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"Ligfol" is an adaptogenic stress-corrective medication of the new generation that assists in an increase of animals' productive health and resistance.

1. Introduction. Ligfol - is a new Russian veterinary product with a wide action spectrum. The proposed product - "Ligfol" is a result of many years of hard work and interaction between a big group of businessmen and research workers of different "degrees" starting from laboratory assistants and finishing with doctors of science. Spring 1995 - is the beginning of Ligfol's birth. The product was developed in the N.N.Petrov Institute of Oncology as an antitumoral drug and had a draft title "Olipifat". It was the starting point for showing up many-sided and unique properties of the product.

A number of tendencies of using Ligfol in veterinary medicine appeared during the researches and needed the more profound study. That was done by "Ligfarm" LTD jointly with Russian Scientific Veterinary Institute of Pathology, Pharmacology and Therapy. No direct cytostatic action was revealed, and we organized an extensive study of mechanisms that could help in explanation of the product's antitumoral activity. To tell the truth, this study is not completed and I think that "the whole picture" of mechanisms is unlikely to appear soon. Like the restorers of ancient destroyed paintings, we expose a layer after a layer and restore the original painting by the fragments. Today one of such fragments is "cleared" almost completely. As a result, we can confidently maintain and prove with all convincingness that Ligfol possesses remarkable adaptogenic and stress-corrective properties. Ligfol helps an animal organism to manage diseases by itself, including such complicated diseases as cancer. Ligfol is shown to activate reparative processes on the surface (by activating the processes of reparation of the skin surface and muscular tissues of an animal) and inside the organism (protecting and restoring damaged cells of the liver) and that is why it is an indispensable drug for animals' rehabilitation during postoperative period. Animals with postoperative stitches were treated with Ligfol. Wound repair was taking much faster and with fewer complications. This fact correlates with experimental studies that were held in the Laboratory of Drug Toxicology of Ministry of Public Health Cardiological Scientific Production Department. The main idea is described below. Third and forth - degree scalds were treated with Ligfol straight away after injuring and then the drug was applied every day during 30 days. The result was a remarkable decrease of necrosis processes and wound repair acceleration. The effectiveness of the drug surpassed such widespread drugs as Olazol and Dexona. Consequently, it gives us grounds to recommend the drug for wound and scald repair. Thus, our product is effective in every case, when it is necessary to mobilize all strength of an animal to fight against the illness.

