SCIENCE
PHARMACEUTICAL PREPARATIONS DEVELOPMENT
The search for active components of the thymus extract led to the dipeptide GluTrp which displayed a broad range of immunoprotective effects and was registered in 1990 as a Thymogen. We demonstrated
that Thymogen enhances the expression of Thy-1 receptors on lymphocytes, accelerates the differentiation processes of various subpopulations of lymphocytes, and regulates the number and the ratio of T-helpers
and T-suppressors. Being a popular immunomodulatory drug Thymogen has no allergic or other side reactions. Statistics show that over 35 million patients have used it for 30 years
Stemokin is an immune- and hemopoietic booster, approved on the Russian market for secondary immunodeficiencies and undergoing clinical trials for the treatment of neutropenia. Stemokin is a
patented, fully synthetic peptide with demonstrated hematopoietic and immunostimulatory effects. In addition, multiple studies have shown an enhanced hematologic recovery after myelotoxic insult, anti-
tumor effects, and adjuvant effects. Adverse effects have been studied in an extensive preclinical toxicology program, indicating a very favorable safety profile with few demonstrated toxicities
Thymodepressin exerts a selective inhibitory effect on the immune system, leading to a net depression of the immunostimulating components of psoriatic disease. Thymodepressin inhibits cytokine secretion by Tcells and monocytes and suppresses mitogen-induced proliferation of circulating T cells. Clinical studies have demonstrated that Thymodepressin is well tolerated by patients and is as productive as cyclosporine (Sandimmune) but is devoid of the toxic effects of the latter.
NOVEL NEUROPEPTIDES DEVELOPMENT
The most promising family of psychopharmacology’s new generation products is neuropeptides and their derivatives (agonists and antagonists). Neuropeptides comprise peptide neurotransmitters and neuromodulators occurring primarily in the central nervous system (CNS) but may also be found in peripheral tissues. Rational development of new pharmacologic agents based upon targeting receptors for those neurotransmitters that regulate the neurobiology of anxiety promises to bring forth some exciting therapeutic agents for the treatment of stress and anxiety disorders in the future.
One of the company’s neuropeptide pipelines is the Opilong, the synthetic analog of naturally occurring neuropeptide Dermorphin. Opilong has passed the Face One clinical test in Russia to treat alcohol dependence and submitted it to the Face two clinical study.
The other neuropeptide preparation is Sedatin, a synthetic analog of the natural peptide Dermorphin, but shows no opioid activity according to classical tests in vitro (GPI test) and (MVD test). At the same time, in the in vivo tests in various animal species, Sedatin has a broad spectrum of biological activities and demonstrates a high anxiolytic effect on animals in the wide dose ranging from 0.1 to 100 g/kg. In addition, Sedatin can influence such physiological processes as body weight and wound healing; it can also intensify reparative and anabolic processes.
NUTRACEUTICAL PRODUCT DEVELOPMENT
General Peptidomimetic Structure
In Structure-Activity Research of novel peptide derivatives, we have designed the peptidomimetics orally acting selectively on hematopoietic stem cells like our linear hematopoietic precursor parenterally. Based on the leading cyclopeptide alanyl-gamma-glutamyltryptophan, we developed the novel biologically active food supplement Stvologen®. Introduction Stvologen® to the market opens the new era of safe peptide regulation of body-own stem cells and allows claiming the new perspectives – influence on the “endogenous” stem cell regulation by peptidomimetics.
Calculated Stvologen 3D structure
Yakovlev G.M., Morozov V.G.,
Khavinson V.H., Deigin V.I.,
Korotkov A.M. “Immunomodulatory
Preparation “Thymogen”. Patent Russian
Federation №1582393. Priority Date
30.12.87
Yakovlev G.M., Morozov V.G.,
Khavinson V.H., Deigin V.I., Korotkov
A.M. “Pharmaceutical Preparation for the
Therapy of Immunodeficiency
Conditions”. Patent Australia №616236.
Priority Date 30.12.87.
Yakovlev G.M., Morozov V.G., Khavinson
V.H., Deigin V.I., Korotkov A.M.
“Pharmaceutical Preparation for the
Therapy of Immunodeficiency
Conditions”. Canadian Patent №
13330300. Priority Date 30.12.87.
Bobkova N. V., Plakhinas L. A., Deigin
V. I., Iarova E. P., Iarov A. V. “
Preparation for Lowering of Alcohol
Dependence”. Patent Russian
Federation №2050856. Priority Date
12.02.1992.
Deigin V. I., Baturina E. Yu.,
Kamensky A. A., Iarova E. P.
“Peptide with analgesic activity”.
Patent Russian Federation № 2040272.
Priority Date 15.04.1993.
