimulates the processes of the T-lymphocytes
maturing and cooperative interaction of T-helpers and bone marrow
cells, restores the disturbed balance of T-lymphocytes subpopulations,
intensifies the activity of the natural killers and the oxygen
depended system bacterial action of the neutrophils.
  1.3. On the background of congenital or acquired immunopathology
IMMUNOFAN activates earlier stages of antibody production, increases
synthesis of immunoglobulins M, G, A, but in the case of the Ig E
hyper production it decreases its synthesis level.
  1.4. IMMUNOFAN stimulates disturbed production of the thymic
immunity hormones, including serum thymic factor and increases the
amount of antibody producing cells in 4-6 times.
  1.5. IMMUNOFAN regulates formation of immune system mediators
depending on their production level.  In conditions of decreasing
lymphocytes proliferating activity the drug stimulates expression of
receptors and formation of interleukine-2 (drug induced or ecological
immunodeficiency).  On the background of induced hyperproduction of
tumor necrosis factor the drug decreases its activity.
  1.6. The drug increases the antibacterial and antiviral resistance
of the host, its administration existentially increases the survival
of experimental animals after Klebsiella pneumoniae infection and
viability of the posterity after influenza virus infection.
  1.7. IMMUNOFAN administration in the case of immunization by
antiviral vaccine increases titters and the duration of the antiviral
antibodies circulation sharply.
  1.8. In the case of the chronic infectious process decompensation
the drug normalize the lymphocytes genetic stability according the
DNA structure stabilizing indicator and its ability of reparation.
  1.9. IMMUNOFAN's pharmacological effect does not depend on the
prostaglandin E^2 production level and is reached in combination with
anti-inflammatory drugs of the non steroid group (prostaglandins
inhibitors).
  1.10. IMMUNOFAN has an exceptional low toxicity and provides the
wide safety reserve.  The single dose as higher as 1000 middle
therapeutic dose does not cause deaths in the experimental animals.
  1.11. Determination of the drug chronic toxicity demonstrates its
safety.  Changes of the hematological and biochemical indicators
occurred during the IMMUNOFAN administration to the animals daily
during one month in therapeutic or subtoxic dose come back to the
initial levels after withdrawal of IMMUNOFAN.
  1.12. The IMMUNOFAN administration does not cause local irritating
effect, allergic reactions and mutagenesis.
  1.13. The close analog of IMMUNOFAN is Thymopentin (Thymunox),
produced on the base of synthetic pentapeptid by the firm Cilag AG
International (Switzerland).  The main advantage of the IMMUNOFAN is
its ability to stimulate markedly antiviral immunity. The recommended
single dose of IMMUNOFAN is 1-1,5 mcg/kg of the body mass, but that of
Thymopentin (Thymunox) is about 700 mcg/kg.

                     2. Indications for the study.
  2.1. Limited clinical trials are recommended by the Veterynary
Farmacology Commitee of the Ministgy of Agriculture of Russian
Federation (VFC Russia) in 1987 in farm and pet animals, and by the
Farmacology Commitee of the Ministry of Health of Russian Federation
(FC Russia) in 1989 in the patients with chronic active and persisting
hepatitis B, brucellosis, and HIV infection.  VFC and FC Russia -
analog FDA USA.
  2.2. Clinical trials of the IMMUNOFAN among patients with active
and persisting hepatitis B are performed with the taking into account
their clinical and immunological status. For this before the IMMUNOFAN
administration the individual sensitivity of the patient's blood
lymphocytes to the drug is determined "in vitro":  restoration of the
amount of T-lymphocytes helpers/inducters, suppressors/cytotoxic
lymphocytes and natural killers subpopulations.
  The expression of the HBs and HBe antigens and presence of their
specific antibodies are determined in the patient's sera. The
effectiveness of the treatment is estimated using clinical and
immunological indicators, including the positive dynamics of the
biochemical indicators of the pathological process activity and viral
antigens elimination.
  2.3.During clinical trials in the patients with brucellosis the
cell immunity indicators are estimated, the rise of the IgM, IgG, IgA
antibodies titters, the circulating immune complexes level, the
clinical status of the patient, paying special attention on the
presence of inflammatory reactions and on the range of the joints
movement.
  2.4. During IMMUNOFAN clinical trials in the HIV infected patients
the individual lymphocytes sensitivity to IMMUNOFAN "in vitro" should
be taken into account - restoration of the immuno-regulation index
CD4/CD-8 as well as inhibition the synthesis of the tumor necrosis
factor and induction of the immune interferon.  Administration of
Imunofan is indicated to patients on the earlier stages of the
disease in combination with specific antiviral therapy
(azothymidine).
  2.5. Enlarged clinical trial under the control of the Farmacology
Commitee of Ministry of Health of Russian Federation beginned in 1993
andn lasted now.