2. Ligfol - structure and pharmacological properties. Various salts (sodium, potassium, nitrohumics, etc) of natural humic substances nowadays are obtained by modification of the latter. After that the salts are refined and concentrated and in such a way various fertilizers, biologically active additional fertilizing and drugs for use in veterinary science and cattle breeding are created. The examples of such products are Guvitan, Humoksin, sodium humate, nitrohumate, etc. Various functional groups and spatial configurations of that groups cause a wide range of pharmacological properties. Ligfol is a medical substance that is obtained by natural lignin multi-step hydrolysis, which is controlled on every stage of technological process. Such method allows guaranteeing standard and repeatability of the product's clinical effects. The product is a brown or dark brown sterile liquid assigned for intramuscular administration. "Ligfol" is prepacked in glassy flasks from 1.0 to 100.0 ml. It is stored in a dry place, impenetrable for light, optimal temperature - 10-25°C. Working life is 2 years from the moment of production. Pharmacotoxicological studies showed that the product possesses little toxicity, does not exhibit mutagenic or embryotoxic activities. Basic properties of the product include adaptogenic, antioxidative, antitumoral and regenerative properties. Such effects of the drug are determined by its chemical structure and presence of modified humic substances, obtained by natural lignin hydrolysis. Lignin (lat. - a tree, timber) is a universal compound of higher plants tissues and mass portion of it yields only to cellulose. Primary products of lignin hydrolysis are, so called, humic substances (lat. Humus - ground, soil). Under natural conditions humic substances formation takes place in a soil and peatbogs during oxidative degradation of plants fragments (lignin, tannins and melanines). It is known, that the range of pharmacological activity of lignin and humic substances medications include distoxicational and enterosorbing properties, an influence on circulatory and immune system, antioxidative, antihypoxic, generally metabolic, biostimulating and adaptogenic action. Obviously, it is very difficult to combine the variety of biological effects named below into one common mechanism. For instance, mechanisms of humic substances antitoxical action (and Ligfol accordingly) are of different directions and are connected by common ability to form complex compounds with heavy metals, to adsorb toxins and microorganisms, to decrease penetrability of histohematogenous barrier and also by bioantioxidative action. Disintoxicative and sorbtive properties of humic substances allow recommending the product for treating various disorders of animals' digestive system including metabolic disorders. It is important, that the medication and its metabolites where completely eliminated from the organism and no side effects were registered. It is known that drugs that contain humic substances are able to prevent the development of ulcers in gastrointestinal tract and even are able to cause ulcer healing without scars (activation of phagocytosis, bactericidal and lisozyme activities, increase of albuminous and globulinous fractions of serum protein). Antioxidative action of Ligfol assures normalization of free radical oxidation processes. This action is a nonspecific step in development of various disorders; in particular, hepatoprotective action mechanism of many medications is connected with antioxidative activity. Antitumoral mechanism of action of Ligfol is controversial at the moment. However, antitmoral properties of the drug were confirmed by a number of scientific researches and clinical studies. Moreover, evidently, many of Ligfols' effects are caused by its adaptogenic properties that allow increase of basic nonspecific resistance of an organism (i.e. tolerance to unfavorable conditions) and consequently having a positive nonspecific effect independently of the nature of an illness. The medication is registered in the Ministry of Agriculture RF (№PO№"-2-5.0-2756), is patented in Russian Federation, USA, most of the European Council countries and Korea. The finding was registered after the studies of biological activity of Ligfol. Finally, I would like to underline, that Ligfol exhibit its effectiveness in various complicated clinical situations including situations when the recovery forecast is unfavorable. The examples cited and the results of various studies attest that Ligfol exhibit its positive activity even in cases, when common therapy is not effective. This fact allows recommending the medication in broad application in veterinary practice.

3. Clinical effectiveness of Ligfol in treating small domestic and exotic animals. It is known in veterinary medicine, that, prophylactic of an illness is much better than treatment. But if a pet is already ill, valeopositive effect is achieving by using combined therapy of different groups of medications: antimicrobial, anti-inflammatory, sedative, vitaminous, detoxicative and so on. However, the fact, that an organism is impaired by the fight with a long time developing disease is often forgotten. A course of treatment may appear to be ineffective against such an unfavorable background. Every prescription must be logically well-founded and arise from etiological, pathogenetic and symptomatic features of an illness in that period. Qualification and medical way of thinking is very important in successful treatment. For such veterinary specialists, that always try to find some new drugs, which would be not so "hard" as antibiotics with a wide range of action, but would be more physiological to a living organism, with not so vivid, but a very important in any combined therapy action, new medication "Ligfol" is produced. As it was described above, the active principle of the drug are humic substances that exhibit activity in different points of attack in a living organism and possess a powerful potential of biological activity. Positive effect of the drug in treating various species of animals with different types of deseases has many examples. Ligfol was used in Moscow veterinary clinic "Artemis" under the direction of N.M.Laryonova. An owner of spectacled caiman appealed to the clinic. The reason of the owner's anxiety was: intense languor of the reptile, refusal to eat during a week, food eructation in several minutes after forced feeding. During anamnestic data acquisition it became clear, that devices providing an appropriate temperature rate in the terrarium cage where the animal lived were switched off. The temperature came to +22 - +24°C. In addition, the water in terrarium cage was not changed for a long time. A number of disturbances in the feeding schedule were revealed (monotone, fish most of the times, besides, dead aquarian fish feeding was sometimes allowed). No vitamin-mineral additions or ultraviolet irradiation were used. The provisional diagnosis was formed: acute gastritis caused by temperature rate disorder or as a result of stressful desadaptation syndrome. After a course of treatment (antibacterial therapy with a drug enrosept, vitamins B1 and B12, trivit) and normalization of living conditions, general habitus of an animal has improved: sleepiness has disappeared, and activity has increased. However, refusal to eat persisted. In 10 days after the beginning of the treatment veterinary specialists introduced Ligfol into the therapy and administered intramuscularly in a dose 0.1 ml per 1 kg of a body weight in 1:1 dilution with physiologic saline. The course consisted of 5 injections with 1 week interval. After the third Ligfol injection spectacled caiman began to eat without assistance. No repeated complaints were registered. Another example of successful use of Ligfol.