Deigin V.I., Iarova E. P. “Peptide, a Method for Its
Preparation and a Pharmaceutical Composition
Containing the Peptide (Sedatin)”. European
Patent # 779076. Priority Date 29.06.1994
Deigin V.I., Iarova E. P. “Peptide, a Method for Its
Preparation and a Pharmaceutical Composition
Containing the Peptide (Sedatin)”. Canadian
Patent # 2,193,969. Priority Date 29.06.1994
Deigin V.I., Iarova E. P. “Peptide, a Method for Its
Preparation and a Pharmaceutical Composition
Containing the Peptide (Sedatin)”. USA Patent #
US 6,184,208 B1. Priority Date 29.06.1994
Deigin V.I. “Branched piperazin-2,5-dion derivatives (2,5- DKP) of peptides and small molecules”. PCT: “Multifunctional Bioactive Compounds”. WO
2008/014613-1- PCT/CA2007/001357.
Deigin V.I. “Multifunctional bioactive compounds”. European Patent # 2046778. Priorities Date 01.08.2007.
Deigin V.I. “Multifunctional bioactive compounds”. Canadian Patent # 2,659,875. Priorities Date 01.08.2007.
Deigin V.I. “Substituted Piperazin-2,5-diones Amultifunctional Bioactive Compounds”. USA Patent #9,108,931B2. Priorities Date 01.08.2007.
Deigin V.I. “Multifunctional bioactive compounds”. Eurasian Patent # 018548. Priorities Date 01.08.2007.
Deigin V.I. “Substituted Piperazin-2,5-diones and their use as multifunctional Bioactive Compounds”. USA Patent #8,637,521
Scientific and marketing activities
Pharmaceutical peptide publications
Yakovlev G.M., Morozov V.G., Khavinson V.H., Deigin V.I., Korotkov A.M. “Immunomodulatory Preparation “Thymogen”. Patent Russian Federation №1582393. Priority Date 30.12.87
Nutraceutical products information
As a result of our research, we have designed and developed peptidomimetics orally acting selectively on hematopoietic stem cells similar to a linear precursor parenterally.
Public
relations
Most mammals’ protective system functions on maintaining equilibrium in the hematopoietic-immune-system cells and the cell balance from naive pluripotent stem cells to the committed precursors of hematopoiesis cell lineage.
THYMOGEN
The search for active components of the thymus extract led to the dipeptide GluTrp which displayed a broad range of immunoprotective effects and was registered in 1990 as a Thymogen. We demonstrated that Thymogen enhances the expression of Thy-1 receptors on lymphocytes, accelerates the differentiation processes of various subpopulations of lymphocytes, and regulates the number and the ratio of T-helpers and T-suppressors. Furthermore, the drug stimulates the activity of cAMP-dependent protein kinases in the thymus and spleen lymphocytes. A change in differentiation receptors accompanied the incubation of T-lymphocyte precursors with the dipeptide: the expression of the SC-1 antigen was replaced by the expression of the Thy-1 antigen, which indicates the transformation of the T-lymphocyte precursor into a mature T-cell. Being a popular immunomodulatory drug Thymogen shows no allergic or other side reactions. Statistics show that over 25 million patients have used it for 30 years.
Stemokin is an immune– and hemopoietic booster, approved on the Russian market for secondary immunodeficiencies and undergoing clinical trials for the treatment of neutropenia. Stemokin is a patented, fully synthetic peptide with demonstrated hematopoietic and immunostimulatory effects. Multiple studies have shown an enhanced hematologic recovery after myelotoxic insult, anti-tumor effects, adjuvant effects, and an enhanced adaptive immune response in the setting of antigenic challenge. In vitro data suggest that Stemokin may also augment innate immunity by enhancing neutrophil function. Adverse effects have been studied in an extensive preclinical toxicology program which indicates a very favorable safety profile with few demonstrated toxicities.
The results of non-clinical and clinical studies demonstrate that Stemokin stimulates stem cell proliferation through both innate and cellular immune responses. Stemokin helps preserve the immune status of healthy animals and has a pronounced immunostimulating effect on animals with radiation-induced immunodeficiencies. It also improves hematopoiesis that might have been impaired by various factors (ionizing radiation or cytostatic therapeutic agents).
The cytopenia effect correction by Stemokin of hematopoietic organs induced by cytostatic has been studied in mice. Stemokin treatment resulted in an earlier reconstitution of nucleated cell counts in the bone marrow and CFU–S–12 pool cells. In addition, Stemokin effectively restored the compartment of pluripotent precursors (CFU–S–12), hitch produces not only hematopoietic lines but also cells of the immune system.
In clinical studies, Stemokin helped speed up the reconstitution of the hematopoietic precursor population, which, in turn, ensured the reconstitution of mature blood cells (leukocyte counts and the percentage of lymphocytes) practically to normal levels.
THYMODEPRESSIN®
A new generation of immunosuppressors.