          3. Administration methods and recommended dosage.
  3.1. In veterinary and experiments.
  3.1.1. For experimental warmblooded animals - for stimulation of
buster effect during immunization to increase titters of specific
antibodies.
  3.1.2. For farm, zoo and pet warmblooded animals IMMUNOFAN is
used for correction of immunodeficiency states, complex prophylaxis
and treatment of intestinal and respiratory diseases caused by viruses
and bacteria; in intrauterine bacterial and viral infections, and for
stimulation of buster effect during immunization of animals.
Experience with administration of IMMUNOFAN for prevention and
treatment diseases in farm animals (young cattle, pigs, male, cows
etc.); poultry, pet animals (dogs, cats) shows its high effectiveness
for:
- prevention and treatment of viral enteritis, hepatitis, viral
conjunctivitis, influenza, parainfluenza, ARI and other viral
diseases,
- prevention and treatment of pneumonia, bronchitis, mastitis,
endometritis, colitis and other diseases, caused by bacterial flora,
- due to increase of the host immune defence,
- prevention and treatment of lung intestinal forms of animal pest, as
well as complications in animals after that disease,
- liver function disturbance and intoxications caused by various toxic
substances (zookumarin etc.) and spoiled nutritional products.
     IMMUNOFAN prevents complications caused by immunization, induces
potent post vaccinate immunity and increase animal resistance to
infection, prevents hypo nutrition in fetus and newborns increases
survival and viability in offspring, synchronizes sexual cycle,
increase fertility, decreases spontaneous abortion and still birth
rate, helps with favorable course of gestation.
  3.1.3. The drug is administered by courses for subcutaneous or
intermuscular injections in dose 1-1.5 mcg/kg of the body mass once a
day with the interval of 3 days during 2-6 weeks.  If it is necessary
according to clinical and immunological indicators the repeated
maintaining courses are carried out for 1-2 weeks.
  3.1.4. To produce the booster effect the drug is administered
once 1 hour before the immunization by the subcutaneous or
intermuscular injection in dose 1-1.5 mcg/kg of the body mass.  Under
the immunization of the patients with marked disturbance of the immune
status IMMUNOFAN is administered 1 hour before the immunization and in
every 3 days for 2-3 weeks.
  3.2. In clinical practice.
  3.2.1. IMMUNOFAN is intended for treatment of immunodeficiency
states of various ethiology and diseases with concurrent immunity
disturbances.  The drug has immunoregulating, antiinflammatory,
disintoxicating, hepatoprotective and radioprotective action.
  3.2.2. IMMUNOFAN may be recommended for adults as a drug for
prophylaxis and treatment of the chronic viral and bacterial
infections including chronic active and persisting viral hepatitis B,
HIV infection, brucellosis, yersiniosis and for producing of booster
effect after vaccination.
  3.2.3. IMMUNOFAN is used with preventive and curative aims for
restoration of cell-mediated and humoral immunity in congenital and
acquired immune deficiency of various etiology.
  The drug is administered subcutaneously and intramuscularly in a
single dose of 1-2 mcg/kg according to the following schedule:
  - in 4-6 months for prevention and treatment of aging-related
immune deficiency in persons older than 40-45 years under emotional
and physical stress;
  - immediatly before and in 4-6 days after exposure;
  - in 3 days for 9 days for prevention and treatment of acute
respiratory viral infections (influenza, parainfluenza, viral
conjunctivitis) or in the drop form, as well as for inhalation use 2
times a day;
  - in 3 days for a month for treatment of chronic viral and
bacterial infections (Chronic hepatitis B, Yersiniosis, brucellosis,
tuberculosis etc.);
  - in 1-2 days for 10-12 days in sepsis, wound infection;
  - in 1-3 days for 10-14 days in severe burning lesion, congelation
and radiaton disease, as well as in the period between courses of
chemo/radiation therapy in oncological patients;
  - in 1-2 days for 3 weeks in atopic dermatitis, psoriasis and
rheumatoid arthritis;
  - in 3-4 days for 4 weeks in congenital hypogammaglobulinemia;
  - under immunization to induce booster effect and to reduce
complications 1.0 ml of the drug is mixed with a vaccine in the same
syringe or is used as a solvent for dry vaccines.