An owner of 10 months old slider turtle appealed to the clinic, as her pet refused to eat during 3 weeks and motion activity of an animal decreased. During anamnesis data acquisition it became clear that feeding and living conditions as a whole correlated with the species and the age of the turtle. Clinical examination has not ascertained any systems and organs disorders. Specialists concluded that anorexia has a seasonal nature. The following treatment was prescribed: parenteral administration of Ringer and Lokk's solution (for water-salt balance recovery), intramuscular administration of Ligfol in a dose 0.01 ml in 1:1 dilution with physiological saline, once a week (for appetite stimulation). The appetite was recovered after the second injection. An owner of 4 years old budgerigar appealed to the clinic. Last 3 weeks the bird became less communicative, faeces had a yellow color, normal stool alternated with diarrhea. Clinical examination has not ascertained any other features of an illness. The provisional diagnosis was hepatopathy. Prescribed therapy (hepatoprotectors, vitamins, symptomatic therapy) brought to temporary improvement of the bird's habitus. After 3 weeks from the beginning of the treatment an apathy returned and refusal to eat was observed. A course of Ligfol was prescribed in a dose 0.01 ml by intramuscular administration once a week and included 4 injections. In a day after the first injection the appetite of the bird was recovered, an improvement of the habitus apathy disappearance was observed. Gradually the stool normalized and yellow colour of faeces disappeared. During the course of treatment with Ligfol (approximately 3 weeks) the bird's habitus stabilized, good appetite and activity remained. An owner of a 15 years old small poodle, female, appealed to the clinic. 2 years ago a dog had a neoplasm and ovariohysterectomy and mastectomy were done. Anamnesis data acquisition revealed refusal to eat during 4 days, dark brown discharges from edea during 4 months, alopecia in dorsal area. Clinical examination showed: transmissible sarcoma, right eyeball melanoma, mammary tumor. The treatment with Ligfol in a dose 0.1 ml per 1 kg of a bodyweight, a course of 7 injections every 3 days was prescribed. On a second day after the first injection the habitus of the dog improved, activity increased and appetite normalized. After complete course of treatment with Ligfol, general habitus of the animal was satisfactory, discharges from edea became light and the volume decreased, hair-coat was recovered, sizes of neoplasmas did non change.

