Multicentered open researches of efficiency and safety of the preparation which has been carried out in 8 leading scientific - practical institutions of Ukraine (see the table), have shown, that "Liasten" is not only effective, but also a safe preparation. At its use in therapeutic dozes the by-effects of the preparation arise extremely seldom and has brief and not difficult character.

Sometimes short-term slight increase of body temperature, occurrence of local reactions, pains in joints are possible. In such cases it is necessary to increase the interval between injections of the preparation from 5-7 till 10 days.

Open studies of the effectiveness and safety of the drug
The name of research Place and year of carrying out The basic results
1 "Experimental studying of specific and general pharmacological activity of the substance and ГЛС of Blastolen" Institute of experimental oncology and radiobiology by R.E.Kavetskiy НАНУ, Kiev, 1994 Dozadepending smmunomodulation of cellular and humoral immunity, stimulation of haemopoiesis, functions of macrophages is proved.
2 "Experimental studying of harmlessness of a substance and GLS of Blastolen" Institute of pharmacology and toxicology АМНУ, Kiev, 1994 Absence of sharp toxic, sensitizing and allergitising activity is proved. It is revealed dozadepending locally irritating action.
3 "The results of clinical test (1-st phase) of preparation "Blasten" at patients with meningitoencephalitis and leptospirosis" The Kiev scientific research institute of epidemiology and infectious diseases by L.V.Gromashevskiy, Kiev, 1995 Absence of the expressed positive clinical effect, absence of the expressed by-effects of the preparation
4 "Clinical test of the new medical product immunomodulator "Blasten" (2-nd phase)" National medical university by A.A.Bogomolets, department of faculty surgery №1, Kiev, 1996 Reduction of frequency of postoperative complications, improvement of regeneration of wounds, improvement of the general state
5 "Clinical test of the new medical product immunomodulator "Blasten" (2-nd phase)" Scientific research institute of oncology and radiology MH of Ukraine, Kiev, 1996 Reduction of by-effects of chemo- and radiotherapy, immuno- modulating influence
6 "Clinical test of the new medical product immunomodulator "Blasten" (2-nd phase)" The Kiev scientific research institute of otolaryngology МH of Ukraine, Kiev, 1996 Reduction of by-effects of chemo- and radiotherapy, immuno- modulating influence
7 "Clinical test of the new medical product immunomodulator "Blasten" (2-nd phase)" Institute of experimental oncology and radiobiology by R.E.Kavetskiy НАНУ, Kiev, 1996 Reduction of by-effects of chemo- and radiotherapy, immuno- modulating influence
8 "Studying of efficiency of "Blasten" clinical application in complex treatment of patients with chronic obstructive bronchitis" National medical university by A.A.Bogomolets, department of clinical immunology and allergology, Kiev, 1999 Immunotropic action on a nonspecific part, phagocytosis, humoral immunity is proved, the scheme of application at ХОЗЛ is offered.

Note: since 2006 the improved formula of the preparation is produced by enterprise "ENZIM " under new commercial name "LIASTEN".

CONFIRM
Deputy Director of main state
sanitarydoctor of Ukraine
L.M. Mukharskaya
"19" may 2006 y.

instruction
for application medical immunological preparation
liasten (liasten)
bacterial preparation of immunomodulating action

General characteristic:
the international not patented name: glucosaminilmuramilpentapeptide;
the basic properties of the medicinal form: lyophilized powder or porous substance of white or white with yellowish shade color, easily soluble in water for injections and in solution of isotonic sodium chloride 0,9% for injections.

Composition:
the working substance -1 vial contains 0,002 г glucosaminilmuramilpentapeptide (N-acetylglucosamine -N-acetylmuraminil-L-alanyl-D-glucosaminil-L-lyzyl-D-alanyl-L-asparanyl) in recalculation on peptides;
auxiliary substance - dextran 40.

The form of release.
Powder for preparation of solution for injections.

Code ATC.
L 03A. Cytokines and immunomodulators.

Immunological and biological properties.
Liasten refers to immunomodulators of natural origin with wide spectrum of action. It represents fragments of the cellular wall of lactobacterium. Liasten stimulates function of macrophage and normalizes the quantity of Т- lymphocytes. Liasten activates the cells of monocyte-macrophage lines, phagocytosis, increases the activity of lysosome ferments, production of oxygen active form, strengthens macrophage cytotoxin effect with respect to tumor cells. The preparation strengthens the synthesis of anti-inflammatory cytokines in particular interleukin -1. Liasten increases cytotoxic activity of the natural cells-killers (NC). The immunomodulation activity of Liasten shows up in keeping of endocrine function of tymus, in some cases reduces the level of circulating immune complexes. Liasten promotes the stimulation of leucopoiesis, has light antimetastatic and antitumor action, reduces by-effects of chemotherapy and radiotherapy. The preparation does not have embryotoxic, mutagenic and teratogenic action.

Indications for application.
Liasten is prescribed as immunomodulating remedy for the diseases accompanying with the secondary immunodeficiency and leukopenia, in particular at chemotherapy and radiotherapy of oncological patients and patients with leucosis with the purpose of increase of cytostatics' efficiency and decrease of their toxic effect; at sharp and chronic radiation injuries, especially in conditions of long-term irradiation of low intensity in small dozes; at surgical treatment of oncological and other diseases of mamma (breast), of gastrointestinal tract, a chest cavity, genitals, etc; in complex antibacterial and antiviral therapies of sharp and chronic diseases of respiratory tract, otolaryngologic organs, skin, a tuberculosis. Liasten is also prescribed for treatment of patients with leukopenia a various origin.