THYMODEPRESSIN is an initial preparation for treating pathologies associated with hyperimmune reactions.
THYMODEPRESSIN is approved for the treatment of diseases:
Recurrent autoimmune one-, two- and three-lineage cytopenia (including secondary ones).
Hypoplastic anemia.
Systemic diseases of connective tissue (rheumatoid arthritis).
Psoriasis.
Thymodepressin exerts a selective inhibitory effect on the immune system, leading to a net depression of the immunostimulating components of psoriatic disease. Thymodepressin inhibits cytokine secretion by T cells and monocytes and suppresses mitogen-induced proliferation of circulating T cells.
Clinical studies have demonstrated that Thymodepressin is well tolerated by patients and is as productive as cyclosporine (Sandimmune) but is devoid of the toxic effects of the latter.
THYMODEPRESSIN
is not accumulated in the body;
has no side effects;
has no nephro- or hepatotoxic effects.
THYMODEPRESSIN reversibly binds to immunocompetent cells, inhibits the functional activity of hemopoietic precursors in the bone marrow of healthy animals, inhibits the proliferation of PHA-stimulated human lymphocytes, and the regeneration of E-receptors on the surface of trypsin-treated T-lymphocytes.
What are the advantages of Thymodepressin over known immunodepressants?
THYMODEPRESSIN protects and preserves stem cells exposed to cytostatic chemotherapy or radiation. It accelerates recovery from granulocytopenia and allows to begin the next course of chemotherapy in due time.
THYMODEPRESSIN®
selectively acts on hemopoietic precursors in the bone marrow;
has no side effects typical for all known immunodepressants;
has high stability in the body and long-lasting effect;
is effective in a wide range of therapeutic doses;
non-toxic.
What is the principal feature of THYMODEPRESSIN?
THYMODEPRESSIN suppresses the functional activity of immunocompetent cells without affecting the cells of other organs and tissues!
THYMODEPRESSIN retards the development of autoimmune processes that selectively acts on the proliferation of immunocompetent cells.
Neuropeptide Research and Development.
Over 50 million Americans suffer panic, anxiety, depression, and phobia problems. These problems are often considered to result from run-away brain chemistry. Yet, it is not commonly recognized that by the choices we make and the actions we take, we are constantly adjusting brain biochemistry in significant ways that affect these problems.
Psychopharmacology seems to be well on developing new anxiolytic drugs that are fast-acting and free from the unwanted effects of traditional medications.
The most promising family of psychopharmacology’s new generation products is neuropeptides and their derivatives (agonists and antagonists). Neuropeptides comprise peptide neurotransmitters and neuromodulators occurring primarily in the central nervous system (CNS) but may also be found in peripheral tissues.
Neuropeptide receptor agonists and antagonists with analgesics, stress-protective and anxiolytic properties may represent one of the most striking new classes of potential neurobiological drugs, but this is an emerging field that still requires considerable more systematic clinical testing.
Rational development of new pharmacologic agents based upon targeting receptors for those neurotransmitters that regulate the neurobiology of anxiety promises to bring forth some exciting therapeutic agents for the treatment of stress and anxiety disorders in the future.
One of the company’s neuropeptide pipelines is the Opilong, the synthetic analog of naturally occurring neuropeptide Dermorphin, initially separated from the poisoning skin of South American frog.
The peripheral opioid activity of the peptides was assessed based on the ability to inhibit the electrically-induced contractions of isolated guinea pig ileum (GPI).
The standard control preparation in all experiments was Dermorphin. To confirm opioid activity, we used the specific antagonist naloxone in the concentration of 10-5 М. Each molecule was tested in 5 independent replications, and relative activity was calculated as the negative logarithm of EC50 (pD2).
Besides its analgesic effect, Opilong possesses anti-alcohol activity, i.e., it reduces alcohol consumption in animals, is artificially addicted to alcohol, and suffers from chronic alcoholism.
Opilong has passed the Face one clinical test in Russia to treat alcohol dependence and submitted it to the Face two clinical study. (For financial reasons, this study is on hold now).
The preparation of Sedatin relates to the opioid peptides and is a synthetic analog of the natural peptide Dermorphin. However, according to classic tests in vitro (GPI test) and (MVD test), Sedatin shows no opioid activity.
In the in vivo tests in various animal species, Sedatin has a broad spectrum of biological activities and can influence such physiological processes as body weight, activation of the epithelium growth zone, hair growth, and wound healing; it can also intensify reparative and anabolic processes. In addition, Sedatin demonstrates a high anxiolytic effect on animals in the wide dose ranging from 0.1 to 100 g/kg.
Sedatin has passed the Face one clinical test in Russia for the treatment of the alcohol dependance and submitted it to Face two clinical studies. (For financial reasons, this study is on hold now).
