Method of hemostasis
(57) Abstract:The invention relates to medicine and, in particular, to surgery and is designed to stop bleeding from wounds, including, of spongy bone. The objective of the invention is fast and reliable hemostasis, including in the conditions of deficiency of coagulation factors and activation of fibrinolysis. The method includes the impact on wound low-frequency ultrasound. New in the way of exposure introduced into the wound hemostatic solution containing fibrinogen and-aminocaproic acid in ratios of: fibrinogen - 0,4-1,0 %; -aminocaproic acid to 5.0 %; water - the rest. 1 C.p. f-crystals. The invention relates to medicine and, in particular, to surgery and is designed to stop bleeding from wounds, including, of spongy bone.Known methods of hemostasis by treating bleeding wounds preparations containing exogenous procoagulant in high concentrations (33), protease inhibitors and other components, by applying a powder, aerosol or glue.A common disadvantage of known methods is the surface effect of hemostatic drugs, not penetrating deep into the tissues, so obrazumit to continue bleeding and hematoma formation.The second common disadvantage of these methods is the need for a fast and full simultaneous inclusion in the process of hemostasis large amount of fibrinogen many procoagulant components - thrombin, prothrombin extract platelets or factor XII clotting.A third common disadvantage of these methods is that they do not include the process of hemostasis own procoagulant.Closest to the proposed method is a method of hemostasis, in which the wound surface impose hygroscopic material and influence of ultrasonic vibrations with a frequency of 20-100 kHz and an amplitude of 5-80 μm in C. for 1-60The disadvantage of this method is the use of alien hygroscopic material, which must be subsequently removed from the wound. Educated bunch, fixed to the surface of the tissue and absorbent material, when you remove the last is destroyed, which can cause re-bleeding.The second disadvantage of this method is used for the formation of a clot only coagulation factors in a patient's own blood, that when de is cha invention fast reliable hemostasis, including, in the conditions of deficiency of coagulation factors and activation of fibrinolysis.The problem is solved in that in the method of hemostasis, including the effects on wound low-frequency ultrasound in wound impose hemostatic solution containing fibrinogen and inhibitor of fibrinolysis, and through it influence of ultrasonic vibrations to the formation of a clot, as a hemostatic solution using a solution containing fibrinogen and-aminocaproic acid in the following proportions,
S-aminocaproic acid 5
Water the Rest
The use of hemostatic drugs in solution facilitates the wicking in gaverova channels bones, megalocnus space, the end sections of the capillaries, aided and processing of ultrasonic vibrations.The use of fibrinogen in a concentration of less than 0.4 is impractical because of its content in the blood at the rate of 0.2 to 0.4 In the preparation of solution with a concentration of more than 1 is fast collapsing right in the tank where it is diluted, making it difficult intraoperative application.S-aminocaproic acid is used for the inhibition of f the th acid is allowed Pharmacopoeia and manufactured medical industry.Ultrasonic vibrations can deliver the hemostatic solution of the drug in the mouth of the capillaries and hold it there until the formation of a blood clot and its attachment to the walls of blood vessels. Accelerate the formation of a blood clot is due to the rapid release of a large amount of tissue, eritrocitarnah and platelet thromboplastin when exposed to ultrasound. This prevents the device from the hemostatic composition of the drug and to provide simultaneous inclusion in the process of coagulation of the total volume of concentrated solution of exogenous fibrinogen to blood clots in the Lumina of the end sections of the capillaries.Deficiency of fibrinogen in the blood under pathological conditions is compensated by exogenous drug, increased under these conditions fibrinolytic activity of blood is compensated by the use of an inhibitor of fibrinolysis - S-aminocaproic acid. The proposed method eliminates the need for subsequent removal from the wound for foreign material that promotes integrity clots and blood clots.The method is as follows.After execution of the main floor is provide hemostatic solution, prepared ex tempore. In a sealed sterile vial containing 0.8 to 1 g of dry powder of fibrinogen (standard packaging) using a system for transfusion fluids or syringe administered 100 or 200 ml of a 5 solution of S-aminocaproic acid, based on the capacity of the wound, and stir, shaking to dissolve the powder of fibrinogen. Get solution with a fibrinogen concentration of 0.4-1 which can be stored no more than 30-40 minutes, during which it must be used, otherwise there is a transition of soluble fibrinogen into insoluble fibrin to form a clot in a bottle.Bathed in the wound solution is injected ultrasonic waveguide attached to the acoustic node of the ultrasonic device of the type URSC-7H (URSC-7H-18, URSC-7H-22, etc) connecting the machine to a network and setting the resonance produced in advance. Turning on the device, sequentially perform processing of all the bleeding wound walls ultrasound through the solution of a circular or reciprocating movements with exposure time up to 30 s/cm from a distance of 1-2 mm to the soft tissues and 0.5-1 mm to the bone, the frequency of ultrasonic vibrations 26,52 kHz, the amplitude of 30-50 μm. The end face of the waveguide have a parallel to the work surface t is Aleut from the wound and hold it