Method of treating diabetic foot syndrome

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to surgery, and can be used for treating trophic ulcers and purulonecrotic involvements of lower extremities in diabetic patients. That requires a baseline therapy and a regional fibrinolytic therapy. Conducting the regional fibrinolytic therapy following applying a rubber bandage on the lower one-third of the shin is accompanied by administering Urokinase medac in a dose of 100 thousand units into the heel bone once a day within 5 days.

EFFECT: in the setting of reducing the total dosage of the preparation, the invention enables providing the high concentration of Urokinase medac in a pathological centre, improving microcirculation and metabolic processes in the involved tissues, accelerating the wound healing and reducing the length of hospital admission of the patients suffering from diabetic foot syndrome.

2 ex

 

The invention relates to medicine, namely to the treatment of trophic ulcers and purulent-necrotic lesions of the lower extremities in patients with diabetes mellitus.

It is known that the most important direction in the treatment of complicated forms of diabetic foot syndrome (DFS) is the use of drugs that improve the macro - and microcirculation. Treatment is primarily inflammatory in nature and obturation of the arterioles and capillaries does not lead to significant clinical effect. Drugs with thrombolytic properties, allow to dissolve small blood clots in the arteries of small caliber and arterioles, thus improving the trophic and tissue oxygenation.

The known efficacy of urokinase in the treatment for patients with atherosclerotic changes in the vascular bed of diabetic origin. In addition to the basic treatment, patients received the drug intravenously slowly drip in the dosage of 300 thousand ME for 1.5-2 h, pre-diluted in 200 ml of 0.9% NaCl solution (Karaba K. A. thrombolytic drugs in treatment of diabetic foot syndrome // Actual problems of diagnosis, treatment and prevention of diabetic foot syndrome: proceedings of the IV all-Russian scientific-practical conference with international. - Kazan, 2012. - S. 79-82).

The disadvantage of this method is the following: skin is Amy injection of urokinase, quickly create high concentrations of the drug in the blood that is transported in a variety of self-tissues and accumulate mainly in ekskretiruyutsya organs (kidneys and liver). In this situation, drugs are rapidly eliminated from the body and do not allow to create a sufficiently high concentration of the drug in the area of inflammation, therefore, to maintain their high therapeutic concentrations to be constant introduction of maintenance doses of the drug.

The technical result consists in the reduction of terms of treatment of patients with diabetic foot syndrome due to a more pronounced and rapid positive dynamics of wound healing, hemostasis, free radical oxidation and endogenous intoxication.

The invention consists in that in the method of treatment of diabetic foot syndrome, including basic therapy and regional fibrinolytic therapy, in which the heel bone of the affected limb injected urokinase Medak at a dose of 100 thousand UNITS, 1 time per day for 5 days.

The method is as follows. To assess the effectiveness of therapy, patients were divided into 2 groups.

The first group included 35 patients with diabetic foot syndrome receiving conventional treatment (comparison group). The main group who left the 30 patients, in complex treatment which included regional intraosseous in the heel bone of the affected limb introduction urokinase Medak at a dose of 100 thousand UNITS, within 5 days. For monitoring of laboratory parameters studied a group of healthy individuals (30). The indicators examined in the admission of patients to hospital on the 5th, 10th and 20th days of treatment in both groups.

Traditional treatment was carried out with regard to complications and comorbidities. Patients received diet, subcutaneous administration of adequate doses of short-acting insulin (Actrapid, Humulin R, Insuman rapid) and ultra-short action (Novorapid, Humalog) in combination with insulin average duration (protoman, Humulin N, Insuman basal) based on the type of diabetes, lower energy consumption, as well as ascorbic and nicotinic acid, b vitamins, kokarboksilaza, ATP, xantinol nicotinate. Surgical treatment combined with active antibacterial therapy, which was conducted using a broad-spectrum antibiotic or combination of antibiotics with different mechanisms and range. The treatment was performed with sensitivity sown microflora. Used angioprotectors (trental, prodektina), vasodilator (papaverine, no-Spa), drugs antiplatelet action (citiesalive acid), the direct action anticoagulant (heparin). Poured the blood substitutes (reopoliglyukin).

