Inflammatory diseases of the veins (phlebitis, thrombophlebitis) and non-inflammatory ones (arteriosclerosis, thrombosis) are rather common. [6] About 20% of the population have varicose veins and haemorrhoids [5, 7]. Patients with these diseases are often found to have inflammation of the affected vessels.

Thrombophlebitis is an inflammation of vascular walls, which is associated with a blood clot formation within a blood vessel. The formed blood clot may be dissolved or may block (occlude) the vessel lumen, which leads to circulation disorders and, consequently, to impaired blood supply of the relevant tissues and organs. A blood clot can break loose from the wall of the vessel and be carried by the bloodstream and block the lumen of another vessel. This is especially dangerous if the lumen of a vessel supplying blood to the heart, lungs or brain is blocked.

The treatment of thrombophlebitis involves some measures to dissolve the thrombus. Moreover, the measures undertaken to reduce inflammation of the blood vessels help prevent the formation of new blood clots. An early treatment of inflammations of blood vessels helps preserve functions of body organs. Now the treatment of the disease often includes topical medicine, which allows to apply the medicine on the affected areas, and avoid side effects.

In Ukraine, PJSC SIC “Borshchahivskiy Chemical Pharmaceutical Plant” manufactures highly effective topical medicinal products VENOHEPANOL and INDOVENOL.

100 g of VENOHEPANOL gel contains 2 g of troxerutin, 3000 IU of heparin sodium, and 3.0 g of dexpanthenol.

VENOHEPANOL gel has its pronounced therapeutic effect due to its components: troxerutin, heparin, and dexpanthenol, which are angioprotective agents for metabolic therapy [1, 2]. Medicaments used for metabolic therapy are similar in chemical structure to compounds involved in the body's normal metabolism, such as vitamins, purine derivatives, amino acids, etc., and they have shown a wide range of biological and pharmacological activities, their combined effect on physiological and biochemical processes in the human body. This combined effect on the human body helps eliminate the pathological process [3]. Usually these medications do not have any significant side effects.

VENOHEPANOL contains an analogue of troxerutin that is a benzopyrone semisynthetic bioflavonoid (mixture of 3, 4`and 7 (b-hydroxyethyl) rutosides), which is involved in metabolic redox processes.

Bioflavonoids are a large group of phenolic compounds with a number of pharmacological properties and are used for the treatment of many diseases associated with impaired peripheral circulation. The therapeutic effect of bioflavonoids is due to their P-vitamin activity, vessel protective action, improving the microcirculation, tissue trophism and regeneration of damaged tissues. Bioflavonoids strengthen capillary walls, reduce their fragility. Some of these compounds may have antiallergic, antidiabetic, antihypertensive, antispasmodic, or cholesterol-lowering effects, as well as dilate coronary vessels and increase myocardial contractility.

Due to the P-vitamin properties, troxerutin has a pronounced venotonic and angioprotective action; it improves microcirculation and tissue trophism, reduces the blood congestion in the veins and paravenous tissues, has anti-oedema and anti-inflammatory action. After oral administration, it partially enters the enterohepatic circulation. It is excreted mainly in the faeces.

Heparin is produced by body hepatocytes, mastocytes and basocytes, and it is found in many body organs and tissues (liver, lungs, intestine, muscles, etc.). Heparin sodium, which is a component of VENOHEPANOL, provides local anticoagulant, antithrombotic, anti-oedema and anti-inflammatory effects, and improves the local blood flow.

The third component of VENOHEPANOL gel is dexpanthenol, which is pro-vitamin B3 (or B5), which action is similar to the action of pantothenic acid. Dexpanthenol is better absorbed when applied topically. Pantothenic acid is a component of coenzyme A as acetyl-CoA plays a significant role in cellular metabolism (e.g., of carbohydrates, fatty acids), amino acid metabolism, corticosteroid synthesis. Pantothenic acid reduces the toxicity effects in the body, it is essential for the formation and regeneration of skin and mucous membranes. Dexpanthenol accelerates granulation and epithelialization of tissues, and also improves absorption of heparin, and it is rapidly absorbed when spread on the skin.

The combination of three biologically active substances involved in various metabolic processes in the human body ensures the wide clinical use of VENOHEPANOL.

The topical product VENOHEPANOL is indicated for the prevention and treatment of varicose veins, thrombosis, thrombophlebitis, inflammatory infiltrates in paravenous tissues, thrombophlebitis of the haemorrhoidal veins; crus ulcer caused by disorders of local blood circulation; closed injury (including sports injury); injuries of soft tissue with haemorrhages, hematomas, sprains; tendovaginitis; post-surgical treatment of varicose veins; surface inflammation and infiltrates (abscesses, furunculosis, bedsores, irritation in skin folds, cracked and sore nipples during breastfeeding).