             4. Contraindication and drugs interactions.
  4.1. IMMUNOFAN is contraindicated in clinical practice during
pregnancy. Inspite of many reports about the successful treatment of
any diseases in pregnant animals without mutagenic effects (IMMUNOFAN
prevents the development of fetus anomalies), IMMUNOFAN not
recommended during pregnancy.
  4.2. IMMUNOFAN can force the effect of sedatives and tranquilizers,
durating and deepening the drug-relative sedation and sleeping time.
  4.3. IMMUNOFAN force the unti-inflammatory effect of steroids, but
defence from its immunosuppressive effect.
  4.4. No direct or indirect IMMUNOFAN antagonist has been found.
However, the drug should not be administered in a combination with
other biostimulators and immunomodulating pharmaceuticals.

                         5. Side effects.
  5.1. Side effects was not observed.
  5.2. During the IMMUNOFAN therapy sometimes was observed the period
of provocation of the chronic inflammation sights since 4 till 11 days
from the beginning of therapy (1st injection). The provocation
indicates with subfebril fiver (37.1-37.6'C), light local pain in
discharge organs, and general discharge.  The non-steroid anti-
inflammatory drugs (aspirin, etc) effectively helps in this period.

                       6. Pharmaceutical forms.
  IMMUNOFAN produced as 0.005% sterile solution in isotonic sodium
chloride, pH 6.4 - 6.6, for subcutaneous or intermuscular injections
in glass ampules of 1.0 ml, 10 ampules/box.

                        7. Storage condition.
  The drug is stored in dry dark place at 4-8 C. The storage period
is 2 years.

              8. Questions and "How to order IMMUNOFAN ?"
  All questions except ordering or commercial, send to this group
with word "IMMUNOFAN" in field Subject: or to our E-mail address.
  If you interest in experimental trial of IMMUNOFAN ask me for
ordering information by E-mail: root at amtis.kaluga.su
                       Subject: How to order IMMUNOFAN ?

                        9. Our questions.
  1. Is it right to send this letter to sci.med or bionet.immunology?
What other groups more suitable for this?
  2. If you know any analogous drugs (polypeptids or other immuno-
stimulants), please, let me know too.
  3. If you know any companies (production or trading), interest in
immunostimulants, please, let me know too (E-mail and other contact
information).

         Thank you!

         From: mr. Vladimir Bolibok,
      Head of Clinical Immunology Laboratory,
      Consultative physician-immunologist,
      City Hospital No 5 of Kaluga,
      phone +7(084)-2249648  (Russian or English)
         E-mail: root at amtis.kaluga.su





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