When you open the management of wounds her cavity was loosely campanulales gauze drains with hypertonic sodium chloride solution or antiseptic solution. To speed up the cleansing of the wounds of necrotic tissue used chymotrypsin, trypsin. After cleansing the wound, applied a bandage with ointment: iruksol, levsin, levomekol, toxicol.

On the background of traditional treatment patients received regional intraosseous in the heel bone of the affected limb introduction urokinase Medak by the following method.

In compliance with the rules of asepsis, at the level of the lower third of the leg of the affected limb was put rubber bandage, with the aim of compression of the superficial veins of the leg. To conduct intraosseous infusions used medical diagnostic bone marrow needle with a diameter of 1.5 mm mandrel. The skin on the outer surface of the heel bone and the periosteum of the affected limb was obezbolivaet 5-10 ml of 0.5% solution of novocaine. Then in cancellous bone rotational movements at moderate pressure along the axis, was introduced to the needle to a depth of 1-1,5 cm Urokinase Medak was administered at a dose of 100 thousand UNITS, dissolved in 10 ml of 0.9% sodium chloride solution, 1 times a day, daily for 5 days. After intraosseous injection cramps the new bandage on the level of the lower third of the leg was kept for 15 minutes The needle was left in the bone tissue for subsequent intraosseous infusions.

As criteria for assessing the effectiveness of therapy identified the following indicators:

1) the effectiveness of the treatment was assessed clinically by the rate of growth of granulation tissue, the appearance of epithelialization.

2) evaluation of the course of reparative processes were carried out according to cytological study of wound exudate obtained when the surface of the biopsy wound according to the method of M. F. Kamaeva (1970). Smears were stained and fixed according to the method Romanovsky.

3) the dynamics of hemostasis was assessed on blood clotting time, activated partial thromboplastin time (APTT), thrombin time, the content of fibrinogen in the plasma level; fibrin monomer complex and prothrombin index, anti-thrombin III.

4) dynamics of indicators of oxidative reactions and antioxidant protection - malondialdehyde (MDA), catalase plasma and erythrocytes.

Clinical criteria intraosseous injection of urokinase in the complex treatment of complicated forms of diabetic foot showed improvement of the course of wound process in group 2, the appearance of a full granulation and epithelialization occurred on 2, 3 and 4 days earlier than in the control group.

Before treatment in they of the surface layers of the wound was noted to mind the counter the number of unchanged polymorphonuclear leukocytes (15-20 per field). The number of Poliplast and macrophages came to 1-3 in the field of view, the meager amount of microflora. Strands of fibrin.

At 12-14 day in patients with conventional treatment they noted polymorphonuclear unmodified cells to 8-10 in the field of view. The number of macrophages and Poliplast was observed to 7-9 in the field of view.

In the group of patients, where he held regional introduction of urokinase for 12-14 days of treatment, indicators of a favorable course of the wound process was to reduce the number of polymorphonuclear leukocytes (3-5 in the field of view), the microflora was absent. There were single macrophages. The number of Poliplast increased to 12-15 in sight, occurring singly and in groups of 2-3 cells. Traced the transformation of Poliplast in the Pro fibroblasts, indicating the activation of the regeneration process of the wound.

At admission, patients were observed activation of coagulation hemostasis with a strong fibrinogenesis. There was an increase in level; fibrin monomer complex by 68% (P<0,001). The presence in the plasma; fibrin monomer complex with anticoagulant activity, led to the lengthening of thrombin time by 11% (P<0,001). Increased clotting ability of the blood resulted in a significant consumption of anti-thrombin III. It was noted reduced levels of anti-thrombin III 39.1% (P<0.001) and shortening time, features resouses tolerance to heparin plasma, 1.4 times (P<0,001) compared to the control, which contributes to ischemic and thrombotic events, particularly in the area of peripheral blood flow.