Way of application and doze.
Liasten is injected hypodermically or intramuscularly. Before preparation use 1-2 ml of the isotonic sodium chloride 0,9 % solution for injections or waters for injections are added in a vial. If it is the hypodermic injection of the preparation it is possible to use 1 ml of solvent. After the solvent addition the vial is thoroughly shaked up before full dissolution of its contents. The usual daily doze of the preparation for adult persons makes 0,002 g of glucosaminilmuramilpentapeptide. For course of treatment 3-5 injections are used with the interval of 5-7 day between them. If necessary it is possible to run repeated courses in 3-6 and 12 months.

Collateral action.
The preparation is usually well endurable. Sometimes probably short-term slight increase of a body temperature, occurrence of local reactions, pains in joints. In such cases it is necessary to increase the interval between the injections of the preparation till 10 days.

Contra-indications.
Hypersensitivity to components of the preparation. Application features. With care it is prescribed for the patient with allergic diseases. Experience of application of the preparation by pregnant women, mothers nursing, and children is not present.

Interaction with other medical products.
The preparation shows synergism immunomodulating effect at the combination with immunomodulators of tissue origin.

Storage conditions.
To store at temperature not higher than +25°С. Keep the preparation solution not more than 24 hours the refrigerator at temperature from -4°С up to +6°С.

Shelf life. 3 years.

Packing. 0,002 g of active substance in glass vials №5 in a cardboard box.

The manufacturer. DP "ENZIM".
The address. 24321. Ladyzhyn, Vinnytsya region, Khlibozavodska street, 2.

APPROVED
by Order of Ukraine Ministry of Health
№71 dd 04.02.2010
Certificate about state registration
№ 781/10-300200000 dd 04.02.2010

instruction
for application of medical immunobiological preparation
Liasten® (liasten)
immunomodulator of bacterial origin

General description:
the international not patented name: LIASTENUM;
The basic properties of the drug form: lyophilized powder or porous mass of white or white with yellow tint color, easily soluble in water for injection and in the solution of isotonic sodium chloride 0,9% for injections.

General description:
the international not patented name: LIASTENUM
The basic properties of the drug form: rounded tablets of white or nearly white with yellow tint color, without a coat. Auxiliary substances-lactose, cellulose microcrystalline, sodium salt of croscarmelose, sorbitol, hydroxypropylmethylcellulose, magnesium stearate.

Composition:
Reactant-1 tablet contains 0,002 g glucosaminilmuramilpentapeptide in recalculation on peptides;

Release form: Tablets.

Code of ATC:
L 03A. Cytokines and immunomodulators.

Immunological and biological properties:
Liasten® refers to immunomodulators of natural origin with a wide spectrum of action. It represents the fragments of lactobacteria cell wall. Liasten® stimulates the function of macrophages and normalizes the quantity of T-lymphocytes. Liasten® activates the cells of monocytic-macrophage row, phagocytosis, raises the activity of lysosomal enzymes, the production of oxygen active forms, strengthens the cytotoxic effect of macrophages in relation to tumor cells. The preparation strengthens the cytokine synthesis, in particular interleukin -1. Liasten® raises the cytotoxic activity of the natural cells - killers. Immunomodulating activity of Liasten® is also revealed in preservation of the endocrine function of thymus, promotes the decrease of circulating immune complexes. Liasten® promotes the stimulation of leukopoiesis, has weak antimetastatic and antitumoral action, reduces by-effects of chemo-and radio therapy. The preparation has no embryotoxic, mutagen and teratogen action.

Indications for application:
Liasten® is prescribed as immunomodulating substance at the various diseases accompanying with secondary immunodeficiency, leukopenia, in particular at chemo-and radio therapy of oncological patients and patients with leukosis with the purpose of decrease of cytostatic toxic action; at acute and chronic radiation injuries; at surgical treatment of oncological and other categories of patients. Liasten® is prescribed at acute and chronic bacterial and virus infections, for treatment of patients with leukopenia of various origins.

Way of application and doses:
Liasten® in tablets is intended for slow resorption in a mouth cavity. It is desirable to resorp a tablet slowly under the tongue. Usually it is prescribed 1 tablet 2 times a day. The course of treatment by the preparation usually makes 10 - 20 days. If necessary it is possible to repeat courses of treatment by Liasten® in 3 - 6 and 12 months.

Side action:
The preparation is usually well beared. Sometimes short-term slight increase of a body temperature is possible which does not demand the cancellation of the preparation and doing of special medical actions.

Contra-indications:
Hypersensitiveness to the components of preparation.

Features of application:
With care it is prescribed to the patient with allergic and autoimmune diseases. There is no experience of application of the preparation by pregnant and nursing mothers. Tablet ingestion by the child or the adult is safe and does not demand carrying out of additional medical actions.

Storage conditions:
Store at temperature not higher than +25°С.

Shelf-life: 3 years.

Packing:
Tablets 2 mg of plano-cylinder form with a bevel №20 (10х2) in the contour cell-type packing and in №20 polymeric containers.

Manufacturer:
DE "Enzim" jointly with CJSC "Technolog".

Address:
DP "Enzim", 24321. Ladyzhyn, Vinnitsa region, Khlebozavodskaya street, 2.
CJSC "Technolog", 20300, Uman', Cherkasy region., Zheleznyaka street, 3.