Dogs parvoviral enteritis is an acute contagious disease. Dogs of all ages are susceptible to disease, but if the complete course of vaccination was passed, the illness is developing on the background of immunosuppressive condition. Viral replication takes place in cells with a high level of mitosis, and thus cells of the bowels crypts, immature erythrocytes and granulocytes, tissues of lymphopoiesis (lymphoid plaques, lymph nodes, thymus and spleen) and cells of a myocardium are damaged until they are dividing. At the same time, the virus induces necrosis. As a result of blood absorption of the products of necrosis and liquid loss microthrombuses in capillaries begin to form (DVS-syndrome, some features of endotoxical hypovolemic shock appear. Toxicosis is accompanied by the irritation of the vomiting center which causes an intractable vomiting. The damage of cardiac muscle leads to cardiovascular collapse and pulmonary edema. Duration of the illness is 1-6 days. Death rate is up to 70 %. The treatment of parvoviral enteritis includes complex symptomatic therapy and is directed to eliminate vomiting, exsiccosis, acidosis and secondary infection. There were 4 dogs of different breeds (German shepherd - 2, terrier - 1, Caucasian shepherd - 1) in the experiment. All are males aged 3-6 months. The diagnosis was formed by clinical features of the illness. Blood analysis was made. The complex symptomatic treatment was held. Medications included infusion solutions in a dose 30-40 ml per 1kg of a body weight, parenteral administration of antibiotics, vitamins (ascorbic acid 5% - 2-4 ml; B1 - 1ml; B6 - 1 ml; B12 - 200 µgr) - once a day, urotropin - 3 ml, sulfocamfocaine - 1ml 2 times a day, cycloferone - 2 ml 2 times a day, cerukal - 1 ml, diphenhydramine hydrochloride - 1 ml once a day. Ligfol was used on the background of the symptomatic therapy in the following scheme: 0.1 ml per 1kg of the body weight every 1-3-5 day. Parameters of the effectiveness control were the general habitus of animals, appetite and leukocyte content. Results of the treatment showed that introduction of Ligfol caused improvement of the general habitus and termination of vomiting. When a common therapy was prescribed from the second till the fifth day decrease of leukocytes up to 2500 in 10 -3 ml is observed. Ligfol treatment caused an increase of leukocyte content up to 18000 in 10-3ml. It is considered to be a favorable prognostic feature. Usage of Ligfol in a complex therapy provided acceleration of the general habitus improvement for 1-3 days, depressed diarrheic syndrome, and termination of vomiting. Summarizing the experiment of using the drug Ligfol, we can suggest following schemes of using it for treating small domestic pets:

Dogs parvoviral enteritis. Comparing with a common therapy, introduction of Ligfol leads to general habitus improvement, termination of vomiting. When a common therapy was prescribed from the second till the fifth day decrease of leukocytes up to 2500 in 10 -3 ml is observed. When Ligfol was used leukocyte content increased up to 18000 in 10-3ml. It is considered to be a favorable prognostic feature. Use of Ligfol in a complex therapy provided acceleration of the general habitus improvement for 1-3 days, depressed diarrheic syndrome, termination of vomiting.

Medical regimen
The drug should be administered intramuscularly in a dose:

  • For dogs and cats up to 10 kg    0.1 ml/kg
  • For dogs and cats up more than 10 kg     1.0 - 1.5 ml per animal

Course of treatment
Once a day on 1-3-5 day.

Oncology.Treatment of tumorous diseases; improvement of results of the surgical treatment of tumorous diseases; usage in common with cytostatic agents and roentgenotherapy.

Medical regimen
The drug should be administered intramuscularly in a dose:

  • For dogs and cats up to 10 kg     0.1 ml/kg
  • For dogs and cats up more than 10 kg     1.0 - 1.5 ml per animal

Course of treatment

According to severity of an illness the course include 6-12 injections, 1 injection in a day, every third day - 4-5 injections, than 1 time every 7-th day.

Notice: for malignant tumors with metastasis - 1-2 times every month for term of life in recommended doses.

Infectious diseases. Commonly with complex therapy of diseases infective ethiology; before a vaccination for physical respond increase caused by immune system activation. For reduction of an acute period of illness and for acceleration of recovery period.

Medical regimen
The drug should be administered intramuscularly in a dose:

  • For dogs and cats up to 10 kg    0.1 ml/kg
  • For dogs and cats up more than 10 kg     1.0 - 1.5 ml per animal

Course of treatment
Once a day on a 1-3-5-10-th day.