On the 5th day, in spite of adequate conventional therapy, changes gemostaziogramma moved towards hypercoagulation, which was due to the activation of tissue thromboplastin and accumulation of plasma thromboplastin in the postoperative period, caused by mechanical injury of tissues. To 10-12-day traditional therapy has been a clear tendency towards a slight decrease in the coagulation activity of the blood, continued to 20-22-day.

Already on the 5th day of intraosseous injection of urokinase compared with the traditional treatment, was observed distinct changes of coagulation hemostasis towards its improvement, to 10-12 m day time rekaltsifikatsii lengthened by 10% (P<0,001), APTT - 9% (P<0.05), and the shortening of the thrombin time was observed in 6% (P<0,001), decreased fibrinogen level by 6% (P<0,05), prothrombin index decreased by 8.6% (P<0,001), activity fibrinstabilizirueshchego factor was increased by 11%(P<0,001).

At admission in patients with diabetic angiopathy of the lower extremities was observed significant activation processes lipoperoxidative on a background of depression of the antioxidant system. There was an increase from what the actual content of MDA in plasma 3.53 times. In erythrocytes of patients also reported the strengthening of processes of lipid peroxidation. The spontaneous oxidation of lipids content of malondialdehyde was increased by 92%, while Fe-induced oxidation - 90,15% (P<0,001) relative to normal values. The catalase activity of plasma was decreased by 69.3%, catalase activity in erythrocytes is 66.7%. These results indicate the important role of improving the processes of lipid peroxidation in the pathogenesis of purulent-necrotic complications of the diabetic foot and taking into account literature data (Balabolkin M. I., Klebanov E. M., 2000; Ceriello A., 2003 and others) you can talk about the development of oxidative stress in the studied group of patients

Traditional treatment has contributed to the reduction processes of lipid peroxidation and to a certain extent stimulated production of catalase in plasma and erythrocytes, however, significant differences in the studied parameters were observed only at 20-22 days of treatment. By this time the content of MDA in plasma decreased by 18,53%, Fe-MDA plasma - 7,88%. The level of MDA in erythrocytes was decreased by 10,48%, Fe-MDA in erythrocytes at 10.16 per cent in relation to the data upon receipt. The measure of catalase activity in plasma and erythrocytes increased 24.56 and 33,55%.

Thus, traditional therapy contributed only to 20-22 days minor reduction of the structure intensity of the processes of lipoperoxidation and stimulation of antioxidant defenses, which indicates the inclusion of the complex therapy of drugs specifically affecting these processes.

On the background of intraosseous application of urokinase already to 14 days of treatment were recorded marked reduction indices of the processes of lipoperoxidation. The values of MDA in plasma and erythrocytes was decreased by 36,23 and 15,67% (P<0,001). The measure of catalase activity in plasma and erythrocytes increased by 73,33 and 91,74% (P<0,001), in relation to data with traditional treatment.

To 20-22 days comprehensive treatment using the intraosseous injection of urokinase of MDA in plasma and erythrocytes was decreased by 42,59 and 25%, respectively. The decline in the intensity of the processes of lipoperoxidative noted an increase in the level of catalase in plasma and erythrocytes at 69,44 and 83.8% (P<0,001) compared to data with traditional treatment. From the data obtained it follows that the direct consequence of membrane processes is the improvement of microcirculation and increase delivery to the tissues of oxygen.

Clinical example 1.

Patient K., 69 years old, was admitted in the Department of purulent surgery the establishment of health care of the Republic of Moldova "MRCB" 12.09.12, Clinical diagnosis: Diabetes mellitus type 2, severe, insulin dependent form. Diabetic angiopathy, neuropathy of the lower extremities. Trophic ulcer stump I finger the eve of the foot. Ischemic heart disease. Angina II FC. Atherosclerotic cardiosclerosis, atherosclerosis of the aorta, coronary and cerebral vessels. Hypertension III senior, very high risk. HSN IIA.