Spread a 5-cm column of gel on the affected area 1 to 3 times a day. For the treatment of venous disease, use gauze bandage containing the gel. Spread the gel in 4-cm circles for the treatment of varicose ulcers.

Side effects are rare. Local hypersensitivity reactions may rarely occur. If it is the case, stop using VENOHEPANOL.

Do not apply the gel on open wounds. Make sure that the gel did not get into the eyes or onto the mucous membranes.

Pregnant women can use the medicine only under close medical supervision.

VENOHEPANOL gel contains active ingredients, which are involved in body metabolic processes and have a synergistic action, and low toxicity; they well penetrate the skin, demonstrating a pronounced local action.

INDOVENOL is advisable if a vascular disease is accompanied by severe pain. 100 g of the gel contains troxerutin 2 g and indomethacin 3 g.

Indomethacin is a non-steroidal anti-inflammatory medication, and has potent analgesic and anti-inflammatory effects [3]. Indomethacin sometimes cannot be used orally due to a number of side effects: ulcero-haemorrhagic disorders of the digestive tract, liver and kidney disorders, and allergic reactions. When it is used topically, these side effects are almost absent [4].

INDOVENOL has its pronounced action due to the synergism of pharmacological effects of indomethacin and troxerutin.

It should be mentioned that the excipients propylene glycol and dimethyl sulfoxide help the active substances of INDOVENOL penetrate the tissue. In addition, dimethyl sulfoxide has anti-inflammatory and analgesic effects.

In the first place INDOVENOL has an analgesic action, and anti-oedema and anti-inflammatory effects. It also has angioprotective properties; it reduces vascular permeability, reduces congestion in the veins and paravenous tissues, normalizes microcirculation and tissue trophism, inhibits platelet aggregation.

The therapeutic Indications for the use of INDOVENOL gel: oedema and pain syndrome, microcirculatory and trophic disorders caused by acute or chronic lower extremity and rectum venous insufficiency (acute and chronic thrombophlebitis, post-thrombophlebitic syndrome, chronic lymphostasis, acute thrombosed haemorrhoids, etc..) and bursitis, tenosynovitis, synovitis, myositis and soft tissue injuries (bruises, sprains).

Use a 1–2-cm (0.3-0.5 g) column of gel. Spread a thin even layer on the affected area (by rubbing gently into the skin) 2-3 times a day. Do not spread the gel on open wounds. Make sure that the gel does not get into the eyes or onto the mucous membranes. Duration of the treatment should be determined individually, depending on the efficacy and tolerability of INDOVENOL. Hypersensitive patients may have some allergic reactions. If it is the case, stop using INDOVENOL.

After the gel has been spread on large areas or when the recommended doses have been exceeded, resorptive side effects may occur, which are typical for indomethacin medications: nausea, epigastric pain, ulcero-haemorrhagic disorders of the digestive tract.

Caution should be exercised if INDOVENOL should be prescribed to patients with a history of liver, kidney, or digestive tract disorders, as well as to pregnant or breastfeeding women. Occlusive dressing should be used in order to increase the efficacy of INDOVENOL.

Therefore, VENOHEPANOL and INDOVENOL are domestic medications for topical use for the treatment of inflammatory diseases associated with peripheral circulation disorders, in particular disorders of microcirculation and tissue trophism. These medications are used for the treatment of lower extremity vein diseases and their complications. They have shown their effectiveness in the treatment of superficial inflammation, soft tissue injuries, and healing of postoperative wounds. VENOHEPANOL and INDOVENOL are available in an appropriate dosage form (gel), which allows topical application of these products and ensures that the active substances well penetrate body tissues.
 
REFERENCES.

1. P.A. Galenko-Yaroshevsky, I.S. Chekman, N.A. Gorchakova. Notes on the Pharmacology of Products for Metabolic Therapy. - M .: Medicine, 2001 - 240 p.

2. Compendium 2001/2002 - Drugs/Under editorship of V.N.Kovalenko, A.P. Viktorova. - K.: Morion, 2001 - 536 p.

3. I.S. Chekman. Biochemical pharmacodynamics. — Kyiv: Zdorovia, 1991 - 200 p.

4. Brody T., Larner J., Minneman K. Human Pharmacology. Molecular to Clinic. — Mosby, 1998. — 1001 p.

5. Salerno E. Pharmacology for Health professionals. — Mosby. — 1999. — 827 p.

6. Callam M.J. (1994) Epidemiology of varicous veins. Brit. J. Surgery, 81(2): 167–173.

7. V.I. Rivkin, L.L. Kapuller. Haemorrhoids. - M .: Medicine, 1994 - 175 p.
 
23.02.2004    I.S.Chekman, the Head of the Pharmacology Department of the National Medical University. a Corresponding Member of the National Academy of Sciences, the Ukrainian Academy of Medical Sciences, Honorary Worker of Science and Technology of Ukraine, Professor