Application in surgery practice. For injuries, wounds, including infected scalds, curing; for acceleration of stitches healing. Application: irrigation of surgical injures directly before stitching (primary intention healing). The drug is applied by intramuscular administration or by irrigation of injured areas.

Medical regimen
The drug should be administered intramuscularly in a dose:

  • For dogs and cats up to 10 kg    0.1 ml/kg
  • For dogs and cats up more than 10 kg     1.0 - 1.5 ml per animal

Course of treatment

1 injection every third day, until stable improvement of regenerative processes and stabilization of animal's habitus will be observed. Local irrigation of injured areas 1-4 times a day.

Notice: it is highly recommended to use Ligfol during preoperative period no less than 5 days before the operation!

An increase of resistance. Before the stress load (transportation, bench-show, vaccination), for lessening of stress consequences, for activation of protective forces of an organism, during treatments of impaired animals commonly with substances of specific therapy.

Medical regimen
The drug should be administered intramuscularly in a dose:

  • For dogs and cats up to 10 kg    0.1 ml/kg
  • For dogs and cats up more than 10 kg     1.0 - 1.5 ml per animal

Course of treatment
Once, intramuscularly, 3-5 days before the supposed procedure.

Hepatoprotective action. Hepatitis, hepatopathy, cirrhosis.

Medical regimen
The drug should be administered intramuscularly in a dose:

  • For dogs and cats up to 10 kg    0.1 ml/kg
  • For dogs and cats up more than 10 kg     1.0 - 1.5 ml per animal

Course of treatment
Jointly with complex therapy - once a day, intramuscular administration, every third day, 4-8 injections.