Admitted with complaints on the availability of long-term unhealed sores stump of the first finger of the left foot, pain in the ulcer. From the anamnesis: diabetes suffers from 1992 Correction of blood glucose using glucose-lowering drugs (manini). In 2008 produced the amputation of the first finger of the left foot at the level of the middle third of the main phalanx. Trophic ulcer of the stump of the first finger of the left foot there for 3 months. It was treated at the surgeon's clinic without significant positive dynamics. Objective: swelling of the left foot no ripple on a. dorsalis pedis and a.tibialis posterior is missing. The first finger of the left foot amputated at the level of the middle third of the main phalanx, on the cult has a trophic ulcer size 1×2 cm with mild perifocal edema. On the periphery of the wound made by necrosis of soft tissues, in the center of the granulation tissue, covered fibrin. According to the VAT of lower extremity arteries: atherosclerosis of lower limb arteries with stenosis BOTH 20% PBA 30-40%, PKA left 50% right 40%, SBA, PBBA left up to 60%. When the smear-imprint revealed necrotic type cytogram. The patient was naznachen course complex conservative therapy in combination with regional intraosseous introduction urokinase Medak at a dose of 100 thousand IU once a day for 5 days.

During the course of treatment achieved a distinct positive clinical dynamics. Cleansing the wound occurred 4 days after the start of treatment, the foci of granulation tissue in the wound appeared on day 7. According to smears, fingerprints: 14 days was detected regenerative type cytogram. The patient was discharged to outpatient phase aftercare 28.09.2012.

Clinical example 2.

Patient, 42 years old, was admitted to the Department of purulent surgery the establishment of health care of the Republic of Moldova "MRCB" 20.11.12, Clinical diagnosis: Diabetes mellitus type 1, severe. Diabetic angiopathy of the lower extremities, polyneuropathy. Diabetic osteoarthropathy of the right foot. Rotten-necrotizing cellulitis of the right foot. Exarticulation of I-II of the toes of the right foot with resection of metatarsal bones, necrectomy from 23.11.12. Amputation stump of the left tibia. Diabetic nephropathy. Arterial hypertension II senior risk III. HSN I. Anemia of moderate severity.

Was admitted with complaints of General weakness, pain in the right foot. Diabetes suffers since 1981. In 1998 produced amputation of the left lower extremity at the level of the upper third of the leg about the rotten-necrotizing cellulitis of the left foot. In August 2012, hurt his right foot. For a long time was treated as outpatients, with no effect.

When entering the right stop and the lower third of the tibia swollen. The rear foot hyperemia, on the plantar surface I of the metatarsophalangeal joint of the wound 3*4 cm with abundant purulent discharge. The bottom of the wound are destroyed purulent-destructive process of the articular surfaces of the 1st metatarsophalangeal joint. The left lower limb is amputated at the level of the upper third of the leg.

Radiograph of the right foot from 21.12.12 By the destruction of the allied departments of the articulated bones of the 1st metatarsophalangeal joint: proximal phalanx to the border of the lower third and middle third of the diaphysis, metatarsal bone to the distal metaphysis, without distinct outlines. The surrounding soft tissues are thickened, uneven, due to the presence of free gas on the plantar surface of the edge defect. Bones marked osteoporosis. Conclusion: Osteomyelitis of the articulated bones I metatarsophalangeal joint. RVG lower extremities from 22.11.12: Right foot: pulse volume significantly reduced, the tone of the afferent vessels moderately elevated, the tone of the arterioles and precapillaries moderately elevated venous outflow saved, peripheral vascular resistance is slightly increased; right leg: pulse volume is significantly reduced. The tone of the afferent vessels moderately elevated. The tone of the arterioles and precapillaries moderately elevated venous outflow is slightly difficult, peripheral SOS is vascular resistance moderately raised.