suturing.Example 1. The rabbit is anesthetized by intramuscular introduction of 0.4-th solution hexanal, fixed in the machine by the limbs in position on the abdomen. After processing the shaved areas of the skin in the pelvic region for symmetric sections formed 2 wounds with exposed cancellous bone in the area of 1 see the wounds entered hemostatic solution containing 0.5 fibrinogen and 5 S-aminocaproic acid. On the right side (experience) the solution is expressed by the apparatus URSC-7H-22 with a frequency of 26.5 kHz and an amplitude of 30 μm. Time stop bleeding wound in the left (control) 65, right in the wound (experience) -27 C. Rabbit out of experience. The bone specimens from the surgical area when painting on fibrinogen on the left side of the latter lies on the surface of the bone, penetrating the depth of bezbalochnykh spaces to 0.03 mm on the right side of the depth of penetration of fibrinogen in megalocnus space spongy bone to 3 mm.Example 2. Patient B. 57 years, operated on for right coxarthrosis III degree with pain caused by avascular necrosis of the femoral head. Performed hip replacement surgery, after removal of the proximal thigh (above the greater trochanter), boring cost 5th solution S - aminocaproic acid introduced into the vial with 0.8 g of powder of fibrinogen. During the dissolution of the powder produced connecting and configuring the resonance of the ultrasonic device was URSC-7H-18. Received hemostatic solution containing 0.8 fibrinogen and 5 S-aminocaproic acid poured into the wound, it entered the waveguide machine, and then made the sound of all the walls of the wound through the hemostatic solution with a focus on the bottom of the acetabulum. Stop the bleeding from the wound walls came after 2 min, from the bottom of the acetabulum after 3 minutes then installed the endoprosthesis of the hip joint construction of the Sivash. From the bottom of the acetabulum re-emerged bleeding. Similarly cooked described hemostatic solution, introduced into the wound and voiced by the same apparatus, with the processing of the walls and bottom of the wound in the area of the endoprosthesis Cup. After 2 minutes the bleeding stopped. Produced by wound closure with passive drainage PVC pipe with perforations. Postoperative drainage in the 1st day went 150 ml of blood was pouring 150 ml of erythromyci. On the second day after surgery for drainage discharge no drainage deleted. The nearest postoperative period smooth, sutures were removed, the healing of primary education is wildly clinical effectiveness of the invention is:
fast reliable hemostasis in the operating wound, including, in conditions of impaired functioning of the coagulation and fibrinolytic systems of blood;
in reducing postoperative blood loss;
to prevent the formation of hematomas;
prevention of suppurative complications after complex planned reconstructive surgeries;
ensuring the full surgical hemostasis of RAS spongy bone.Sources of information
1. EPO N 0068149, class a 61 K 37/54, publ.05.01.83.2. EPO N 0068048, class a 61 K 37/54, publ.05.01.83.3. EPO N 0068047, publ. A 61 K 37/54, publ.05.01.83.4. U.S. patent N 4414976, NCI 128/334R, publ.184.108.40.206. Auth.St. USSR N 6147880, CL A61 In 17/00, publ.15.07.78. 1. Method of hemostasis, including the effects on the wound by low-frequency ultrasound, characterized in that the wound is injected hemostatic solution containing fibrinogen and inhibitor of fibrinolysis, and through it influence of ultrasonic vibrations to the formation of a clot.2. The method according to p. 1, wherein the use solution containing fibrinogen and-aminocaproic acid in the following proportions,
Fibrinogen 0,4 1,0
S-Aminocaproic acid 5
FIELD: pharmaceutical chemistry.
SUBSTANCE: invention relates to (i) essentially crystalline melagatran in the form of hydrate, which is characterized by x-ray diffraction pattern on powder having crystalline peaks with following d values: 21.1, 10.5, 7.6, 7,0, 6.7, 6.4, 6.2, 5.7, 5.4, 5.3, 5.22, 5,19, 5.07, 4.90, 4.75, 4,68, 4.35, 4.19, 4.00, 3.94, 3.85, 3.81, 3.73, 3.70, 3.63, 3.52, 3.39, 3.27, 3,23, 3.12, 3.09, 3.06, 2.75, 2.38, and 2.35 Å and/or water content 4.3%; and (ii) essentially crystalline melagatran in the form of anhydrate, which is characterized by x-ray diffraction pattern on powder having crystalline peaks with following d values: 17.8, 8.9, 8.1, 7.5, 6.9, 6.3, 5.9, 5.6, 5.5, 5.4, 5.3, 5.2, 5.0, 4.71, 4.43, 4.38, 4.33, 4.14, 4.12, 4.05, 3.91, 3.73, 3.61, 3.58, 3.56, 3.47, 3.40, 3.36, 3,28, 3.24, 3.17, 3.09, 3.01, 2.96, 2.83, 2.54, 2.49, 2.41, 2.38, and 2.35 Å. Invention also relates to a method for preparation of indicated form, a method for interconversion of anhydrite form, to use of indicated compounds as pharmaceutical agent, and to preparation of drugs. Pharmaceutical preparation is suitable for treatment of condition, in case of which inhibition of thrombin is needed or desirable. Invention provides a method for treatment of such condition.
EFFECT: increased chemical stability and solid state stability as compared to amorphous forms of melagatran.
14 cl, 4 dwg, 3 tbl, 9 ex
FIELD: medicine, pharmaceutics, pharmacology.
SUBSTANCE: one should apply mammalian anti-HBP-antibodies. The ways are being suggested to identify monoclonal antibody bound, at least, with one epitope upon native HBP (heparin-binding protein) and methods to detect whether a mammal produces HBR being bound with a monoclonal antibody and, also, the kits for the above-mentioned purpose. The present innovation provides the opportunity to apply the mentioned antibodies in preventing and treating disorders associated with bradykinin releasing.
EFFECT: higher efficiency of application.
25 cl, 11 dwg, 3 ex, 1 tbl