4. Clinical effectiveness of Ligfol in farming animals' treatment.
There are some examples of the drug's action in real working environment. The first of them took place in a large pig-breeding farm. In a last period of sow's pregnancy a negative effect of stress load is shown most distinctly and is reflected on the yield of healthy young animals. We carried out a productive experiment, the goal of which was to conduct prophylaxis of technologic and generic stresses of late in pregnancy sows with Ligfol. For the experiment 2 groups of animals on the 97-th day of gestation were formed. Each group contained 68 experimental individuals and 45 as a control. Animals of experimental and control groups were put into equal status and feeding conditions. Ligfol was once administered intramuscularly to the sows of experimental group in a dose 5.0 ml per individual. Estimation of the experiment was carried out after posterity receiving. All basic characteristics of reproduction effectiveness, such as yield of still-born piglets, impaired piglets and piglets that conform to the standards were taken into consideration. The yield of piglets that conform to the standards in experimental group was 81,7%. This value is 1,5% higher than in a control group. The yield of impaired piglets in the experimental group was 17,6%, while in the control group this value was 5,5% lower. Stillbirth in the experimental group was 0,55% and in the control group - 8,03%. Results of the experiment show, that Ligfol, being administered to the sow's organism in the period of late gestation, has a mediate influence on the quality of posterity, decrease the yield of still-born piglets and increase healthy birth rate. A very interesting result was shown when the drug was used in cattle-breeding. Cows are known to be one of the most difficult animals as far as the process of accouchement is concerned. It is caused by specific features of caxal bones structure, on the one hand, and by various post-natal complications, on the other. Observations revealed that expulsion of placenta of the control group animals takes place in 7 hours after accouchement. At the same time retention and artificial removal of placenta is registered in 40% of cows. As a result all animals of the control group have subinvolution of uterus and puerperal endometritis. Our medication in a dose 3-5 ml per animal, once, intramuscularly, shows no negative influence on pregnant animals 20-30 days before the accouchement. On the contrary, the drug exhibits a remarkable tonic effect and promotes the physiological process of accouchement. After Ligfol treatment the time of expulsion of afterbirth was 2 times less than as usual. Consequently, no subinvolution of uterus and puerperal endometritis were observed. For its part, this fact influenced on animal's time ranges of coming to desire and, accordingly, to insemination. An optimum was achieved when Ligfol was administered in a dose 5,0 ml per animal. Thus, when such a therapy was used, a term of insemination was 30% shorter comparing to the control. Conclusions resulting from the experiment are obvious: shortening of sterile period, an ability to cut down expenses (treatment and living conditions), receiving healthy posterity. A remarkable effect was shown in fur farming. The goal of the first experiment was to study the influence of Ligfol on resistance, reproductive function and on the quality of posterity of minks, breed "Orchid". The medication was once administered intramuscularly in a dose 0,3 ml per animal 30 days before a heat. 20 of experimental and control (0,3ml of sterile physiological saline by intramuscular introduction) females were monitored for 120 days. Clinical studies revealed high effectiveness of the drug. Thus, quantity of whelped females in the experiment was 100,0 % and was 12,4% greater than in control. In such a way, Ligfol contributed to the full and complete fertilization of minks. Ligfol treatment furthered decrease of still-birth (0,44% less). In a whole, the increase of whelps yield and some decrease of still-birth resulted in a remarkable increase of the yield of the whelps that conform to the standards. Ligfol treatment also increased minks resistance in a period of pregnancy and accouchement. It appeared on a remarkable decrease of pathological course of pregnancy and of a process of whelping. The loss of females was 5,3% lower than in control after 120 days of monitoring. In that way, the experiment revealed 2 ways of improving furry animals' reproduction in farm industry. The first side of the problem - an obvious stressor of the process from a heat to the whelping, the second side - an ability to regulate and decrease negative effects of the process. In such an environment Ligfol exhibited high effectiveness as adaptogen stress-corrector. The purpose of the second experiment was to estimate effectiveness of Ligfol in increasing pregnant minks' resistance and in providing normal physiologic proceeding of whelping. Experimental and control groups contained 20 pregnant minks for each group. Ligfol was administered intramuscularly in a dose 0,3 ml per animal 30 days before the whelping. The corresponding quantity of physiologic saline was given to the animals of a control group. Observations were held for 60 days. The experiment revealed that Ligfol treatment promotes 5% increase of whelping females. In average, one female of a control group had 0.2 cubs less than a female of the control group. However, still-birth was 1,8 times less. The drug did not influence on the yield of whelps that conform to the standards. Ligfol furthered the process of whelping and completely prevented the loss of females during the latest period of pregnancy and whelping, comparing to the 7% of death rate in the control group. The experiment showed high effectiveness of Ligfol treatment of pregnant animals for increasing their resistance and providing physiologically normal whelping. Amusing results were received when Ligfol was used in horse breeding. Obtained data indicate the remarkable tonic and adaptogenic influence of the drug on race-horses during physical activity. It was established, that primary (body temperature, pulse, breathing, sweat secretion) and profound characteristics of race-horses' physiologic condition in dynamics can objectively reflect organisms abilities during physical activity. The example of Ligfol treatment of race-horses showed the ability to influence on organism regulatory mechanisms that provide an adequate reaction on the physical activity. Realized experiments revealed an ability of a new, not a dope way of optimization of race-horses sport achievements not only without subsequent exhaustion, but with the recreation in a short period of time. Besides all that, various studies showed that Ligfol is effective in many other cases.'

  • For post-natal diseases prophylaxis and ensuring normal passing of pregnancy and accouchement;
  • For increase of young animals safety;
  • For hepatocytes protection and recovery;
  • For increase of resistance to stress, caused by living conditions, transport or regrouping;
  • For immunodeficiency state correction;
  • For increasing antiviral and antibacterial activity of an immune system;
  • For increase of treatment effectiveness and toxical effect removal during dehelmintization;
  • For increase of vaccination effectiveness (immune response strengthening);
  • For moving function recovery during motive system diseases.

A very important fact, that being use in fattening, Ligfol had a positive effect on practically all species of animals and birds.

This is just a small part of the whole amount of various studies that were carried out using Ligfol.

 
 
 
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