Assigned to traditional therapy with regard to complications and comorbidities. 23.11.12 was done exarticulation I-II of the toes of the right foot with resection of metatarsal bones, necrectomy. The wound had been opened. In the heel bone of the right foot installed intraosseous needle. Once a day for 5 days was carried out by regional intraosseous introduction urokinase Medak at a dose of 100 thousand UNITS.

The postoperative period was uneventful. Necrolysis and cleansing the wound surface occurred on the 3rd day, the foci of granulation tissue in the wound appeared on the 5th day. On day 7, according to the smears, fingerprints were identified regenerative type cytogram imposed by secondary sutures. The patient in a satisfactory condition and was discharged on the 20th day.

Compared with the known solution proposed allows decreasing the total dosage of the drug to create a high concentration of urokinase Medak in the pathological focus, improve microcirculation and metabolic processes in the affected tissues, accelerate wound healing and reduce the time of hospital treatment of patients with diabetic foot syndrome.

A method of treatment of diabetic foot syndrome, including basic therapy and regional fibrinolytic therapy, characterized in that in the implementation of regional fibrinolytic therapy after applying rasinovo the bandage on the lower third of the tibia in the heel bone of the affected limb injected urokinase Medak at a dose of 100 thousand ED, 1 time per day for 5 days.



 

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9 cl, 39 dwg, 7 tbl, 31 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to combinations of peptides in each case with the same sequence length (SEQL) which can be prepared in a stable reproducible quality and quantity of a mixture (A) containing a number of x amino acid with protected acid groups or a number of z peptides with the acid groups protected by the protective groups and the activated amino groups, with the amino acids in the mixture (A) found in a specific molar ratio, and a mixture (B), containing a number of y amino acids with the amino groups protected by the protective groups, with a molar ratio of the amino acids of the mixture (B) being the same as the molar ratio of the amino acids of the mixture (A), and the number x=y, and x is a figure from 11 to 18.

EFFECT: new combinations of the peptides are presented.

13 cl, 2 dwg, 1 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely gynaecology, and may be used for treating chronic inflammatory genital diseases in females. That is ensured by the use of Promed balm which is introduced into vagina once a day, as well as taken orally 3 times a day. Promed balm may be introduced into vagina taking into account biological rhythms from 19 to 21 o'clock, and taking into account biological rhythms 9 to 11 o'clock, from 13 to 15 o'clock and from 19 to 21 o'clock. The method provides the improved clinical effectiveness ensured by providing the local and systemic anti-inflammatory effect due to the delayed growth of pathogens and toxin purification of the female body as a result of a diuretic and choleretic effect, immunomodulatory action, as well as due to activation of biological centres and their rhythm functioning, and regulation of metabolism and genital glands. In addition, it has a regenerating effect on skin and mucous membranes and recovers the nervous system.

EFFECT: achieved diet fortification and prevented recurrence of the disease.

3 cl, 2 ex

FIELD: medicine.

SUBSTANCE: pharmacological composition contains a therapeutic agent and a pharmaceutically acceptable base. As a therapeutic agent, it contains recombinant interferon specified in a group: recombinant interferon alpha, recombinant interferon beta, recombinant interferon gamma, as well as hypromellose, boric acid as an antiseptic, anesthesin or lidocaine as local anaesthetics in the following proportions, g per 1 ml of the mixture: recombinant interferon, IU 100-10,000,000, hypromellose 0.00001-0.5, boric acid 0.00001-0.5, anesthesin or lidocaine 0.00001-0.5, a pharmaceutically acceptable base - the rest. Besides, the pharmaceutical composition contains heparin in an amount of 0.00001-0.5 g; antibiotics specified in a group of: baneocin, levomycin, tetracycline, amoxicilline in an amount of 0.00001-0.5 g. And as a pharmaceutically acceptable base, the pharmaceutical composition contains macrogol 400, or macrogol 1500, or macrogol 4000.

EFFECT: more effective treatment.

4 cl, 9 ex

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